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Blood and bone marrow

Chronic myeloid leukemia

How CML care moved from early case reports and the Philadelphia chromosome to BCR::ABL1 inhibitors and attempts to stop treatment.

5-year relative survival · United States, SEER 8 registries

17.99%→72.39%

1975 (observed value; first year in the table) to 2018 (observed value; last observed year in the table). Read these with the caveats under “Then and now”.Source

28 milestones, by decade

  • In October 1845 an Edinburgh medical journal printed two case reports, by David Craigie and John Hughes Bennett, of patients who died with very large spleens and pus-like material in the blood. Later historical accounts count these among the early descriptions of leukemia; the article itself interprets the findings as pus, and its open-access text does not use the word leukemia.
  • In US registry data on the SEER Cancer Stat Facts page, observed five-year relative survival for chronic myeloid leukemia was 17.99% in 1975 and 72.39% in 2018 (SEER 8 series; the page does not say whether the year is the year of diagnosis), while the age-adjusted US death rate fell from 1.00 per 100,000 in 1975 to 0.65 in 2000 and 0.29 in 2024. Single-year survival values in the series fluctuate, and the page does not say how much of the change reflects treatment, case definition or other factors.
  • EURO-SKI, a non-randomised study in which people with chronic-phase CML who had taken a tyrosine kinase inhibitor for at least 3 years and had a confirmed deep molecular response for at least 1 year stopped treatment, reported molecular relapse-free survival of 61% (95% CI 57-64) at 6 months and 50% (46-54) at 24 months in its prespecified interim analysis of 755 evaluable people. The 2025 European LeukemiaNet recommendations state that about 40-50% of people in discontinuation trials remain off treatment.

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

A guided tour of 12 milestones. You can pause or step through it yourself.

Filter milestonesshowing all 28
Treatment type
Setting

Anatomists & surgeons

  1. 1845 · Origin · Understanding1845: Early case reports later recognised as leukemiaIn October 1845 an Edinburgh medical journal printed two case reports, by David Craigie and John Hughes Bennett, of men with very large spleens and pus-like material in the blood. Later historical accounts count these among the early descriptions of leukemia, alongside observations by Rudolf Virchow the same year.Two autopsy-based case reports (Craigie case 1, Bennett case 2) of men with very large spleens and purulent-looking venous blood. Case 2 also had a greatly enlarged liver and enlarged lymph nodes; Bennett judged the corpuscles to be pus. No blood count is given; the article does not use the word leukemia. The leukemia reading, leucocythemia (Bennett, 1845) and leukämie (Virchow, 1847) come from Kampen 2012.

Chemotherapy

  1. 1953 · Treatment · ChemotherapyBusulfan (Myleran) reported in chronic myeloid leukaemiaOn 31 January 1953 the Lancet published D. A. Galton's results of treating chronic myeloid leukaemia with busulfan (Myleran), alongside a paper on the drug's chemistry. A report from 1961 describes this as the first use of busulfan in the disease and as a challenge to radiotherapy, the standard until then.Galton DA, Lancet, 31 January 1953: results of treatment with busulfan (Myleran) in chronic myeloid leukaemia, published with a companion paper by Haddow and Timmis. PubMed holds no abstract for either paper and the full texts were not read, so no patient numbers or response data are given. A 1961 Belfast series of 25 patients states that Galton was first to use busulphan in chronic granulocytic leukaemia.
  2. 1960 · Understanding · Understanding⚑ needs reviewThe Philadelphia chromosome: a consistent minute chromosomeIn 1960 Peter Nowell and David Hungerford, working in Philadelphia, reported chromosome studies of leukemia cells. A 1961 paper found a similar shortened chromosome in nine of ten patients with chronic granulocytic (now myeloid) leukemia, and the authors called it a consistent change in a specific human cancer. It was later named the Philadelphia chromosome.Pre-banding cytogenetics. JNCI 1960: in 2 chronic granulocytic leukemia cases an abnormality probably involving the Y chromosome. Science 1960 abstract (not opened): seven cases per Radich 2022; Nowell 2007 differs. JNCI 1961 abstract: 10 patients, similar abnormality in 9 (loss of about half the long arm of a small acrocentric chromosome). A 9;22 translocation was demonstrated in the 1970s (Nowell 2007).
  3. 1973 · Understanding · UnderstandingRowley: banding suggests a 9;22 translocation in CML (1973)In 1973 Janet Rowley studied cells from nine consecutive people with chronic myelogenous leukemia using new chromosome staining methods. The Philadelphia chromosome in all nine was a shortened chromosome 22, and extra material appeared at the end of one chromosome 9 in all cells. She suggested that material had been exchanged between the two chromosomes, a translocation.Nature 1973 letter (publisher abstract): 9 consecutive CML patients, quinacrine fluorescence and Giemsa banding. Ph1 was a 22q- deletion in all 9; all cells carried added material on the long arm of one chromosome 9 (9q+), about equal to that missing from 22q-. The author suggested a previously undetected 22q;9q translocation. Later accounts describe a demonstrated reciprocal t(9;22) (Radich 2022; Minciacchi 2021).

