G. Sanz

Peripheral blood is safer than bone marrow as a source of hematopoietic progenitors in patients with myelodysplastic syndromes who receive an allogeneic transplantation. Results from the Spanish registry.

Summary:Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for patients with myelodysplastic syndromes (MDSs). We have analyzed the outcome of 81 patients who underwent an allogeneic transplant from an HLA-identical sibling donor. The overall survival (OS) was 31% and disease-free survival was 30% at 5.8 years. Transplant-related complications were the cause of death in 44% and disease progression in 16% of patients. Acute graft-versus-host disease (aGVHD) grades II–IV occurred in 32 cases (39%). Extensive chronic GVHD (cGVHD) was observed in 27% of patients. When the log-rank test was performed, we observed that patients transplanted more than 6 months after diagnosis, and those transplanted with bone marrow (BM) displayed a shorter survival (P=0.009 and 0.005, respectively). Patients who developed cGVHD showed a trend towards better OS (P=0.07). Patients receiving BM had a higher incidence of aGVHD (65 vs 50%) and less cGVHD (52 vs 30%), although the differences did not reach statistical significance. Moreover, patients who received PB-HSC displayed a faster engraftment (P=0.000) and showed a significantly lower early transplant-related mortality (14 vs 42%; P=0.006) and longer OS (P=0.005). In summary, our results show that hematopoietic transplantation should be performed as soon as possible in MDS patients and that PB is preferable to BM as a source of HSC.

Expression of APO2.7, bcl-2 and bax apoptosis-associated proteins in CD34- bone marrow cell compartments from patients with myelodysplastic syndromes.

Expression of APO2.7, bcl-2 and bax apoptosis-associated proteins in CD34 − bone marrow cell compartments from patients with myelodysplastic syndromes

Results of allogeneic stem cell transplantation in the Spanish MDS registry: Prognostic factors for low risk patients

Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics.

Toxicity and efficacy of busulfan and fludarabine myeloablative conditioning for HLA-identical sibling allogeneic hematopoietic cell transplantation in AML and MDS.

The safety and efficacy of a 4-day myeloablative conditioning (MAC) regimen consisting of Bu 3.2 mg/kg and fludarabine 40 mg/m2/day for HLA-identical sibling allogeneic hematopoietic cell transplantation (HCT) in myeloid malignancies was investigated in 133 patients (median age, 47 years; range 19–74 years) with de novo AML (60%), secondary AML (20%) or myelodysplastic syndrome (20%). All patients engrafted. Hepatic veno-occlusive disease occurred in five patients (4%), and severe toxicities, mostly mucositis, occurred in twenty-three (17%) patients. The non-relapse mortality (NRM) at 100 days was 1.5%. The incidences of acute GVHD grade 2–4 and grade 3–4 were 32 and 13%, respectively. At a median follow-up of 38 months, the cumulative incidence of chronic GVHD was 67%. The relapse incidence was 30% (27 and 31%, respectively, in patients with early- and late-stage disease), and the overall NRM was 15%. The actuarial 4-year disease-free survival (DFS) and overall survival (OS) were 54 and 62%, respectively. Patients aged <50 years had better outcomes compared with older patients (DFS 64 vs 42%, P=0.006; OS 73 vs 47%, P<0.001, respectively).

Effectiveness of azacitidine for the treatment of higher-risk myelodysplastic syndromes in daily practice: the authors' reply.

There is an increasing interest on the effectiveness of azacitidine for the treatment of higher-risk myelodysplastic syndromes (MDS) outside clinical trials. We recently reported the lack of effect of this drug in an unselected population of 821 patients.1 In response to our work, Dinmohamed et al.2 have performed a similar retrospective analysis of a cohort including 121 patients with higher-risk MDS included in the Dutch registry and treated with either chemotherapy, azacitidine or best supportive care (BSC). Both studies are aimed to analyze the potential effect of the different treatment alternatives on overall survival (OS) in large population-based registries of higher-risk MDS patients. A common finding in both series is the lack of a survival advantage of azacitidine compared with intensive chemotherapy.