Relevance of the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) On Non-Relapse Related Mortality (NRM) in Patients with Acute Lymphoblastic Leukemia (ALL) Receiving Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in First Complete Remission: Results From the GMALL Study Group.
Authors: Stelljes Matthias , David Mareike , Arnold Renate , Beelen Dietrich W , Bethge Wolfgang A , Bornhäuser Martin , Dengler Jolanta , Finke Juergen , Kolb Hans J , Kolbe Karin , Kröger Nicolaus , Niederwieser Dietger , Rösler Wolf , Schwerdtfeger Rainer , Kienast Joachim , Goekbuget Nicola , Hoelzer Dieter 
Published: October 2019

Abstract
Abstract 3352
Poster Board III-240
Allogeneic HSCT is established as a potent curative therapy in adult patients with high risk ALL. However, due to transplant-related morbidity and lethality the gains in relapse prevention do not necessarily translate into survival advantages in the overall patient population. Defining the role of allogeneic HSCT in ALL patients in first complete remission (CR1) according to leukemia related risk factors, to transplant related risk factors (e.g. HLA matching, conditioning therapy and immunosuppressive treatment), and to comorbidity related risks, remains a major task for upcoming clinical trials. Several retrospective studies suggest that the HCT-CI is suitable in capturing patients with comorbidities, in distributing them into risk groups and in prediction of NRM and overall survival (OS) during the first 2 years after allogeneic HSCT. The aim of this study was to evaluate if the HCT-CI might be predictive in patients with ALL receiving allogeneic HSCT in CR1. The prospective studies of the German multicenter study group for adult ALL (GMALL 06/99 and 07/2003) include indication for HSCT from HLA-matched related donor (MRD) or HLA-matched unrelated donor (MUD) in CR1 in patients with high risk features after uniform induction and first consolidation therapy. Between December 1999 and April 2008, 541 patients with high risk or very high risk ALL in CR1 underwent HSCT as part of their treatment according to the GMALL protocols. Of this patient cohort full data sets allowing the definition of individual HCT-CI were available for 251 patients. Median age of all evaluable patients was 35 years. Seventy-six of these patients (30%) received an allograft from MRD and 175 patients (70%) were transplanted from MUD. Most patients (86%) received conditioning consisting of total body irradiation (8-14 Gy) in combination with cyclophosphamide, fludarabine and/or etoposide. Seventy-seven (30%, median age 34 years) patients had a HCT-CI of 0, 78 patients (31%, median age 32 years) of 1, 45 (18%, median age 38 years) of 2, 27 (11%, median age 40 years) of 3, 15 (6%, median age 34 years) of 4, and 9 patients (4%, median age of 52 years) had an index ≥5. Cumulative incidence of NRM two years after transplantation for patients with a HCT-CI of 0, 1-2, 3-4 and ≥5 were 18%, 25%, 15% and 48%, respectively, and differed not significantly (p=.21). Corresponding estimated OS rates at 2 years were 64% (95% C.I., 58-70%), 64% (95% C.I., 59-69%), 66% (95% C.I., 58-74%) and 52% (95% C.I., 34-70%), respectively. Single organ comorbidities included in the HCT-CI (e.g. pre-transplant existing cardio-vascular, pulmonary or hepatic diseases) showed no significant association with higher risks of NRM. In addition, neither donor origin (MUD versus MRD), nor the combination male patients / female donor versus other sex combinations, nor high risk for cytomegalovirus (CMV) reactivation (patient CMV positive/donor CMV negative versus other combinations) were associated with higher risk for NRM. Only age (e.g. <40 years versus ≥40 years) remained a patient related significant risk factor for NRM with cumulative incidence of 17% and 40%, respectively (p=.028). In conclusion, our preliminary data suggest that the HCT-CI or other transplant related risk factors are insufficient to predict NRM in ALL patients of younger age compared to studies with HCT-CI in other diseases such as acute myeloid leukemia. In addition, the majority (65%) of our patients were transplanted after December 2003 and showed a significantly decreasing risk for NRM at two years after transplantation (17% versus 31%, p=.005). With improving survival rates, probably associated with the optimizations of transplantation procedures, introduction of reduced intensity conditioning, high resolution HLA-typing and better supportive care, stratifications according to scores established retrospectively from historic patient populations should not be used for clinical decisions. Therefore, at least in elderly patients future transplant studies should include prospective evaluations of comorbidities and other transplant related risk factors to identify factors that could be helpful in the decision which patient might benefit from allogeneic HSCT. Supported by Dt.Krebshilfe 702657Ho2

Disclosures:
No relevant conflicts of interest to declare.