Molecular origins

  1. 1979 · Treatment · Cell therapy & transplantMarrow transplant in CML: identical twins, then matched siblingsIn 1979 doctors reported four people with chronic myeloid leukaemia who received marrow from a healthy identical twin after intensive treatment; no leukaemic cells with the Philadelphia chromosome were found afterwards. In 1986 a larger series of seventy people given marrow from matched siblings reported about seven in ten chronic-phase patients alive at two years.Fefer 1979: four patients (CGL history 12, 10, 11 and 106 months) given dimethyl busulfan, cyclophosphamide and 920 rads total-body irradiation, then syngeneic marrow; no Ph1-positive cells afterwards; haematologically normal 22 to 31 months. Goldman 1986: HLA-identical sibling allografts (Feb 1981 to Dec 1984). Chronic phase (n=52): actuarial 2-year survival 72%, relapse risk 7%. Advanced phase (n=18): 18% and 42%.
  2. 1982 · Understanding · UnderstandingBCR-ABL: from a translocated gene to leukemia in mice (1982-1990)Between 1982 and 1990 laboratories traced the Philadelphia chromosome to the genes involved. The ABL gene moves from chromosome 9 to chromosome 22 next to a region called BCR, the two genes are read as one fused RNA, and in 1990 mice that received bone marrow carrying the fused gene developed several blood cancers, including one closely resembling chronic-phase CML.Laboratory studies, no trial data. 1982: c-abl sequences translocated from chromosome 9 to 22q- (somatic cell hybrids). 1983: Ph breakpoint position variable; in one patient immediately 5' of or within c-abl. 1984: breakpoints within up to 5.8 kb (bcr) in 17 of 19 patients (the other 2 lacked Ph). 1985: 8-kb CML-specific RNA shown to be a fused abl-bcr transcript. 1990: P210bcr/abl in murine marrow gave a myeloproliferative syndrome resembling chronic-phase CML.
  3. 1983 · Treatment · ImmunotherapyInterferon alfa in CML: early clinical reports, 1983 and 1986In 1983 a team reported giving human leukocyte interferon to seven people with chronic myeloid leukaemia, and five reached a hematologic remission. In 1986 a report of seventeen people given recombinant interferon found fourteen responded; in six, Philadelphia-positive cells were undetectable on at least one test. The authors called the data preliminary.Talpaz 1983 (Blood): partially purified human leukocyte interferon alfa, 9 to 15 million units daily intramuscularly, 7 patients; hematologic remission in 5. Talpaz 1986 (NEJM): recombinant interferon alfa A (Roferon-A), 5 million units per square metre daily, 17 Ph-positive patients; 14 responded (13 hematologic remission, 1 partial); complete suppression of Philadelphia cells at least once in 6 patients. Authors: preliminary.
  4. 1984 · Understanding · UnderstandingPrognostic scores for CML: Sokal, Hasford and ELTSRisk scores use age, spleen size and blood counts to estimate how a person with CML is likely to fare. The Sokal score (1984) came from patients treated with chemotherapy, the Hasford score (1998) from patients treated with interferon, and the ELTS score (2016) from patients treated with imatinib. A 2020 comparison found ELTS discriminated survival better than Sokal.Sokal 1984: 813 Ph-positive patients from six series, median survival 47 months; Cox model (blasts, spleen size, platelets, age). Hasford 1998: data on 1573 patients from 14 interferon studies; median survival 98, 65 and 42 months across three risk groups. Pfirrmann 2016: 2290 imatinib-treated patients, 8-year OS 89%, 44% of 208 deaths due to CML; long-term survival score. Pfirrmann 2020: ELTS 60% low-risk versus Sokal 40% (5154 patients).
  5. 1990 · Treatment · Cell therapy & transplant⚑ needs reviewDonor leukocyte transfusions for relapse after transplant (1990)In 1990 a group reported three people whose CML returned after a marrow transplant; treated with interferon and white cells from their donor, all three reached complete remission lasting 32 to 91 weeks, and two developed graft-versus-host disease. A 1995 European series of 84 patients with CML reported 54 complete remissions.Kolb 1990: 3 patients with hematologic relapse of CML after marrow transplant given interferon alpha plus donor buffy coat; all had complete hematologic and cytogenetic remission, lasting 32 to 91 weeks; GVHD in 2. Kolb 1995 (EBMT Working Party; 135 patients, 84 with CML): complete remission in 54 patients with CML (published as 73%; denominator unconfirmed); probability of remission 87% at 3 years in chronic phase; GVHD grade 2 or more in 52 (41%).
  6. 1993 · Treatment · ChemotherapyHydroxyurea versus busulfan: the German CML Study Group trialIn a randomised trial of 441 people with chronic-phase CML, the German CML Study Group compared hydroxyurea with busulfan. Among Philadelphia-positive patients, median survival was about 58 months with hydroxyurea and 45 months with busulfan. The authors concluded hydroxyurea should be the first drug used.German CML Study Group, randomized multicenter (n=441, July 1983 to January 1991; 90.7% Ph-positive; Sokal risk 25.7% low, 38.2% intermediate, 36.2% high). Median survival of Ph-positive patients: busulfan 45.4 months, hydroxyurea 58.2 months (P=.008); advantage in all risk groups. Fewer adverse reactions with hydroxyurea. Authors: hydroxyurea first line; busulfan as secondary therapy.
  7. 1994 · Treatment · ImmunotherapyRandomized trials of interferon alfa in CML, 1994 to 1997Three randomised trials tested interferon alfa in chronic-phase CML. In Italy, median survival was 72 months with interferon versus 52 with standard chemotherapy. In Germany, survival was longer with interferon than with busulfan but not significantly longer than with hydroxyurea. In France, adding cytarabine raised three-year survival from about 79 to 86 percent.ICSG (n=322): interferon alfa-2a vs hydroxyurea/busulfan, median survival 72 vs 52 months (P=0.002); karyotypic response 30% vs 5%. German CML Study Group (n=513): median survival 5.5 years interferon, 3.8 busulfan (P=.008), 4.7 hydroxyurea (P=.44). French study: interferon plus cytarabine vs interferon, 3-year survival 85.7% vs 79.1%, relative risk of death 0.64 (95% CI 0.44 to 0.93).
  8. 1996 · Understanding · TargetedSelective Abl kinase inhibitor suppresses Bcr-Abl-positive cellsIn 1996 laboratory work reported that a compound designed to block the Abl enzyme stopped Bcr-Abl-positive cells from multiplying and forming tumours in test systems. In blood or marrow samples from people with CML, it cut the number of Bcr-Abl colonies by more than nine in ten without stopping normal colonies. The paper's abstract does not name the compound.Preclinical study: a compound designed to inhibit the Abl protein tyrosine kinase specifically inhibited cellular proliferation and tumor formation by Bcr-Abl-expressing cells; in colony-forming assays of peripheral blood or bone marrow from patients with CML there was a 92-98% decrease in bcr-abl colonies and no inhibition of normal colony formation. The bcr-abl oncogene is present in 95% of patients with CML (abstract).

