Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

Fraison, J.B.; Mékinian, A.; Grignano, Éric; Kahn, Jean‐Emmanuel; Arlet, Jean‐Benoît; Decaux, Olivier; Denis, Guillaume; Buchdahl, Anne-Laure; Omouri, Mohamed; Maigné, G.; Aouba, Achille; Leon, Nathalie; Berthier, S.; Liozon, É.; Park, Sophie; Gardin, Claude; Lortholary, Olivier; Rossignol, Julien; Fenaux, Pierre; Fain, Olivier; Braun, Thorsten

doi:10.1016/j.leukres.2016.02.005

Cited by 98 publications

(60 citation statements)

References 19 publications

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“…Among our 6 cases treated with 5-azacytidine or decitabine, 4 showed SAIDs remission associated with hematological response. In 20 MDS/CMML patients with steroid-refractory or dependent SAIDs, we recently showed a 80% overall response with 5-azacytidine, with significantly decreased steroid amounts and steroid dependence rates, suggesting a potential interest for HMAs in this context (21).…”

Section: Discussionmentioning

confidence: 93%

Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: A series of 26 cases and literature review

et al. 2016

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We wanted to describe the characteristics, treatment and outcome of autoimmune and inflammatory diseases (SAIDs) associated with chronic myelomonocytic leukemia (CMML), and conducted a French multicenter retrospective study and a literature review.We included 26 cases of CMML (median age 75 years, 54% female), 80% with CMML-1. CPSS score was low (0 or 1) in 75% of cases. SAIDS was systemic vasculitis in 54%. Diagnosis of the 2 diseases was concomitant in 31% cases, and CMML was diagnosed before SAIDs in 12 cases (46%). First line treatment for SAIDs consisted mostly of steroid, with 85% of response. Second-line treatment was needed in 40% cases. Six patients received hypomethylating agents, with 66% response on SAIDs. A literature review found 49 cases of CMML-associated SAIDs, in whom SAIDs was systemic vasculitis in 29% cases. Hence, vasculitis is the most frequent SAIDs associated with CMML. After initial response to steroids, recurrence and steroid-dependence were frequent. Hypomethylating agents may be interesting in this context.

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Section: Discussionmentioning

confidence: 93%

Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: A series of 26 cases and literature review

et al. 2016

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“…Proliferative CMML could develop leukocytosis with circulating blast cells upon therapy, an effect whose long-term consequences has to be evaluated. 62 Finally, molecules that target the mature cells of the clone have been identified preclinically. An adenosine-containing cyclic dinucleotide induces the selective apoptosis of monocytes, in vitro and in vivo, 139 whereas trabectedin, a DNA minor groove binder that has been tested in solid tumor patients, could selectively deplete myelomonocytic cells by inhibiting their growth and triggering their apoptosis.…”

Section: Currently Explored Therapeutic Strategies In Cmml Patientsmentioning

confidence: 99%

How I treat chronic myelomonocytic leukemia

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Itzykson

2017

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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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“…The clinical spectrum of these AIDs, notably including immune thrombocytopenia or seronegative arthritis, is somewhat distinct from that associated to MDS, with a higher frequency of systemic vasculitis [30,31]. These AIDs can be treated conventionally with steroids, and hypomethylating agents (HMA) can also prove useful [32].…”

Section: Clinical Presentationmentioning

confidence: 99%