A randomized trial of hydroxyuea (HY) versus VP16 in advanced adult chronic myelomonocytic leukemia

Wattel, Éric; Guerci, Agnès; Hecquet, B; Economopoulos, T.; Copplestone, Adrian; Resegotti, L; Voglova, V.; Foussard, Charles; Pégourie, Brigitte; Michaux, Jean Louis; Deconinck, Eric; Stoppa, A. M.; Mufti, G J; Oscier, DG; Fenaux, Pierre

doi:10.1016/0145-2126(94)90156-2

Cited by 18 publications

(23 citation statements)

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“…[102][103][104] Nevertheless, splenomegaly is a poor prognostic factor in CMML treated with HMAs. 105 …”

Section: Myeloproliferative Cmmlmentioning

confidence: 99%

“…106 A randomized trial demonstrated that the outcome was better in patients treated with hydroxyurea compared with oral etoposide. 105 Low-risk CMML patients with MPN-like features can be effectively managed with hydroxyurea. There is no formal demonstration that control of myeloproliferative features improves outcome, and molecular studies have shown continuing clonal evolution under hydroxyurea, 86 but this phenomenon has also been reported with HMA.…”

Section: Cytoreductive Therapymentioning

confidence: 99%

“…They remain required frontline in patients with initial leukocytosis .50 3 10 9 /L, severe constitutional symptoms, splenomegaly, or extramedullary hematopoiesis. 99,105 Even when HMAs are initiated, an initial cytoreduction may be required. 106 A randomized trial demonstrated that the outcome was better in patients treated with hydroxyurea compared with oral etoposide.…”

Section: Cytoreductive Therapymentioning

confidence: 99%

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How I treat chronic myelomonocytic leukemia

Solary

Itzykson

2017

Blood

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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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“…[102][103][104] Nevertheless, splenomegaly is a poor prognostic factor in CMML treated with HMAs. 105 …”

Section: Myeloproliferative Cmmlmentioning

confidence: 99%

Section: Cytoreductive Therapymentioning

confidence: 99%

Section: Cytoreductive Therapymentioning

confidence: 99%

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How I treat chronic myelomonocytic leukemia

Solary

Itzykson

2017

Blood

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“…2,3 There is a paucity of clinical trial data specific for CMML. 4 Current management decisions are based on studies, which included patients with CMML in large studies for patients with MDS, a group now felt to biologically represent a different disease process. 1 Allogeneic stem cell transplantation is currently the only known curative therapeutic option.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia

Elliott

Tefferi

Hogan

et al. 2006

Bone Marrow Transplant

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Prognosis in chronic myelomonocytic leukemia (CMML) is unfavorable and the optimal therapy remains uncertain. Currently, allogeneic stem cell transplantation is the only known curative therapeutic option. However, the data available are limited and restricted to small retrospective series. There is even less information on the use of donor lymphocyte infusions (DLI) for this disease. We reviewed our experience of allogeneic stem cell transplantation and DLI for adults with CMML. Seventeen consecutive adults underwent allogeneic stem cell transplantation from related (n ¼ 14) or unrelated (n ¼ 3) donors. Median age was 50 years (range 26-60). Seven patients (41%) demonstrated relapse or persistent disease at a median of 6 months (range 3-55.5). Five patients underwent DLI for morphologic relapse and one for mixed donor chimerism. Two patients achieved durable complete remissions of 15 months each. The overall transplantrelated mortality was 41% (n ¼ 7). With a median followup of 34.5 months, three patients (18%) currently remain alive and in continuous CR. The current study demonstrates a graft-versus-leukemia effect in CMML, both for allogeneic stem cell transplantation and for DLI. Nevertheless, consistent with reported experience of others, overall outcomes remain less than optimal and unpredictable.

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“…Only a single CMML-specific randomized trial has ever been completed: 20 years ago, a French study demonstrated the superiority of hydroxyurea to oral etoposide. 4 More recently, however, a clearer picture of the unique biology of CMML has begun to emerge, including the overrepresentation of certain leukemic driver mutations (eg, SRSF2, ASXL1, CBL, SETBP1) in CMML compared with other myeloid neoplasms. 5 Recognition of the importance of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling via the JAK-STAT pathway in CMML pathobiology 6 prompted a successful MDS Clinical Research Consortium pilot trial of the JAK1/2 inhibitor ruxolitinib in CMML, 7 and MDS/MPN overlap-specific consensus response criteria were recently proposed.…”

mentioning

confidence: 99%

Putting it all together in CMML risk stratification

Steensma

2016

Blood

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A randomized trial of hydroxyuea (HY) versus VP16 in advanced adult chronic myelomonocytic leukemia

Cited by 18 publications

References 0 publications

How I treat chronic myelomonocytic leukemia

How I treat chronic myelomonocytic leukemia

Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia

Putting it all together in CMML risk stratification

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