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Reducing Pyrrhic Victories in Allogeneic Stem Cell Transplantation
Allogeneic peripheral-blood stem cell transplantation (alloSCT) is curative for many patients with relapsed or high-risk hematologic malignancies. However, chronic graft-versus-host disease (GVHD) can lead to persistent complications, poor quality of life, and increased mortality — a “Pyrrhic victory” for cured patients. In a phase 3, multicenter study, patients with acute leukemia or myelodysplastic syndrome undergoing matched related donor alloSCT were randomized to experimental GVHD prophylaxis with high-dose cyclophosphamide on days 3 and 4 posttransplant plus cyclosporine (n=61) or standard prophylaxis with methotrexate plus cyclosporine (n=68).
During a median follow-up of 36 months, the experimental-prophylaxis group had:
- A significantly higher rate of GVHD-free, relapse-free survival at 3 years than the standard-prophylaxis group (49% vs. 14%)
- A lower rate of grade 3/4 acute GVHD at 3 months (3% vs 10%), with no difference in serious adverse events during the first 100 days post-alloSCT
- A significantly higher rate of overall survival at 2 years (83% vs 71%)
Comment
The rationale for cyclophosphamide in GVHD prophylaxis includes depleting donor T cells while sparing infused hematopoietic stem cells. This study confirms a clear role for this regimen in patients undergoing alloSCT from matched related donors (and, as recently shown, mismatched unrelated donors [J Clin Oncol 2025 Jun 16; e-pub]), leading to its use in most transplant centers, including our own. Importantly, cyclophosphamide-based prophylaxis enhances the safety of haploidentical alloSCT by mitigating severe GVHD risk, thus making curative alloSCT available via parent or child donors for patients in racial and ethnic groups that are underrepresented in transplant donor registries.
Citation(s)
Author:
Curtis DJ et al.
Title:
Graft-versus-host disease prophylaxis with cyclophosphamide and cyclosporin.
Source:
N Engl J Med
2025
Jun
13; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Michael E. Williams, MD, ScM