Targeted therapy

  1. 2001 · Treatment · Targeted⚑ needs reviewSTI571/imatinib: first clinical results and FDA approvalIn 2001 a dose-finding trial of STI571, later called imatinib, a drug aimed at the BCR-ABL enzyme, reported normal blood counts in 53 of 54 people with chronic-phase CML who had stopped responding to interferon and took 300 mg or more daily. Side effects were mild. The US regulator approved imatinib in May 2001 on response rates, not survival.Phase 1 dose escalation (83 patients, chronic phase, interferon alfa failure): complete hematologic response in 53 of 54 patients at 300 mg or more daily; major cytogenetic response 31%, with complete cytogenetic remission in 7 of 54. Companion pilot (58 patients, blast crisis or Ph-positive ALL): responses 55% (myeloid) and 70% (lymphoid or ALL), nearly all lymphoid and ALL patients relapsing. FDA accelerated approval 10 May 2001 on response rates.
  2. 2001 · Understanding · UnderstandingImatinib resistance linked to BCR-ABL mutation or amplificationIn 2001 a Science paper studied people whose leukemia had stopped responding to the first BCR-ABL-blocking drug. In six of nine people, the resistant cells carried a single amino-acid change in the drug's target enzyme. In three people the BCR-ABL gene had been copied many more times. In all cases examined, the BCR-ABL signal had switched back on.Analysis of clinical material from patients who relapsed on STI-571: resistance was associated with reactivation of BCR-ABL signal transduction in all cases examined; in 6 of 9 patients with a single amino acid substitution of a threonine residue in the Abl kinase domain that forms a critical hydrogen bond with the drug (threonine to isoleucine, shown sufficient to confer resistance in a reconstitution experiment); in 3 patients with progressive BCR-ABL gene amplification.
  3. 2002 · Treatment · Targeted⚑ needs reviewIRIS: imatinib versus interferon plus cytarabine, first lineIn late 2002 imatinib was approved in the US for newly diagnosed chronic myeloid leukemia. The IRIS trial compared it with interferon alfa plus low-dose cytarabine in 1,106 people. At 18 months, about 76% on imatinib had no Philadelphia-chromosome-positive cells in the marrow, against 15%. At ten years, about 83% of those who started imatinib were estimated to be alive.IRIS, open-label randomized phase 3 (n=1106; imatinib 553 vs interferon alfa plus low-dose cytarabine 553; crossover permitted). At 18 months (median follow-up 19 months): MCyR 87.1% vs 34.7%, CCyR 76.2% vs 14.5% (both P<0.001); freedom from progression to accelerated phase or blast crisis 96.7% vs 91.5% (P<0.001). At median follow-up 10.9 years, 10-year OS with imatinib was 83.3%; 65.6% of the control arm crossed over, so no valid OS comparison between arms.
  4. 2003 · Understanding · UnderstandingBCR-ABL1 transcript monitoring and the international scaleIn 2003 an IRIS substudy measured BCR-ABL RNA in the blood and found that a fall of at least three log (one-thousand-fold) by 12 months was more common with imatinib and went with very low progression risk. In 2006 an expert meeting proposed reporting such results on one international scale and using serial blood tests to follow treatment.IRIS substudy: in patients with complete cytogenetic remission, BCR-ABL transcript levels had fallen by at least 3 log at 12 months in 57% of the imatinib group vs 24% of the interferon plus cytarabine group (P=0.003); estimated 39% vs 2% of all patients (P<0.001). With CCyR and a 3-log reduction at 12 months, progression-free probability at 24 months was 100%, vs 95% (CCyR, under 3 log) and 85% (no CCyR) (P<0.001). 2006 consensus: international scale; serial RQ-PCR.
  5. 2006 · Treatment · Targeted⚑ needs reviewDasatinib and nilotinib for imatinib resistance or intoleranceIn 2006 two early-phase studies reported hematologic and cytogenetic responses to dasatinib and nilotinib in many people whose CML had stopped responding to imatinib; the dasatinib study also enrolled people who could not tolerate imatinib. The US regulator approved dasatinib in June 2006 and nilotinib in October 2007, both under its accelerated approval regulations.Dasatinib phase 1 (15 to 240 mg per day): complete hematologic response in 37 of 40 chronic-phase patients; major cytogenetic response 45% (chronic phase) and 25% (accelerated, blast or Ph-positive ALL); responses across BCR-ABL genotypes except T315I. Nilotinib phase 1 (n=119): complete hematologic remission in 11 of 12 chronic-phase patients; hematologic response in 33 of 46 accelerated-phase and 13 of 33 blastic-phase patients. FDA accelerated approvals: dasatinib 28 June 2006, nilotinib 29 October 2007.
  6. 2010 · Treatment · Targeted⚑ needs reviewDASISION and ENESTnd: second-generation TKIs first lineIn 2010 two randomised trials compared dasatinib and nilotinib with imatinib as first treatment for chronic-phase CML. After 12 months more people on either newer drug had no Philadelphia-chromosome-positive cells in the marrow, and more had a major molecular response. The US regulator approved both drugs for newly diagnosed CML that year.DASISION (n=519): confirmed CCyR by 12 months 77% with dasatinib 100 mg daily vs 66% with imatinib 400 mg (P=0.007); MMR 46% vs 28% (P<0.0001). ENESTnd (n=846): MMR at 12 months (primary) 44% (nilotinib 300 mg twice daily), 43% (400 mg twice daily) vs 22% (imatinib), P<0.001; CCyR by 12 months 80%, 78% vs 65%. Separate trials with different primary endpoints, not compared with each other.
  7. 2010 · De-escalation · TargetedSTIM: stopping imatinib after sustained molecular responseIn 2010 French investigators reported what happened when 100 people with CML whose disease was undetectable for at least two years stopped imatinib. Of the 69 followed for a year, about two in five were still in remission off treatment; nearly all relapses came within six months, and everyone who relapsed responded again when imatinib was restarted.STIM (NCT00478985): prospective, non-randomised, 19 French institutions; imatinib stopped in 100 patients with undetectable BCR-ABL transcripts after more than 2 years of treatment. Interim analysis (69 patients with 12 months' follow-up): persistent complete molecular remission at 12 months 41% (95% CI 29-52); 42 relapsed, 40 before 6 months; all responded to imatinib reintroduction. Final analysis (median 77 months): molecular recurrence-free survival 38% (95% CI 29-47) at 60 months.

