CBL mutations in chronicmyelomonocyticleukemia often occur in the RING domain with multiple subclones per patient: Implications for targeting. Chronicmyelomonocyticleukemia (CMML) is a rare blood cancer of older adults (3 in every 1,000,000 persons) characterized by poor survival and lacking effective mutation-specific therapy. Mutations in the ubiquitin ligase Cbl occur frequently in CMML
Oral decitabine-cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronicmyelomonocyticleukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. The DNA methyltransferase inhibitors azacitidine and decitabine for individuals with myelodysplastic syndromes or chronicmyelomonocyticleukaemia are available in parenteral form. Oral therapy with similar exposure for these diseases would offer potential treatment benefits. We aimed to compare the safety and pharmacokinetics of oral decitabine plus the cytidine deaminase inhibitor cedazuridine versus intravenous decitabine. We did a registrational, multicentre, open-label, crossover, phase 3 trial of individuals with myelodysplastic syndromes or chronicmyelomonocyticleukaemia
Oral decitabine plus cedazuridine and venetoclax in patients with higher-risk myelodysplastic syndromes or chronicmyelomonocyticleukaemia: a single-centre, phase 1/2 study. Hypomethylating agents are approved in higher-riskmyelodysplastic syndromes. The combination of a hypomethylating agent with venetoclax is standard of care in acute myeloid leukaemia. We investigated the safety and activity of the first totally oral combination of decitabine plus cedazuridine and venetoclax in patients with higher-risk-myelodysplastic syndromes and chronicmyelomonocyticleukaemia. We did a single-centre, dose-escalation and dose-expansion, phase 1/2, clinical trial. Patients with treatment-naive higher-risk-myelodysplastic syndromes or chronicmyelomonocyticleukaemia (risk level categorised as intermediate-2
Chronicmyelomonocyticleukemia with NPM1 mutation or acute myeloid leukemia? The 2022 WHO revision and the ICC classification have recently modified the diagnostic criteria for chronicmyelomonocyticleukemia (CMML) and acute myeloid leukemia. However, there is no consensus on whether CMML with NPM1 mutation (NPM1mut) should be diagnosed as AML. Nowadays, it is a subject of discussion because
Perspectives on drug development in chronicmyelomonocyticleukemia: changing the paradigm. Drug development for chronicmyelomonocyticleukemia (CMML) has failed to parallel the recent success observed in related myeloid neoplasms. To address these shortcomings, the US Food and Drug Administration (FDA) held a "Mini-symposium on CMML: Current State of the Art and Trial Design" in September 2023
CPX-351 in higher risk myelodysplastic syndrome and chronicmyelomonocyticleukaemia: a multicentre, single-arm, phase 2 study. CPX-351, an encapsulated form of cytarabine and daunorubicin, has shown greater efficacy than the classic 3 + 7 treatment administration in secondary acute myeloid leukaemia. Given that higher-risk myelodysplastic syndrome and chronicmyelomonocyticleukaemia share was stopped for lack of inclusion (ie, not enough patients met the inclusion criteria), for patients with hypomethylating agent failure that is not reported here. Cohort A enrolled patients with newly diagnosed higher-risk myelodysplastic syndrome or chronicmyelomonocyticleukaemia (aged 18-70 years old) with an Eastern Cooperative Oncology Group performance status of 0-1. Intravenous CPX-351 (100 mg/m
A randomized phase II/III study of 'novel therapeutics' versus azacitidine in newly diagnosed patients with acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS), or chronicmyelomonocyticleukemia (CMML), age 60 or older: a report of th
Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronicmyelomonocyticleukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Therapies beyond hypomethylating agents such as azacitidine are needed in high-risk myelodysplastic syndromes. Venetoclax is an orally bioavailable small molecule BCL-2 inhibitor that is synergistic with hypomethylating agents. We therefore aimed to evaluate the safety, tolerability, and preliminary activity of azacitidine combined with venetoclax for treatment-naive and relapsed or refractory high-risk myelodysplastic syndromes or chronicmyelomonocyticleukaemia. We did a single centre, dose-escalation, dose-expansion, phase 1-2 trial at the University of Texas MD Anderson Cancer Center
Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronicmyelomonocyticleukemia or low-blast-percentage AML. PANTHER is a global, randomized phase 3 trial of pevonedistat+azacitidine (n = 227) vs azacitidine monotherapy (n = 227) in patients with newly diagnosed higher-risk myelodysplastic syndromes (MDS; n = 324), higher-risk chronicmyelomonocyticleukemia (n = 27
Volasertib as a monotherapy or in combination with azacitidine in patients with myelodysplastic syndrome, chronicmyelomonocyticleukemia, or acute myeloid leukemia: summary of three phase I studies. This report summarizes three phase I studies evaluating volasertib, a polo-like kinase inhibitor, plus azacitidine in adults with myelodysplastic syndromes (MDS), chronicmyelomonocyticleukemia
Myelodysplasia cutis as the presenting sign of chronicmyelomonocyticleukaemia. We describe an unusual case of myelodysplasia cutis in a patient with chronicmyelomonocyticleukaemia.
Abnormal monocyte differentiation and function in chronicmyelomonocyticleukemia. Monocytes serve as the phagocytic defense surveillance system of the human body. Although there is comprehensive evidence regarding monocyte development, characterization and function under steady state hematopoietic continuum, the deviations and complexities in the monocyte secretome during myeloid malignancies have not been comprehensively examined and delineated. This review summarizes the aspects of development, functions, transcriptional and cytokine-mediated regulation of monocytes during steady state hematopoiesis and also contrasts the aberrations observed in myelomonocytic leukemias like chronicmyelomonocyticleukemia (CMML). It presents the findings from the major studies highlighting the novel
Cooperation between KDM6B overexpression and TET2 deficiency in the pathogenesis of chronicmyelomonocyticleukemia. Loss-of-function TET2 mutations are recurrent somatic lesions in chronicmyelomonocyticleukemia (CMML). KDM6B encodes a histone demethylase involved in innate immune regulation that is overexpressed in CMML. We conducted genomic and transcriptomic analyses in treatment naïve CMML
A retrospective study of cladribine and low-dose cytarabine-based regimens for the treatment of chronicmyelomonocyticleukemia and secondary acute myeloid leukemia. Patients with higher risk chronicmyelomonocyticleukemia (CMML) have limited therapeutic options beyond hydroxyurea and hypomethylating agents (HMAs). Regimens based on a backbone of cladribine (CLAD), low-dose cytarabine (LDAC
Decitabine Versus Hydroxyurea for Advanced Proliferative ChronicMyelomonocyticLeukemia: Results of a Randomized Phase III Trial Within the EMSCO Network. Hydroxyurea (HY) is a reference treatment of advanced myeloproliferative neoplasms. We conducted a randomized phase III trial comparing decitabine (DAC) and HY in advanced myeloproliferative chronicmyelomonocyticleukemias (CMML). Newly
Srsf2(P95H/+) co-operates with loss of TET2 to promote myeloid bias and initiate a chronicmyelomonocyticleukemia-like disease in mice. Recurrent mutations in RNA splicing proteins and epigenetic regulators contribute to the development of myelodysplastic syndrome (MDS) and related myeloid neoplasms. In chronicmyelomonocyticleukemia (CMML), SRSF2 mutations occur in ~50% of patients and TET2
Role of allogeneic transplantation in chronicmyelomonocyticleukemia: an international collaborative analysis. To determine the survival benefit of allogeneic hematopoietic cell transplantation (allo-HCT) in chronicmyelomonocyticleukemias (CMML), we assembled a retrospective cohort of CMML patients 18-70 years old diagnosed between 2000 and 2014 from an international CMML dataset (n = 730