Predictive factors of response and survival among chronic myelomonocytic leukemia patients treated with azacitidine

Adès, Lionel; Sekeres, Mikkael A.; Wolfromm, Alice; Teichman, Melissa L.; Tiu, Ramon V.; Itzykson, Raphaël; Maciejewski, Jaroslaw P.; Dreyfus, F.; List, Alan F.; Fenaux, Pierre; Komrokji, Rami S.

doi:10.1016/j.leukres.2013.01.004

Cited by 108 publications

(97 citation statements)

References 15 publications

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“…91 Extramedullary disease, which occasionally infiltrates the skin, 92,93 lymph nodes, 94,95 gingiva, 96 kidneys, 97 pericardium, 98 and other sites, 99,100 could regress upon treatment with hydroxyurea, 96 methylprednisolone, 101 or HMA. [102][103][104] Nevertheless, splenomegaly is a poor prognostic factor in CMML treated with HMAs. 105 …”

Section: Myeloproliferative Cmmlmentioning

confidence: 99%

How I treat chronic myelomonocytic leukemia

Solary

Itzykson

2017

Blood

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101

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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that may deserve specific management. Defined by a persistent peripheral blood monocytosis ≥1 × 109/L and monocytes accounting for ≥10% of the white blood cells, this aging-associated disease combines cell proliferation as a consequence of myeloid progenitor hypersensitivity to granulocyte-macrophage colony-stimulating factor with myeloid cell dysplasia and ineffective hematopoiesis. The only curative option for CMML remains allogeneic stem cell transplantation. When transplantation is excluded, CMML is stratified into myelodysplastic (white blood cell count <13 × 109/L) and proliferative (white blood cell count ≥13 × 109/L) CMML. In the absence of poor prognostic factors, the management of myelodysplastic CMML is largely inspired from myelodysplastic syndromes, relying on erythropoiesis-stimulating agents to cope with anemia, and careful monitoring and supportive care, whereas the management of proliferative CMML usually relies on cytoreductive agents such as hydroxyurea, although ongoing studies will help delineate the role of hypomethylating agents in this patient population. In the presence of excessive blasts and other poor prognostic factors, hypomethylating agents are the preferred option, even though their impact on leukemic transformation and survival has not been proved. The therapeutic choice is illustrated by 4 clinical situations among the most commonly seen. Although current therapeutic options can improve patient’s quality of life, they barely modify disease evolution. Improved understanding of CMML pathophysiology will hopefully lead to the exploration of novel targets that potentially would be curative.

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Section: Myeloproliferative Cmmlmentioning

confidence: 99%

How I treat chronic myelomonocytic leukemia

Solary

Itzykson

2017

Blood

Self Cite

101

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“…The hypomethylating agents (HMA) azacitidine (AZA) and decitabine (DAC) seem active in CMML, though they have mostly been explored retrospectively [69,70], reporting overall response rates in the 40-70% range. In retrospective studies controlling for biases, there does seem to be a significant difference between DAC and AZA in this population (Duchmann et al, manuscript in preparation), even though several authors have suggested that DAC could be beneficial in proliferative CMML [70,71], possibly because standard regimens of DAC are slightly more myelotoxic than AZA regimens.…”

Section: Treatmentmentioning

confidence: 99%

CMML: Clinical and molecular aspects

et al. 2017

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“…This finding may suggest that CDA is involved in a gender-specific response, although the observations in this study are indirect. However, conflicting results exist, with another study showing gender-specific differences in overall survival (33), while in others a negative impact of male gender was not observed (6,8,34,35). Given that SGI-110 is designed to overcome the effects of CDA (36), it will be interesting to observe whether male patients do relatively better in the SGI-110 trial.…”

Section: Pharmacologic Factors With Potential Impact On Dnmti Resistancementioning

confidence: 99%

“…Recent multicenter studies demonstrated that DNMTis have significant efficacy in the treatment of hematological malignancies (5)(6)(7)(8)(9) and have led to the approval of two DNMTis, azacytidine and decitabine, by the FDA and EMA. However, the FDA and EMA have not approved the drugs for similar indications (Table 2).…”

Section: Predicting Response To Dnmtismentioning

confidence: 99%

“…The impact of different clinical factors was evaluated in 76 patients with chronic myelomonocytic leukemia (CMML) treated with azacytidine (8). No predictive factors for clinical response were identified, while increased bone marrow blasts, splenomegaly, and high white blood cell counts were associated with significantly shorter survival.…”

Section: Clinical Predictorsmentioning

confidence: 99%

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Predicting response to epigenetic therapy

Treppendahl¹,

Kristensen²,

Grønbæk

2014

J. Clin. Invest.

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Drugs targeting the epigenome are new promising cancer treatment modalities; however, not all patients receive the same benefit from these drugs. In contrast to conventional chemotherapy, responses may take several months after the initiation of treatment to occur. Accordingly, identification of good pretreatment predictors of response is of great value. Many clinical parameters and molecular targets have been tested in preclinical and clinical studies with varying results, leaving room for optimization. Here we provide an overview of markers that may predict the efficacy of FDA-and EMA-approved epigenetic drugs.

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Predictive factors of response and survival among chronic myelomonocytic leukemia patients treated with azacitidine

Cited by 108 publications

References 15 publications

How I treat chronic myelomonocytic leukemia

How I treat chronic myelomonocytic leukemia

CMML: Clinical and molecular aspects

Predicting response to epigenetic therapy

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