Treatment of chronic myelomonocytic leukemia with 5-Azacitidine: A case series and literature review

Thorpe, Michael; Montalvão, Ana; Pierdomenico, Francesca; Moita, Filipa; Almeida, António

doi:10.1016/j.leukres.2012.04.024

Cited by 49 publications

(46 citation statements)

References 8 publications

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“…There is no phase III data supporting the use of HMA in CMML, however, several phase II studies have been completed with overall response rates ranging from 25–70%, and median OS ranging from 12 to 37 months. 6, 7, 8, 9, 10, 11, 12 Unfortunately, the retrospective nature of the vast majority of the studies along with the lack of a comparator arm makes it difficult to draw cross-study conclusions. While AHSCT is a curative strategy, it is currently not widely utilized given issues with donor eligibility (advanced age), limited donor pools and the risk of complications such as graft rejection, acute and chronic graft versus host disease (GVHD) and non-relapse mortality (NRM).…”

Section: Introductionmentioning

confidence: 99%

Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome

Patnaik

Wassie

Padron

et al. 2015

Blood Cancer Journal

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In patients with chronic myelomonocytic leukemia (CMML), age>65 years is an adverse prognostic factor. Our objective in the current study was to examine risk factors for survival and treatment outcome in 261 ‘young' adults with CMML, as defined by age ⩽65 years. In multivariable analysis, lower HB (P=0.01), higher circulating blast % (P=0.002), ASXL1 (P=0.0007) and SRSF2 mutations (P=0.008) and Mayo-French cytogenetic stratification (P=0.04) negatively impacted survival. Similarly, leukemia-free survival was independently affected by higher circulating blast % (P<0.0001), higher bone marrow blast % (P=0.0007) and the presence of circulating immature myeloid cells (P=0.0002). Seventy-five (29%) patients received hypomethylating agents (HMA), with the median number of cycles being 5, and the median duration of therapy being 5 months. The over-all response rate was 40% for azacitidine and 30% for decitabine. Fifty-three (24%) patients underwent an allogeneic hematopoietic stem cell transplant (AHSCT), with a response rate of 56% and a non-relapse mortality of 19%. Survival in young adults with CMML, although higher than in older patients, is poor and even worse in the presence of ASXL1 and SRSF2 mutations. Treatment outcome was more impressive with AHSCT than with HMA and neither was influenced by ASXL1/SRSF2 mutations or karyotype.

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Section: Introductionmentioning

confidence: 99%

Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome

Patnaik

Wassie

Padron

et al. 2015

Blood Cancer Journal

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“…Several phase II studies have now been completed using HMA in CMML [6,34,[65][66][67][68][69][70][71]. A complete list of the studies is shown in Table 2.…”

Section: Epigenetic Modifying Agentsmentioning

confidence: 99%

Chronic Myelomonocytic Leukemia: a Genetic and Clinical Update

McCullough

Patnaik

2015

Curr Hematol Malig Rep

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Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder, characterized by peripheral blood monocytosis and overlapping features between myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs). Clonal cytogenetic changes are seen in up to 30 % patients, while approximately 90 % have detectable molecular abnormalities. Most patients are diagnosed in the seventh decade of life. Gene mutations in ten-eleven translocation (TET) oncogene family member 2 (TET2) (60 %), SRSF2 (50 %), ASXL1 (40 %), and RAS (20-30 %) are frequent, with only frame shift and nonsense ASXL1 mutations negatively impacting overall survival. With the lack of formal guidelines, management and response criteria are often extrapolated from MDS and MPN. Contemporary molecularly integrated CMML-specific prognostic models include the Groupe Francais des Myelodysplasies (GFM) model and the Molecular Mayo Model, both incorporating ASXL1 mutational status. Hypomethylating agents and allogeneic stem cell transplant remain the two most commonly used treatment strategies, with suboptimal results. Clinical trials exploiting epigenetic and signal pathway abnormalities, frequent in CMML, offer hope and promise.

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“…Moreover, AML can arise from CMML during its natural course [1]. AML transformation during hypomethylating therapy for CMML is quite common because of the lack of response to the hypomethylating agent and/or of disease progression [3, 7, 8, 9]. The present 2 cases did not provide any evidence that hypomethylating therapy is related to leukemic transformation, clonal selection, or evolution into AML.…”

mentioning

confidence: 73%

Acute myeloid leukemia arising from chronic myelomonocytic leukemia during hypomethylating therapy

et al. 2014

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Treatment of chronic myelomonocytic leukemia with 5-Azacitidine: A case series and literature review

Cited by 49 publications

References 8 publications

Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome

Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome

Chronic Myelomonocytic Leukemia: a Genetic and Clinical Update

Acute myeloid leukemia arising from chronic myelomonocytic leukemia during hypomethylating therapy

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