幹細胞研究と治療のジャーナル

概要

Should a More Personalized Approach be Applied to Hematopoietic Stem-Cell Transplantation?

Stefan O Ciurea, Piyanuch Kongtim, Gabriela Rondon, Julianne Chen, Ciprian Tomuleasa and Richard E Champlin

Background: Allogeneic stem cell transplantation for older patients with hematological malignancies has generally been performed with reduced-intensity conditioning, as regimen-related toxicity prohibits a fully myeloablative conditioning regimen. We hypothesized that differences in intensity of conditioning are needed for different disease status.
Patients and Methods: We analyzed 115 older patients with AML (55 years or older) who received conditioning with fludarabine and melphalan, with a melphalan dose of 140 mg/m2 (FM140) (N=73) or 100 mg/m2 (FM100) (N=42).
Results: Overall, FM100 was associated with less TRM (18.1% versus 43.5%, p=0.007), and acute GVHD (aGVHD) (28.2% versus 36.7%, p=0.021) while relapse was similar (21.5% versus 25.5%, p=0.489). The lower TRM with comparable relapse rate resulted in higher survival for FM100 as compared with FM140 conditioning regimen, 3-year PFS was 60.2% and 28.6% (p=0.014). Conversely, patients with high-risk SWOG cytogenetics and adverse ELN risk had better survival outcomes with FM140 regimen due to lower relapse, while TRM was not different. In multivariable analysis, high-risk SWOG cytogenetics, adverse ELN risk and the development of grade 2-4 aGVHD predicted for worse PFS whereas using FM140 conditioning and aGVHD were an independent factor for TRM.
Conclusion: These results suggest as a proof-of-principle that a differential approach should be applied for patients receiving an allogeneic hematopoietic stem cell transplant, not only based on age, but also on disease characteristics impacting the risk of relapse. Further studies are needed to develop a more personalized approach to hematopoietic stem cell transplant recipients.