Immunotherapy

  1. 2012 · Treatment · TargetedBosutinib: from a missed first-line endpoint (BELA) to BFOREIn the BELA trial, bosutinib did not beat imatinib on its main goal, complete cytogenetic response at 12 months, in newly diagnosed chronic-phase CML. In the later BFORE trial, whose main goal was major molecular response, rates were higher with bosutinib (about 47% against 37%). The FDA approved it for previously treated people in 2012 and new diagnoses in 2017.BELA (n=502): CCyR at 12 months 70% (95% CI 64-76) with bosutinib 500 mg vs 68% (62-74) with imatinib 400 mg, P=0.601 (primary endpoint not met); MMR 41% vs 27% (P<0.001). BFORE (n=536; efficacy population 246 vs 241): MMR at 12 months (primary) 47.2% vs 36.9% (P=0.02); CCyR by 12 months 77.2% vs 66.4% (P=0.0075). Grade 3 or higher ALT increase 19.0% vs 1.5%.
  2. 2012 · Treatment · Targeted⚑ needs reviewPonatinib: activity against T315I (PACE)Ponatinib was approved in the US in December 2012 for people whose CML or Philadelphia-chromosome-positive ALL no longer responded to, or could not tolerate, other kinase inhibitors. In the PACE trial, 56% of people with chronic-phase CML had a major cytogenetic response, including 70% of those with the T315I mutation. Serious arterial blood-clot events occurred in 9% of all participants.PACE, single-arm phase 2 (449 heavily pretreated patients; ponatinib 45 mg daily; median follow-up 15 months). Chronic phase (267 evaluable): MCyR 56% (51% resistant or intolerant; 70% T315I), CCyR 46%, MMR 34%. Serious arterial thrombotic events 9% (3% treatment-related). Final analysis (56.8 months): MCyR 60%, MMR 40%, 5-year OS 73%, cumulative arterial occlusive events 31%. OPTIC (n=283): BCR-ABL1 IS ≤1% at 12 months 44.1%, 29.0%, 23.1% by 45, 30, 15 mg start.
  3. 2013 · Reversal · TargetedPonatinib marketing suspended over arterial occlusive eventsIn October 2013 the maker of ponatinib voluntarily suspended US marketing after reports and trial data pointed to more serious blood-vessel blockages. On 20 December 2013 the US regulator approved new warnings and a risk-management programme, and said the suspension would no longer be warranted once that programme was fully operational.FDA letter of 20 December 2013 (S-007 and S-008) acknowledges the sponsor's voluntary suspension of marketing from 31 October 2013 after postmarketing reports and trial follow-up data showing an increased frequency of serious vascular occlusive events, approves revised labeling and a REMS, and requires postmarketing studies. PACE reported serious arterial thrombotic events in 9% of patients (3% treatment-related); at final analysis cumulative arterial occlusive events were 31% in chronic phase.
  4. 2015 · Understanding · UnderstandingLife expectancy in CML approaches that of the general populationTwo analyses from the TKI era found that survival with CML has come close to that of the general population. In an MD Anderson cohort of 483 trial participants with chronic-phase CML, five-year survival was about 95% of that of a matched general population. In Sweden, people diagnosed in 2013 were predicted to lose fewer than three years of life.Sasaki 2015: 483 patients with newly diagnosed CML-CP in six consecutive TKI trials at one institution (2000-2012): 5-year relative survival 94.7% (95% CI 92.1-97.4) against a matched general population. Bower 2016: Swedish Cancer Registry, 2,662 patients diagnosed 1973-2013; modelled life-years lost to CML for patients of all ages diagnosed in 2013 <3. Different designs; figures are not combined.
  5. 2017 · De-escalation · TargetedDESTINY: reducing the TKI dose before stoppingIn 2017 a UK trial asked whether people doing well on a TKI could safely take half the usual dose. Over 12 months about one in fourteen had a molecular recurrence, and all regained their response within four months of returning to the full dose. Recurrence was much less common in people whose response was deeper at entry.DESTINY (NCT01804985): non-randomised phase 2, 20 UK hospitals, 174 patients on half-dose TKI for 12 months. Interim analysis: molecular recurrence (loss of MMR on two consecutive samples) in 12 patients (7%), all regaining MMR within 4 months of full-dose resumption (median 77 days). Recurrence 2% (3/121 evaluable) in the MR4 cohort vs 19% (9/48) in the MMR cohort; hazard ratio 0.12 (90% CI 0.04-0.37; p=0.0007).
  6. 2017 · De-escalation · TargetedStopping TKIs: EURO-SKI, ENESTfreedom, ENESTop, DASFREE, labelFour studies of stopping a TKI after a long, deep response each reported their own results. In EURO-SKI, half the 755 people evaluated had not lost major molecular response two years after stopping. Eligibility and relapse definitions differed, so percentages cannot be compared. In 2017 the US nilotinib label allowed eligible patients to be considered for stopping.Single-arm studies with different eligibility and relapse definitions; rates are not comparable. EURO-SKI (758 enrolled): molecular relapse-free survival (loss of MMR) 61% at 6 months, 50% at 24 months. ENESTfreedom (190 in TFR phase): 51.6% in MMR or better at 48 weeks. ENESTop: 57.9% at 48 weeks, 42.9% at 5 years. DASFREE (84 patients): 46% at 2 years, 44% at 5 years. FDA nilotinib label supplement 22 December 2017.

Precision & engineered

  1. 2021 · Treatment · TargetedAsciminib approved after ASCEMBL versus bosutinibIn 2021 a trial of 233 people with CML who had already taken two or more TKIs compared asciminib, which acts at a different site on BCR-ABL1, with bosutinib. At 24 weeks about one in four on asciminib and about one in eight on bosutinib had a major molecular response. The FDA granted accelerated approval in October 2021.ASCEMBL (NCT03106779): open-label phase 3, 233 patients with CML-CP after 2 or more TKIs, asciminib 40 mg twice daily vs bosutinib 500 mg once daily (2:1). MMR at week 24: 25.5% vs 13.2% (adjusted difference 12.2%, 95% CI 2.19-22.30; P=.029). Week 96: 37.6% vs 15.8% (difference 21.7%, 95% CI 10.53-32.95). Grade 3 or higher adverse events 50.6% vs 60.5% at the primary analysis. FDA accelerated approval 29 October 2021.
  2. 2024 · Treatment · TargetedASC4FIRST: asciminib in newly diagnosed chronic-phase CMLIn 2024 a trial of 405 adults with newly diagnosed chronic-phase CML compared asciminib, which acts on BCR-ABL1 at a different site from older drugs, with a TKI chosen by the treating doctor. At 48 weeks about two in three on asciminib and about half on the comparators had a major molecular response. US approval is accelerated, pending confirmation.ASC4FIRST (NCT04971226): open-label phase 3, 405 adults, asciminib 80 mg daily vs investigator-selected TKI (1:1). MMR at week 48: 67.7% vs 49.0% (difference 18.9 percentage points, 95% CI 9.6-28.2; P<0.001); imatinib stratum 69.3% vs 40.2%. Second-generation TKI stratum: 66.0% vs 57.8% (difference 8.2, 95% CI -5.1 to 21.5), not a primary objective. Week 96: 74.1% vs 52.0%.
  3. 2025 · Today · TargetedEuropean LeukemiaNet recommendations, 2006 to 2025European LeukemiaNet, a network of CML specialists, has issued five versions of its treatment recommendations; this entry follows 2006, 2013, 2020 and 2025. They track the shift from imatinib alone, judged mainly by blood and chromosome tests, to a choice of several drugs, molecular monitoring and, for selected people, a planned attempt to stop treatment.ELN expert-panel recommendations. 2006: imatinib 400 mg daily preferred initial treatment; failure defined by haematologic and cytogenetic response. 2013: imatinib, nilotinib or dasatinib; BCR-ABL1 International Scale milestones at 3, 6 and 12 months. 2020: lists bosutinib first-line; ELTS score; discontinuation may be considered. 2025: dose reduction rather than switching for toxicity; treatment discontinuation guidance; six TKIs approved first-line.

