Chronic myelomonocytic leukemia: 2018 update on diagnosis, risk stratification and management

Patnaik, Mrinal M.; Tefferi, Ayalew

doi:10.1002/ajh.25104

Cited by 101 publications

(133 citation statements)

References 117 publications

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“…10 Ever since, data with regards to HMA efficacy in CMML has been largely retrospective, with overall response rates (ORR) ranging from 40%-50% and true complete remission rates (CR) generally being <20%. 8 A recent prospective phase II study of DAC in CMML (n = 43) demonstrated a CR rate of 16%, with an ORR of 47%. 11 When analyzed by CMML specific subcategories, the response rates were even lower in MP-CMML; CR 14% (vs 21% in MD-CMML) and ORR 39% (vs 64% in MD-CMML).…”

Section: Introductionmentioning

confidence: 98%

“…7 While allogeneic hematopoietic stem cell transplant (allogeneic-HCT) remains the only curative modality for CMML, it is not an option for the vast majority, as most patients are diagnosed in their 7 th decade of life and have limiting comorbidities. 8 Hypomethylating agents (HMA) such as 5-azacitidine (AZA) and decitabine (DAC), remain the only US FDA approved agents for the management of CMML, with approval of these agents based on the inclusion of small numbers of CMML patients in MDS-predominant clinical trials. The pivotal North American CALGB study (n = 191) only included 14 CMML patients; 7 being assigned to the AZA arm and 7 to the best supportive care (BSC) arm.…”

Section: Introductionmentioning

confidence: 99%

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Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

et al. 2019

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Hypomethylating agents (HMA) are currently the only FDA approved therapy for patients with chronic myelomonocytic leukemia (CMML). In the current retrospective study, we assessed response rates as adjudicated by the IWG (International Working Group) MDS (myelodysplastic syndrome) and MDS/MPN myeloproliferative neoplasm overlap syndrome response criteria, in 121 CMML patients treated with Azacitidine (AZA, n = 56) and Decitabine (DAC, n = 65). The overall response rates were 41% by the IWG MDS (AZA-45%, DAC-39%), and 56% by the IWG MDS/MPN (AZA-56%, DAC-58%) response criteria, with CR (complete remission) rates of <20% for both agents, by both criteria. There were no significant differences in response rates between proliferative and dysplastic CMML. Moreover, 29% of CMML patients in a CR with HMA progressed to AML (blast transformation), underscoring the limited impact of these agents on disease biology. Progression after HMA response was associated with a median overall-survival (OS) of 8 months, while median OS in patients with primary HMA failure was 4 months. Lower serum LDH levels (<250 Units/L) were associated with HMA responses by both criteria; while ASXL1 and TET2 mutational status had no impact. HMA treated patients had a longer median OS (31 vs 18 months; P = .01), in comparison to those treated with conventional care regimens (excluding observation only patients), without any differences between AZA vs DAC (P = .37). In conclusion, this study highlights the inadequacies of HMA therapy in CMML, retrospectively validates the IWG MDS/MPN response criteria and underscores the need for newer, rationally derived therapies.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

et al. 2019

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“…Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by a pathologic accumulation of monocytic cells manifesting with coexisting signs of myeloproliferation and myelodysplasia and associated with an increased risk of transformation to secondary acute myeloid leukemia (AML). The overall incidence of CMML is estimated to be around four cases per 100 000 persons/y; it usually affects elderly patients with a median age at diagnosis of 75 years and a slight male predominance . Survival time is highly variable, ranging from 1 to >100 months.…”

Section: Introductionmentioning

confidence: 99%

“…The overall incidence of CMML is estimated to be around four cases per 100 000 persons/y; it usually affects elderly patients with a median age at diagnosis of 75 years and a slight male predominance. 1 Survival time is highly variable, ranging from 1 to >100 months. High white blood cell count (WBC), anemia, splenomegaly, high lactate dehydrogenase level, thrombocytopenia, and lymphocytosis are associated with a poor prognosis 2 and are therefore included in a CMML-specific prognostic scoring system.…”

