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Bending the Curve Trial by Trial
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Blood and bone marrow

Childhood acute lymphoblastic leukemia (ALL)

How childhood acute lymphoblastic leukemia care moved from antifolate remissions in 1948 to risk-adapted chemotherapy and immunotherapy.

5-year relative survival · United States (NCI fact sheet; registry not stated on the page)

57%→92.3%

1975 to 2014-2020. Read these with the caveats under “Then and now”.Source

29 milestones, by decade

  • In US registry data on the SEER Cancer Stat Facts childhood leukemia page (ages 0-19, all leukemia types, not ALL alone), the age-adjusted death rate was 2.03 per 100,000 in 1975 and 0.49 in 2024, while the age-adjusted rate of new cases in the SEER 8 column was 3.13 per 100,000 in 1975 and 4.85 in 2023. Observed five-year relative survival in the SEER 8 series was 36.58% for 1975 and 90.71% for 2018 (the page does not say whether the year is the year of diagnosis). The page does not say how much of the change reflects treatment, leukemia-type mix or classification.
  • The NCI fact sheet on cancer in children and adolescents says that improved treatments for ALL, introduced beginning in the 1960s and 1970s, raised the five-year survival rate for children diagnosed with the disease from 57% in 1975 to 92.3% in 2014-2020. For 2013-2019 it gives lower five-year survival for lymphoid leukemias, mostly ALL, in children younger than 1 year (61%) and in adolescents (78%) than at ages 1-4 (96%), 5-9 (94%) and 10-14 (86%). The page does not state the age range behind the ALL figures, the registry set, or whether the survival is relative.
  • A 2009 trial of 498 evaluable children with newly diagnosed ALL omitted prophylactic cranial irradiation in every patient, with treatment intensity set by presenting features and minimal residual disease after remission induction. It reported a five-year cumulative risk of isolated CNS relapse of 2.7% (95% CI 1.1 to 4.3) and five-year event-free and overall survival probabilities of 85.6% and 93.5%. The 71 patients who previously would have received irradiation had longer continuous complete remission than 56 historical controls (P=0.04); the comparison was with historical controls, not a randomised control group.

Evidence current to October 2026 · Checked against primary sources to the extent possible

A guided tour of 11 milestones. You can pause or step through it yourself.

Filter milestonesshowing all 29
Treatment type
Setting

Chemotherapy

  1. 1948 · Treatment · Chemotherapy⚑ needs reviewAminopterin produces temporary remissions in childhood leukemiaIn 1948 Sidney Farber and colleagues reported that aminopterin, a drug that blocks folic acid, brought temporary remissions to some children with acute leukemia. The remissions were short and the drug caused serious side effects, but a 2013 review describes the report as opening the era of chemotherapy for the disease.Uncontrolled clinical series of children with acute leukemia given the folic acid antagonist aminopterin (N Engl J Med, 3 June 1948). A later account (Spain and Kadan-Lottick 2012) reports 16 critically ill children treated: 10 had remissions that were temporary, 2 had none and 4 died within a few months; the paper documents 5 of the 10. Toxicity included stomatitis with mouth ulceration, internal hemorrhage and marrow aplasia. Counts come from the later account, not the paywalled 1948 text.
  2. 1953 · Treatment · ChemotherapyMercaptopurine and methotrexate: from 1953 to ALL maintenanceIn 1953 doctors reported that mercaptopurine, a drug designed to interfere with purine metabolism, produced remissions in some children with acute leukemia, including some whose disease had stopped responding to a folic acid blocker. Mercaptopurine and methotrexate are now given together in the continuation phase of ALL treatment.Burchenal et al. (Blood, November 1953), uncontrolled series: 6-mercaptopurine produced good clinical and hematologic remissions in 15 of 45 children with acute leukemia and partial remissions in 10 more; among 24 children with disease resistant to amethopterin (methotrexate), 5 had good and 5 partial remissions. Resistance to 6-MP appeared to develop somewhat faster than to folic acid antagonists. FDA's table dates mercaptopurine 11 September 1953 and methotrexate 7 December 1953 (original approvals in Drugs@FDA).
  3. 1961 · Treatment · Chemotherapy⚑ needs reviewCombination antileukemic agents tested in children with ALLIn 1961 Emil Frei and colleagues reported a comparison of mercaptopurine and methotrexate, given in sequence or together, in acute leukemia. In children, remissions were more frequent with both drugs than with either alone, and the typical remission lasted 4 to 5 months with all three. A 1965 report found that adding methotrexate did not lengthen remission beyond mercaptopurine alone.Frei 1961 (Blood; abstract), children with acute lymphocytic leukemia: remission rate 59% with mercaptopurine plus methotrexate, 47% with mercaptopurine, 29% with methotrexate; median duration of complete remission 4 to 5 months for all three; n and remission definition not in the abstract. Frei 1965 (Blood; abstract): combinations gave at least additive remission rates; alternating versus concurrent agents, and combination versus mercaptopurine alone, did not prolong remission; intrathecal folic acid antagonist did not either but reduced meningeal leukemia.
  4. 1967 · Treatment · Chemotherapy⚑ needs reviewAsparaginase: from 1967 leukemia reports to a core ALL drugIn 1967 a JAMA report described remissions in human leukemia with L-asparaginase, an enzyme that breaks down the amino acid asparagine. It later became a component of ALL regimens, and a 2013 review describes a long-acting pegylated form as the first-line asparaginase in the United States.Hill et al. (JAMA, 27 November 1967) reported remission in human leukemia with L-asparaginase (title only; no abstract). FDA: asparaginase (Elspar) January 1978; pegaspargase February 1994 (hypersensitivity to native forms) and 24 July 2006 (first-line, multi-agent ALL). DFCI 05-001 (Place 2015): 463 randomised; asparaginase-related toxicity 28% IV pegaspargase vs 26% IM native E coli (p=0.60); 5-year DFS 90% vs 89% (p=0.58).
  5. 1971 · Treatment · Chemotherapy⚑ needs reviewTotal Therapy and CNS-directed prophylaxis at St JudeSt. Jude Children's Research Hospital began "total therapy" for childhood leukemia in 1962, adding treatment aimed at the central nervous system to combination chemotherapy. Early reports described fewer nervous-system relapses, and a 2013 review credits an early study with cures in about half of 35 patients.St Jude single-institution series: cranial irradiation (2400 R) plus intrathecal methotrexate added early in remission to combination chemotherapy. Aur 1971 (Blood): of 35 consecutive children, 20 of 30 who attained remission and completed the initial phases were in continuous complete remission for 23 to 30 months; nervous system relapse ended remission in 3, hematological relapse in 5. Earlier regimens: CNS leukemia ended remission in over half the patients, median 11 months. Abstract-level; no randomised comparison described.

Molecular origins

  1. 1996 · Understanding · UnderstandingUniform NCI risk classification for childhood ALLA 1996 report from a 1993 US workshop of four research groups and the National Cancer Institute set common risk groups for children with B-precursor ALL. Standard risk meant age 1 to 9 years with a white-cell count below 50,000 per microlitre; everyone else was high risk. The authors expected common labels to make trials more efficient.NCI Cancer Therapy Evaluation Program workshop, September 1993 (CCG, POG, DFCI, St Jude): outcome data from the groups were combined using weighted averages. B-precursor ALL: standard risk = age 1 to 9 years and WBC below 50,000/microL (4-year EFS approximately 80%); remaining patients high risk (approximately 65%). T-cell ALL: groups differed on risk assignment. DNA index, cytogenetics, early response, immunophenotype and CNS status were to be collected uniformly.

