Thiotepa, busulfan and fludarabine compared to busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplant from matched siblings and unrelated donors for acute myeloid leukemia.

Abstract

Busulfan plus cyclophosphamide (BuCy) is the traditional conditioning regimen for allogeneic stem cell transplant (allo-SCT) for young, fit patients with acute myeloid leukemia (AML). The thiotepa-busulfan-fludarabine (TBF) protocol has recently demonstrated promising outcome in cord blood and haploidentical SCT; however, there is limited evidence about this regimen in transplant from matched siblings (MSD) and unrelated donors (UD). We retrospectively compared outcomes of 2523 patients aged 18-50 with AML in remission, undergoing transplant from MSD or UD prepared with either TBF or BuCy conditioning. A 1:3 pair-matched analysis was performed: 146 patients receiving TBF were compared with 438 patients receiving BuCy. Relapse risk was significantly lower in the TBF when compared with BuCy group (HR 0.6, P = .02), while NRM did not differ. No significant difference was observed in LFS and OS between the two regimens. TBF was associated with a trend towards higher risk of grades III-IV aGVHD (HR 1.8, P = .06) and inferior cGVHD (HR 0.7, P = .04) when compared with BuCy. In patients undergoing transplant in first remission, the advantage for TBF in terms of relapse was more evident (HR 0.4, P = .02), leading to a trend for better LFS in favor of TBF (HR 0.7, P = .10), while OS did not differ between the two cohorts. In conclusion, TBF represents a valid myeloablative conditioning regimen providing significantly lower relapse and similar survival when compared with BuCy. Patients in first remission appear to gain the most from this protocol, as in this subgroup a tendency for better LFS was observed when compared with BuCy.

• Authors: Francesco Saraceni, Eric Beohou, Myriam Labopin, William Arcese, Francesca Bonifazi, Polina Stepensky, Mahmoud Aljurf, Benedetto Bruno, Pietro Pioltelli, Jakob Passweg, Gerard Sociè, Stella Santarone, Ibrahim Yakoub-Agha, Francesco Lanza, Bipin N Savani, Mohamad Mohty, Arnon Nagler, Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
• Journal: American journal of hematology (Am J Hematol) Vol. 93 Issue 10 Pg. 1211-1219 (10 2018) ISSN: 1096-8652 [Electronic] United States
• PMID: 30033639 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Myeloablative Agonists
• Cyclophosphamide
• Thiotepa
• Vidarabine
• Busulfan
• fludarabine

Topics

• Adolescent
• Adult
• Allografts
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bone Marrow Transplantation
• Busulfan (administration & dosage, adverse effects, therapeutic use)
• Combined Modality Therapy
• Confidence Intervals
• Cyclophosphamide (administration & dosage, adverse effects, therapeutic use)
• Disease-Free Survival
• Drug Evaluation
• Female
• Graft vs Host Disease (epidemiology, etiology)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, therapy)
• Living Donors
• Male
• Middle Aged
• Myeloablative Agonists (administration & dosage, adverse effects, therapeutic use)
• Peripheral Blood Stem Cell Transplantation
• Proportional Hazards Models
• Retrospective Studies
• Siblings
• Survival Analysis
• Thiotepa (administration & dosage, adverse effects, therapeutic use)
• Transplantation Conditioning (adverse effects, methods)
• Vidarabine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Young Adult