Section: Introductionmentioning

confidence: 99%

How I investigate chronic myelomonocytic leukemia

Sangiorgio

Arber

Orazi

2019

Int J Lab Hematology

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The 2016 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms updated the diagnostic criteria for chronic myelomonocytic leukemia (CMML). Persistent peripheral blood monocytosis of at least 1 × 109/L and a percentage of monocytes ≥10% of the circulating white blood cell count (WBC) are both prerequisite criteria for this diagnosis. CMML represents the prototype of “overlapping” myeloid neoplasms with concurrent myeloproliferative and myelodysplastic features. However, clinical presentation is heterogeneous, with cases showing prevailing “dysplastic” features and others a predominant “proliferative” phenotype. Accounting for this diversity, two variants of CMML are recognized: “dysplastic” CMML defined by WBC < 13 × 109/L and “proliferative” CMML with WBC ≥ 13 × 109/L often showing features mimicking a myeloproliferative neoplasm. Although not an official WHO category, the “oligomonocytic” variant of CMML is defined by relative monocytosis with an absolute monocyte count of 0.5‐0.9 × 109/L. It can be considered a “pre‐phase,” as it frequently anticipates the development of an overt, classic CMML. In an attempt at improving disease prognostication, the blast count based grading system for CMML of the WHO 2008 Classification has been expanded in 2016 to include a new “CMML‐0” category. Lastly, the large body of knowledge on the molecular events occurring in CMML has been used to assist diagnosis and assess prognosis. Despite the step forwards, diagnosis of CMML still remains one of exclusion as no clinical, pathologic or molecular findings are specific for this disease. The current review brings insight into the spectrum of CMML and provides practical advice to approach suspected cases of CMML.

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“…The cytogenetic risk was based on the comprehensive cytogenetic scoring system (CCSS) for MDS, on the ELN risk stratification for AML, and on the Spanish CMML-specific cytogenetic risk stratification for CMML, respectively. 21,[30][31][32] In summary, the standard operating procedures in our center recommended using 5-AZA as frontline therapy for patients with AML and high-risk MDS with an adverse karyotype in patients younger than 75 years old, with a good performance status (ECOG < 2), without severe comorbidities (the hematopoietic cell transplant comorbidity index (HCTI) <4). Those with the same characteristics but with lower risk cytogenetics were treated with 5-AZA as maintenance after induction chemotherapy.…”

Section: Treatment Protocolmentioning

confidence: 99%

Bone marrow WT1 levels in patients with myeloid neoplasms treated with 5‐azacytidine: Identification of responding patients

Santaliestra

Garrido

Carricondo

et al. 2019

European J of Haematology

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| INTRODUC TI ONWilms' tumor (WT1) is a transcription factor originally identified as a tumor suppressor gene, which plays a pivotal role in kidney and blood development. Wilms' tumor is overexpressed in most de novo acute myeloid leukemia (AML) cases and in other myeloid neoplasms. 1,2 It is essential in mesenchymal tissue maintenance through the Wnt4 pathway and it is physiologically expressed in a small percentage of bone marrow CD34+ cells. As these precursors mature, the WT1 expression is downregulated. [2][3][4][5] In human leukemias, the WT1 gene is mutated in 10% of AML and in 12%-13% of T-cell lineage ALL. 6 Despite extensive research in this field, it is not fully understood how WT1 overexpression and mutations give rise to the leukemic phenotype. Based on these findings, its upregulation in

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Chronic myelomonocytic leukemia: 2018 update on diagnosis, risk stratification and management

Cited by 101 publications

References 117 publications

Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

How I investigate chronic myelomonocytic leukemia

Bone marrow WT1 levels in patients with myeloid neoplasms treated with 5‐azacytidine: Identification of responding patients

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