Targeted therapy

  1. 1998 · Treatment · ChemotherapyAugmented post-induction therapy for slow early respondersIn a 1998 randomised trial of 311 children with high-risk ALL whose leukemia cleared slowly at the start of treatment, a more intensive course of post-induction chemotherapy was followed by better five-year event-free survival than the standard course: about 75 in 100 versus 55 in 100. The extra treatment had considerable but manageable side effects.Randomised trial, January 1991 to June 1995: 311 children with newly diagnosed high-risk ALL, slow early response (more than 25 percent marrow blasts on day 7) and remission after induction; standard (156) versus augmented (155) post-induction chemotherapy. Five-year Kaplan-Meier EFS from end of induction 75.0% versus 55.0% (P<0.001); OS 78.4% versus 66.7% (P=0.02). Difference most pronounced at ages 1 to 9 years. Toxicity considerable but manageable.
  2. 1998 · Understanding · UnderstandingMinimal residual disease predicts relapse in childhood ALLIn 1998 a European study of 178 children in remission from ALL found that leukemia cells still detectable with a sensitive gene-based test were linked to later relapse. Later studies using other methods supported this, and residual disease became a way to choose how intensive treatment should be.Prospective EORTC Children Leukemia Group study at 11 centres: 246 patients enrolled, 178 monitored for residual disease by competitive polymerase chain reaction on clonal immunoglobulin or T-cell receptor rearrangements; median follow-up 38 months. Presence and level of residual leukemia correlated with early relapse at each time studied (P<0.001). In multivariate analysis it was the most powerful independent prognostic factor, ahead of immunophenotype, age, risk group and white-cell count.
  3. 2005 · Treatment · ChemotherapyNelarabine for T-cell ALLNelarabine, a drug activated inside T cells, was tested in children and young adults whose T-cell cancer had returned or not responded. In first relapse with marrow involvement more than half responded, and FDA granted accelerated approval in 2005. A later randomised COG trial reported better disease-free survival when it was added to first-line treatment.COG phase II (121 enrolled, 106 assessable): CR+PR rates at final doses 55% (stratum 1, first marrow relapse), 27%, 33% and 14%; grade 3 or higher neurologic events in 18% of patients. COG AALL0434 (phase III, 1,562 evaluable T-ALL; randomised intermediate- and high-risk patients): 5-year DFS 88.2% with nelarabine (n=323) vs 82.1% without (n=336), P=0.029; 5-year CNS relapse incidence 1.3% vs 6.9%; 5-year OS 90.3% vs 87.9% (P=0.168).
  4. 2007 · Understanding · UnderstandingGenome-wide analysis: IKZF1 loss, Ph-like and other subtypesLarge genetic studies of leukemia cells from children and young adults found repeated changes in genes that guide B-cell development, such as PAX5 and IKZF1. Loss of IKZF1 was linked to poorer outcomes. A further group, Ph-like ALL, resembles Philadelphia chromosome-positive disease and often carries changes in kinase genes that approved drugs might block.Mullighan 2007 (242 paediatric ALL cases, SNP arrays and sequencing): B-cell development genes altered in 40% of B-progenitor cases, PAX5 in 31.7%. Mullighan 2009 (221 high-risk children; IKZF1 altered in 28.6%): a copy-number predictor of poor outcome, strongly associated with IKZF1, validated in 258 patients. Roberts 2014: Ph-like ALL 10% of standard-risk children to 27% of young adults; kinase-activating alterations in 91%.
  5. 2007 · Treatment · ChemotherapyInterfant protocols for infants with ALLInfants younger than one year with ALL have had worse outcomes than older children. An international group treated 482 infants with a hybrid regimen drawn from both ALL and AML treatment; just under half were event-free at four years. A randomised extra intensive course did not help, and the later Interfant-06 study did not improve outcomes.Interfant-99 (17 study groups, 22 countries): hybrid ALL/AML regimen, risk-stratified by prednisone prophase response. In 482 treated infants 4-year EFS was 47.0% (95% CI 41.9-52.1). Randomised late intensification (95 vs 96 patients): 4-year DFS 60.9% vs 57.0% (p=0.81). Interfant-06 (n=651): 6-year EFS 46.1%; randomised myeloid- vs lymphoid-style courses, 6-year DFS 39.3% vs 36.8% (p=0.47).
  6. 2008 · Understanding · UnderstandingLate effects in survivors of childhood ALL (CCSS)A study of survivors of childhood ALL diagnosed in 1970-1986 who had lived at least five years followed them to 25 years after diagnosis. About 13 in 100 had died, mostly from relapse or second cancers, and survivors reported more serious chronic health conditions than their siblings. Radiotherapy and relapse carried the greatest risk.Childhood Cancer Survivor Study: 5760 eligible five-year ALL survivors diagnosed 1970-1986 (4151 participants), compared with the general population and 3899 siblings. Cumulative mortality 13% at 25 years; recurrent ALL (483 deaths) and second neoplasms (89 deaths) were the major causes of death. Severe or life-threatening chronic conditions: OR 3.6 (95% CI 3.0-4.5) versus siblings. Cumulative incidence of severe conditions including death at 25 years 23.3% in irradiated and 13.4% in nonirradiated survivors.
  7. 2009 · Treatment · TargetedImatinib added to chemotherapy for Ph-positive ALLImatinib blocks the abnormal BCR-ABL1 protein found in Philadelphia chromosome-positive leukemia. When children received it for longer alongside intensive chemotherapy in a Children's Oncology Group study, about eight in ten were free of relapse or other events at three years, compared with about one in three earlier-treated children.COG AALL0031 (non-randomised; N=92 Ph+ ALL, ages 1-21): imatinib 340 mg/m2/day with intensive chemotherapy in five cohorts of increasing exposure. Cohort 5 (280 days, n=50): 3-year EFS 80% (95% CI 64%-90%) vs 35% in historical controls (P<0.0001). EsPhALL2004 randomised good-risk patients: 4-year DFS 72.9% vs 61.7% with vs without imatinib (p=0.24; MRD-adjusted HR for any event 0.63, 95% CI 0.28-1.41).
  8. 2009 · De-escalation · ChemotherapyTreating ALL without prophylactic cranial irradiationIn 2009 St Jude reported treating 498 children with ALL without routine radiotherapy to the brain, using chemotherapy matched to risk and early response. About 3 in 100 had a relapse confined to the nervous system within five years. The comparison with earlier patients who had radiotherapy was not randomised.St Jude Total Therapy XV: 498 evaluable patients, intensity set by presenting features and MRD after induction, no prophylactic cranial irradiation. 5-year EFS 85.6% (95% CI 79.9-91.3), OS 93.5% (89.8-97.2); cumulative isolated CNS relapse 2.7% (1.1-4.3), any CNS relapse 3.9% (1.9-5.9). Continuous complete remission was longer in 71 patients who would formerly have been irradiated than in 56 historical controls given irradiation (P=0.04). Total Therapy 16 (598 patients): any CNS relapse 1.5% (0.5-2.5).
  9. 2010 · Treatment · ChemotherapyMitoxantrone in first relapse; TBI before transplant in childhood ALLIn a trial in the UK, Ireland, Australia and New Zealand, children with a first relapse given mitoxantrone instead of idarubicin during induction did better at three years, and randomization stopped early. In a later international trial of children in remission before stem cell transplant, total body irradiation gave better survival and fewer relapses than chemotherapy conditioning.ALL R3 (open-label RCT, first relapse, 216 randomly assigned, MRD-guided transplant): mitoxantrone vs idarubicin induction, 3-year PFS 64.6% vs 35.9% (p=0.0004), 3-year OS 69.0% vs 45.2% (p=0.004). FORUM (noninferiority phase 3, complete remission before transplant, 54% in first remission; 212 TBI vs 201 chemoconditioning): 2-year OS 91% (95% CI 86 to 95) with TBI plus etoposide vs 75% (95% CI 67 to 81) (p<0.0001); relapse incidence 12% vs 33%.

