Reduced Relapse and Improved Survival in Chemosensitive Hodgkin Lymphoma Patients Undergoing Haploidentical Related Donor Compared to HLA-Identical Donor Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential curative option for patients with relapsed or refractory Hodgkin's lymphoma (RR HL).

Allo-HSCT from haploidentical donor (haplo-HSCT), when HLA identical donor is not available, is considered a good alternative. Using haploidentical donors, the immunological activity against HL seems to be particularly high. In this retrospective study, we analysed the results obtained using HLAid donors or haploidentical donor in RR HL patients.

Inclusion criteria were allo-HSCT performed during the same period (2010-2014); chemosensitive disease at allo-HSCT (complete + partial remission); T-cell replete haplo-HSCT using post-transplantation Cy. Haplo-HSCT were performed in 3 Centers (Humanitas Research Hospital, Rozzano; Ospedale San Martino, Genova; Institut Paoli Calmettes, Marseille, France) and HLA identical transplantation, both from related or unrelated donor, in centers from the Gruppo Italiano Trapianto di Midollo e cellule staminali periferiche (GITMO). 65 patients received Haplo-HSCT and 133 HLA-identical (HLA-id) transplantation. The institutional review board of each center approved the study. Patients and transplant characteristics were reported in Table 1. The median follow up was 30.6 months (range 0.2-74.1).

Myeloid engraftment was slower in haplo group than HLAid group (20 days vs 14 day). In the haplo group, 2 out 3 patients had graft failure because of donor specific antibodies (DSA), and 1 patient dead from pneumonia before engraftment.

In the Haplo and HLA-id group, the incidence of grade 2-4 acute GVHD was 15% vs 16% (p= 0.9) and chronic GVHD were and 18% vs 32% (p 0.06), respectively.

For the whole cohort, the 2-year PFS, OS, relapse incidence (RI), and 1y-NRM were 45%, 66%, 38%, and 14%, respectively. The PFS, OS, and RI were significantly better in patients in CR compared to those in PR (55% vs 29% p= 0.001, 74% vs 55% p= 0.03, 27% vs 55% p<0.001, respectively), whereas the 1-year NRM was similar (15% vs 16% p= 0.9). After Haplo-HSCT and HLA-id HSCT, 2-year PFS was 63% vs 37% (figure 1A, p= 0.03), the 2-year OS was 67% vs 63% (p= 0.6), and the 1-year NRM was 13% vs 15%, (p= 0.9), respectively. The 2-year RI was significantly lower in the haplo group (figure 1B, 24% vs 44%, p= 0.008). We analyzed the clinical outcome in specific sub-groups of patients, coupling disease status and donor. Patients in CR receiving haplo-HSCT showed a significantly better 2-year PFS and lower 2-year RI compared to those allografted by HLA-id donor (figure 1C75% vs 47%, p<0.001 and 11% vs 34%, p<0.001, respectively). No statistically differences were founded in terms of OS and NRM. In PR patients, we found a similar outcome between patients receiving haploidentical donor or HLAid donor. The 2-year PFS was 44% vs 22%, p<0.001; and the 2-year RI was 44% vs 60%, p<0.001 (figure 1D).

In multivariate analysis, donor type (haplo vs HLA-id HR 0.51, p<0.001) and disease status before transplantation (CR vs PR HR 0.37, p= 0.014) were independent predictors of PFS as well as they predict the risk of relapse (donor type HR 0.37, p<0.001; disease status, HR 0.43, p= 0.006). Disease status at transplantation and age (as continuous variable) were independently associated to OS (CR vs PR HR 0.57, p= 0.02; age HR 0.04, p= 0.006).

This analysis suggested that haplo-HSCT using T-cell replete stem cells and PT-Cy is more effective than HLA-id donor because of a significant reduction of relapse risk in chemosensitive RR HL patients, challenging the question of donor choice. However, prospective comparative studies are needed to draw definitive conclusions.

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