Laurence Legros

The revised IPSS is a powerful tool to evaluate the outcome of MDS patients treated with azacitidine: the GFM experience

To the editor:nnThe International Prognostic Scoring System (IPSS), which is based on cytogenetics, BM blast percentage, and number of cytopenias, has played a major role in prognosis assessment in myelodysplastic syndrome (MDS) since its publication in 1997. The recently published revised IPSS (

Does addition of erythropoiesis stimulating agents improve the outcome of higher-risk myelodysplastic syndromes treated with azacitidine?

We studied a retrospective cohort of 282 higher-risk MDS treated with azacitidine, including 32 patients who concomitantly received an ESA for a median of 5.8 months after azacitidine onset. Forty-four percent of ESA and 29% of no-ESA patients reached HI-E (p=0.07); 48% and 20% achieved transfusion independence (p=0.01). Median OS was 19.6 months in the ESA and 11.9 months in the no-ESA groups (p=0.04). Addition of an ESA significantly improved OS (p=0.03) independently of azacitidine schedule and duration, and of our proposed azacitidine risk score (Blood 2011;117:403-11). Adding an ESA to azacitidine in higher-risk MDS should be studied prospectively.

Pegylated IFN-α2a combined to imatinib mesylate 600 mg daily can induce complete cytogenetic and molecular responses in a subset of chronic phase CML patients refractory to IFN alone or to imatinib 600 mg daily alone

This phase I/II study was designed to demonstrate the tolerance and the efficacy of a combination of pegylated interferon-α 2a to Imatinib mesylate (IM) 600mg daily in cytogenetically IM-resistant but in CHR chronic phase CML patients. The combination was generally well tolerated in the 15 evaluable patients. A significant reduction of the Ph1(+) BM metaphases was observed in these poor prognosis patients, with 2 long-term CCyR including 2 MMR. After a median follow-up of 43 months, 93% of patients are alive. The addition of PegIFNα2a to IM600 is feasible, and able to overcome resistance within this context.

Treatment of myelodysplastic syndromes with excess of blasts by bevacizumab is well tolerated and is associated with a decrease of VEGF plasma level

Myelodysplastic syndromes (MDS) are associated with increased bone marrow vascularity and increased levels of various angiogenic factors including Vascular Endothelial Growth Factor (VEGF) which is implicated in the proliferation and survival of leukemic cells. Before the approval of hypomethylating agents in this indication, the GFM conducted a multicenter phase II trial testing the efficacy and tolerance of bevacizumab, a humanized monoclonal antibody against VEGF, in MDS with excess of marrow blasts and its impact on bone marrow angiogenesis. Twenty-one patients were enrolled (16 males and five females) with a median age of 70xa0years and 19 were evaluable for haematological response after treatment (5xa0mg/kg IV every 2xa0weeks for 12xa0weeks). WHO diagnosis at baseline was RAEB-1 (38%) and RAEB-2 (62%). Treatment was well tolerated and was associated with significant decrease of VEGF plasma level [median (low quartile–high quartile)] from 65.5xa0pg/ml [LQ (low-quartile)–HQ (high quartile), 35.3–87.3 to 30.4xa0pg/ml (LQ–HQ, 22.5–34.0xa0pg/ml)] (pu2009<u20090.01) and reduction of bone marrow angiogenesis from a median of 20xa0vessels/mm3 (LQ–HQ, 16.5–33xa0vessels/mm3) to 15.5xa0vessels/mm3 (LQ–HQ, 10–23.2xa0vessels/mm3) (pu2009=u20090.03). On the other hand, only one patient had a significant haematological response with achievement of RBC transfusion independence. Thus, although bevacizumab had a significant impact on VEGF levels and angiogenesis in our patients, very few responses were seen when this drug was used as single agent. Given its good tolerability profile, however, combination of bevacizumab with other drugs, especially hypomethylating agents, could be considered in MDS.

O-010 Prognostic factors of response to azacitidine (AZA) in low-risk MDS resistant to erythroid stimulating agents (ESA). The GFM Azaepo 08 study

Conclusions: Our data demonstrate that HSCs are disease-initiating cells in MDS. While MDS HSCs exhibit relatively few functional differences from their normal counterparts, committed myeloid progenitors in low-risk MDS exhibit numerous alterations including loss of GMPs, upregulation of CRT, and increased phagocytosis by macrophages, with increased expression of CD47 and decreased phagocytosis associated with disease progression. These findings are consistent with a model in which committed progenitors in MDS undergo molecular alterations that promote programmed cell removal, thereby resulting in the cytopenias that characterize MDS, but this mechanism does not appear to be critical for disease maintenance by HSCs.