Investigating the Relationship between CD34+and CD3+ Cell Doses, One-Year Graft-Versus-Relapse-Free-Survival, Graft-Versus-Host Disease, and Overall Survival in Haploidentical Hematopoietic Stem Cell Transplantation Using Post Transplant Cytoxan: A Single Center Experience

Abstract

Background Haploidentical hematopoietic cell transplantation (haplo-HCT) is a popular alternative to traditional HLA-matched HCT. The dose of CD34+ cells used during haplo-HCT to ensure favorable outcomes using PTCy has not yet been reported though 2-5.00 × 106 cells/kg is common. The optimal dose of CD3+ cells is also unknown but recent data suggests ≤3.00 × 108 cells/kg may prevent the development of acute GVHD. The importance of studying the impact of CD34+/CD3+ cell dosing may improve outcomes in this setting. Methods We retrospectively analyzed adult patients at USC Norris Cancer Hospital who received haplo-HCT from 2014 to 2019. The primary end-point assessed was 1-year GVHD-free/relapse-free survival (GRFS). Secondary end-points included 1-, 2-, and 3-year relapse-related mortality (RRM) and overall survival (OS) in addition to 1-year transplant related mortality (TRM) and incidence of acute and chronic GVHD. Results 67 adult haplo-HCT recipients were reviewed with 50% (n = 33) male and 49% (n = 32) female. The age range was 21-71 years old (median = 44) and the most common underlying hematologic disorders included AML (40%), ALL (38%), and aplastic anemia (7.7%). 67% received myeloablative conditioning while 33% received reduced intensity. 70% (n = 47) received peripheral blood and 30% (n = 20) received bone marrow stem cells. The mean CD34+ and CD3+ doses were 6.07 × 106 cells/kg and 2.94 × 108 cells/kg. The mean time to recovery of platelets, ANC, and lymphocytes was 25, 18, and 37 days respectively. CD34+ ≥5.00 × 106 cells/kg was associated with shorter time to lymphocyte recovery (p = 0.0265) though recovery less than 30 days was not associated with OS (p = 0.5268). Incidence of 1-year GRFS was 71% (n= 46) and 1-, 2-, and 3-year RRM were 4.6%, 6%, and 7.7% respectively. 1-year TRM was 15.3% with 50% of deaths from acute GVHD. 1-, 2-, and 3-year OS were 80%, 78%, and 77%. 33% (n = 22) and 30% (n = 20) developed acute and chronic GVHD. Subgroup analysis of those who received CD34+ dose ≥7.00 × 106 cells/kg (n = 24) and ≥10 × 106 cells/kg (n = 7) were found to have 1-year OS of 87.5% and 85.7% compared with 77% and 80% in those that received lower doses (p= 0.2229 and p = 1.00). Discussion Our results demonstrate 71% survived 1 year without experiencing at least 1 GRFS event compared with reports of 24-35% and 3-year OS of 77% when compared with 48%. The mean CD34+ dose of our population is higher than the standard which may have lead to improved outcomes however the CD34+/CD3+ dose was not significantly associated with our end-points but significantly associated with shorter time to lymphocyte recovery, a factor that has been reported to be associated with decreased RRM and therefore improved OS. Subgroup analysis of higher CD34+ doses also did show improved 1-year OS though not significant. Further research with a prospective study identifying the optimal CD34+/CD3+ cell dose is warranted to improve haplo-HCT outcomes.