Survival of Patients with High Risk Hematological Malignancy after Allogeneic Transplant from HLA Identical Siblings Is Comparable to That of Patients Transplanted from Haploidentical, Unmanipulated Bone Marrow Donor: Results of a Matched-Pair Analysis from the Rome Transplant Network
Authors: Arcese William , Cerretti Raffaella , Cudillo Laura , De Angelis Gottardo , Picardi Alessandra , de Fabritiis Paolo , Dentamaro Teresa , Tendas Andrea , Cupelli Luca , Mengarelli Andrea , Marchesi Francesco , Chierichini Anna , Anaclerico Barbara , Tirindelli Maria Cristina , Cerchiara Elisabetta , Montefusco Enrico , Ferrari Antonella , Mariotti Benedetta , Ceresoli Eleonora , Adorno Gaspare , Di Piazza Fabio , Gentile Giuseppe , Sarmati Loredana 
Published: October 2019

Abstract
Patients and Methods. At the Rome Transplant Network, a JACIE accredited metropolitan transplant program, a matched-pair analysis has been conducted on 116 of 255 patients transplanted between January 2008 and December 2012. The patients transplanted from Id Sib (n=58) or Haplo related donors (n=58) were completely matched for the following features: patient age, gender, diagnosis (7 subgroups), disease phase (early: CR1+CR2; advanced: >CR2+active disease), myeloablative or reduced intensity conditioning regimen consisting of Thiotepa, i.v. Busulphan and Fludarabine (TBF) association, donor age and donor/recipient sex, AB0 and CMV combinations. As GVHD prophylaxis, all patients received the standard CSA and MTX combination with the addition of ATG, MMF and Basiliximab in Haplo bone marrow recipients. The transfusion policy, supportive care and antinfectious prophylaxis were identical for all patients.
Results. By comparingId Sib to Haplo recipients, the cumulative incidence (CI) of grade II-IV and III-IV acute-GVHD was 18±5% vs 42±7% (p=0.002) and 7±3% vs 14±5% (p=ns), respectively. The CI of extensive chronic GVHD was 23±6% for both patient series. The 5-year CI of TRM was 30±6% vs 36±6% (p=ns), respectively. The main causes of TRM were infections and the 6-month CI of Infection Related Mortality (IRM) was 26±6% in Haplo transplant and 10±4% in Id Sib (p=0.04). Although not statistically significant, the 5-year CI of relapse was higher in Id Sib (40±7%) than in Haplo recipients (28±6%). With a median follow-up of 3.5 years (range, 1 - 6), the 1- and 5-year disease free survival (DFS) was respectively 50±7% and 37±6% for Id Sibs and 45±7% and 36±6% for Haplo (Figure 1). Since 2 years after transplant, DFS curves of Id Sib and Haplo patients remained at plateau and were overlapping.
Conclusions. This analysis considered a high number of factors for matching patients, who were grafted according to an identical transplant program. We can conclude that as consequence of a more intensive GVHD prophylaxis and therapy ensuing from higher incidence of >II grade acute GVHD, Haplo recipients are mainly exposed to a risk of early infection mortality. On the other hand, Id Sib patients seem to express less graft-versus-tumor activity with increasing risk of relapse after transplant. The identical long-term DFS justifies to consider the unmanipulated bone marrow transplant from haploidentical donor a valid alternative for patients lacking an HLA identical sib. Finally, it can appear at present provocative, but certainly realistic in perspective, the hypothesis that the donor choice in a familiar setting will mainly take into account other favourable donor/recipient combined characteristics rather than HLA compatibility.
Figure 1 - Disease Free Survival Figure 1. - Disease Free Survival

Disclosures
No relevant conflicts of interest to declare.