Role of Hematopoietic Cell Transplantation Co-Morbidity Index (HCT-CI) in Selection of Conditioning Regimen for Patients Undergoing Allogeneic Hematopoetic Cell Transplantation (Allo-HCT) – a Single Institutio

Objective:  To compare Overall Survival (OS), Treatment Related Mortality (TRM), and Relapse Rate (RR) between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) regimens in patients with high/intermediate risk disease status. The hypothesis to be tested is that HCT-CI can be effectively used to decide on the preference of conditioning regimen and that RIC will decrease TRM without increasing relapse so that OS will be improved even in high/intermediate risk disease status patients with high HCT-CI.

Patients and methods:  Patients with high HCT- CI (≥ 3) underwent RIC regimen and those with low HCT CI (≤ 2) underwent MAC regimen despite high/intermediate risk disease status. We analyzed the outcome of 92 patients with high or intermediate risk disease status (CIBMTR criteria) who underwent Allo- HCT at our institution between the years 2009 and 2013 inclusive. RIC regimen consisted of IV Fludarabine 30 mg/m²/day infused over 30 minutes for 5 days on days -6 through -2 and IV Busulfan 3.2 mg/kg/day on days -3 and -2 (infusion rate 80 mg/hour). MAC regimen consisted of IV  Fludarabine 50mg/m2/day  infused over 1 hour on days -6 through -2, IV Busulfan 3.2mg/m2/kg/day on days -5 through -2 (infusion rate 80mg mg/hr), and TBI 200 cGY on days -2 and -1. All patients received Thymoglobulin at a total dose of 4.5 mg/kg or 6 mg/kg administered in divided doses on days -2, -1 and 0. Post-transplantation graft versus host disease (GVHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil. Diagnoses included Acute Lymphoblastic Leukemia (n=4), Myeloproliferative disorder (n=7), Hodgkins Lymphoma (n=8), Myelodysplastic Syndrome (n=20), Acute myeloid leukemia (n=25), and Non-Hodgkin's Lymphoma (n=28). Median age of the recipients was 52. 1 years. The HCT- CI was high (≥ 3) in 41 recipients (47%) and 75 patients (83%) were in high risk disease status.

Results:  At a median follow up of 13.2 months, the OS for patients undergoing RIC was 74.3% compared to 38.1% with MAC (p=0.014). The cumulative incidence of TRM at 12 months was 27.6% in patients undergoing MAC compared to <1 % in RIC (p=0.041). Relapse related mortality at 12 months in RIC (25.7%) compared to MAC (50.5%) was not statistically different (p=0.206).

Conclusion:  Our data demonstrates that use of HCT- CI is a simple but effective way to appropriately stratify patients with high/intermediate disease risk status to a particular conditioning regimen.  The use of RIC in patients with high HCT-CI is non-inferior to MAC with our institutional data showing RIC is associated with low TRM, improved OS without any statistically significant increase in mortality from disease progression or relapse.  Prospective studies are necessary to validate these findings.