Then and now

  • 5-year relative survival · United States, SEER 8 registries

    • 17.99%

      1975 (observed value; first year in the table)

    People with chronic myeloid leukemia, all races, both sexes (chart note); SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts CML page. Age range and disease-phase mix are not stated for this series, and the page states that there is no standard staging system for leukemia.

    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 (24.32% 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. SEER 8 covers a limited set of registries and single-year values fluctuate (for example 17.72% in 1979 and 23.50% in 1976 in the same series). The page does not state which histology codes or case definition it uses for CML, or whether that definition stayed the same over 1975-2018; SEER's published site-recode table (ICD-O-3/WHO 2008) assigns histology codes 9863, 9875-9876 and 9945-9946 to its 'Chronic Myeloid Leukemia' category, and the labels of those codes were not checked for this page. The page does not attribute any change in this series to a treatment or other cause. Compare only with other values from the same SEER 8 series.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 47.15%

      2000 (observed value)

    People with chronic myeloid leukemia, all races, both sexes (chart note); SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts CML page. Age range and disease-phase mix are not stated for this series, and the page states that there is no standard staging system for leukemia.

    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 (46.53% 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. SEER 8 covers a limited set of registries and single-year values fluctuate (for example 17.72% in 1979 and 23.50% in 1976 in the same series). The page does not state which histology codes or case definition it uses for CML, or whether that definition stayed the same over 1975-2018; SEER's published site-recode table (ICD-O-3/WHO 2008) assigns histology codes 9863, 9875-9876 and 9945-9946 to its 'Chronic Myeloid Leukemia' category, and the labels of those codes were not checked for this page. The page does not attribute any change in this series to a treatment or other cause. Compare only with other values from the same SEER 8 series.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 71.32%

      2010 (observed value)

    People with chronic myeloid leukemia, all races, both sexes (chart note); SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts CML page. Age range and disease-phase mix are not stated for this series, and the page states that there is no standard staging system for leukemia.

    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 (70.64% 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. SEER 8 covers a limited set of registries and single-year values fluctuate (for example 17.72% in 1979 and 23.50% in 1976 in the same series). The page does not state which histology codes or case definition it uses for CML, or whether that definition stayed the same over 1975-2018; SEER's published site-recode table (ICD-O-3/WHO 2008) assigns histology codes 9863, 9875-9876 and 9945-9946 to its 'Chronic Myeloid Leukemia' category, and the labels of those codes were not checked for this page. The page does not attribute any change in this series to a treatment or other cause. Compare only with other values from the same SEER 8 series.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 72.39%

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

    People with chronic myeloid leukemia, all races, both sexes (chart note); SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts CML page. Age range and disease-phase mix are not stated for this series, and the page states that there is no standard staging system for leukemia.

    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 (71.33% 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. SEER 8 covers a limited set of registries and single-year values fluctuate (for example 17.72% in 1979 and 23.50% in 1976 in the same series). The page does not state which histology codes or case definition it uses for CML, or whether that definition stayed the same over 1975-2018; SEER's published site-recode table (ICD-O-3/WHO 2008) assigns histology codes 9863, 9875-9876 and 9945-9946 to its 'Chronic Myeloid Leukemia' category, and the labels of those codes were not checked for this page. The page does not attribute any change in this series to a treatment or other cause. After 2018 the table shows only modelled trend values (71.15% for 2019 to 70.45% for 2023). Observed values from 2010 to 2018 range from 65.99% (2014) to 77.96% (2011). Compare only with other values from the same SEER 8 series.

    Source

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

    • 71.1%

      2016-2022

    People with chronic myeloid leukemia; the headline five-year relative survival figure on the SEER Cancer Stat Facts CML page (SEER 21, excluding IL). Race, sex and age range are not stated beside the figure, and the page states that there is no standard staging system for leukemia.

    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. The page labels the period '2016-2022' and does not say whether this is year of diagnosis. Relative survival excludes deaths from other causes. The page does not state which histology codes or case definition it uses for CML, or whether that definition stayed the same over 1975-2018; SEER's published site-recode table (ICD-O-3/WHO 2008) assigns histology codes 9863, 9875-9876 and 9945-9946 to its 'Chronic Myeloid Leukemia' category, and the labels of those codes were not checked for this page. The page gives no breakdown by age, sex, race or disease phase for this figure.

    Source

  • 5-year relative survival · United Kingdom (Cancer Research UK)

    • 81.8%

      2010-2019

    People diagnosed with chronic myeloid leukaemia in the UK; the headline figure on the Cancer Research UK CML survival page for health professionals. The page does not state an age range or sex, and refers readers to the HMRN website for survival data.

    A different country, data source and period from the SEER series: do not compare or subtract. The page words the figure as the proportion who 'survive their disease for five years or more (2010-2019)', and elsewhere on the page calls it five-year relative survival; it does not say whether the period is year of diagnosis or how the estimate was derived. The page states that survival trends reflect a combination of changes in treatment and stage distribution, which vary by age, sex and deprivation. The page gives no case definition for CML.

    Source

  • Age-standardised mortality · United States

    • 1per 100,000

      1975 (observed)

    • 0.86per 100,000

      1995 (observed)

    • 0.58per 100,000

      2001 (observed)

    • 0.31per 100,000

      2010 (observed)

    People of all races and both sexes in the United States; age-adjusted death rate from US mortality data (not SEER registries), 'Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts CML page (chart note: deaths come from U.S. Mortality; all races, both sexes; rates are age-adjusted).

    Observed value from the table; the adjacent modelled trend column is not used. Death rates describe the whole US population and are not measured from the date of diagnosis, so they are not a survival measure. Deaths are attributed by cause-of-death coding; the page does not say how CML was defined across the years or how coding revisions affect the series, and it does not attribute any change in the rate to a treatment or other cause. The page does not address screening, so no screening-related mortality pairing is made here.

    Source

  • Age-standardised mortality · United States

    • 0.29per 100,000

      2024 (observed; last year in the table)

    People of all races and both sexes in the United States; age-adjusted death rate from US mortality data (not SEER registries), 'Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts CML page (chart note: deaths come from U.S. Mortality; all races, both sexes; rates are age-adjusted).

