The Hematopoietic Cell Transplant-Co-Morbidity Index (HCT-CI) Predicts Outcomes After T Cell Depleted (TCD) Allogeneic HCT For AML and MDS
Authors: Ratan Ravin , Ceberio Izaskun , Hilden Patrick , Devlin Sean M. , Malloy Molly A , Barker Juliet N , Castro-Malaspina Hugo , Jakubowski Ann A. , Koehne Guenther , Papadopoulos Esperanza B , Ponce Doris M , Sauter Craig S. , van den Brink Marcel R.M. , Young James W. , O'Reilly Richard J. , Giralt Sergio , Goldberg Jenna D , Perales Miguel-Angel 
Published: October 2019

Abstract

Introduction
Ex vivo TCD Allogeneic-HCT results in long-term relapse-free (RFS) and overall survival (OS) in patients with AML in CR or MDS, with a low incidence of acute and chronic graft-versus-host disease (GVHD). The HCT-CI predicts non-relapse mortality (NRM) and 1-year survival in recipients of conventional grafts. We investigated whether HCT-CI also predicted outcomes in ex vivo TCD-HCT in order to improve patient selection.

Methods
A retrospective chart review was conducted to evaluate 218 pts (median age 50.4) with AML in CR (n=155) or MDS (n=63) undergoing TCD-HCT between 1997-2008. All pts received myeloablative conditioning. The majority received ATG for graft rejection prophylaxis. No GVHD prophylaxis was administered post-transplant. TCD of BM utilized soybean agglutination+sheepRBC rosetting (sRBCR). CD34+ selection +/- sRBCR was used for PBSC TCD. HCT-CI was determined according to Sorror et al. (Blood 2005). Prognostic factors relating to OS and RFS, including age, conditioning-regimen (TBI vs. chemo), HLA match (identical vs. other), and HCT-CI were evaluated using log-rank test statistics. Univariate and multivariate Cox proportional-hazards regression were performed for OS & RFS.

Results
The median HCT-CI score was 2 (range 0-9). HCT-CI score was 0 (low) in 25% patients, 1-2 (intermediate) in 36% and ≥3 (high) in 39%. Median follow-up of survivors is 70 months (range 6.1-182.6). Outcomes of the univariate and multivariate analysis are summarized in Table 1. Age and HCT-CI score were significantly associated with OS and RFS by univariate and multivariate analysis. In addition, in the multivariate analysis, HLA-match was associated with OS and RFS, while regimen was only associated with RFS. Patients with a high HCT-CI had significantly lower OS and RFS than those with a low or intermediate HCT-CI (Figure 1). Furthermore, while the cumulative incidence of relapse did not differ based on HCT-CI, patients with a high HCT-CI had a significantly higher incidence of NRM compared to patients with low or intermediate HCT-CI (not shown).

Conclusions
These results support the use of the HCT-CI to stratify patients with AML and MDS who are eligible for myeloablative TCD-HCT and identify patients who are candidates for other approaches. Interestingly, unlike conventional grafts, we do not see worse outcomes (OS/RFS/NRM) in patients with intermediate vs. low HCT-CI, suggesting that patients with intermediate HCT-CI may better tolerate a TCD-HCT than a conventional HCT. A planned prospective three arm randomized Phase III, comparing two calcineurin inhibitor-free strategies for GVHD prophylaxis (CD34-selection and post-HCT Cy) to standard tacrolimus and methotrexate (BMT-CTN 1301) will further address these questions.

Disclosures:
No relevant conflicts of interest to declare.