Immunotherapy

  1. 2012 · Understanding · UnderstandingChildhood ALL survival trends 1990-2005 (COG)A Children's Oncology Group analysis of 21,626 young people treated on its ALL trials found that five-year survival rose from about 84 in 100 in 1990-1994 to about 90 in 100 in 2000-2005. Survival changed little for infants. NCI's fact sheet separately reports a rise from 57 in 100 in 1975 to 92 in 100 in 2014-2020.COG analysis of 21,626 persons aged 0 to 22 years enrolled on ALL trials 1990-2005 (55.8% of estimated US cases). Five-year survival rose from 83.7% (1990-1994) to 90.4% (2000-2005), P<.001; all subgroups improved except infants (age 1 year or younger). Deaths after relapse or progression decreased and treatment-related deaths increased; 36% of deaths occurred in NCI standard-risk patients. Separate NCI fact sheet: ALL 5-year survival 57% (1975) to 92.3% (2014-2020).
  2. 2013 · Understanding · UnderstandingAcute lymphoblastic leukemia in children with Down syndromeChildren with Down syndrome have a higher risk of B-cell ALL. Two large analyses, one international and one from the Children's Oncology Group, found that they relapse more often and are more likely to die of treatment complications than other children, so survival is lower. Both called for less toxic treatment or better supportive care.Ponte di Legno (653 DS-ALL patients, 16 trials, 1995-2004) vs non-DS reference cohorts: 8-year EFS 64% vs 81%, OS 74% vs 89%, cumulative incidence of relapse 26% vs 15%, 2-year TRM 7% vs 2.0%. COG (743 DS vs 20,067 non-DS, ages 1-30, four B-ALL trials): 5-year EFS 79.2% vs 87.5%, OS 86.8% vs 93.6%; death in remission 4.9% vs 1.7%.
  3. 2013 · De-escalation · Chemotherapy⚑ needs reviewMRD-guided treatment reduction for low-risk ALL (UKALL 2003)In the UK trial UKALL 2003, children and young adults whose leukemia cleared quickly were randomly given one or two courses of delayed intensification chemotherapy. Five-year event-free survival was 94.4 in 100 with one course and 95.5 in 100 with two, a difference that was not statistically significant.UKALL 2003 (UK and Ireland), ages 1 to 25 years: 3207 registered; 521 MRD low-risk patients randomised to one (260) or two (261) delayed intensifications; median follow-up 57 months. 5-year EFS 94.4% (95% CI 91.1-97.7) versus 95.5% (92.8-98.2); odds ratio 1.00 (0.43-2.31), P=0.99. Actuarial relapse 5.6% versus 2.4% (P=0.23). Treatment-related deaths: 3 with two courses (1.2%), none with one (P=0.08).
  4. 2013 · Treatment · Cell therapy & transplantCD19 CAR T cells induce remissions in children with relapsed ALLIn 2013 doctors reported two children with relapsed leukemia who were given their own T cells, re-engineered to recognize CD19 on leukemia cells. Both reached remission. One stayed in remission for at least 11 months; in the other the leukemia returned about two months later without CD19. A 2014 report of 30 patients found remission in nine of ten.Grupp 2013: two children with relapsed, refractory pre-B-cell ALL given CTL019 CAR T cells; both reached complete remission, ongoing at 11 months in one, while the other relapsed about 2 months later with CD19-negative blasts. Maude 2014 (30 children and adults): complete remission 27 of 30 (90%); 6-month EFS 67% (95% CI 51 to 88), OS 78% (95% CI 65 to 95); severe cytokine-release syndrome in 27%.
  5. 2016 · Treatment · ChemotherapyDexamethasone and high-dose methotrexate in high-risk B-ALLIn a Children's Oncology Group trial of 2,914 randomised patients aged 1 to 30 with high-risk B-cell ALL, high-dose methotrexate gave better five-year event-free survival than escalating-dose methotrexate: about 80 in 100 versus 75 in 100. Dexamethasone was linked to better outcomes in children aged 1 to 9 on high-dose methotrexate, not in older patients, who had more bone damage.COG AALL0232: 3,154 participants aged 1-30 with high-risk B-ALL, 2,914 randomised 2 x 2 (dexamethasone 14 days versus prednisone 28 days in induction; high-dose methotrexate versus Capizzi methotrexate plus pegaspargase in interim maintenance 1). Interim analysis, enrolment stopped: 5-year EFS 82% versus 75.4% (P=.006); mature final data 79.6% versus 75.2% (P=.008). Ages 1-9: dexamethasone plus high-dose methotrexate 91.2% versus 83.2%, 80.8%, 82.1% (P=.015). Older participants: no dexamethasone benefit, more osteonecrosis.
  6. 2016 · Treatment · ImmunotherapyBlinatumomab for relapsed or refractory paediatric B-ALLA 2016 study tested blinatumomab, an antibody that links a patient's T cells to leukemia cells, on its own in children whose B-cell leukemia had relapsed or resisted treatment. At the dose later recommended, about two in five children reached complete remission within two cycles, and about half of those also had a complete response on residual-disease testing.Open-label phase I/II study of single-agent blinatumomab in 93 children (49 in phase I, 44 in phase II) with relapsed or refractory BCP-ALL. Recommended dosage 5 µg/m2/d for 7 days, then 15 µg/m2/d. Among 70 patients at that dosage, complete remission within two cycles 39% (95% CI 27 to 51); 14 of 27 (52%) had a complete MRD response. Cytokine-release syndrome of grade 3 in 3 patients (4%) and grade 4 in 1 (1%).
  7. 2017 · Treatment · Cell therapy & transplantFDA approves tisagenlecleucel for relapsed or refractory B-ALLIn August 2017 the US regulator approved tisagenlecleucel, made from a patient's own T cells, for people up to 25 whose B-cell leukemia was refractory or in second or later relapse. About four in five patients in the main study had remission. Cytokine release syndrome occurred in about three in four, and fewer than half were event-free at three years.FDA regular approval (30 August 2017) for B-cell precursor ALL up to age 25, refractory or in second or later relapse. ELIANA, single-arm phase 2 (75 infused patients evaluable): overall remission rate within 3 months 81%, all responders MRD-negative; EFS 73% at 6 and 50% at 12 months; OS 90% and 76%. Three-year update (79 patients, median follow-up 38.8 months): remission rate 82%, EFS 44% (95% CI 31 to 57), OS 63% (95% CI 51 to 73).
  8. 2018 · Treatment · TargetedDasatinib with chemotherapy for Ph-positive ALLDasatinib is a more potent BCR-ABL1 blocker than imatinib. In a Children's Oncology Group study of 60 patients aged 1 to 30, adding it to intensive chemotherapy was feasible, with outcomes similar to the earlier imatinib study. A randomised trial in China reported better event-free survival with dasatinib than imatinib.COG AALL0622 (single-arm, n=60, ages 1-30): dasatinib from induction day 15 plus intensive chemotherapy; 5-year EFS 60%, OS 86%; 5-year CNS relapse incidence 15.4% in 40 non-transplanted, non-CNS3 patients; 5-year DFS 60% vs 68% for AALL0031 imatinib (P=0.31). CA180-372/AALL1122 (n=106): 3-year EFS 65.5% vs 49.2% historical chemotherapy alone (p=0.032) and 59.1% historical imatinib (p=0.27). Randomised China trial (n=189): 4-year EFS 71.0% vs 48.9% (p=0.005).

Precision & engineered

  1. 2020 · Treatment · Antibody–drug conjugateInotuzumab ozogamicin for relapsed paediatric CD22+ ALLInotuzumab ozogamicin is an antibody joined to a cell-killing drug that targets CD22 on leukemia cells. In a European phase 1 study, four in five heavily pretreated children responded after the first course; a Children's Oncology Group study reported remission in about three in five. The FDA approved it for children aged 1 year and older in March 2024.Single-arm studies. ITCC-059 phase 1 (25 patients): overall response after course 1 80% (95% CI 59 to 93), 84% of responders MRD-negative complete response, 12-month OS 40% (95% CI 25 to 66). COG AALL1621 phase 2 (48 evaluable, ages 1 to 21): CR/CRi 58.3% (90% CI 46.5 to 69.3). FDA label, 6 March 2024, ITCC-059 analysis of 53 patients: CR 22 of 53 (42%; 95% CI 28.1 to 55.9).
  2. 2021 · De-escalation · ChemotherapyFewer vincristine and dexamethasone pulses in standard riskIn a Children's Oncology Group trial, 2,364 average-risk children with standard-risk B-cell ALL were randomly given vincristine and dexamethasone pulses every 4 or every 12 weeks during maintenance. Five-year disease-free survival was about 94 in 100 versus 95 in 100, with no significant difference. A higher methotrexate starting dose did not help.COG AALL0932: 9,229 NCI standard-risk B-ALL patients enrolled; 2,364 average-risk patients randomised (2 x 2) at the start of maintenance. Vincristine/dexamethasone every 4 versus 12 weeks: 5-year DFS 94.1% versus 95.1% (P=.86), OS 98.3% versus 98.6% (P=.69). Methotrexate starting dose 20 versus 40 mg/m2: DFS 95.1% versus 94.2% (P=.92), OS 98.8% versus 98.1% (P=.89). All eligible patients (9,226): 5-year EFS 92.0%, OS 96.8%.
  3. 2021 · Treatment · ImmunotherapyBlinatumomab versus chemotherapy in first relapse of B-ALLTwo randomized trials published in 2021 compared the antibody blinatumomab with chemotherapy given before stem cell transplant in children and young adults with first relapse of B-cell leukemia. The trial in high-risk children stopped early because blinatumomab did better. The larger trial, which included intermediate-risk patients, stopped early with no statistically significant difference in disease-free survival.Two phase 3 RCTs (JAMA, 2021). Amgen high-risk first-relapse trial, children (108 randomized; one blinatumomab cycle before transplant): EFS HR 0.33 (95% CI 0.18 to 0.61), events 31% vs 57%; stopped early for benefit. COG AALL1331, ages 1 to 30 (208 randomized; two cycles): 2-year DFS 54.4% vs 39.0%, HR 0.70 (95% CI 0.47 to 1.03), 1-sided P=.03 against a threshold of .025; terminated early.
  4. 2023 · Treatment · ImmunotherapyBlinatumomab added to chemotherapy in infant ALLInfants with KMT2A-rearranged ALL have had poor outcomes with chemotherapy alone. In a study of 30 infants, one course of blinatumomab, a drug that links T cells to CD19-bearing leukemia cells, was added to Interfant-06 chemotherapy. Disease-free survival at two years was about 82%, compared with about 49% in earlier Interfant-06 patients.Single-arm study, 30 infants with newly diagnosed KMT2A-rearranged ALL: Interfant-06 chemotherapy plus one 28-day post-induction blinatumomab course (15 µg/m2/day). Primary end point, clinically relevant toxic effects: none occurred. 2-year DFS 81.6% (95% CI 60.8-92.0) vs 49.4% (42.5-56.0) in historical Interfant-06 controls; OS 93.3% vs 65.8%. Follow-up at median 4.2 years: 4-year DFS 83.3% vs 44.0%, OS 93.3% vs 60.2%.
  5. 2024 · Treatment · ImmunotherapyBlinatumomab added to chemotherapy in standard-risk B-ALLIn a large Children's Oncology Group trial of children with newly diagnosed standard-risk B-cell ALL, adding two cycles of the antibody blinatumomab to chemotherapy was followed by better disease-free survival at three years: about 96 in 100 versus about 88 in 100. Infections were more common with blinatumomab in one subgroup. This is an early interim analysis.COG AALL1731, phase 3: NCI standard-risk B-ALL with average or higher relapse risk; chemotherapy alone (722) versus chemotherapy plus two 28-day blinatumomab cycles (718). First interim analysis, median follow-up 2.5 years: 3-year DFS 96.0% versus 87.9% (RMST difference 72 days, 95% CI 36 to 108; P<0.001, stratified log-rank). Average relapse risk 97.5% versus 90.2%; higher risk 94.1% versus 84.8%. Randomisation stopped early on committee recommendation.
  6. 2026 · Treatment · ImmunotherapyBlinatumomab replaces chemotherapy cycles in high-risk B-ALLIn a European trial, 709 children with high-risk B-cell ALL were randomly given two cycles of blinatumomab or two cycles of chemotherapy after consolidation. At a planned interim analysis, about 83 in 100 of the blinatumomab group and 70 in 100 of the chemotherapy group were free of relapse and other events at four years, with fewer infections.AIEOP-BFM ALL 2017, phase 3: 709 of 768 eligible patients with high-risk B-ALL randomised after consolidation to two blinatumomab cycles (358) or two chemotherapy cycles (351). Planned interim analysis, median follow-up 2.9 years: 4-year EFS 83.0% (95% CI 77.4-87.4) versus 70.3% (63.8-75.9), HR 0.51 (0.35-0.73), P=0.0002 (ITT). Trial-related infection 23.9% versus 69.4%; neurotoxic events 12.0% versus 3.2%.

