Modified combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) as compared with standard ATG protocol in haploidentical peripheral blood stem cell transplantation for acute leukemia

Abstract

In haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), the combination of anti-thymocyte globulin and post-transplant cyclophosphamide (ATG/PTCy) has a synergistic impact in preventing graft-versus-host disease (GvHD). However, little is known about the long-term consequences of the new combination approach. Our goal is to evaluate the efficacy of ATG/PTCy versus a standard ATG regimen by focusing at long-term outcomes in a more homogeneous group of patients. We retrospectively included 118 adult patients up to 60 years with acute leukemia who underwent haplo-PBSCT at our single institution, following the same myeloablative conditioning regimen. From 2010 to 2020, 78 patients received a modified combination of ATG (2.5 mg/kg/day, on days −3, −2, and −1) and PTCy (40 mg/kg/day on days +3 and +4) compared to 40 patients who had a standard ATG-based regimen (2.5 mg/kg/day from days −4 to −1) from 2008 to 2015. The median follow-up time for all patients was 5.36 years, respectively. The cumulative incidence (CI) of neutrophil and platelet engraftment, as well as CMV reactivation, did not differ statistically between the two groups. The CI of the acute GvHD of grades II–IV and III–IV and extensive chronic GvHD were considerably lower in the ATG/PTCy (34.6%, 8.97%, and 13.63%) than in the ATG cohort (57.5%, 30%, and 38.23%) as validated by multivariable modeling. Additionally, compared to the ATG arm, the ATG/PTCy was a hazard factor associated with a higher risk of relapse (HR = 2.23, p = 0.039). The probability of 5-year overall survival, disease-free survival, and GvHD-free relapse-free survival in the ATG/PTCy group (53.34%, 49.77%, and 36.04%) was comparable with the ATG group (47.5%, 42.5%, and 22.5%), respectively. Our finding suggested that a modified ATG/PTCy combination resulted in a lower risk of acute and chronic GvHD and a higher risk of relapse than the standard ATG-based protocol but had no effect on long-term outcomes. However, certain adjustments in the immunosuppression protocol are warranted to improve the outcome.

Real-World Challenges of Haplo-Identical Hematopoietic Stem Cell Transplant in a Developing Country: A Single Center Experience

“…Incidence of GVHD was 44.1% in ATG + PTCy arm and it was higher at 66.7% in PTCy alone arm. Our results of the PTCy+ATG arm are in keeping with data published by Barkhordar et al [24].…”

The MAGIC algorithm probability (MAP)‐guided preemptive therapy of acute graft versus host disease with methylprednisolone: A randomized controlled trial

“…However, recent investigations have showed that preemptive therapy with glucocorticoids for aGvHD did not increase the incidence of infection 23,24 . Meanwhile, many studies have reported that the high incidences of CMV reactivation and hemorrhagic cystitis (ranging from 31% to 70% and 27.8% to 36%, respectively) in the setting of PTCy‐based aGvHD prevention regimens 25–31 . In our study, preemptive therapy with methylprednisolone for aGvHD did not show a significant increase in infection‐related events, cumulative incidences of CMV reactivation, or grade 2 or higher hemorrhagic cystitis, as determined by the chi‐square test.…”

“…23,24 Meanwhile, many studies have reported that the high incidences of CMV reactivation and hemorrhagic cystitis (ranging from 31% to 70% and 27.8% to 36%, respectively) in the setting of PTCy-based aGvHD prevention regimens. [25][26][27][28][29][30][31] In our study, preemptive therapy with methylprednisolone for aGvHD did not show a significant increase in infection-related events, cumulative incidences of CMV reactivation, or grade 2 or higher hemorrhagic cystitis, as determined by the chi-square test. These findings suggested that MAP-guided preemptive therapy for aGvHD with methylprednisolone is safe and feasible, complementing the existing routine prophylaxis for aGvHD while maintaining definite efficacy.…”

Determining the predictive impact of donor parity on the outcomes of human leukocyte antigen matched hematopoietic stem cell transplants: a retrospective, single-center study

“…Data provided by the Center for International Blood and Marrow Transplant Research (CIBMTR) in a large cohort study revealed that donor sex, donor pregnancy history, and recipient age were significantly associated with the onset of cGVHD ( 2 ), while donor parity was the sole variable that significantly influenced the risk of extensive cGVHD in our study. Regarding the augmented risk of cGVHD, the predictive effects of other factors such as aGVHD grades I-IV, males receiving grafts from allo-immunized females, and donors age have all been recognized significant in the multivariate analyses by previous studies ( 10 , 22 – 24 ).…”