Treatment of myelodysplastic syndromes with 5q deletion before the lenalidomide era; the GFM experience with EPO and thalidomide
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).
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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)
- et al.
The 5q-anomaly
Cancer Genet Cytogenet
(1985) - et al.
5q-, twenty-five years later: a synopsis
Cancer Genet Cytogenet
(1997) - et al.
Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial
Blood
(2004) - et al.
World Health Organization(WHO) international working group. Report of an international working group to standardize response criteria for myelodysplastic
Blood
(2000) - et al.
Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia
Blood
(2006) - et al.
Treatment of anemia in myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin
Blood
(1993) - et al.
Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients
Blood
(1998) - et al.
The WHO classification of MDS does make a difference
Blood
(2004) - et al.
Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes
Blood
(2001) - et al.
All-trans retinoic acid in patients with myelodysplastic syndromes: results of a pilot study
Blood
(1993)