Abstract
Posttransplant cyclophosphamide, sirolimus and mycophenolate mofetil (PTCy/siro/MMF) constitutes an innovative and well-tolerated acute graft-versus-host disease (aGVHD) prophylaxis after allogeneic stem cell transplantation (allo-HSCT), but risk factors for aGVHD incidence and therapy failure in this setting are scarce. This study prospectively registered all consecutive adult patients with hematologic malignancies who received a myeloablative allo-HSCT using PTCy/siro/MMF prophylaxis at our institution between 2017 and 2023. A total of 385 patients were included, of whom 44%, 34% and 22% were transplanted from matched sibiling, matched unrelated and haploidentical donors, respectively. The 180-day cumulative incidence of aGVHD was 21% (95% confidence interval [CI] 17–25%) for grade II–IV and 11% (95% CI 8–14%) grade III–IV aGVHD. The use of haploidentical donors was associated with an increased risk of severe aGVHD. Among 75 patients receiving first-line systemic corticosteroids, 49% achieved a sustained complete response, while 23% and 24% developed steroid-dependent (SD-aGVHD) and steroid-refractory aGVHD (SR-aGVHD), respectively. SR-aGVHD was associated with worse salvage treatment response and overall survival compared to SD-aGVHD. The 1-year cumulative incidence of aGVHD-related mortality was 5.4% (95% CI, 3.3–8.1). Risk factors for aGVHD-related mortality included haploidentical donors, older donors, diagnosis of myeldysplastic neoplasms, and grade IV aGVHD. This study confirms a low incidence aGVHD with PTCy/siro/MMF prophylaxis. SR-aGVHD showed poorer response to salvage therapies and worse survival, while haploidentical donors and older donor age were negative predictors for aGVHD-related deaths.
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Project “CM23/00215”, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union.
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PAC, IGS, MAS, AB and JS conceptualization and writing original draft. JM, MVM, PC, PSA, MSB, PLM, JSR, CSP, DMC, PGS, JEDR, AL, PR, PA, RB, and JDLR review and editing
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This project was approved by an ethical committee (Comité de Ética de la Investigación con Medicamentos – Hospital Universitario y Politécnico La Fe). Registry number: 09/2019-465. All methods were performed in accordance with the relevant guidelines and regulations. Informed consent was obtained from all participants.
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Asensi Cantó, P., Gómez-Seguí, I., Montoro, J. et al. Incidence, risk factors and therapy response of acute graft-versus-host disease after myeloablative hematopoietic stem cell transplantation with posttransplant cyclophosphamide. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02391-3
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DOI: https://doi.org/10.1038/s41409-024-02391-3