Publications
1380 results found
Claudiani S, Chee L, Fernando F, et al., 2024, Treatment-free remission in CML patients with additional chromosome abnormalities in the Philadelphia-positive clone or variant Philadelphia translocations., Am J Hematol
Probability of treatment-free remission (TFR) in CML patients with additional chromosomal abnormalities (ACA) in the Philadelphia-positive clone or variant Philadelphia translocations (ACA/Var-Ph group, blue panel), in those with no cytogenetic abnormality other than the classical Philadelphia translocation (c-Ph group, green panel) and in the subgroups of CML patients with high-risk ACA (HR-ACA, yellow panel) and Var-Ph (red panel).
Jabbour E, Apperley J, Cortes J, et al., 2024, Dose modification dynamics of ponatinib in patients with chronic-phase chronic myeloid leukemia (CP-CML) from the PACE and OPTIC trials., Leukemia, Vol: 38, Pages: 475-481
Ponatinib, the only approved all known-BCR::ABL1 inhibitor, is a third-generation tyrosine-kinase inhibitor (TKI) designed to inhibit BCR::ABL1 with or without any single resistance mutation, including T315I, and induced robust and durable responses at 45 mg/day in patients with CP-CML resistant to second-generation TKIs in the PACE trial. However, cardiovascular toxicities, including arterial occlusive events (AOEs), have emerged as treatment-related AEs within this class of TKIs. The OPTIC trial evaluated the efficacy and safety of ponatinib using a novel, response-based, dose-reduction strategy in patients with CP-CML whose disease is resistant to ≥2 TKIs or who harbor T315I. To assess the dose-response relationship and the effect on the safety of ponatinib, we examined the outcomes of patients with CP-CML enrolled in PACE and OPTIC who received 45 mg/day of ponatinib. A propensity score analysis was used to evaluate AOEs across both trials. Survival rates and median time to achieve ≤1% BCR::ABL1IS in OPTIC were similar or better than in PACE. The outcomes of patients with T315I mutations were robust in both trials. Patients in OPTIC had a lower exposure-adjusted incidence of AOEs compared with those in PACE. This analysis demonstrates that response-based dosing for ponatinib improves treatment tolerance and mitigates cardiovascular risk.
Claudiani S, Chughtai F, Khan A, et al., 2024, Long-term outcomes after upfront second-generation tyrosine kinase inhibitors for chronic myeloid leukemia: managing intolerance and resistance., Leukemia
Second-generation tyrosine kinase inhibitors (2GTKI) are more effective in inducing rapid molecular responses than imatinib when used first-line in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, failure of first line-2GTKI (1L-2GTKI) still occurs and there is no consensus regarding subsequent management. We retrospectively analyzed the outcome of 106 CML-CP patients treated with 1L-2GTKI and with a median follow-up of 91 months. 45 patients (42.4%) switched to an alternative TKI, 28 for intolerance (26.4%) and 17 (16%) for resistance. Most patients who remained on 1L-2GTKI achieved deep molecular responses (DMR) and 15 (14.1%) are in treatment-free remission (TFR). Intolerant patients also obtained DMR, although most required multiple TKI changes and were slower to respond, particularly if treated with 2L-imatinib. Inferior outcomes were observed in resistant patients, who failed alternative 2L-2GTKI and required 3/4GTKI and/or allogeneic hematopoietic stem cell transplant (alloSCT). 7yr-OS was significantly lower for these individuals (66.1%) than for intolerant patients and those who remained on 1L-2GTKI (100% and 97.9%, respectively; p = 0.001). It is apparent that failure of 1L-2GTKI is a challenging problem in modern CML therapy. Intolerance can be effectively managed by switching to an alternative 2GTKI, but resistance requires early consideration of 3/4GTKI.
Chelysheva E, Apperley J, Turkina A, et al., 2024, Chronic myeloid leukemia diagnosed in pregnancy: management and outcome of 87 patients reported to the European LeukemiaNet international registry., Leukemia
The management of chronic myeloid leukemia (CML) diagnosed during pregnancy is a rare and challenging situation. We report the treatment and outcome of 87 cases diagnosed in chronic phase from 2001-2022 derived from the largest international observational registry, supported by the European LeukemiaNet (ELN), of 400 pregnancies in 299 CML women. Normal childbirth occurred in 76% without an increased rate of birth abnormalities or life-threatening events, including in patients untreated or treated with interferon-α and/or imatinib in 2nd-3rd trimester. The low birth weight rate of 12% was comparable to that seen in the normal population. Elective and spontaneous abortions occurred in 21% and 3%, respectively. The complete hematologic response rate before labor was 95% with imatinib and 47% with interferon only. No disease progression during pregnancy was observed, 28% of the patients switched their therapy at varying times after delivery. Treatment options balance the efficacy and safety for mother and infant: interferon-α can commence in the 1st trimester and continued throughout in cases of good disease control and tolerability. Because of limited placental crossing, selected tyrosine kinase inhibitors (imatinib and nilotinib) seem to be safe and effective options in 2nd and 3rd trimester while hydroxycarbamide offers few benefits.