    Observed value from the table; the adjacent modelled trend column is not used. Death rates describe the whole US population and are not measured from the date of diagnosis, so they are not a survival measure. Deaths are attributed by cause-of-death coding; the page does not say how CML was defined across the years or how coding revisions affect the series, and it does not attribute any change in the rate to a treatment or other cause. The page headline gives 0.3 per 100,000 for 2020-2024 deaths and a fall of 0.7% per year on average over 2015-2024; use one or the other, not both. The page does not address screening, so no screening-related mortality pairing is made here.

    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.

Newly diagnosed chronic phase, first line: major molecular response

Adults with newly diagnosed chronic-phase CML starting first-line treatment · Any setting · endpoint: MMR

Results are not comparable across trials.

Eras, comparator drugs and the time point differ. The earliest value comes from an IRIS substudy that measured a three-log fall in BCR-ABL transcripts at 12 months against interferon plus cytarabine; the authors estimated it for all treated patients from cytogenetic response rates, so it is a model-based estimate and not an observed proportion. DASISION, BELA and BFORE compare a newer drug with imatinib at 12 months, ENESTnd's drawn arm is nilotinib 300 mg twice daily (its 400 mg arm is not drawn), and BFORE assessed patients with typical transcripts. ASC4FIRST assessed response at week 48, and its control arm is a TKI chosen by the treating doctor (imatinib or a second-generation TKI), not imatinib alone. Compare only each trial's own two 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.

020406080100MMR (%)200320102010201220122024IRIS molecular substudyDASISIONENESTndBELABFOREASC4FIRST
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
MMR, rate, across 6 trials in this lane. IRIS molecular substudy (2003): experimental 39 % vs control 2 %; DASISION (2010): experimental 46 % vs control 28 %; ENESTnd (2010): experimental 44 % vs control 22 %; BELA (2012): experimental 41 % vs control 27 %; BFORE (2012): experimental 47.2 % vs control 36.9 %; ASC4FIRST (2024): experimental 67.7 % vs control 49 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
IRIS molecular substudy2003MMR2 %39 %
DASISION2010MMR28 %46 %
ENESTnd2010MMR22 %44 %
BELA2012MMR27 %41 %
BFORE2012MMR36.9 %47.2 %
ASC4FIRST2024MMR49 %67.7 %

Chronic phase before TKIs: overall survival

People with chronic-phase CML, mostly Philadelphia-chromosome-positive, treated with chemotherapy or interferon alfa · Any setting · endpoint: OS

Results are not comparable across trials.

These randomized trials ran from the 1980s to the 1990s with different comparators. The German hydroxyurea and busulfan trial reports Philadelphia-positive patients only, and the German interferon trial's drawn control arm is hydroxyurea (its busulfan arm is not drawn). The Italian trial compared interferon alfa-2a with hydroxyurea or busulfan together. The French trial compared interferon plus cytarabine with interferon alone and reports a 3-year survival percentage, not a median, so it is listed but not drawn on the median axis. Analysis populations and follow-up differ. Compare only each trial's own arms. The busulfan milestone has no trial values.

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.

020406080OS, median (months)199319941994german-cml-hu-vs-busulfan-1993icsg-ifn-vs-chemo-1994german-cml-ifn-vs-bu-hu-1994
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
OS, median, across 3 trials in this lane. german-cml-hu-vs-busulfan-1993 (1993): experimental 58.2 months vs control 45.4 months; icsg-ifn-vs-chemo-1994 (1994): experimental 72 months vs control 52 months; german-cml-ifn-vs-bu-hu-1994 (1994): experimental 66 months vs control 56.400000000000006 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
german-cml-hu-vs-busulfan-19931993OS45.4 months58.2 months
icsg-ifn-vs-chemo-19941994OS52 months72 months
german-cml-ifn-vs-bu-hu-19941994OS56.400000000000006 months66 months
french-cml-ifn-arac-19971994OS (not plotted: different measure or time point)79.1 %85.7 %

Chronic phase after two or more TKIs: major molecular response

Adults with chronic-phase CML previously treated with two or more TKIs · Relapsed / refractory · endpoint: MMR

Results are not comparable across trials.

Only ASCEMBL, which randomized asciminib against bosutinib at week 24, can be drawn as a pair; it excluded patients with T315I or V299L mutations. PACE (a single-arm trial that included T315I) and OPTIC (three ponatinib starting-dose cohorts) have no control arm, so they are not drawn. Prior therapy, mutation status and endpoints differ across the three trials, and results from different trials should not be compared with one another.

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.

020406080100MMR (%)2021ASCEMBL
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
MMR, rate, across 1 trial in this lane. ASCEMBL (2021): experimental 25.5 % vs control 13.2 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
ASCEMBL2021MMR13.2 %25.5 %

Stopping or reducing TKI treatment: treatment-free remission

Adults with chronic-phase CML in sustained deep molecular response who stopped, or reduced the dose of, a TKI · Maintenance · endpoint: TFR

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.

Chronic-phase CML: first-line treatment

Adults with newly diagnosed chronic-phase CML · Any setting

  1. Targeted11st line: imatinibIRIS: imatinib versus interferon plus cytarabine, first line (2002)
  2. Targeted21st line: dasatinib or nilotinibDASISION and ENESTnd: second-generation TKIs first line (2010)
  3. Targeted31st line: bosutinibBosutinib: from a missed first-line endpoint (BELA) to BFORE (2012)
  4. Targeted41st line: asciminibASC4FIRST: asciminib in newly diagnosed chronic-phase CML (2024)
Today. Based only on the trials cited in each step. Bosutinib was approved for new diagnoses in 2017; asciminib has US accelerated approval for this use, pending confirmation.
Text version
  • 1994: Hydroxyurea or busulfan → Interferon alfa, tested against chemotherapy → Matched-sibling marrow transplant
  • 2002: 1st line: imatinib
  • 2010: 1st line: imatinib → 1st line: dasatinib or nilotinib
  • Today: 1st line: imatinib → 1st line: dasatinib or nilotinib → 1st line: bosutinib → 1st line: asciminib

CML after imatinib: resistance or intolerance

People with CML whose disease no longer responded to, or who could not tolerate, earlier TKIs · Relapsed / refractory

  1. Targeted1After imatinib: dasatinib or nilotinibDasatinib and nilotinib for imatinib resistance or intolerance (2006)
  2. Targeted2After other TKIs or T315I: ponatinibPonatinib: activity against T315I (PACE) (2012)
  3. Targeted3After two or more TKIs: asciminibAsciminib approved after ASCEMBL versus bosutinib (2021)
2021. Based only on the trials cited in each step. Asciminib was compared with bosutinib in people previously treated with two or more TKIs and received US accelerated approval in October 2021.
Text version
  • 2006: After imatinib: dasatinib or nilotinib
  • 2012: After imatinib: dasatinib or nilotinib → After other TKIs or T315I: ponatinib
  • 2021: After imatinib: dasatinib or nilotinib → After other TKIs or T315I: ponatinib → After two or more TKIs: asciminib

Reversals and dead ends

Approaches that were abandoned or withdrawn, and trials whose results were later questioned, are part of the story.

