Elsevier

Leukemia Research

Volume 32, Issue 7, July 2008, Pages 1049-1053
Leukemia Research

Treatment of myelodysplastic syndromes with 5q deletion before the lenalidomide era; the GFM experience with EPO and thalidomide

https://doi.org/10.1016/j.leukres.2007.11.037Get rights and content

Abstract

Anemia in MDS with 5q deletion was generally considered, until the advent of lenalidomide, unresponsive to available treatments. We analyzed erythroid response to erythropoetin (EPO) or darbepoetin (DAR) and thalidomide in MDS with 5q deletion treated by French centers (GFM) and in whom karyotype was successfully performed. Of 345 patients treated with EPO or DAR ± G-CSF, 48 had 5q deletion. The response rate was 46% (31% major, 15% minor) according to International Working Group (IWG) 2000 criteria versus 64% in patients without 5q deletion (p = 0.03). According to IWG 2006 criteria, the response rate in patients with 5q deletion was 39% versus 52% in patients without 5q deletion (p = 0.10). Mean duration of response was 14 months versus 25 months (IWG 2000) and 13 months versus 27 months (IWG 2006) in 5q deletion and non-5q deletion patients (p = 0.019 and 0.003, respectively). Of 120 MDS treated with thalidomide, all of whom had successful cytogenetic analysis, 37% of the 24 patients with 5q deletion responded (IWG 2000 criteria, 20% major, 17% minor) with a mean duration of 9.5 months, versus 32% (18% major, 14% minor) in MDS without 5q deletion and a mean response duration of 9 months (p = NS). Our results confirm that response rates to EPO or DAR and thalidomide are clearly inferior to those obtained with lenalidomide.

Introduction

Interstitial deletion of 5q (del 5q) is the most frequent chromosomal abnormality seen in myelodysplastic syndromes (MDS). MDS with del 5q include (i) the so called “5q-syndrome”, defined by isolated del 5q and no excess of marrow blasts, and characterized by female predominance, typical dysmegakaryopoiesis, thrombocytosis, favorable outcome (ii) MDS with del 5q associated with an excess of marrow blasts and/or chromosomal abnormalities in addition to del 5q, that usually do not have the typical features of the 5q-syndrome and carry poorer prognosis [1], [2], [3]. Anemia is however a constant finding in MDS with del 5q which, until the recent introduction of lenalidomide, was considered generally unresponsive to available treatments. We tried to reevaluate the outcome of anemia in those patients in the pre-lenalidomide era by reviewing cases of MDS with del 5q treated with EPO or darbepoetin (DAR) ± granulocyte-colony stimulating factor (G-CSF) or thalidomide by centers of the Groupe Francophone des Myélodysplasies (GFM).

Section snippets

Patients and methods

Between 1998 and May 2006, 403 generally low or int-1 risk MDS were treated with EPO or DAR ± G-CSF by 25 centers of the GFM, in 3 prospective clinical trials (n = 158) or according to guidelines of the GFM and the French Society of Hematology for the use of EPO (or darbepoetin alfa) in MDS with anemia (hemoglobin <10 g/dL, with or without transfusion requirement). Patients received at least 60,000 U/w of EPO (alpha or beta) or 300 μg/w of DAR, with or without G-CSF, during at least 12 weeks. Results

Treatment results in del 5q patients

48 MDS with del 5q received EPO (or DAR) ± G-CSF including 18, 10, 11 and 9 patients treated by EPO (alfa or beta) alone, EPO + G-CSF, DAR alone and DAR + G-CSF, respectively. Of the 48 patients, 30 had del 5q alone, 17 of them with <5% marrow blasts fulfilling WHO criteria of the “5q-syndrome” (Table 1).

22/48 patients (46%) had erythroid response to EPO or DAR, including 15 major and 7 minor responses according to IWG 2000 criteria (Table 2). The response rate was 52%, 55%, 22% and 33%, respectively

Discussion

In this retrospective study, MDS patients with del 5q had significantly (IWG 2000 criteria) or a strong trend (IWG 2006 criteria) for lower response rates, and significantly shorter response to EPO or DAR ± G-CSF than MDS without del 5q. Response rates and response duration were not significantly better in the 5q-syndrome than in other MDS with del 5q. However, the response rate of MDS with del 5q decreased sharply in cases with more than one additional cytogenetic abnormality and/or an excess of

Conflict of interest

The authors have no financial support or conflict of interest to declare.

Acknowledgements

Contributions: CK and SP contributed equally as first authors to the work. CK and SP collected the data, made the statistical analysis and wrote the paper; SB, LM, NV, HV, LA, AS, LA, SG, SdB and SR provided clinico-biological data; PL, FP, GL and MTD performed cytology; DB collected and analyzed data on thalidomide; FD and PF designed the study; PF supervised the manuscript preparation.

References (26)

  • N.L. Harris et al.

    World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting-Airlie House

    J Clin Oncol

    (1999)
  • L. Mannone et al.

    High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study

    Br J Haematol

    (2006)
  • S. Park et al.

    Prognostic factors and response duration in 419 MDS treated with erythropoietin ± GCSF: the GFM experience

    Blood

    (2007)
  • Cited by (0)

    View full text