Xu D, Bewicke-Copley F, Close K, et al., 2024, Targeting lysine demethylase 5 (KDM5) in mantle cell lymphoma., Blood Cancer J, Vol: 14
Apperley JF, 2024, Richard Szydlo, July 1 1959-December 18 2023., Bone Marrow Transplant
Rivera D, Cui W, Gao J, et al., 2024, Aleukemic Chronic Myeloid Leukemia Without Neutrophilia and Thrombocytosis: A Report From the BCR::ABL1 Pathology Group., Mod Pathol, Vol: 37
Chronic myeloid leukemia (CML) is characterized by leukocytosis with left-shifted neutrophilia, basophilia, eosinophilia, and variable thrombocytosis. However, extremely rare cases of patients with CML without significant leukocytosis and thrombocytosis (aleukemic phase [ALP] CML, or CML-ALP) have been reported. Due to its rarity and limited awareness, there remains a significant knowledge gap concerning the pathologic diagnosis, disease progression, and optimal patient management and outcomes. In this multi-institutional study, we investigated 31 patients with CML-ALP. Over half (54.8%) of patients had a history of or concurrent hematopoietic or nonhematopoietic malignancies. At time of diagnosis of CML-ALP, approximately 26.7% of patients exhibited neutrophilia, 56.7% had basophilia, and 13.3% showed eosinophilia. The median number of metaphases positive for t(9;22)(q34;q11.2) was 15, with a median of 38.5% of interphase nuclei positive for BCR::ABL1 by fluorescence in situ hybridization. The median BCR::ABL1 level was 26.14%. Remarkably, 14 (45.2%) patients were initially misdiagnosed or not diagnosed before karyotype or fluorescence in situ hybridization information for BCR::ABL1 became available. Twenty-five patients received tyrosine kinase inhibitors (TKIs). One patient developed blast crisis while on TKI treatment 8 months after initial diagnosis. With a median follow-up time of 46.1 months, 20 of 22 patients who received TKI therapy and had detailed follow-up information achieved complete cytogenetic remission or deeper, 15 achieved major molecular remission or deeper, and 10 achieved molecularly undetectable leukemia. In conclusion, given the frequent occurrence of prior or concurrent malignancies, aleukemic presentation, and low level of t(9;22)(q34;q11.2)/BCR::ABL1, misdiagnosis or delayed diagnosis is common among these patients. While these patients generally respond well to TKIs, rare patients may develop blastic transformation. It is therefore import
Sweet KL, Cortes JE, Apperley JF, et al., 2024, Project Confirm: Accelerated Drug Approvals for CML-Response., Clin Cancer Res, Vol: 30, Pages: 237-238
Ortí G, Gras L, Koster L, et al., 2024, Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT)., Transplant Cell Ther, Vol: 30, Pages: 93.e1-93.e12
Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for chronic myeloid leukemia (CML) with post-transplantation cyclophosphamide (PTCy) using an unrelated donor (UD) or a mismatched related donor (MMRD) remain unknown. We report a retrospective comparison of PTCy-based allo-HCT from a UD, non-PTCy allo-HCT from a UD, and PTCy allo-HCT from an MMRD. Inclusion criteria were adult patients with CML undergoing first allo-HCT between 2012 and 2019 from a UD with either PTCy or non-PTCy graft-versus-host disease (GVHD) prophylaxis or from an MMRD using PTCy. The primary endpoint was GVHD-free/relapse-free survival (GRFS). A total of 1341 patients were included (82% in the non-PTCy UD cohort). With a median follow-up of 34.9 months, the 3-year GRFS was 43% in the non-PTCy cohort, 37% in the PTCy-UD cohort, and 39% PTCy-MMRD cohort (P = .15). Multivariable analyses revealed no significant differences among the 3 cohorts in terms of overall survival (OS), progression-free survival, RI, and nonrelapse mortality. Factors independently associated with worse OS in the overall cohort were Karnofsky Performance Status <90 (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.41 to 2.45; P < .001), older age (HR, 1.24, 95% CI, 1.11 to 1.38; P < .001), and disease stage (compared to chronic phase [CP] 1): blast phase (HR, 2.25; 95% CI, 1.60 to 3.16; P < .001), accelerated phase (HR, 1.63; 95% CI, 1.05 to 2.54; P = .03), and CP >2 (HR, 1.58; 95% CI, 1.15 to 2.17; P = .005). These results suggest that allo-HCT in patients with CML using either a UD or an MMRD with PTCy-based GVHD prophylaxis are feasible transplantation, platforms and that the disease stage at allo-HCT remains a major prognostic factor, highlighting the importance of closely monitoring CML patients and proposing transplantation when indicated when still in CP1.
