Favorable Immune Reconstitution Profile after Allogeneic Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide
Authors: Jamy Omer Hassan , Saad Ayman , Orlandella Rachael , Langford Samantha B , Paluri Ravi K. , Innis-Shelton Racquel , Mineishi Shin , Lamb Lawrence S. 
Published: October 2019

Abstract
Background: The administration of post-transplant high-dose cyclophosphamide (PTCy) has been shown to be an effective strategy for GvHD prophylaxis following allogeneic peripheral blood stem cell transplantation(PBSCT) from alternative donors. PTCy is toxic to allogeneic activated proliferating T lymphocytes, such as effector T cells. Conversely, it may not materially affect memory T cells.
Methods: We evaluated immune reconstitution profile and transplant outcome in patients who received PBSCT with and without PTCy. PTCy was given on day +3 and +4 following haploidentical transplant (HAPLO), or only on day +3 following HLA-matched unrelated donor (MUD) transplant. No PTCy was given to patients with HLA-matched related donors (MRD). All patients received GvHD prophylaxis as tacrolimus (day +5 to +180) and MMF (day +5 to +35). Preparative regimens were myeloablative regimens (fludarabine/busulfan, fludarabine/TBI 12 Gy, or CY/TBI 12) in all patients except 4 patients (received fludarabine/melphalan). Immune reconstitution profile (IRP) was tested via serial flow cytometry analysis of peripheral blood lymphocytes after transplant were done on days +30, +100, and +180.
Results: Data of 70 patients who underwent allogeneic PBSCT in our institution were analyzed in 3 groups; MRD (n=22), MUD (n=35), and HAPLO (n=13). The total cohort had 33 males (47%), and had median age of 52 years (range 20-70). All patients had hematological malignancy except one patient with HLH. The median duration of follow up was 6 months (range 1-17). The median day of neutrophil and platelet engraftment were 13, 12, 17 and 18, 15, 22 days for MRD, MUD and HAPLO groups respectively. The one-year overall survival of the whole group was 67% (95% confidence interval: 48-80) with no difference in OS among the 3 cohorts (log rank P value 0.4) (Figure 1). Lymphocyte and lymphocyte subset (T, B, NK) count recovery for MUD and HAPLO was significantly less (p<0.05) than MRD during the first month post-HSCT but these differences were statistically insignificant by day +60 and remained so through day +365. Recovery of both CD4+ and CD8+ naïve T cell (CD45RA+CD27+CD197+) population was generally slower for HAPLO patients during the first year and significantly less through day+ 180 for CD4+ T cells. As predicted, central memory (CD45RA-CD27+CD197+) CD4+ and CD8+ T cells remained proportionately equivalent at 40% and 28% respectively for all groups during the first year. The effector memory (CD45RA-CD27+CD197-) population was also proportionately consistent at 25% of total for both CD4+ and CD8+ subsets. Interestingly, the effector T cell population (CD45RA+CD27-CD197-) trended higher for all three recipient groups at each time point for both CD4+ and CD8+ populations increasing from 20% at one month to over 40% at one year.
Conclusion: Post-PBSCT survival was not significantly different from alternative donor graft recipients and those that received MRD PBSCT. Lymphocyte recovery was impaired for the PTCy groups in the immediate post-PBSCT period but quickly recovered to that seen in MRD recipients.
Figure 1 Figure 1.

Disclosures
Saad: Spectrum: Honoraria; American Porphyria foundation: Research Funding; Astellas: Research Funding; Alexion: Honoraria. Lamb:Incysus, Ltd: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding.