Reduced intensity versus non-myeloablative conditioning regimen for haploidentical transplantation and post-transplantation cyclophosphamide in complete remission acute myeloid leukemia: a study from the ALWP of the EBMT.

Abstract

The optimal conditioning regimen prior haploidentical stem cell transplantation (Haplo-SCT) with post transplantation cyclophosphamide (PT-Cy) for acute myeloid leukemia (AML) remains unknown. A non-myeloablative conditioning (NMAC) regimen (cyclophosphamide + fludarabine + TBI 2 Gy [CyFluTBI]) is a safe approach, but relapse incidence remains high in this setting. Alternatively, a reduced intensity conditioning (RIC) regimen combining thiotepa and reduced-dose busulfan with fludarabine (TBF) may decrease AML relapse. However, an excess of toxicity may counterbalance this potential benefit. We retrospectively compared CyFluTBI vs. TBF in CR AML patients who underwent Haplo-SCT with PT-Cy, in two different populations based on age. We analyzed 490 patients. In patients aged <60 years (n = 203), we observed a higher RI (HR = 3.59, 95% CI = 1.75-7.37, p < 0.01), lower LFS (HR = 1.98, 95% CI = 1.22-3.22, p < 0.01) and lower OS (HR = 1.73, 95% CI = 1.04-2.88, p = 0.04) in the CyFluTBI group, without significant difference in NRM. In older patients (n = 287), we observed that conditioning regimen did not significantly influence LFS (HR = 0.90, 95% CI = 0.56-1.44, p = 0.65), OS (HR = 0.81, 95% CI = 0.49-1.32, p = 0.39) and RI (HR = 1.78, 95% CI = 0.90-3.50, p = 0.10), but showed that CyFluTBI was associated with a significantly lower risk of NRM (HR = 0.48, 95% CI = 0.25-0.92, p = 0.03). Thus, younger patients seem to benefit from conditioning intensification from CyFluTBI to TBF regimens prior PT-Cy Haplo-SCT for CR AML, while older ones do not.

• Authors: Raynier Devillier, Jacques-Emmanuel Galimard, Myriam Labopin, Didier Blaise, Anna Maria Raiola, Jiri Pavlu, Luca Castagna, Gerard Socié, Yves Chalandon, Massimo Martino, Friedrich Stölzel, Gesine Bug, Benedetto Bruno, Radovan Vrhovac, Amandine Charbonnier, Attilio Olivieri, Jacques-Olivier Bay, Herrera Arroyo, Ibrahim Yakoub-Agha, Daniele Avenoso, Andreas Neubauer, Stéphanie Nguyen, Edouard Forcade, Eolia Brissot, Bipin Savani, Arnon Nagler, Mohamad Mohty
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 57 Issue 9 Pg. 1421-1427 (09 2022) ISSN: 1476-5365 [Electronic] England
• PMID: 35752739 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Cyclophosphamide
• Busulfan

Topics

• Aged
• Busulfan (therapeutic use)
• Cyclophosphamide (therapeutic use)
• Graft vs Host Disease (etiology)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Leukemia, Myeloid, Acute (complications, therapy)
• Recurrence
• Retrospective Studies
• Transplantation Conditioning (adverse effects)
• Transplantation, Haploidentical (adverse effects)