Then and now

  • 5-year relative survival · United States (NCI fact sheet; registry not stated on the page)

    • 57%

      1975

    • 92.3%

      2014-2020

    Children diagnosed with acute lymphoblastic leukemia (ALL), as worded in one sentence of the NCI fact sheet 'Cancer in Children and Adolescents' (page updated 27 August 2024): 'children diagnosed with this disease'. The page does not state an age range for 'children', the registry or registry grouping, race or sex.

    The page calls the figure the '5-year survival rate' and does not say whether it is relative or observed survival, so it is filed under the nearest metric. The sentence has no reference number on the page and does not say whether the years are years of diagnosis. The page attributes the rise to improved treatments introduced beginning in the 1960s and 1970s and does not apportion it between treatment and other factors (for example changes in diagnosis or classification). This is a different source from the SEER series below: do not subtract it from them or chain them. Read it beside the death-rate values in the SEER childhood leukemia series.

    Source

  • 5-year relative survival · United States (NCI fact sheet; registry not stated on the page)

    • 96%

      2013-2019; lymphoid leukemias, ages 1-4 years

    Lymphoid leukemias (the page says 'mostly acute lymphoblastic leukemia') in children aged 1 to 4 years, as printed in the NCI fact sheet 'Cancer in Children and Adolescents' (page updated 27 August 2024). Race and sex are not stated.

    Five values for lymphoid leukemias (mostly ALL, in the page's words) by age group are printed in one sentence of the fact sheet: ages 1-4 years 96%, 5-9 years 94%, 10-14 years 86%, younger than 1 year 61%, adolescents 78%. Lymphoid leukemias are not exclusively ALL, so the figure is not an ALL-only value. The page defines adolescents as ages 15 to 19 in an earlier paragraph, does not name the measure (relative or observed survival) or the registry set, and does not label the years 2013-2019 as years of diagnosis. The by-age 2013-2019 survival figures printed earlier on the same page (83.2% for children younger than 1 year to 87.8% for ages 1-4) are for all cancers of children and adolescents combined, not ALL, and are not entered here. This entry is the ages 1-4 years value; read the five together, and do not combine with the SEER series.

    Source

  • 5-year relative survival · United States (NCI fact sheet; registry not stated on the page)

    • 94%

      2013-2019; lymphoid leukemias, ages 5-9 years

    Lymphoid leukemias (the page says 'mostly acute lymphoblastic leukemia') in children aged 5 to 9 years, as printed in the NCI fact sheet 'Cancer in Children and Adolescents' (page updated 27 August 2024). Race and sex are not stated.

    Five values for lymphoid leukemias (mostly ALL, in the page's words) by age group are printed in one sentence of the fact sheet: ages 1-4 years 96%, 5-9 years 94%, 10-14 years 86%, younger than 1 year 61%, adolescents 78%. Lymphoid leukemias are not exclusively ALL, so the figure is not an ALL-only value. The page defines adolescents as ages 15 to 19 in an earlier paragraph, does not name the measure (relative or observed survival) or the registry set, and does not label the years 2013-2019 as years of diagnosis. The by-age 2013-2019 survival figures printed earlier on the same page (83.2% for children younger than 1 year to 87.8% for ages 1-4) are for all cancers of children and adolescents combined, not ALL, and are not entered here. This entry is the ages 5-9 years value; read the five together, and do not combine with the SEER series.

    Source

  • 5-year relative survival · United States (NCI fact sheet; registry not stated on the page)

    • 86%

      2013-2019; lymphoid leukemias, ages 10-14 years

    Lymphoid leukemias (the page says 'mostly acute lymphoblastic leukemia') in children aged 10 to 14 years, as printed in the NCI fact sheet 'Cancer in Children and Adolescents' (page updated 27 August 2024). Race and sex are not stated.

    Five values for lymphoid leukemias (mostly ALL, in the page's words) by age group are printed in one sentence of the fact sheet: ages 1-4 years 96%, 5-9 years 94%, 10-14 years 86%, younger than 1 year 61%, adolescents 78%. Lymphoid leukemias are not exclusively ALL, so the figure is not an ALL-only value. The page defines adolescents as ages 15 to 19 in an earlier paragraph, does not name the measure (relative or observed survival) or the registry set, and does not label the years 2013-2019 as years of diagnosis. The by-age 2013-2019 survival figures printed earlier on the same page (83.2% for children younger than 1 year to 87.8% for ages 1-4) are for all cancers of children and adolescents combined, not ALL, and are not entered here. This entry is the ages 10-14 years value; read the five together, and do not combine with the SEER series.

    Source

  • 5-year relative survival · United States (NCI fact sheet; registry not stated on the page)

    • 61%

      2013-2019; lymphoid leukemias, younger than 1 year

    Lymphoid leukemias (the page says 'mostly acute lymphoblastic leukemia') in children younger than 1 year, as printed in the NCI fact sheet 'Cancer in Children and Adolescents' (page updated 27 August 2024). Race and sex are not stated.

    Five values for lymphoid leukemias (mostly ALL, in the page's words) by age group are printed in one sentence of the fact sheet: ages 1-4 years 96%, 5-9 years 94%, 10-14 years 86%, younger than 1 year 61%, adolescents 78%. Lymphoid leukemias are not exclusively ALL, so the figure is not an ALL-only value. The page defines adolescents as ages 15 to 19 in an earlier paragraph, does not name the measure (relative or observed survival) or the registry set, and does not label the years 2013-2019 as years of diagnosis. The by-age 2013-2019 survival figures printed earlier on the same page (83.2% for children younger than 1 year to 87.8% for ages 1-4) are for all cancers of children and adolescents combined, not ALL, and are not entered here. This entry is the younger than 1 year value; read the five together, and do not combine with the SEER series.

    Source

  • 5-year relative survival · United States (NCI fact sheet; registry not stated on the page)

    • 78%

      2013-2019; lymphoid leukemias, adolescents

    Lymphoid leukemias (the page says 'mostly acute lymphoblastic leukemia') in adolescents (defined on the page as ages 15 to 19 years), as printed in the NCI fact sheet 'Cancer in Children and Adolescents' (page updated 27 August 2024). Race and sex are not stated.

    Five values for lymphoid leukemias (mostly ALL, in the page's words) by age group are printed in one sentence of the fact sheet: ages 1-4 years 96%, 5-9 years 94%, 10-14 years 86%, younger than 1 year 61%, adolescents 78%. Lymphoid leukemias are not exclusively ALL, so the figure is not an ALL-only value. The page defines adolescents as ages 15 to 19 in an earlier paragraph, does not name the measure (relative or observed survival) or the registry set, and does not label the years 2013-2019 as years of diagnosis. The by-age 2013-2019 survival figures printed earlier on the same page (83.2% for children younger than 1 year to 87.8% for ages 1-4) are for all cancers of children and adolescents combined, not ALL, and are not entered here. This entry is the adolescents value; read the five together, and do not combine with the SEER series.

    Source

  • 5-year relative survival · United States, SEER 8 registries; leukemia ages 0-19

    • 36.58%

      1975 (observed value; first year in the table)

    Children and young people aged 0-19 years with leukemia of all types (ALL, acute myeloid and others; the page gives no breakdown by type), all races, both sexes (chart note). SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page.

    This is not an ALL-only series: the page covers all leukemia types in ages 0-19 and ALL is not separated. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column (48.36% for 1975). The table column is headed 'Year' and the chart is titled 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; neither labels the year as year of diagnosis. Single-year values fluctuate (for example 59.66% in 1977, 54.57% in 1978 and 49.31% in 1979 in the same series). The page does not say how much of the change reflects treatment, leukemia-type mix, or classification. First year in the table. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 8 registries; leukemia ages 0-19

    • 70.15%

      1990 (observed value)

    Children and young people aged 0-19 years with leukemia of all types (ALL, acute myeloid and others; the page gives no breakdown by type), all races, both sexes (chart note). SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page.

