Thiotepa, busulfan and fludarabine conditioning regimen in T-cell replete HLA-haploidentical hematopoietic stem cell transplantation.

Fiche publication

Date publication

mars 2019

Journal

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

Auteurs

Membres identifiés du Cancéropôle Est :
Pr RUBIO Marie Thérèse

Tous les auteurs :
Duléry R, Bastos J, Paviglianiti A, Malard F, Brissot E, Battipaglia G, Médiavilla C, Giannotti F, Banet A, de Wyngaert ZV, Ledraa T, Belhocine R, Sestili S, Adaeva R, Lapusan S, Isnard F, Legrand O, Vekhoff A, Rubio MT, Ruggeri A, Mohty M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/30871978

Résumé

We report the outcome of 51 patients receiving an unmanipulated haploidentical hematopoietic stem cell transplantation with post-transplantation cyclophosphamide (PT-Cy) and anti-thymocyte globulin (ATG), from peripheral blood stem cells or bone marrow, after a TBF (thiotepa, busulfan, fludarabine) conditioning regimen. Their median age was 55 years (range, 16-72). Hematological diagnosis comprised acute leukemias (n=31), lymphoid neoplasm (n=12), myeloproliferative neoplasm (n=5) and myelodysplastic syndromes (n=3). Thirty-seven patients (73%) were in complete remission. GVHD prophylaxis consisted of cyclosporine and mycophenolate for all patients, associated with ATG in 39 cases (76.5%). Median time to neutrophil engraftment was 17 days (range, 12-34). The cumulative incidence (CI) of grade II-IV and grade III-IV acute GVHD were 27.5% and 14%, respectively. In patients receiving peripheral blood stem cells graft and ATG prophylaxis, grade II-IV aGVHD occurred in 16% cases. The use of ATG and a lower thiotepa dose (5 vs. 10 mg/kg) were associated with a reduced CI of grade II-IV acute GVHD (p=0.03 and p=0.005). The 2-year CI of chronic GVHD was 29% and was significantly reduced to 13% with lower thiotepa dose (p=0.002). After a median follow-up of 25 months (12-62), the CI of non-relapse mortality, relapse, overall survival, disease-free survival and GVHD-free, relapse-free survival were 20%, 22.5%, 67%, 58% and 51%, respectively. Pre-transplant disease status (complete remission vs. others) was the main factor associated with overall survival, disease-free survival and GVHD-free, relapse-free survival. In conclusion, the TBF conditioning regimen is an appealing platform in the haplo setting with PT-Cy, in terms of engraftment rate, toxicity and disease control. We found no benefit of a thiotepa dose at 10 mg/kg compared to 5 mg/kg. ATG reduced the risk of acute GVHD without comprising the outcomes.