Haploidentical Second Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Acute Leukemia Relapse after First Allo-HSCT: A Retrospective Registry Analysis of 60 Patients on Behalf of the German Cooperative Transplant Group

Background: Relapse of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is frequently treated with 2^nd allo-HSCT. Donor change has not yielded a significantly different outcome over choosing the original HLA-identical donor (Christopeit et al., JCO 2013). Using a haploidentical donor at second allo-HSCT might represent a feasible option (Tischer et al., BMT 2014)

Study design and population: To define the role for second haploidentical allo-HSCT for AL relapsing after 1^st allo-HSCT, a retrospective analysis was conducted 63 consecutive patients (female n=30, male n=33; AML n=51, ALL n=12) from 9 German centers were included. Median age was 40 years (range, 16-65). Grafts at 1^st allo-HSCT were from matched related (32%), matched unrelated (33%), mismatch unrelated (18%), haploidentical donors (6%), and other donors, including cord blood (8%). Median duration of complete remission (CR) after 1^st allo-HSCT was 414 days (range, 18-1633). Relapse was initially treated by cytoreductive chemotherapy in all cases; stage at start of conditioning for haploidentical second allo-HSCT was CR in 27%, active disease in 66% and not evaluated in 8%. Conditioning for second HSCT was myeloablative/reduced in 14%/86% To overcome the HLA barrier, 23 patients (36%) received ex vivo T-cell depletion (TCD), following either CD3/CD19 negative or CD34 positive selection. 4 patients received in vivo TCD only, two received no TCD at all, and 35 patients (55%) received high-dose cyclophosphamide post-transplant according to the Baltimore protocol.

Results: Neutrophil engraftment was achieved after a median of 12 days (range, 8-26). 50 patients (78%) achieved CR after 2^nd haploidentical allo-HSCT, out of which 23 (46%) relapsed again. After a median follow-up of 425 days, 47 patents had died, 22 from leukemia, and 25 from treatment-related causes. Kaplan-Meier estimated overall survival at one and two years from haploidentical second HSCT was 41+/-6% and 19+/-6%.

Conclusions: Haploidentical second allo-HSCT is a promising approach to the treatment of AL relapse after first allogeneic transplant. OS rates at least comparable to alternative treatments were observed. Different strategies to overcome the HLA barrier seem feasible. This retrospective study was registered as NCT01997918 at clinicaltrials.gov.

Maximilian Christopeit and Johanna Tischer as well as Wolfgang Bethge and Christoph Schmid contributed equally to this work.