    This is not an ALL-only series: the page covers all leukemia types in ages 0-19 and ALL is not separated. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column (68.56% for 1990). The table column is headed 'Year' and the chart is titled 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; neither labels the year as year of diagnosis. Single-year values fluctuate (for example 59.66% in 1977, 54.57% in 1978 and 49.31% in 1979 in the same series). The page does not say how much of the change reflects treatment, leukemia-type mix, or classification. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 8 registries; leukemia ages 0-19

    • 75.29%

      2000 (observed value)

    Children and young people aged 0-19 years with leukemia of all types (ALL, acute myeloid and others; the page gives no breakdown by type), all races, both sexes (chart note). SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page.

    This is not an ALL-only series: the page covers all leukemia types in ages 0-19 and ALL is not separated. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column (78.35% for 2000). The table column is headed 'Year' and the chart is titled 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; neither labels the year as year of diagnosis. Single-year values fluctuate (for example 59.66% in 1977, 54.57% in 1978 and 49.31% in 1979 in the same series). The page does not say how much of the change reflects treatment, leukemia-type mix, or classification. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 8 registries; leukemia ages 0-19

    • 87.97%

      2010 (observed value)

    Children and young people aged 0-19 years with leukemia of all types (ALL, acute myeloid and others; the page gives no breakdown by type), all races, both sexes (chart note). SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page.

    This is not an ALL-only series: the page covers all leukemia types in ages 0-19 and ALL is not separated. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column (85.41% for 2010). The table column is headed 'Year' and the chart is titled 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; neither labels the year as year of diagnosis. Single-year values fluctuate (for example 59.66% in 1977, 54.57% in 1978 and 49.31% in 1979 in the same series). The page does not say how much of the change reflects treatment, leukemia-type mix, or classification. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 8 registries; leukemia ages 0-19

    • 90.71%

      2018 (observed value; last observed year in the table)

    Children and young people aged 0-19 years with leukemia of all types (ALL, acute myeloid and others; the page gives no breakdown by type), all races, both sexes (chart note). SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page.

    This is not an ALL-only series: the page covers all leukemia types in ages 0-19 and ALL is not separated. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column (89.47% for 2018). The table column is headed 'Year' and the chart is titled 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; neither labels the year as year of diagnosis. Single-year values fluctuate (for example 59.66% in 1977, 54.57% in 1978 and 49.31% in 1979 in the same series). The page does not say how much of the change reflects treatment, leukemia-type mix, or classification. Last observed year in the table; after 2018 the table shows only modelled trend values (89.90% for 2019 to 91.44% for 2023). Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL); leukemia ages 0-19

    • 86.7%

      2016-2022

    Children and young people aged 0-19 years with leukemia of all types; the headline five-year relative survival figure on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page ('Based on data from SEER 21 (Excluding IL) 2016-2022'). Race and sex are not stated beside the figure.

    A different registry set and period from the SEER 8 series, so it is not a continuation of the 1975-2018 values and must not be subtracted from them. It is lower than the SEER 8 observed value for 2018 (90.71%); the page does not explain the difference, so it must not be read as a decline in survival. All leukemia types are combined, not ALL alone. The page does not say whether the period is the year of diagnosis. Relative survival excludes deaths from other causes. Read it beside the death-rate values.

    Source

  • Age-standardised mortality · United States; leukemia ages 0-19

    • 2.03per 100,000

      1975 (observed; first year in the table)

    Children and young people aged 0-19 years in the United States, leukemia of all types, all races, both sexes; age-adjusted death rate from US mortality data ('Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page).

    Observed value from the 'Death Rate - U.S.' column; the adjacent modelled trend value (2.09) is not used. Deaths come from US mortality data, not SEER registries, for people aged 0-19 with leukemia of all types (not ALL alone), all races, both sexes, age-adjusted. Death rates describe the whole US population aged 0-19, are not measured from the date of diagnosis, and depend on how many children are diagnosed, so they are not a survival measure. In the same table the age-adjusted rate of new cases in the SEER 8 column was 3.13 per 100,000 in 1975. The page does not attribute the change in the rate to a cause or say how leukemia deaths were coded across the years. Childhood leukemia is not a screened cancer, so no screening-related pairing is made.

    Source

  • Age-standardised mortality · United States; leukemia ages 0-19

    • 1.19per 100,000

      1990 (observed)

    Children and young people aged 0-19 years in the United States, leukemia of all types, all races, both sexes; age-adjusted death rate from US mortality data ('Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page).

    Observed value from the 'Death Rate - U.S.' column; the adjacent modelled trend value (1.19) is not used. Deaths come from US mortality data, not SEER registries, for people aged 0-19 with leukemia of all types (not ALL alone), all races, both sexes, age-adjusted. Death rates describe the whole US population aged 0-19, are not measured from the date of diagnosis, and depend on how many children are diagnosed, so they are not a survival measure. In the same table the SEER 8 rate of new cases was 3.87 per 100,000 in 1990. The page does not attribute the change in the rate to a cause or say how leukemia deaths were coded across the years. Childhood leukemia is not a screened cancer, so no screening-related pairing is made.

    Source

  • Age-standardised mortality · United States; leukemia ages 0-19

    • 0.91per 100,000

      2000 (observed)

    Children and young people aged 0-19 years in the United States, leukemia of all types, all races, both sexes; age-adjusted death rate from US mortality data ('Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page).

    Observed value from the 'Death Rate - U.S.' column; the adjacent modelled trend value (0.89) is not used. Deaths come from US mortality data, not SEER registries, for people aged 0-19 with leukemia of all types (not ALL alone), all races, both sexes, age-adjusted. Death rates describe the whole US population aged 0-19, are not measured from the date of diagnosis, and depend on how many children are diagnosed, so they are not a survival measure. In the same table the SEER 8 rate of new cases was 4.27 per 100,000 in 2000. The page does not attribute the change in the rate to a cause or say how leukemia deaths were coded across the years. Childhood leukemia is not a screened cancer, so no screening-related pairing is made.

    Source

  • Age-standardised mortality · United States; leukemia ages 0-19

    • 0.66per 100,000

      2010 (observed)

    Children and young people aged 0-19 years in the United States, leukemia of all types, all races, both sexes; age-adjusted death rate from US mortality data ('Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page).

    Observed value from the 'Death Rate - U.S.' column; the adjacent modelled trend value (0.67) is not used. Deaths come from US mortality data, not SEER registries, for people aged 0-19 with leukemia of all types (not ALL alone), all races, both sexes, age-adjusted. Death rates describe the whole US population aged 0-19, are not measured from the date of diagnosis, and depend on how many children are diagnosed, so they are not a survival measure. In the same table the SEER 8 rate of new cases was 4.34 per 100,000 in 2010. The page does not attribute the change in the rate to a cause or say how leukemia deaths were coded across the years. Childhood leukemia is not a screened cancer, so no screening-related pairing is made.

    Source

  • Age-standardised mortality · United States; leukemia ages 0-19

    • 0.49per 100,000

      2024 (observed; last year in the table)

    Children and young people aged 0-19 years in the United States, leukemia of all types, all races, both sexes; age-adjusted death rate from US mortality data ('Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts: Childhood Leukemia (Ages 0-19) page).

    Observed value from the 'Death Rate - U.S.' column; the adjacent modelled trend value (0.52) is not used. Deaths come from US mortality data, not SEER registries, for people aged 0-19 with leukemia of all types (not ALL alone), all races, both sexes, age-adjusted. Death rates describe the whole US population aged 0-19, are not measured from the date of diagnosis, and depend on how many children are diagnosed, so they are not a survival measure. In the same table the SEER 8 rate of new cases was 4.85 per 100,000 in 2023 (the 2024 incidence cell is blank), i.e. the rate of new cases did not fall while the death rate did. The page does not attribute the change in the rate to a cause or say how leukemia deaths were coded across the years. Childhood leukemia is not a screened cancer, so no screening-related pairing is made. The page headline gives 0.5 per 100,000 for 2020-2024 deaths and an average fall of 1.1% per year over 2015-2024; use one or the other, not both.

    Source

  • 5-year relative survival · United States, SEER 8 registries; ALL, all ages

    • 30.69%

      1975 (observed value; first year in the table)

    People of all ages with acute lymphocytic leukemia (ALL), all races, both sexes (chart note), SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts: Leukemia - Acute Lymphocytic Leukemia (ALL) page.

    NOT a childhood series. The page covers ALL at all ages: 52.1% of new cases are under 20 years (SEER 21, 2019-2023) and the median age at diagnosis is 18, so adults contribute substantially; the page gives no survival breakdown by age. It is kept separate from the childhood leukemia series (ages 0-19, all leukemia types) and from the NCI fact-sheet values, and none of the three should be subtracted from or chained to another. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column (44.03% for 1975). The column is headed 'Year' and the chart title does not call it year of diagnosis. Single-year values fluctuate (for example 37.99% in 1976 and 51.01% in 1977).

    Source

  • 5-year relative survival · United States, SEER 8 registries; ALL, all ages

    • 82.02%

      2018 (observed value; last observed year in the table)

    People of all ages with acute lymphocytic leukemia (ALL), all races, both sexes (chart note), SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts: Leukemia - Acute Lymphocytic Leukemia (ALL) page.

