Haploidentical Transplantation Outcome Is Not Inferior to Standard Matched Related - Unrelated Donor Transplantation: An Intention-to-Treat Analysis of 611 Patients in 8-Years Experience At San Raffaele Scientific Institute

Background. Allogeneic transplantation of haemopoietic stem cells (HCT) from an HLA-matched related (MRD) or unrelated
donor (MUD) is a curative option for patients (pts) affected by high-risk hematological diseases (HRHD). The trend of growth of HCTs in adult pts with HRHD can be expected to continue based on acceptance and availability of alternative donor. Few data are available for: i) the reliable estimates of the number of HCT and the total number of pts for whom HCT is appropriate, ii) the choice of the different donor sources.

A risk-adapted treatment strategy is crucial to improve the outcome of pts with HRHD. Our policy is to offer a haploidentical
HCT to adult pts lacking a matched donor in the appropriate time according to clinical indications (www.leukemianet.org, www.ebmt.org). This policy is integrated in ongoing protocols for primary disease.

Methods. Here we are reporting the intention-to-treat (ITT) analysis of HCT in all consecutive HRHD pts referred to our Institution between January 2004 and June 2012. 

Results. Indication to HCT was given to 611 pts (median age 49 y, range 10-76; male 394), 120 pts (20%) received a transplant from a MRD; 187 pts (30%) activated a MUD search; 118 pts (19% of total pts, 63% of 
MUD searching) received a MUD transplant; 12 pts (2%) received a umbilical cord blood unit. Overall, 237 pts received a haplo-HCT (49%). The median time from indication to HCT was 87 days. The median time from indication to activation was 12 days and the median time from activation to HCT was 114 days (range 22-824). Lack of donor was not a limiting factor. Age was not a limiting variable to HCT execution: 107 patients (out of 487 SCT – 22%) were in the 60-69 range of age. The overall survival (OS) analysis in ITT for the entire population was 43% at 2 years, with a median time of survival of 767 days. The 2yOS in pts transplanted in CR was 60%, in pts transplanted in PD is 25% (p <0.001).

The OS according to donor source (MRD vs MUD vs haplo-HCT) was comparable (p=ns) in pts transplanted in CR.

The 2-year OS in pts affected by acute myeloid leukemia was 66%, 60% and 13% for patients transplanted in CR1, >CR1 and PD, respectively. The outcome analysis (OS, relapse incidence, transplant related mortality) per donor source was comparable (p=ns) within CR setting.

Conclusion. For many pts with HRHD, HCT from a MRD provides the best chance for long-term survival. However, only approximately 30% of individuals have a MRD. In our experience, haplo-HCT offers a concrete option of cure to HRHD pts: outcome results are superimposable to MRD and MUD in pts in CR at HCT. In ITT analysis, 80% of candidate pts received an HCT as a potential immunotherapy. All patients affected by HRHD, for whom an HCT is part of their therapeutic program, should proceed with a well-timed HCT whatever the stem cell source, and in the absence of a fully HLA-compatible donor the option of a haploidentical donor should be simultaneously considered.