A comparison of clinical and molecular characteristics of patients with systemic mastocytosis with chronic myelomonocytic leukemia to CMML alone

Patnaik, Mrinal M.; Vallapureddy, Rangit; Lasho, Terra L.; Hoversten, Katherine P.; Finke, Christy; Ketterling, Rhett P.; Hanson, Curtis A.; Gangat, Naseema; Tefferi, Ayalew; Pardanani, Animesh

doi:10.1038/s41375-018-0121-1

Cited by 24 publications

(22 citation statements)

References 15 publications

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“…48 The largest study to date comparing patients with SM CMML (n 5 50) vs CMML alone (n 5 501) evaluated differences in clinical, cytogenetic, and genetic features, as well as clinical outcomes. 49 Both groups had similar mutation profiles, with the exception of KIT and CBL mutations in the SM CMML cohort, suggesting that late KIT mutations may alter an initial CMML phenotype into one consistent with SM CMML.…”

Section: Introductionmentioning

confidence: 81%

MDS overlap disorders and diagnostic boundaries

Tanaka

Bejar

2019

Blood

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Myelodysplastic syndromes (MDS) are clonal diseases defined by clinical, morphologic, and genetic features often shared by related myeloid disorders. The diagnostic boundaries between these diseases can be arbitrary and not necessarily reflective of underlying disease biology or outcomes. In practice, measures that distinguish MDS from related disorders may be difficult to quantify and can vary as disease progression occurs. Patients may harbor findings that are not consistent with a single diagnostic category. Several overlap disorders have been formally described, such as the myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). These disorders are characterized by hematopoietic dysplasia with increased proliferation of monocytes, neutrophils, or platelets. They may have mutational profiles that distinguish them from the disorders they resemble and reflect important differences in pathophysiology. MDS also shares diagnostic borders with other diseases. For example, aplastic anemia and hypoplastic MDS can be difficult to distinguish in patients with pancytopenia and bone marrow hypocellularity. Genetic features may help in this regard, because they can identify differences in prognosis and risk of progression. The boundary between MDS and secondary acute myeloid leukemia (sAML) is arbitrarily defined and has been redefined over the years. Genetic studies have demonstrated that sAML clones can precede clinical progression from MDS by many months, suggesting that MDS with excess blasts could be viewed as an overlap between a dysplastic bone marrow failure syndrome and an oligoblastic leukemia. This review will describe the diagnostic boundaries between MDS, MDS/MPNs, sAML, clonal hematopoiesis of indeterminate potential, clonal cytopenia of undetermined significance, and aplastic anemia and how genetic approaches may help to better define them.

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Section: Introductionmentioning

confidence: 81%

MDS overlap disorders and diagnostic boundaries

Tanaka

Bejar

2019

Blood

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“…Additional studies with larger number of informative cases are necessary in order to decipher the issue at hand further in the context of specific myeloid neoplasms (eg, SM‐MPN, SM‐CMML, SM‐MDS, etc.). In a recent study, we compared the clinical and laboratory features of 501 patients with CMML and 50 with SM‐CMML; 22% of patients with SM‐CMML harbored abnormal karyotype and mutations involving TET2 (62%), ASXL1 (35%), SRSF2 (27%), RUNX1 (14%), and other genes. As was the case in the current study, in the aforementioned study, we found mutations to be prognostically more relevant than karyotype.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, we compared the clinical and laboratory features of 501 patients with CMML and 50 with SM‐CMML; 22% of patients with SM‐CMML harbored abnormal karyotype and mutations involving TET2 (62%), ASXL1 (35%), SRSF2 (27%), RUNX1 (14%), and other genes. As was the case in the current study, in the aforementioned study, we found mutations to be prognostically more relevant than karyotype. Our observations are different than those of a recently published study of 109 patients with SM, including 83 advanced (73 SM‐AHN) and 26 indolent variants; the authors reported abnormal karyotype in 22% of SM‐AHN cases and an apparently higher risk of leukemic progression in patients with poor‐risk karyotype, who also displayed shorter survival, in the context of advanced SM, and independent of mutational status; obviously, one cannot endorse such findings because of the inadequate sample size and truncated multivariable analysis that did not include other risk factors as covariates.…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic abnormalities in systemic mastocytosis: WHO subcategory‐specific incidence and prognostic impact among 348 informative cases

et al. 2018

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The World Health Organization (WHO) system lists five morphological categories of systemic mastocytosis (SM): indolent (ISM), smoldering, SM with an associated hematological neoplasm (SM-AHN), aggressive (ASM) and mast cell leukemia (MCL). Recent studies have highlighted the prognostic importance of mutations in SM, including ASXL1, RUNX1, and SRSF2. In contrast, information on incidence of cytogenetic abnormalities in SM and their prognostic relevance, especially in the context of mutations, is limited. In the current study, we retrospectively reviewed the cytogenetic findings in 348 consecutive cases of SM (median age 59 years; 53% males); 41% constituted ISM, 45% SM-AHN, 14% ASM and two cases of MCL. Karyotype was abnormal in 53 (15%) cases with incidences of 6% for ISM, 26% for SM-AHN and 8% for ASM (P < .001); among SM-AHN cases, abnormal karyotype incidences were 0% for SM-AHN-lymphoid and 28% for SM-AHN-myeloid (P < .001). Clinical correlative studies disclosed significant associations between abnormal karyotype and male sex (P = .002), age > 60 years (P = .04), thrombocytopenia (P < .001) and anemia (P < .001), but not with the presence of adverse mutations (P = .19). In univariate analysis, abnormal karyotype was associated with inferior survival (HR 3.0, 95% CI 2.0-4.3), specifically confirmed for ASM (HR 4.9, 95% CI 1.1-16.1) and SM-AHN (HR 1.8, 95% CI 1.2-2.7). Sample size adequacy allowed additional multivariable analysis in SM-AHN-myeloid, which disclosed independent prognostic contribution from adverse mutations (P = .003), anemia (P = .003) and thrombocytopenia (P = .001), but not from abnormal karyotype (P = .31). Our observations suggest that mutations are prognostically more relevant than karyotype in SM.

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“…These cases are classified as “systemic mastocytosis with an associated hematological neoplasm” (SM‐AHM). CMML is the most common AHM occurring in association with SM . Classification of SM‐CMML requires fulfillment of both the diagnostic criteria for SM and CMML.…”

Section: Cmml Variantsmentioning

confidence: 99%

“…CMML is the most common AHM occurring in association with SM. 21,22 Classification of SM-CMML requires fulfillment of both the diagnostic criteria for SM and CMML. For each case, the type of SM (ie, "indolent", "smoldering" and "aggressive") and grading of CMML (CMML-0, CMML-1, and CMML-2) should be reported as such information has clinical and prognostic utility.…”

Section: Systemic Mastocytosis (Sm) With Concomitant Cmml (Sm-cmml)mentioning

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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A comparison of clinical and molecular characteristics of patients with systemic mastocytosis with chronic myelomonocytic leukemia to CMML alone

Cited by 24 publications

References 15 publications

MDS overlap disorders and diagnostic boundaries

MDS overlap disorders and diagnostic boundaries

Cytogenetic abnormalities in systemic mastocytosis: WHO subcategory‐specific incidence and prognostic impact among 348 informative cases

How I investigate chronic myelomonocytic leukemia

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