  • 2013

    Ponatinib marketing suspended over arterial occlusive events

    In October 2013 the maker of ponatinib voluntarily suspended US marketing after reports and trial data pointed to more serious blood-vessel blockages. On 20 December 2013 the US regulator approved new warnings and a risk-management programme, and said the suspension would no longer be warranted once that programme was fully operational.

    FDA letter of 20 December 2013 (S-007 and S-008) acknowledges the sponsor's voluntary suspension of marketing from 31 October 2013 after postmarketing reports and trial follow-up data showing an increased frequency of serious vascular occlusive events, approves revised labeling and a REMS, and requires postmarketing studies. PACE reported serious arterial thrombotic events in 9% of patients (3% treatment-related); at final analysis cumulative arterial occlusive events were 31% in chronic phase.

Today and tomorrow

Standard of care today

Any setting

Newly diagnosed Ph+ CML in chronic phase:

  • regulatory actions read for this page. FDA: imatinib, accelerated approval on 20 December 2002 (the letter notes that follow-up is limited)
  • nilotinib, accelerated approval on 17 June 2010
  • dasatinib, accelerated approval on 28 October 2010
  • bosutinib, accelerated approval on 19 December 2017, with regular approval of the newly diagnosed chronic-phase indication on 14 May 2021 (supplement S-020, which also fulfilled the postmarketing requirements)
  • asciminib, accelerated approval on 29 October 2024, with completion of ASC4FIRST (NCT04971226) listed as the confirmatory requirement. The Scemblix label on DailyMed (SPL version 13
  • document effective time 22 September 2026) still states that the newly diagnosed indication is approved under accelerated approval based on major molecular response rate. Whether the imatinib, nilotinib and dasatinib first-line indications were later converted to regular approval was not established from the documents read. EMA: the EPAR pages for Glivec (page updated 12 November 2025), Sprycel (2 October 2026), Tasigna (19 December 2025) and Bosulif (12 January 2026) list newly diagnosed chronic-phase CML. The Scemblix EPAR page (updated 7 August 2026) gives the indication as adults with Ph+ CML in chronic phase with no prior-treatment qualifier and describes a study in newly diagnosed adults
  • a Novartis release of 17 October 2025 reports a positive CHMP opinion covering all lines. The date of the European Commission decision on that extension is not stated on the pages read
US Food and Drug Administration 2002US Food and Drug Administration 2010US Food and Drug Administration 2010US Food and Drug Administration 2017US Food and Drug Administration 2021US Food and Drug Administration 2024DailyMed 2026European Medicines Agency 2001European Medicines Agency 2006European Medicines Agency 2007European Medicines Agency 2013European Medicines Agency 2022Novartis 2025
Any setting
Newly diagnosed chronic phase, guideline text read: the 2025 European LeukemiaNet recommendations (open-access text) list imatinib, dasatinib, nilotinib, bosutinib, asciminib (in some countries) and radotinib (in South Korea) as TKIs approved for first-line use. They report that randomised comparisons of imatinib with second-generation TKIs show higher response rates and less transformation to advanced phase with the newer drugs but no overall survival difference, and they describe the choice of first-line TKI as depending on the treatment aim (survival or treatment-free remission), ELTS risk score, comorbidities and cost. On asciminib they summarise ASC4FIRST and state that long-term survival data are not yet available; they do not recommend routine addition of interferon. Everything in this entry restates what the ELN text says and is not a ranking of options.
Apperley JF, Milojkovic D, Cross NCP, Hjorth-Hansen H, Hochhaus A, Kantarjian H, et al 2025
Any setting
Other guideline documents on this topic, cited by identifier only with no recommendation summarised: NCCN Clinical Practice Guidelines in Oncology, Chronic Myeloid Leukemia, Version 2.2024 (J Natl Compr Canc Netw 2024;22(1):43-69; a newer version may be current on the NCCN website, which was not checked), and the ESMO Clinical Practice Guidelines for chronic myeloid leukaemia (Ann Oncol 2017;28 suppl 4:iv41-iv51).
Guideline: Shah NP, Bhatia R, Altman JK, Amaya M, Begna KH, Berman E, et al 2024Guideline: Hochhaus A, Saussele S, Rosti G, Mahon FX, Janssen JJWM, Hjorth-Hansen H, et al 2017
Relapsed / refractory

Chronic-phase CML after earlier TKI therapy, FDA actions read:

  • ponatinib, supplement approved on 18 December 2020 adding chronic-phase CML with resistance or intolerance to at least two prior kinase inhibitors and updating the indications for accelerated or blast phase disease and T315I-positive disease
  • a further supplement on 15 February 2022 updated labelling from the final OPTIC report and fulfilled a postmarketing requirement. Asciminib, accelerated approval on 29 October 2021 for Ph+ CML in chronic phase previously treated with two or more TKIs
  • the supplement approved on 12 October 2022, based on ASCEMBL with 96-week follow-up, is stated in its letter to fulfil the commitments made under 21 CFR 314.510
  • a supplement on 29 October 2024 revised the indication to previously treated Ph+ CML in chronic phase. ELN 2025 text: for toxicity in people who are responding, dose reduction is described as the first approach, with a switch for serious events such as recurrent pleural effusions, pulmonary hypertension or arterial and venous occlusive events
  • after imatinib, any suitable second-generation TKI
  • after resistance to a second-generation TKI without a specific mutation, early ponatinib or asciminib (asciminib not licensed second-line in all countries)
  • donor search at resistance to a second-generation TKI and transplant referral at resistance to ponatinib or asciminib for eligible people
US Food and Drug Administration 2020US Food and Drug Administration 2022US Food and Drug Administration 2021US Food and Drug Administration 2022US Food and Drug Administration 2024Apperley JF, Milojkovic D, Cross NCP, Hjorth-Hansen H, Hochhaus A, Kantarjian H, et al 2025
Maintenance

Treatment-free remission. FDA:

