Allogeneic Hematopoietic Cell Transplantation (AHCT) in Post Infusion Cyclophosphamide (PIC) Era: The Switch from Anti-Thymocyte Globulin (ATG) to PIC for Graft Versus Host Disease (GVHD) Prophylaxis in AHCT from Alternative Donors
Authors: Goren Sahin Deniz , Özçelik Nurcan , Özçeli̇k Tülay E , Arat Mutlu 
Published: November 2019

Aim: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (AHCT). As GVHD prophylaxis regimen, post-transplant cyclophosphamide (Post-Cy) has been associated with less acute and chronic GVHD. Anti-Thymocyte Globulin (ATG), which is another GVHD prophylaxis regimen, could reduce the risk of chronic but not acute GVHD. Anti-thymocyte globulin (ATG) in association with a calcineurin inhibitor (CNI) and methotrexate or mycophenolate mofetil (MMF) is widely used in the setting of unrelated donor transplantation (UDT). Recent studies proned non-inferior results of haplotype matched donor transplantation (HMDT) using Post-Cy in comparison with UDT. However, there is no consensus about the optimal GVHD prophylaxis regimen or choosingwisely. Aim of this study was to compare the outcome of two GVHD prophylaxis regimens; Post-Cy used in HIDT or UDT and ATG used for unrelated donors in a single-cohort of consecutive transplant recipients.
Material and Methods: Two hundred adult (17-72 years) patients who underwent HIDT and UDT with a minimum 100 days follow-up at Florence Nightingale Hospital Hematopoietic Stem Cell Transplantation Center between 2011 and 2017 were included in this study. Medical records of patients were reviewed retrospectively. Transplantation was performed in cases with high or very high DRI. HIDT was performed in 73 cases and UDT in 127 cases. One hundred eighty five out of 200 cases with a complete follow-up were included in the statistical analysis. Sixty-seven patients underwent HIDT with Post-Cy (Group 1), 97 patients with UDT receiving ATG (Group 2) and 21 with UDT receiving Post-Cy (Group 3). Patients who completed minimum 100 days post-transplantation follow-up were identified as eligible for survival analysis.
Results: Median age of patients was 42.8±14.9 years. Percentage of male patients was 65.6%, 68% and 38% for HIDT with Post-Cy (Group 1), UDT with ATG (Group 2) and UDT with Post-Cy groups (Group 3), respectively, which is significantly different (p=0.03). Bone marrow was used in 58.2% patients as stem cell source in HIDT, contrary to UDT, which is below 1% (p<0.0001). Median follow-up time was 398 days. Patient characteristics (Table 1), were mainly similar, such as donor age, gender, recipient cytomegalovirus (CMV) status, Karnofsky performance status, conditioning regimens, median neutrophil and platelet engraftment time, engraftment failure, acute GVHD incidence and disease status at post-transplant D100. Since the incidence of donor CMV IgG was significantly higher due to regional reasons in HIDT group, CMV activation rate was also significantly higher in this HIDT (p=0.001). No significant difference was found in Kaplan-Meier survival analysis among the HIDT with Post-Cy, UDT with ATG and UDT with Post-Cy groups, even if they were classified according to primary disease, and post transplant 100th day disease status. Transplant related mortality at 30th and 100th days were similar among three groups. Also, donor CMV status (CMV IgG positivity or negativity) and CMV reactivation was not an important factor on survival (for donor CMV status p=0.307; for CMV reactivation p=0.274).
Conclusion: We did not find any significant difference among three groups with regards to survival rate and acute GVHD development. Reactivation of CMV does not effect 100th day survival. These findings support our hypothesis that post-Cy infusion regimen is an important factor for higher survival rate rather than the donor type. We believe that post Cy infusion GVHD prophylaxis platform along with MMF and CNI is maturing, proved itself as a standard immune suppressive regimen for alternative donor transplantation. The related donor switch will be expectedly soon, and we have to wait for maturation of data both on related matched and alternative donor AHCT using post Cy infusion.

Disclosures
No relevant conflicts of interest to declare.