Safety and feasibility of intermediate-dose post-transplant cyclophosphamide for graft-versus-host disease prophylaxis - CASE REPORT

Q: What dosing strategy was evaluated for intermediate-dose PTCy?

Intermediate-dose PTCy was given at 25–30 mg/kg/day on Days 3 and 4 after transplant in 11 consecutive patients.

Q: How did engraftment and donor chimerism outcomes compare with standard-dose PTCy?

All 11 patients achieved neutrophil engraftment and 10 achieved platelet engraftment. Median engraftment times were shorter than the standard-dose historical cohort, and complete donor chimerism was observed in all patients by Day 30.

Q: What GVHD events and key toxicity outcomes were reported?

Acute GVHD occurred in 3 patients (grades I–III), and severe chronic GVHD developed in 2 of those 3. One patient died from diffuse alveolar hemorrhage, while others remained alive without relapse.

Sep 29, 2026

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Post-transplant cyclophosphamide (PTCy) is widely used for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem-cell transplantation (HSCT), yet optimal dosing remains uncertain. This case series assessed intermediate-dose PTCy (25–30 mg/kg/day on Days 3 and 4) in 11 consecutive patients treated between February 2023 and November 2024. Intermediate-dose PTCy produced prompt neutrophil, platelet, and lymphocyte engraftment, complete donor chimerism by Day 30, and acceptable toxicity compared with a historical standard-dose cohort. Acute GVHD occurred in 3 patients and severe chronic GVHD in 2; one death from diffuse alveolar hemorrhage occurred. Findings suggest feasibility for vulnerable populations and support larger prospective validation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

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Abstract

Main body

GVHD prevention and PTCy background

Intermediate-dose PTCy rationale

Study approval and patient characteristics

Annals of Hematology (2025) 104:6451–6462 [https://doi.org/10.1007/s00277-025-06657-8](https://doi.org/10.1007/s00277-025-06657-8) CASE REPORT Safety and feasibility of intermediate-dose post-transplant cyclophosphamide for graft-versus-host disease prophylaxis Natasha Venugopal1 · Andrew McGowan1 · Yoshitaka Inoue1,2,3 · Hong Zheng1 · Joseph Cioccio1 · Kevin Rakszawski1 · Natthapol Songdej1 · Myles Nickolich1 · Seema Naik1 · Christopher Ehmann1 · Jeffrey Sivik4 · Joseph Mierski1 · Brooke Silar1 · Caitlin Vajdic1 · Hiroko Shike5 · Shin Mineishi1 · Kentaro Minagawa1 Received: 17 June 2025 / Accepted: 22 September 2025 / Published online: 13 October 2025 © The Author(s) 2025 Abstract Post-transplant cyclophosphamide (PTCy) is widely used for graft-versus-host disease (GVHD) prophylaxis in allogeneichematopoietic stem-cell transplant (HSCT) . However, the optimal dosing of PTCy remains uncertain. In this case series, we evaluated intermediate-dose PTCy (25–30 mg/kg/day on Days 3 and 4) in 11 consecutive patients treated at our center between February 2023 and November 2024. Outcomes regarding engraftment were compared to our center’s historical cohort, which received standard-dose PTCy. All 11 patients achieved neutrophil engraftment, and 10 achieved platelet engraftment. Median times to neutrophil, platelet, and lymphocyte engraftment were Day 14, 17, and 21, respectively—significantly shorter than in the standard-dose group (Day 18, 23, and 40; p< 0.05 for all comparisons, Mann–Whitney U test) . Complete donor chimerism was observed in all patients by Day 30. Compared to our center’s historical cohort, significantly more patients in the intermediate-dose group achieved complete donor chimerism in both total cells and T cells (p< 0.01 and p = 0.03, respectively; Fisher’s exact test). Among the 11 patients, acute GVHD occurred in 3 patients (one each of grade I, II, and III); two of those 3 developed severe chronic GVHD. One patient died from diffuse alveolar hemorrhage; the others remain alive without relapse. Intermediate-dose PTCy demonstrated favorable engraftment, high donor chimerism, and acceptable toxicity, suggesting it may be a viable option for GVHD prophylaxis, particularly in vulnerable populations such as elderly patients, those with poor performance status, comorbidities, or splenomegaly. Larger prospective studies are warranted to validate these findings. Keywords Allogeneic hematopoietic cell transplant · Graft-versus-Host-Disease · Post-transplant cyclophosphamide Main body The prevention and management of graft-versus-host disease (GVHD) remains a primary concern for patients undergoing allogeneic hematopoietic stem-cell transplant (HSCT) . 􀀍 Yoshitaka Inoue [yinoue@pennstatehealth.psu.edu](yinoue@pennstatehealth.psu.edu) 1 Blood and Marrow Transplant Program, Division of Hematology and Oncology, Penn State Cancer Institute, 500 University Dr. Hershey, Hershey, PA 17033, USA 2 Penn State College of Medicine, Hershey, PA, USA 3 Department of Hematology, Kumamoto University, Kumamoto, Japan 4 Pharmacy, Penn State Cancer Institute, Hershey, PA, USA 5 Pathology, Penn State Cancer Institute, Hershey, PA, USA Among prophylaxis strategies, post-transplant high-dose cyclophosphamide (PTCy) has emerged as a preferred option. Initially used in haploidentical HSCT [1], PTCy is now also appropriate for transplants with HLA-matched siblings and unrelated donors based on the Phase III BMTCTN 1703 trial [2] . The standard PTCy regimen involves administering 50 mg/kg/day on Day 3 and 4 post-transplant, in combination with tacrolimus (Tac, 0.05–0.06 mg/kg/day orally or 0.02–0.03 mg/kg/day intravenously) and mycophenolate mofetil (MMF, 15 mg/kg per dose orally or intravenously three times daily) [2] . While now a cornerstone of GVHD prophylaxis, the optimal timing and dosing of PTCy remains uncertain [3] . This regimen is also associated with limitations, such as delayed engraftment, graft fai

FAQs

What dosing strategy was evaluated for intermediate-dose PTCy?

Intermediate-dose PTCy was given at 25–30 mg/kg/day on Days 3 and 4 after transplant in 11 consecutive patients.

How did engraftment and donor chimerism outcomes compare with standard-dose PTCy?

All 11 patients achieved neutrophil engraftment and 10 achieved platelet engraftment. Median engraftment times were shorter than the standard-dose historical cohort, and complete donor chimerism was observed in all patients by Day 30.

What GVHD events and key toxicity outcomes were reported?

Acute GVHD occurred in 3 patients (grades I–III), and severe chronic GVHD developed in 2 of those 3. One patient died from diffuse alveolar hemorrhage, while others remained alive without relapse.

Sep 29, 2026

Uploaded by Rhys