Sociodemographic and Patient-Related Determinants of Outcomes after Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based GvHD Prophylaxis
Authors: Chaudhary Sibgha Gull , Shahzad Moazzam , Pfannenstiell Kayla , Amin Muhammad Kashif , Kasaeian Amir , Khalid Muhammad Fareed , Alemi Hediyeh , Khavandgar Naghmeh , Anwar Iqra , McGuirk Matthew , Bukhari Syed Nasir Abbas , Singh Anurag K. , Hamadani Mehdi , McGuirk Joseph P. , Mushtaq Muhammad Umair 
Published: December 2024

Background: Allogeneic hematopoietic cell transplantation (HCT) is a crucial therapy option for several hematological disorders. Sociodemographic factors, performance status, and comorbidities significantly affect post-transplant outcomes. This study aimed to investigate the impact of these sociodemographic and patient-related factors on outcomes following haploidentical hematopoietic cell transplantation (haplo-HCT) using post-transplant cyclophosphamide (PT-Cy)-based graft versus host disease (GVHD) prophylaxis.

Methods: A retrospective multicenter analysis was conducted, including haplo HCT recipients with PT-Cy-based GVHD prophylaxis in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2012 to 2017 using P5737 data by Ustun et al. We examined the impact of recipient age, gender, and ethnicity, donor age and gender match, ethnicity, cytomegalovirus (CMV) status, Karnofsky's performance status (KPS), and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) on overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), grade II-IV acute GVHD, chronic GVHD, and GVHD-free relapse-free survival (GRFS). Patient-, disease- and transplant-related factors were compared between groups using the Chi-square test for categorical variables and the Wilcoxon two-sample test for continuous variables. The median follow-up duration was estimated using the reverse Kaplan-Meier method. Cox proportional hazards regression analyses were performed. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Variables with p-values &lt;0.2 in univariable analysis and the clinically relevant variables were included in the multivariable models. Statistical analyses were conducted using Stata version 18, and significance was defined as p&lt;0.05.

Results: We included 550 patients who received haplo-HCT with PT-Cy-based GVHD prophylaxis. The median age was 59.8 years, and 59% (n=327) were male. The graft source was peripheral blood in 62.5% (n=344) and bone marrow in 37.5% (n=206) of patients. The primary hematologic malignancies included acute myeloid leukemia (54%, n=297), acute lymphoblastic leukemia (17%, n=91), and myelodysplastic syndrome (29%, n=158). Ethnicities were Caucasian (63.5%, n=349), African American (20%, n=108), Hispanic (9.5%, n=52), and Asian and others (7%, n=41). The conditioning regimen was myeloablative in 38% (n=207) of patients. The KPS was 90% or higher in 47% (n=257) of patients. The HCT-CI of less than three was noted in 50% (n=274) of patients. The median follow-up time was 3.83 years (95% CI 3.17-3.94). The median OS, DFS, and GRFS were 2.05 years (95% CI 1.48-3.20), 0.86 years (95% CI 0.69-1.09), and 0.30 years (95% CI 0.25-0.35). Incidence of grade II-IV acute GVHD, chronic GVHD, relapse, and mortality were 35% (n=193), 32% (n=175), 42.5% (n=234), and 45% (n=248). After adjusting for significant variables in multivariate regression analysis, significant predictors of outcomes included - OS: female gender (HR 0.62, 95% CI 0.42-0.90, p=0.011), CMV donor/recipient-negative (HR 0.59, 95% CI 0.39-0.89, p=0.013), HCT-CI &gt;=5 (HR 1.84, 95% CI, 1.14-2.97, p=0.012); DFS: female gender (HR 0.62, 95% CI 0.44 - 0.87, p=0.006), CMV donor/recipient-negative (HR 0.68, 95% CI 0.47-0.99, p=0.043), HCT-CI &gt;=5 (HR 1.79, 95% CI 1.16-2.78, p=0.009); GRFS: female gender (HR 0.76, 95% CI 0.58-0.98, p=0.035), CMV donor/recipient-negative (HR 0.75, 95% CI 0.56-0.99, p=0.044); relapse: none; NRM: female gender (HR 0.59, 95% CI 0.36 - 0.98, p=0.040), CMV donor/recipient-negative (HR 0.42, 95% CI 0.22-0.77, p=0.005); grade II-IV acute GVHD: Asian vs. Caucasian ethnicity (HR 0.24, 95% CI 0.09-0.65, p=0.005); and chronic GVHD: Asian vs. Caucasian ethnicity (HR 0.38, 95% CI 0.17-0.84, p=0.017).

Conclusion: Our study has evaluated the impact of sociodemographic and patient-related factors on outcomes following haploidentical HCT using PT-Cy-based GVHD prophylaxis. We have identified female gender, CMV-negative serostatus, lower comorbidity index, and Asian ethnicity as predictors of superior post-transplant outcomes. Further studies are warranted to address and mitigate these risk factors with patient-centered interventions and tailored selection of disease- and transplant-related factors to improve post-transplant outcomes.