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Thiotepa, Busulfan, and Fludarabine Conditioning Regimen in T Cell-Replete HLA-Haploidentical Hematopoietic Stem Cell Transplantation

Duléry, Rémy
Bastos, Juliana
Paviglianiti, Annalisa
Malard, Florent
Brissot, Eolia
Battipaglia, Giorgia
Médiavilla, Clémence
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Published in Biology of blood and marrow transplantation. 2019, vol. 25, no. 7, p. 1407-1415
Abstract We report the outcomes of 51 patients who underwent unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) and antithymocyte globulin (ATG), from peripheral blood stem cells (PBSCs) or bone marrow, after receipt of a TBF (thiotepa, busulfan, and fludarabine) conditioning regimen. Their median age was 55 years (range, 16 to 72 years). Hematologic diagnoses included 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. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate for all patients, associated with ATG in 39 patients (76.5%). The median time to neutrophil engraftment was 17 days (range, 12 to 34 days). The cumulative incidences of grade II-IV and grade III-IV acute GVHD were 27.5% and 14%, respectively. In patients receiving a PBSC graft and ATG prophylaxis, grade II-IV aGVHD occurred in 16% of patients. The use of ATG and a lower thiotepa dose (5 mg/kg versus 10 mg/kg) were associated with a reduced cumulative incidence of grade II-IV acute GVHD (P = .03 and .005, respectively). The 2-year cumulative incidence of chronic GVHD was 29% and was significantly reduced to 13% with the lower thiotepa dose (P = .002). After a median follow-up of 25 months (range, 12 to 62 months), the cumulative incidences of nonrelapse mortality, relapse, overall survival (OS), disease-free survival (DFS), and GVHD-free, relapse-free survival (GFRFS) were 20%, 22.5%, 67%, 58%, and 51%, respectively. Pretransplantation disease status (complete remission versus others) was the main factor associated with OS, DFS, and GFRFS. In conclusion, the TBF conditioning regimen is an appealing platform in the haplo-HSCT setting with PT-Cy in terms of engraftment rate, toxicity, and disease control. We found no benefit of a thiotepa dose of 10 mg/kg compared with a dose of 5 mg/kg. ATG reduced the risk of acute GVHD without comprising outcomes.
Keywords AdolescentAdultAgedBusulfan/administration & dosageCyclosporine/administration & dosageDisease-Free SurvivalFemaleGraft vs Host Disease/metabolism/mortality/pathology/prevention & controlHLA AntigensHematologic Neoplasms/metabolism/mortality/pathology/therapyHematopoietic Stem Cell TransplantationHumansMaleMiddle AgedMycophenolic Acid/administration & dosageRetrospective StudiesSurvival RateT-Lymphocytes/metabolism/pathologyThiotepa/administration & dosageTransplantation ConditioningVidarabine/administration & dosage/analogs & derivatives
PMID: 30871978
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Research group Leucémie et transplantation allogénique de cellules souches hématopoïétiques (982)
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DULÉRY, Rémy et al. Thiotepa, Busulfan, and Fludarabine Conditioning Regimen in T Cell-Replete HLA-Haploidentical Hematopoietic Stem Cell Transplantation. In: Biology of Blood and Marrow Transplantation, 2019, vol. 25, n° 7, p. 1407-1415. doi: 10.1016/j.bbmt.2019.02.025

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Deposited on : 2020-11-02

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