Low-dose antithymocyte globulin plus low-dose posttransplant cyclophosphamide combined with cyclosporine and mycophenolate mofetil for prevention of graft-versus-host disease after HLA-matched unrelated donor peripheral blood stem cell transplantation

Xi Sun,Kun Zhou,Xueying Ding,Yu Cai,Huiying Qiu,Liping Wan,Jun Yang,Xianmin Song,Chongmei Huang,Yin Tong,Xiaowei Xu

doi:10.1038/s41409-021-01358-y

Abstract

The standard regimens for graft-versus-host disease (GvHD) prophylaxis in matched unrelated donor (MUD) transplantation were based on antithymocyte globulin (ATG) in combination with calcineurin inhibitors (CNIs). To improve the efficiency of GvHD prophylaxis in MUD peripheral blood stem cell transplantation (MUD-PBSCT), 51 patients with hematological malignancies received a novel regimen for GvHD prophylaxis, which is composed of low dose of ATG (5 mg/kg) plus low-dose posttransplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy) combined with cyclosporine A (CsA) and mycophenolate mofetil (MMF). The cumulative incidences (CIs) of grades I–IV and II–IV acute GvHD (aGvHD) were 14.5% (95% CI, 9.4–19.6%) and 6.2% (95% CI, 2.8–9.6%) within 100 days after transplantation, respectively. The CI of mild-to-moderate chronic GvHD (cGvHD) within 1 year was 11.5% (95% CI, 6.6–16.4%). The 1-year probabilities of GvHD and relapse-free survival, relapse-free survival, and over survival were 70.6% (95% CI, 64.2–77.0%), 76.5% (95% CI, 70.6–82.4%), and 82.0% (95% CI, 76.5–87.5%), respectively. The CIs of CMV and EBV reactivation by day 180 were 10.4% (95% CI, 1.5–19.4%) and 8.3% (95% CI, 0.2–16.4%), respectively. The results suggested that low-dose ATG/PTCy combined with CsA/MMF as GvHD prophylaxis in MUD-PBSCT had promising activity.

Highlights

Graft-versus-host disease (GvHD) remains to be the major complication affecting the survival of patients after allogeneic hematopoietic stem cell transplantation a substantial progress in reducing acute and chronic GvHD has been achieved in recent 10Jiao Tong University School of Medicine, Shanghai, China 2 Engineering Technology Research Center of Cell Therapy and Clinical Translation, Shanghai Science and Technology Committee (STCSM), Shanghai, China years
Data from the respective study showed that the cumulative incidences (CIs) of grades I–IV acute GvHD (aGvHD) and grades II–IV aGvHD within 100 days after transplantation and mild-to-moderate chronic GvHD (cGvHD) within one year were 14.5%, 6.2%, and 11.5%, respectively, in matched unrelated donor (MUD)-PBSCT with low-dose Antithymocyte globulin (ATG)/posttransplant cyclophosphamide (PTCy) combined with cyclosporine A (CsA) and mycophenolate mofetil (MMF) regimen for GvHD prophylaxis, which demonstrated the high efficacy of the four drug regimen composed of low-dose ATG, low-dose PTCy, CsA, and MMF in GvHD prophylaxis for patients receiving MUD-PBSCT
Mielcarek et al [27] reported the results with PTCy combined with CsA as GvHD prophylaxis for 43 patients with hematological diseases receiving peripheral blood stem cell (PBSC) from MSD or MUD, a lower CI of cGvHD and no grades III and IV aGvHD developed, the high incidence of grade II aGvHD over 70% highlighted the importance of optimization of the PTCybased regimens for GvHD prophylaxis in MUD-PBSCT

Summary

Introduction

Graft-versus-host disease (GvHD) remains to be the major complication affecting the survival of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) a substantial progress in reducing acute and chronic GvHD (cGvHD) has been achieved in recent 10Jiao Tong University School of Medicine, Shanghai, China 2 Engineering Technology Research Center of Cell Therapy and Clinical Translation, Shanghai Science and Technology Committee (STCSM), Shanghai, China years. Posttransplant cyclophosphamide (PTCy) was used for prevention of GvHD in a growing number of clinical trials for patients with HLA-matched related donor (MRD) or MUD transplantation because of its outstanding results of GvHD prophylaxis in haploidentical MRD transplantation. The results of single-agent PTCy as GvHD prophylaxis in HLA-matched bone marrow transplantation (BMT) were unsatisfactory, especially for patients receiving mobilized peripheral blood stem cell (PBSC) grafts [5,6,7]. PTCy combined with cyclosporine A (CsA) or tacrolimus/MMF for prevention of GvHD in MUD transplantation with PBSC grafts remained to have a relative high incidence of aGvHD with grades II–IV of 28–59% [8,9,10,11,12]

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Results

Conclusion