Cross NCP, Ernst T, Branford S, et al., 2023, European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia, Leukemia, Vol: 37, Pages: 2150-2167, ISSN: 0887-6924
From the laboratory perspective, effective management of patients with chronic myeloid leukemia (CML) requires accurate diagnosis, assessment of prognostic markers, sequential assessment of levels of residual disease and investigation of possible reasons for resistance, relapse or progression. Our scientific and clinical knowledge underpinning these requirements continues to evolve, as do laboratory methods and technologies. The European LeukemiaNet convened an expert panel to critically consider the current status of genetic laboratory approaches to help diagnose and manage CML patients. Our recommendations focus on current best practice and highlight the strengths and pitfalls of commonly used laboratory tests.
Mauro M, Hochhaus A, Hughes T, et al., 2023, Responses With Asciminib Continue to Deepen Over Time in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) After ≥2 Prior Tyrosine Kinase Inhibitors (TKIs) in the Phase III ASCEMBL Study, Publisher: CIG MEDIA GROUP, LP, Pages: S340-S340, ISSN: 2152-2650
Apperley J, Cortes J, Jabbour E, et al., 2023, Molecular Response of ≤10% BCR::ABL1IS Is Predictive of Positive Outcomes in Patients With Treatment-Resistant Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Treated With Ponatinib From the Phase 2 OPTIC Trial, Publisher: CIG MEDIA GROUP, LP, Pages: S339-S339, ISSN: 2152-2650
Cortes J, Deininger M, Lomaia E, et al., 2023, Post Hoc Analysis of Patient Responses by T315I Mutation Status From the 3-Year Update of the OPTIC Trial: A Dose-Optimization Study of 3 Starting Doses of Ponatinib, Publisher: CIG MEDIA GROUP, LP, Pages: S338-S338, ISSN: 2152-2650
Robin M, Gras L, Koster L, et al., 2023, Are syngeneic donors a viable donor option in allogeneic haematopoietic cell transplantation for MDS? A brief report on behalf of the Chronic Malignancies Working Party of the EBMT and review of current literature, BONE MARROW TRANSPLANTATION, Vol: 58, Pages: 942-945, ISSN: 0268-3369
May P, Reid A, Robinson M, et al., 2023, FISH-negative BCR::ABL1-positive e19a2 chronic myeloid leukaemia: the most cryptic of insertions, BMC Medical Genomics, Vol: 16, Pages: 1-6, ISSN: 1755-8794
Background:Chronic myeloid leukaemia (CML) is one of the most well characterised human malignancies. Most patients have a cytogenetically visible translocation between chromosomes 9 and 22 which generates the pathognomonic BCR::ABL1 fusion gene. The derivative chromosome 22 (‘Philadelphia’ or Ph chromosome) usually harbours the fusion gene encoding a constitutively active ABL1 kinase domain. A small subset of patients have no detectable translocation. Historically, these ‘Philadelphia chromosome negative’ patients caused diagnostic confusion between CML and other myeloproliferative neoplasms; it is now well established that the BCR::ABL1 fusion gene can be generated via submicroscopic intrachromosomal insertion of ABL1 sequence into BCR, or, more rarely, of BCR into ABL1. The fusion genes arising from cryptic insertions are not detectable via G-banded chromosome analysis [karyotype] but can nevertheless always be detected using fluorescence in situ hybridisation (FISH) and/or qualitative reverse transcriptase PCR.Case presentation:A 43-year-old female presented with suspected CML in 2007; however, contemporaneous gold standard laboratory investigations, G-banded chromosome analysis and FISH, were both negative. The reverse transcriptase quantitative PCR (RT-qPCR) assay available at the time, which was capable of detecting the common BCR::ABL1 transcripts (e13a2/e14a2), was also negative. Upon review in 2009, the newly recommended reverse transcriptase multiplex PCR (capable of detecting all BCR::ABL1 transcripts including the atypical ones) subsequently detected an e19a2 fusion. The patient then responded to tyrosine kinase inhibitor therapy. In contrast, FISH studies of both samples with three commercially available probes remained consistently negative.Retrospective whole genome sequencing, undertaken as part of the 100,000 Genomes Project, has now revealed that the patient’s BCR::ABL1 fusion gene arose via a uniquely small insertion