  • a supplement approved on 22 December 2017 updated the nilotinib label so that eligible people with newly diagnosed Ph+ CML in chronic phase, and those resistant or intolerant to imatinib, who have taken nilotinib for at least 3 years and have a sustained MR4.5 can be considered for treatment discontinuation. The Tasigna EPAR page says adults whose CML is well controlled may stop treatment with regular tests (date of that wording not stated). ELN 2025, Table 6: stopping is for first chronic phase only, in motivated people with access to quality-controlled International Scale monitoring
  • minimal criteria are first-line therapy (or second-line after intolerance or mutation-sensitive resistance), typical e13a2 or e14a2 transcripts, TKI for more than 5 years (more than 4 years for second-generation TKIs) and deep molecular response for more than 2 years
  • optimal criteria are more than 5 years of TKI and more than 3 years of MR4 or more than 2 years of MR4.5. After stopping, monitoring is every 6 to 8 weeks for 6 months, every 2 months for months 6 to 12 and every 3 to 6 months thereafter, and TKI is restarted if MMR is lost. The text states that about 40-50% of people remain off treatment
US Food and Drug Administration 2017European Medicines Agency 2007Apperley JF, Milojkovic D, Cross NCP, Hjorth-Hansen H, Hochhaus A, Kantarjian H, et al 2025Saussele S, Richter J, Guilhot J, Gruber FX, Hjorth-Hansen H, Almeida A, et al 2018
Relapsed / refractory
Accelerated or blast phase, and transplant. FDA: the ponatinib supplement of 18 December 2020 updated the indications for accelerated or blast phase CML or Ph+ ALL for whom no other kinase inhibitors are indicated and for T315I-positive CML or Ph+ ALL. ELN 2025 text: the authors describe blast phase treatment for eligible people as intensive combination chemotherapy with a TKI, ideally dasatinib or ponatinib, followed by allogeneic stem cell transplantation; transplant is described as remaining important for chronic-phase CML resistant to later-generation TKIs or intolerant to all available TKIs, and for people who present in or progress to blast phase, with transplant of resistant blast phase outside a study not recommended. The ELN text also notes that the 2022 WHO classification omits accelerated phase and sets blast phase at more than 20% blasts, which differs from the ELN 2013 and MD Anderson definitions in use in trials.
US Food and Drug Administration 2020Apperley JF, Milojkovic D, Cross NCP, Hjorth-Hansen H, Hochhaus A, Kantarjian H, et al 2025
Screening
The SEER Cancer Stat Facts CML page does not discuss screening, and states that there is no standard staging system for leukemia (the disease is described as untreated, in remission or recurrent). No screening recommendation is summarised here, and no screening-related mortality comparison is made.
National Cancer Institute, Surveillance, Epidemiology, and End Results Program 2026

Trials to watch

  • POLARIS-2 NCT06423911

    In chronic-phase CML previously treated with at least two approved TKIs, does olverembatinib (HQP1351) differ from bosutinib in the 24-week major molecular response rate (Part A, randomised), and what 24-week major molecular response rate does olverembatinib reach in people with a T315I mutation previously treated with at least one approved TKI (Part B, single-arm)? Registry status: recruiting.

  • Poitiers TKI discontinuation study NCT05753384

    In adults with chronic-phase CML, a typical BCR::ABL1 transcript and at least 1 year of deep molecular response on a TKI, does reducing the TKI dose by 50% for 12 months before stopping, compared with continuing the same dose for 12 months before stopping, change the percentage in treatment-free remission (MMR or better) 24 months after discontinuation? Registry status: active, not recruiting.

  • Radotinib after TKI failure or intolerance NCT03459534

    In adults with chronic-phase Ph+ CML with failure of or intolerance to earlier TKIs including imatinib, what major cytogenetic response rate is seen with radotinib 400 mg twice daily in a single-arm, multinational study that lists a treatment period of 12 months? Registry status: recruiting.

  • TGRX-678 NCT07489755

    In chronic-phase CML intolerant to or failing at least three TKIs, does TGRX-678 improve event-free survival compared with an investigator-selected TKI? Registry status: not yet recruiting.

Pioneers

  • David Craigie

    Physician, author of case 1 in an 1845 journal article on splenic disease

  • John Hughes Bennett

    Lecturer on the Practice of Physic and on Clinical Medicine; pathologist to the Royal Infirmary

  • Peter C. Nowell

    Researcher, University of Pennsylvania faculty from 1956

  • David A. Hungerford

    Graduate student at the time of the discovery

  • Janet D. Rowley

    1925-2013 · Author of the 1973 Nature letter on a consistent chromosomal abnormality in chronic myelogenous leukaemia

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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Links open the primary source. A flag marked ⚑ needs review means a value or claim has not yet been independently confirmed.

2003UnderstandingUnderstanding

majorAny setting

BCR-ABL1 transcript monitoring and the international scale

In 2003 an IRIS substudy measured BCR-ABL RNA in the blood and found that a fall of at least three log (one-thousand-fold) by 12 months was more common with imatinib and went with very low progression risk. In 2006 an expert meeting proposed reporting such results on one international scale and using serial blood tests to follow treatment.

IRIS substudy: in patients with complete cytogenetic remission, BCR-ABL transcript levels had fallen by at least 3 log at 12 months in 57% of the imatinib group vs 24% of the interferon plus cytarabine group (P=0.003); estimated 39% vs 2% of all patients (P<0.001). With CCyR and a 3-log reduction at 12 months, progression-free probability at 24 months was 100%, vs 95% (CCyR, under 3 log) and 85% (no CCyR) (P<0.001). 2006 consensus: international scale; serial RQ-PCR.

Standard before

Response was assessed by hematologic and cytogenetic criteria in the trial endpoints, and the 2006 consensus describes laboratories using differing methods to measure BCR-ABL transcripts.

What changed

The 2006 consensus (provisional) proposed harmonised BCR-ABL measurement with a conversion factor to an internationally agreed scale, serial RQ-PCR in preference to bone marrow cytogenetics or FISH for monitoring, and reporting of kinase domain mutations. The 2006 European LeukemiaNet panel defined failure at 12 months as less than a partial cytogenetic response (Ph+ over 35%) and suboptimal response at 18 months as less than major molecular response.

Why it mattered

The 2003 substudy linked early molecular response to progression-free probability within IRIS, and the 2006 consensus and European LeukemiaNet recommendations moved response assessment toward standardised molecular monitoring with defined response time points. Molecular response measures later became endpoints in first-line trials (MMR in ENESTnd and BFORE).

Caveats

  • In the 2003 paper transcript levels were expressed relative to the median level in 30 untreated patients, not on the international scale; the 3-log reduction is that paper's own definition and is not the same as the international-scale definition of MMR.
  • The 2006 consensus describes its own recommendations as provisional. The conversion-factor method and the reference value that define the international scale were not in the abstract read.
  • The 39% versus 2% figures are estimates the authors derived from complete cytogenetic remission rates of 68% and 7% at 12 months, not observed proportions.