Thiotepa 10 mg/kg Treatment Regimen Is Superior to Thiotepa 5 mg/kg in TBF Conditioning in Patients Undergoing Allogeneic Stem-Cell Transplantation

Abstract

A study evaluating the optimal dose of myeloablation in thiotepa, busulfan, and fludarabine (TBF) conditioning included 29 patients who received TBF conditioning before allogeneic stem-cell transplantation. Thirteen patients received 5 mg/kg thiotepa; the remaining 16 patients received 10 mg/kg. Patients deemed fit to receive 10 mg/kg conditioning had better overall and progression-free survival than those who received 5 mg/kg, with no additional toxicities. Introduction: The optimal intensity of myeloablation with a reduced-toxicity conditioning regimen to decrease relapse rate after allogeneic stem-cell transplantation without increasing transplant-related mortality (TRM) has not been well established. Materials and Methods: We compared outcomes between 5 mg/kg (T5) and 10 mg/kg (T10) thiotepa-based conditioning regimens in 29 adults who underwent allogeneic stem-cell transplantation for hematologic malignancies. Results: After a median follow-up of 11 months, TRM was 0% and 14% at 100 days and 1 year, respectively, with TRM observed only in the T5 group (P = .016). The relapse incidence at 1 year was 20%. No patient had disease in first complete remission at the time of transplantation. At 1 year, progression-free and overall survival were 30% versus 87% (P = .012) and 46% versus 87% (P = .008) in the T5 and T10 groups, respectively. In univariate and multivariate analysis, only age at transplantation and total dose of thiotepa had a significant impact on TRM, overall, and progression-free survival. Conclusion: Patients deemed fit to receive T10-based conditioning for allogeneic stem-cell transplantation to treat high-risk hematologic malignancies had better overall and progression-free survival than those who received T5 with no additional toxicities. Patients should be stratified before conditioning, and those judged fit should receive T10, while the others should consider alternative reduced-intensity conditioning regimens. © 2018 Elsevier Inc.

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Keywords

Dose intensity, Hematological malignancies, High risk, Reduced toxicity conditioning regimens, Adult, Dose-response relationship, drug, Female, Hematologic neoplasms, Hematopoietic stem cell transplantation, Humans, Male, Middle aged, Myeloablative agonists, Remission induction, Retrospective studies, Survival analysis, Thiotepa, Transplantation conditioning, Transplantation, homologous, Young adult, Azacitidine, Busulfan, Dasatinib, Fludarabine, Imatinib, Sorafenib, Myeloablative agent, Age, Aged, Allogeneic stem cell transplantation, Article, Cancer chemotherapy, Cancer survival, Chimera, Clinical article, Drug dose comparison, Engraftment, Hematologic malignancy, Human, Leukemia relapse, Leukemia remission, Myeloid leukemia, Neutrophil, Outcome assessment, Overall survival, Progression free survival, Retrospective study, Surgical mortality, Thrombocyte, Treatment duration, Allotransplantation, Comparative study, Dose response, Hematologic disease, Mortality, Procedures, Remission

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