Fernando F, Innes AJ, Claudiani S, et al., 2023, The outcome of post-transplant asciminib in patients with chronic myeloid leukaemia, BONE MARROW TRANSPLANTATION, Vol: 58, Pages: 826-828, ISSN: 0268-3369
Sweet KL, Cortes JE, Apperley JF, et al., 2023, Project Confirm: Accelerated Drug Approvals for Chronic Myeloid Leukemia, CLINICAL CANCER RESEARCH, Vol: 29, Pages: 2179-2183, ISSN: 1078-0432
Robertson HF, Buckton MJ, Apperley JF, 2023, Managing women of childbearing age with chronic myeloid leukemia: safety and treatment considerations, EXPERT REVIEW OF HEMATOLOGY, Vol: 16, Pages: 325-332, ISSN: 1747-4086
Read C, Apperley JF, Hettiaratchy SP, et al., 2023, The impact of mental health comorbidities on patient satisfaction: A population study among US adults with skin cancer, 1st International Societies for Investigative Dermatology Meeting, Publisher: ELSEVIER SCIENCE INC, Pages: S77-S77, ISSN: 0022-202X
Nesr G, Braithwaite B, Mathew P, et al., 2023, Generic imatinib: Data from the UK National Registry for chronic myeloid leukaemia patients, 63rd Annual Scientific Meeting of the British-Society-for-Haematology, Publisher: WILEY, Pages: 92-93, ISSN: 0007-1048
Hochhaus A, Rea D, Boquimpani C, et al., 2023, Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL, LEUKEMIA, Vol: 37, Pages: 617-626, ISSN: 0887-6924
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Ruggeri A, De Wreede LC, Müller CR, et al., 2023, Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation., Haematologica, Vol: 108, Pages: 645-652
Milojkovic D, Reynolds CJ, Sandoval DM, et al., 2023, COVID-19 vaccine boosted immunity against Omicron in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors, LEUKEMIA, Vol: 37, Pages: 244-247, ISSN: 0887-6924
Chalandon Y, Sbianchi G, Gras L, et al., 2023, Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors: A retrospective study by the chronic malignancies working party of the EBMT, AMERICAN JOURNAL OF HEMATOLOGY, Vol: 98, Pages: 112-121, ISSN: 0361-8609
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Robertson HF, Apperley JF, 2022, Treatment of CML in pregnancy, HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM, Pages: 123-128, ISSN: 1520-4391
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Branford S, Apperley JF, 2022, Measurable residual disease in chronic myeloid leukemia, HAEMATOLOGICA, Vol: 107, Pages: 2794-2809, ISSN: 0390-6078
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Cortes JE, Deininger MW, Lomaia E, et al., 2022, Three-Year Update from the Optic Trial: A Dose-Optimization Study of 3 Starting Doses of Ponatinib, 64th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, Pages: 1495-1497, ISSN: 0006-4971
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Apperley JF, Cortes JE, Jabbour E, et al., 2022, Molecular Response of ≤10% <i>BCR::ABL1</i><SUP>IS</SUP> Is Predictive of Positive Outcomes in Treatment-Resistant Patients with Chronic Phase Chronic Myeloid Leukemia (CP-CML) Treated with Ponatinib from the Phase 2 Optic Trial, 64th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, Pages: 6760-6762, ISSN: 0006-4971
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Dominy K, Salmon M, Szydlo R, et al., 2022, Digital Droplet (dd) Polymerase Chain Reaction (PCR) Assays Offer Limited Advantages over Conventional Reverse-Transcriptase Quantitative PCR (RT-qPCR) for the Prediction of Molecular Recurrence after Treatment Discontinuation in Chronic Myeloid Leukemia (CML): Results from the Destiny Study, 64th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, Pages: 9631-9632, ISSN: 0006-4971
Chelysheva EY, Turkina A, Apperley JF, et al., 2022, Chronic Myeloid Leukemia Diagnosed during Pregnancy: How to Manage? Description of 86 Cases from ELN International Registry, 64th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, Pages: 1498-1500, ISSN: 0006-4971
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