    NOT a childhood series. The page covers ALL at all ages: 52.1% of new cases are under 20 years (SEER 21, 2019-2023) and the median age at diagnosis is 18, so adults contribute substantially; the page gives no survival breakdown by age. It is kept separate from the childhood leukemia series (ages 0-19, all leukemia types) and from the NCI fact-sheet values, and none of the three should be subtracted from or chained to another. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column (76.38% for 2018); the observed 2018 value is above the modelled trend value and above the observed values for 2013 to 2017 (71.06% to 77.76%). After 2018 the table shows only modelled trend values (76.91% for 2019 to 78.92% for 2023).

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL); ALL, all ages

    • 73.2%

      2016-2022

    People of all ages with ALL; the headline five-year relative survival figure on the SEER Cancer Stat Facts ALL page ('Based on data from SEER 21 (Excluding IL) 2016-2022'). Race and sex are not stated beside the figure.

    NOT a childhood series. The page covers ALL at all ages: 52.1% of new cases are under 20 years (SEER 21, 2019-2023) and the median age at diagnosis is 18, so adults contribute substantially; the page gives no survival breakdown by age. It is kept separate from the childhood leukemia series (ages 0-19, all leukemia types) and from the NCI fact-sheet values, and none of the three should be subtracted from or chained to another. A different registry set and period from the SEER 8 series, so it is not a continuation of the 1975-2018 values; it is lower than the SEER 8 observed value for 2018 (82.02%) and the page does not explain the difference. Relative survival excludes deaths from other causes.

    Source

  • Age-standardised mortality · United States; ALL, all ages

    • 0.66per 100,000

      1975 (observed; first year in the table)

    People of all ages in the United States with ALL, all races, both sexes; age-adjusted death rate from US mortality data ('Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts ALL page).

    Observed value from the 'Death Rate - U.S.' column; the adjacent modelled trend value (0.64) is not used. Deaths come from US mortality data, not SEER registries, for ALL at all ages, all races, both sexes, age-adjusted. On the same page 14.0% of ALL deaths are under age 20 and the median age at death is 60 (US 2020-2024), so the rate mostly reflects adults. In the same table the SEER 8 rate of new cases was 1.07 per 100,000 in 1975. Death rates are not measured from diagnosis and depend on how many people are diagnosed. ALL is not a screened cancer, so no screening-related pairing is made.

    Source

  • Age-standardised mortality · United States; ALL, all ages

    • 0.36per 100,000

      2024 (observed; last year in the table)

    People of all ages in the United States with ALL, all races, both sexes; age-adjusted death rate from US mortality data ('Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts ALL page).

    Observed value from the 'Death Rate - U.S.' column; the adjacent modelled trend value (0.37) is not used. Deaths come from US mortality data, not SEER registries, for ALL at all ages, all races, both sexes, age-adjusted. On the same page 14.0% of ALL deaths are under age 20 and the median age at death is 60 (US 2020-2024), so the rate mostly reflects adults. In the same table the SEER 8 rate of new cases was 1.73 per 100,000 in 2023 (the 2024 incidence cell is blank). Death rates are not measured from diagnosis and depend on how many people are diagnosed. ALL is not a screened cancer, so no screening-related pairing is made. The page headline gives 0.4 per 100,000 for 2020-2024 deaths and an average fall of 1.8% per year over 2015-2024; use one or the other, not both.

    Source

Survival figures are affected by earlier detection (lead time) and overdiagnosis, and by changes in who is diagnosed. For screened cancers, read them alongside mortality.

Evidence chains

A lane follows one defined population and setting, where each new trial tests against what was then standard. Compare only within a lane, and read every comparison as illustrative.

CNS-directed prophylaxis in newly diagnosed ALL

Children with newly diagnosed ALL treated at St Jude Children's Research Hospital (Total Therapy studies of the 1960s and 1970s; Total Therapy XV and 16 in the 2000s) · Any setting · endpoint: CNS relapse

Results are not comparable across trials.

This is a single-institution chain, not a randomised one. The 1971 milestone has no recorded trial values, and the Total Therapy XV comparison with irradiated historical controls has values only for Total Therapy XV, so neither can be drawn. The one pair shown compares Total Therapy 16 with Total Therapy XV in patients with the same features linked to CNS relapse; neither arm received prophylactic cranial irradiation, and the Total Therapy 16 patients also received two extra intrathecal doses. The comparison is not randomised and the eras and risk-adapted regimens differ. Lower values are better for this endpoint. Compare only within each trial's own arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100CNS relapse at 60 months (%)2009Total 16
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
CNS relapse at 60 months, rate, across 1 trial in this lane. Total 16 (2009): experimental 1.8 % vs control 5.7 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
Total 162009CNS relapse5.7 %1.8 %

Newly diagnosed Ph-positive ALL: chemotherapy plus a TKI

Children and adolescents with newly diagnosed BCR::ABL1 (Ph-positive) ALL; age limits differ (AALL0031 ages 1 to 21; CA180-372 over 1 and under 18) · Any setting · endpoint: EFS

Results are not comparable across trials.

Both pairs are non-randomised comparisons with historical controls: earlier POG patients (1986 to 1999) for imatinib in AALL0031, and an external historical group for dasatinib in CA180-372. Chemotherapy backbones, transplant policies, risk definitions and TKI exposure differ. Not drawn: AALL0622 (its 3-year EFS has no comparator and its 5-year EFS is a different time point from AALL0031), EsPhALL2004 (disease-free survival in good-risk patients, randomised), and the Chinese randomised trial of dasatinib versus imatinib (4-year EFS, different chemotherapy backbone). Compare only within each trial's own arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100EFS at 36 months (%)20092018AALL0031CA180-372/AALL1122
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS at 36 months, rate, across 2 trials in this lane. AALL0031 (2009): experimental 80 % vs control 35 %; CA180-372/AALL1122 (2018): experimental 65.5 % vs control 49.2 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
AALL00312009EFS35 %80 %
CA180-372/AALL11222018EFS49.2 %65.5 %

NCI standard-risk B-ALL: MRD-guided reduction, then adding blinatumomab

Children with newly diagnosed B-ALL at lower risk: UKALL 2003 randomised MRD-low-risk patients aged 1 to 25; AALL1731 randomised NCI standard-risk children at average or higher risk of relapse · Any setting · endpoint: DFS

Results are not comparable across trials.

Populations, endpoints and time points differ. UKALL 2003 reports event-free survival at 5 years in MRD-low-risk patients aged 1 to 25 (drawn as a diamond because its endpoint is not disease-free survival); AALL1731 reports disease-free survival at 3 years in an interim analysis that includes children at higher relapse risk, so it is listed in the data table but not drawn on the same axis. Risk definitions (MRD thresholds, clinical features), randomised questions, backbones and follow-up all differ. The AALL0932 maintenance-phase randomisation (vincristine and dexamethasone pulses, disease-free survival from the start of maintenance in average-risk children) is a separate milestone and is not part of this lane. Compare only within each trial's own arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100DFS at 60 months (%)2013UKALL 2003
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
DFS at 60 months, rate, across 1 trial in this lane. UKALL 2003 (2013): experimental 94.4 % vs control 95.5 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
UKALL 20032013EFS (differs from lane)95.5 %94.4 %
AALL17312024DFS (not plotted: different measure or time point)87.9 %96 %

High-risk B-ALL: intensification, then blinatumomab in place of chemotherapy

Children and young adults with newly diagnosed high-risk B-ALL: CCG-1882 enrolled slow early responders aged 1 to 9 with higher white-cell counts, or 10 and older; AALL0232 enrolled ages 1 to 30; AIEOP-BFM ALL 2017 randomised high-risk children after consolidation · Any setting · endpoint: EFS

Results are not comparable across trials.

The three trials ask different questions in different populations. CCG-1882 randomised slow early responders after remission and measured outcomes from the end of induction; AALL0232 randomised methotrexate regimens in interim maintenance 1 and its time origin is not stated in the recorded abstract; AIEOP-BFM ALL 2017 compares blinatumomab with two chemotherapy cycles after consolidation and reports a planned interim analysis at 4 years, which is a different time point (48 months) from the other two (60 months), so it is listed in the data table but not drawn on the same axis. Backbones, risk definitions and MRD policies differ. Compare only within each trial's own arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100EFS at 60 months (%)19982016augmented-post-induction-slow-respondersAALL0232
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS at 60 months, rate, across 2 trials in this lane. augmented-post-induction-slow-responders (1998): experimental 75 % vs control 55 %; AALL0232 (2016): experimental 79.6 % vs control 75.2 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
augmented-post-induction-slow-responders1998EFS55 %75 %
AALL02322016EFS75.2 %79.6 %
AIEOP-BFM ALL 20172026EFS (not plotted: different measure or time point)70.3 %83 %

Infants with ALL: Interfant protocols and blinatumomab

Infants younger than 1 year with ALL (Interfant-99 and Interfant-06: all infants, randomised questions among those in remission or at medium and high risk; blinatumomab study: KMT2A-rearranged ALL only) · Any setting · endpoint: DFS

Results are not comparable across trials.

