Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome.
ABSTRACT Any role for reduced-intensity conditioning (RIC) before hematopoietic cell transplantation (HCT) from a human leukocyte antigen (HLA)-haploidentical donor remains to be defined. We therefore assessed 83 patients (age, 16-70 years): 68 with acute leukemia (including 34 in remission and 34 with refractory disease) and 15 patients with myelodysplastic syndrome, in HCT trials using RIC with busulfan, fludarabine, and antithymocyte globulin. The HLA-haploidentical donors, offspring (n = 38), mothers (n = 24), or siblings (n = 21) of patients, underwent leukapheresis after receiving granulocyte colony-stimulating factor, and donated cells were transplanted without further manipulation. Cyclosporine and methotrexate were given for GVHD prophylaxis. The cumulative incidences of neutrophil engraftment, grade 2 to 4 acute GVHD, chronic GVHD, and transplantation-related mortality after HCT, were 92%, 20%, 34%, and 18%, respectively. After a median follow-up time of 26.6 months (range, 16.8-78.8 months), the event-free and overall survival rates were 56% and 45%, respectively, for patients with acute leukemia in remission; 9% and 9%, respectively, for patients with refractory acute leukemia; and 53% and 53%, respectively, for patients with myelodysplastic syndrome. HCT from an HLA-haploidentical family member resulted in favorable outcomes when RIC containing antithymocyte globulin was performed. This study is registered at www.clinicaltrials.gov as #NCT00521430 and #NCT00732316.
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ABSTRACT: Abstract In this study, twenty-five children with high-risk acute leukemia have received haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) with co-transfusion of umbilical cord multipotent mesenchymal cells (UC-MSCs). Adverse effects, hematopoietic recovery, complications and the outcome are observed during the median follow-up of 12.8 months (range: 3-25months). Myeloid engraftment was rapid and the median time to neutrophil and platelet recovery was 15.12 and 20.08 days respectively. Eight patients developed grade I skin acute graft-versus-host disease (aGVHD) that responded well to the standard steroid therapy. Of note, cytomegalovirus viremia was observed in most of the patients (23/25 cases). 23/25 cases). Patients died mainly of leukemia relapse and pulmonary complication. Fourteen patients are currently alive and remain full donor chimerism at the time of reporting. The results here appeal further clinical trials to testify the effectiveness of UC-MSCs to prevent aGVHD in Haplo-HSCT for treating children with high-risk leukemia.Leukemia & lymphoma. 08/2014;
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ABSTRACT: Cytoreductive treatment before allogeneic hematopoietic stem cell transplantation (allo-SCT) with the objective of reducing the incidence of disease relapse post-transplant in patients with myelodysplastic syndrome (MDS) is a matter of debate. The achievement of complete remission (CR) before allo-SCT improves post-transplantation outcome, although it is not clear whether this reflects the selection of patients with more responsive disease or is related to a reduction in disease burden. Higher CR rates in patients with MDS are obtained with induction chemotherapy (ICT) than observed with hypomethylating agents (HMA), although HMA may be active in patients with complex karyotypes in whom ICT almost invariably fails. Furthermore, HMA have a good toxicity profile compared with ICT and may, therefore, be considered especially in older patients and in patients with comorbidities. However, all interventions aimed at reducing disease burden before allo-SCT expose patients to the risk of complications, which may prevent them from undergoing transplantation. Therefore, up-front allo-SCT is an option, particularly for patients with life-threatening cytopenias. In this review we discuss the main pre-transplant therapeutic approaches and propose a decision-model based on clinical considerations. However, only prospective randomized trials would be able to address the issue definitively.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2014; · 3.15 Impact Factor
- Blood research. 06/2014; 49(2):80-2.