Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial

Abstract

The online version of this article has a Supplementary Appendix. BackgroundAllogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old. Design and MethodsWe evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine. ResultsThe 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49-1.35) for survival and of 0.67 (95% CI, 0.42-1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22-1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22-1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40-3.42) and that for disease-free survival was 1.02 (99% CI, 0.40-2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65-2.27) for survival and 1.02 (95% CI, 0.56-1.85) for disease-free survival. ConclusionsPatients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy. ( © F e r r a t a S t o r t i F o u n d a t i o n

Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial

“…Recent results of a larger prospective randomized transplantation study showed no prognostic influence of IPSS or blast count on survival while advanced age, number of cytopenias and intermediate to high-risk cytogenetic characteristics were adverse prognostic factors. 40 A low and encouraging 2-year relapse incidence of only 16% was observed in this study, comparing favorably with incidences in previously published series. 5,33,40 Thus far, relapses have occurred only within the first 220 days after transplantation and no relapses have been reported beyond this time.…”

“…40 A low and encouraging 2-year relapse incidence of only 16% was observed in this study, comparing favorably with incidences in previously published series. 5,33,40 Thus far, relapses have occurred only within the first 220 days after transplantation and no relapses have been reported beyond this time. Rare late disease recurrences were noted by Nemecek et al who used the treosulfan-based conditioning regimen in a prospective allogeneic HSCT protocol, which included several disease entities.…”

How we treat higher-risk myelodysplastic syndromes

“…100,101 In the absence of prospective data, but given the acceptable toxicity and potential for cytoreduction, we recommend pre-HCT azacitidine or decitabine therapy for patients in whom transplantation is being contemplated. Consistent with recommendations from the European LeukemiaNet and results from the European Intergroup Criant study, in which younger patients (,55 years) achieving CR to induction chemotherapy followed by HCT had a 4-year overall survival rate of 55%, compared with 41% for those not then receiving HCT (HR .81, 95% confidence interval .49-1.35), 102,103 a reasonable pretransplant strategy includes induction chemotherapy for younger MDS patients with very high blast percentages (.15%), favorable or intermediate-risk karyotype disease, and good performance status, or for those who progress on hypomethylating agent therapy. Patients with good-risk cytogenetics may enjoy durable remissions even without HCT.…”

Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome

“…21,22 As a consequence, the implementation of comorbidity assessment into clinical practice requires the combined use of different scores. MDS-CI and HCT-CI are based on the same classification of comorbidities and may be used in a complementary manner to estimate the impact of comorbidity on the natural course of the disease and on the outcome after allogeneic transplantation, [31][32][33] respectively, thus providing the information for a proper evidence-based evaluation of the risk-benefit related to the transplantation choice.…”