The Interfant results are randomised comparisons within each protocol (Interfant-99: late intensification at 4 years; Interfant-06: myeloid-style versus lymphoid-style consolidation at 6 years), and the 6-year point is listed in the data table but not drawn on the same axis as the 4-year points. The blinatumomab study is single-arm (30 infants with KMT2A-rearranged ALL) and is compared with selected historical Interfant-06 controls, not randomised. It is not directly comparable with the all-infant cohorts. Compare only within each trial's own arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100DFS at 48 months (%)20072023Interfant-99blinatumomab-infants-kmt2a
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
DFS at 48 months, rate, across 2 trials in this lane. Interfant-99 (2007): experimental 60.9 % vs control 57 %; blinatumomab-infants-kmt2a (2023): experimental 83.3 % vs control 44 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
Interfant-992007DFS57 %60.9 %
blinatumomab-infants-kmt2a2023DFS44 %83.3 %
Interfant-062007DFS (not plotted: different measure or time point)36.8 %39.3 %

First relapse of B-ALL: chemotherapy and transplant, then blinatumomab consolidation

Children with first relapse of ALL: ALL R3 ages 1 to 18, all risk groups; AALL1331 ages 1 to 30, high or intermediate risk B-ALL · Relapsed / refractory · endpoint: OS

Results are not comparable across trials.

Both trials are randomised, but they test different questions and populations. ALL R3 compared mitoxantrone (experimental) with idarubicin (control) in induction at 3 years, with transplant for high-risk patients. AALL1331 compared two cycles of blinatumomab with two cycles of chemotherapy before transplant at 2 years, in a population that excluded earlier transplant and blinatumomab exposure, and it ended without meeting stopping rules for efficacy or futility. Overall survival is the only endpoint common to both. The 2-year AALL1331 point is a different time point from the 3-year ALL R3 point, so it is listed in the data table but not drawn on the same axis. The FORUM transplant-conditioning trial belongs to the same milestone but is not a first-relapse population (54 percent were in first remission) and is not in this lane. The Amgen 20120215 trial reports a hazard ratio without arm values and is not drawn. Compare only within each trial's own arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100OS at 36 months (%)2010ALL R3
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
OS at 36 months, rate, across 1 trial in this lane. ALL R3 (2010): experimental 69 % vs control 45.2 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
ALL R32010OS45.2 %69 %
AALL13312021OS (not plotted: different measure or time point)58.4 %71.3 %

Refractory or multiply relapsed B-ALL: new agents

Children and young adults with refractory or multiply relapsed B-ALL; eligibility, number of prior treatments and remission definitions differ by study · Relapsed / refractory · endpoint: Overall remission rate

No comparable values to plot for this lane yet.

Standard of care, then and now

How the usual sequence of treatment changed for one setting. Choose a point in time; each step links to the milestone behind it.

Relapsed B-ALL: lines of treatment

Children and young adults with relapsed or refractory B-ALL · Relapsed / refractory

  1. Chemotherapy11st relapse: mitoxantrone inductionMitoxantrone in first relapse; TBI before transplant in childhood ALL (2010)
  2. Immunotherapy2Pre-transplant: blinatumomab or chemoBlinatumomab versus chemotherapy in first relapse of B-ALL (2021)
  3. Immunotherapy3Relapsed or refractory: blinatumomabBlinatumomab for relapsed or refractory paediatric B-ALL (2016)
  4. Antibody–drug conjugate4Relapsed CD22+: inotuzumabInotuzumab ozogamicin for relapsed paediatric CD22+ ALL (2020)
  5. Cell therapy & transplant52nd or later relapse: tisagenlecleucelFDA approves tisagenlecleucel for relapsed or refractory B-ALL (2017)
Today. Based only on the trials cited in each step. The two 2021 randomised trials of blinatumomab before transplant had different results; see the milestone. Inotuzumab was studied in CD22-positive disease.
Text version
  • 2010: 1st relapse: mitoxantrone induction
  • 2017: 1st relapse: mitoxantrone induction → Relapsed or refractory: blinatumomab → 2nd or later relapse: tisagenlecleucel
  • Today: 1st relapse: mitoxantrone induction → Pre-transplant: blinatumomab or chemo → Relapsed or refractory: blinatumomab → Relapsed CD22+: inotuzumab → 2nd or later relapse: tisagenlecleucel

Today and tomorrow

Standard of care today

Any setting

Newly diagnosed B-cell precursor ALL. FDA action read:

  • 14 June 2024 (supplement S-028, corrected letter), blinatumomab for CD19-positive, Philadelphia chromosome-negative B-cell precursor ALL in the consolidation phase of multiphase chemotherapy in adult and pediatric patients one month and older. The letter calls it a new indication, does not describe it as an accelerated approval and does not name the trials behind it. EMA: the indications text on the Blincyto EPAR page (read 20 October 2026
  • the page lists an update of 22 September 2026) names, for pediatric patients aged 1 month or older, relapsed or refractory disease and consolidation in high-risk first relapse, and, for adults, consolidation in newly diagnosed Philadelphia chromosome-negative disease
  • no indication for pediatric patients with newly diagnosed disease appears in that text. Two published randomised trials in newly diagnosed pediatric B-ALL tested blinatumomab added to chemotherapy (Gupta 2025, standard-risk disease) and blinatumomab replacing two chemotherapy cycles (Schrappe 2026, high-risk disease)
  • their results are covered in the milestone material and are not restated here. NCCN Pediatric Acute Lymphoblastic Leukemia, Version 2.2025, is cited by identifier only: its text was not read, and a later version may exist. This entry is not a guideline recommendation
US Food and Drug Administration 2024European Medicines Agency 2015Gupta S, Rau RE, Kairalla JA, Rabin KR, Wang C, Angiolillo AL, et al 2025Schrappe M, Locatelli F, Valsecchi MG, Zugmaier G, Vossen-Gajcy M, Starý J, et al 2026Inaba H, Teachey D, Annesley C, Batra S, Beck J, Colace S, et al 2025
Any setting

Asparaginase products, as listed in the FDA Pediatric Oncology Drug Approvals table (table current as of February 2026; the underlying letters were not read for this page):

  • pegaspargase, 1 February 1994 (ALL with hypersensitivity to native forms of L-asparaginase) and 24 July 2006 (a component of first-line multi-agent chemotherapy for pediatric and adult patients with ALL)
  • calaspargase pegol, 20 December 2018 (pediatric and young adult patients aged 1 month to 21 years)
  • recombinant Erwinia asparaginase (Rylaze), 30 June 2021 (patients aged 1 month or older with hypersensitivity to E. coli-derived asparaginase). No EMA document on asparaginase products was read
U 2026
Any setting

Philadelphia chromosome-positive (BCR::ABL1) ALL. FDA actions read:

  • 25 January 2013, imatinib for pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy (supplement S-037)
  • 21 December 2018, dasatinib for pediatric patients one year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy (supplement S-021). Neither letter describes the approval as accelerated. EMA (EPAR pages read, 20 October 2026): the Glivec page (authorised 7 November 2001) lists adult and paediatric patients with newly diagnosed Ph+ ALL integrated with chemotherapy
  • the Sprycel page (authorised 20 November 2006) lists paediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy
  • the dates of those paediatric extensions were not established. The COG randomised phase 3 trial AALL1631 (imatinib with two chemotherapy backbones) is active and not recruiting (see horizon). NCCN Pediatric Acute Lymphoblastic Leukemia, Version 2.2025, is cited by identifier only
  • its text was not read
US Food and Drug Administration 2013US Food and Drug Administration 2018European Medicines Agency 2001European Medicines Agency 2006Inaba H, Teachey D, Annesley C, Batra S, Beck J, Colace S, et al 2025
Any setting
Infants. No FDA or EMA action specific to infant ALL was read. The labelled populations of blinatumomab start at one month of age (FDA letter of 14 June 2024; EMA indications text above), and the pediatric indications of inotuzumab ozogamicin start at 1 year. The NCI fact sheet reports a five-year survival of 61% for lymphoid leukemias in children younger than 1 year in 2013-2019, against 94% to 96% at ages 1 to 9 (series described under then versus now). Interfant-21 (NCT05327894), registered as a non-randomised phase 3 protocol that includes blinatumomab, is recruiting infants under 1 year with KMT2A-rearranged ALL or mixed phenotype acute leukemia (see horizon). Guideline text for infant ALL was not read.
US Food and Drug Administration 2024European Medicines Agency 2015European Medicines Agency 2017National Cancer Institute 2024ClinicalTrials 2026
Any setting

T-cell ALL. FDA actions read:

  • 28 October 2005, nelarabine approved under the accelerated approval regulations for T-cell ALL and T-cell lymphoblastic lymphoma that had not responded to, or had relapsed after, at least two chemotherapy regimens
  • the letter lists submission of results of the COG phase 3 trial AALL0434 as the confirmatory commitment. 31 July 2019 (supplement S-010): the letter is headed 'Subpart H fulfilled', states that approval of the supplement fulfils the commitments made under 21 CFR 314.510, records postmarketing requirement 1284-1 (results of AALL0434) as fulfilled, and provides for clarification of the age range in Section 1 and for safety results from AALL0434 in Section 6
  • the letter does not use the word 'converted'. The FDA table lists the nelarabine indication as adult and pediatric patients age 1 year and older. NCCN Pediatric Acute Lymphoblastic Leukemia, Version 2.2025, is cited by identifier only
  • its text was not read
US Food and Drug Administration 2005US Food and Drug Administration 2019U 2026Inaba H, Teachey D, Annesley C, Batra S, Beck J, Colace S, et al 2025
Relapsed / refractory

Relapsed or refractory B-cell precursor ALL:

  • immunotherapy and cell therapy. FDA actions read: blinatumomab, 11 July 2017 (supplement S-008, replacement letter signed 12 July 2017), expanding the population to relapsed or refractory Ph+ B-ALL and fulfilling the commitments under 21 CFR 601.41 made at the accelerated approval of 3 December 2014 (the FDA table lists this action as relapsed or refractory CD19-positive B-ALL in adult and pediatric patients one month and older)
  • blinatumomab, 29 March 2018 (S-013), accelerated approval for B-cell precursor ALL in first or second complete remission with minimal residual disease of 0.1% or more in adults and children, with a postmarketing requirement that includes a randomised trial in pediatric patients (protocol AALL1331, primary endpoint disease-free survival)
  • whether this approval was later converted was not established from the FDA letters read
  • tisagenlecleucel, 30 August 2017, patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse
  • inotuzumab ozogamicin, 6 March 2024 (S-003), relapsed or refractory CD22-positive B-cell precursor ALL in pediatric patients 1 year and older, with the letter naming studies ITCC-059 and INO-Ped-ALL-1 as the basis. EMA (EPAR pages read): Kymriah authorised 23 August 2018 for paediatric and young adult patients up to and including 25 years of age with B-cell ALL that is refractory, in relapse post transplant or in second or later relapse
  • Blincyto given a conditional authorisation on 23 November 2015 and a standard authorisation on 18 June 2018, with paediatric indications for refractory disease or relapse after at least two prior therapies or after transplant and for consolidation in high-risk first relapse
  • Besponsa authorised 28 June 2017, with paediatric indications from 1 year of age. Randomised trials in first relapse and of transplant conditioning are covered in the milestone material (Brown 2021, Locatelli 2021, Peters 2021). NCCN Pediatric Acute Lymphoblastic Leukemia, Version 2.2025, is cited by identifier only
  • its text was not read
US Food and Drug Administration 2017US Food and Drug Administration 2018US Food and Drug Administration 2017US Food and Drug Administration 2024U 2026European Medicines Agency 2018European Medicines Agency 2015European Medicines Agency 2017Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, et al 2021Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, et al 2021Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, et al 2021Inaba H, Teachey D, Annesley C, Batra S, Beck J, Colace S, et al 2025
Relapsed / refractory
Relapsed or refractory ALL: clofarabine. FDA action read: 28 December 2004, accelerated approval of clofarabine for pediatric patients 1 to 21 years old with relapsed or refractory ALL after at least two prior regimens, a use the letter says is based on induction of complete responses, with randomised trials showing increased survival or other clinical benefit not having been conducted. A letter of 18 July 2022 (supplement S-027) is headed 'Subpart H fulfilled', states that approval of the supplement fulfils the commitments made under 21 CFR 314.510, and records postmarketing requirement 1253-2 (a controlled clinical study to verify and describe clinical benefit in pediatric ALL) as fulfilled; the letter does not use the word 'converted', and the July 2022 label read keeps the same indication. No EMA document on clofarabine was read.
US Food and Drug Administration 2004US Food and Drug Administration 2022
Any setting
Adolescents and young adults. The NCI fact sheet says that adolescents and young adults with ALL may have better outcomes with pediatric treatment regimens than with adult regimens, and that their survival has improved in recent years while remaining poorer than that of younger children; it reports a five-year survival of 78% for adolescents with lymphoid leukemias in 2013-2019, against 94% to 96% at ages 1 to 9. The American Society of Hematology 2026 guidelines for frontline management and for relapsed or refractory ALL in adolescents and young adults are cited by identifier only; their text was not read. No FDA or EMA action specific to this age group was read beyond the age ranges quoted in the entries above.
National Cancer Institute 2024DuVall AS, McNeer J, Cheung MC, Adrianzen-Herrera DA, Advani A, Aljurf M, et al 2026O'Dwyer K, Winestone LE, Cheung MC, Benitez L, Buldini B, Cole PD, et al 2026

Trials to watch

  • COG AALL1732 NCT03959085

    In newly diagnosed high-risk B-ALL (registry ages 1 to 25 years), does adding inotuzumab ozogamicin to post-induction chemo-immunotherapy that includes blinatumomab maintain or improve outcomes, with post-induction 5-year event-free survival as the registered primary outcome? The registry also covers mixed phenotype acute leukemia and disseminated B-lymphoblastic lymphoma treated without inotuzumab ozogamicin or blinatumomab. Registry status: recruiting; primary completion estimated 31 March 2032.

  • ALLTogether1 NCT04307576

    In newly diagnosed ALL in people aged 0 to 45 years, do the protocol's randomised and interventional questions change event-free or disease-free survival? The registered arms include omission of doxorubicin from delayed intensification, omission of vincristine and dexamethasone pulses from maintenance, addition of inotuzumab or of 6-thioguanine in intermediate-risk high disease, imatinib for ABL-class fusions, and blinatumomab replacing two consolidation courses in Down syndrome. Registry status: recruiting; primary completion estimated June 2033.

  • Interfant-21 NCT05327894

    In infants under 1 year with KMT2A-rearranged ALL or mixed phenotype acute leukemia, what 5-year event-free survival (the registered primary outcome) is achieved with a risk-stratified protocol that includes blinatumomab? Registered as a non-randomised phase 3 trial with medium-risk and high-risk groups. Registry status: recruiting; primary completion estimated September 2027.

  • COG AALL1631 (EsPhALL2017) NCT03007147

    In newly diagnosed Philadelphia chromosome-positive ALL (registry ages 1 to 21 years), does imatinib with COG/BFM chemotherapy differ from imatinib with EsPhALL chemotherapy in disease-free survival among randomised standard-risk participants? The registry also describes a cohort with ABL-class fusion-positive ALL. Registry status: active, not recruiting; primary completion date 30 June 2026 (recorded as actual); no results posted on 20 October 2026.

  • IntReALL BCP 2020 NCT07476729

    In children with relapsed precursor B-cell ALL, does replacing chemotherapy elements with inotuzumab (standard-risk induction, randomised 1:1 against the ALL-R3 mitoxantrone arm per the arm description) or with blinatumomab (single-arm groups compared with historical controls) change induction event-free survival or consolidation disease-free survival? Registry status: not yet recruiting; the record was last updated on 17 March 2026 and gives an estimated start of 1 April 2026, which has passed, so the status may be out of date.

Pioneers

  • Sidney Farber

    1903-1973 · Paediatric pathologist, Pioneer of modern chemotherapy

  • Emil Frei III

    Investigator of combination antimetabolite studies in leukemia

  • Donald Pinkel

    Investigator of the St Jude Total Therapy studies

References

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Every figure was checked against its primary source to the extent possible. Items that could not be fully confirmed are marked “needs review”. Educational history, not medical advice.

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1996UnderstandingUnderstanding

majorAny setting

Uniform NCI risk classification for childhood ALL

A 1996 report from a 1993 US workshop of four research groups and the National Cancer Institute set common risk groups for children with B-precursor ALL. Standard risk meant age 1 to 9 years with a white-cell count below 50,000 per microlitre; everyone else was high risk. The authors expected common labels to make trials more efficient.

NCI Cancer Therapy Evaluation Program workshop, September 1993 (CCG, POG, DFCI, St Jude): outcome data from the groups were combined using weighted averages. B-precursor ALL: standard risk = age 1 to 9 years and WBC below 50,000/microL (4-year EFS approximately 80%); remaining patients high risk (approximately 65%). T-cell ALL: groups differed on risk assignment. DNA index, cytogenetics, early response, immunophenotype and CNS status were to be collected uniformly.

Standard before

Groups used different criteria for risk-based treatment assignment, which the workshop set out to make more uniform.

What changed

For B-precursor ALL, standard risk was defined as age 1 to 9 years with a white-cell count below 50,000/microL at diagnosis, and the remaining patients as high risk. Groups could modify a patient's risk category with additional prognostic factors.

Why it mattered

Common risk labels let trial groups describe populations in the same terms. Later trials in this timeline, such as AALL0932 and AALL1731, define their populations as NCI standard-risk B-ALL.

Caveats

  • The criteria apply to B-precursor ALL. For T-cell ALL the workshop did not agree a single approach: some groups classed all as high risk and others used the age and white-cell criteria.
  • The 4-year EFS values (approximately 80% and 65%) are pooled by weighted averages across groups for the purpose of setting categories; they are not results of a single trial and are not a comparison between treatments.
  • Risk assignment has since been refined with response, MRD and genetics; this entry documents the age and white-cell classification only.