Outcomes of Cord Blood Transplantation for Adult Patients with Hodgkin Lymphoma, a Eurocord and EBMT Lymphoma Working Party Study

Allogeneic stem cell transplantation represents an alternative for relapsed or refractory patients (pts) with Hodgkin Lymphoma (HL). In this setting, only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 133 adult pts with HL who underwent UCBT in EBMT centers. Histological subtype was nodular sclerosis in 65% of the pts. Median age at UCBT was 29 (18-65) years. Median follow-up was 37 (2-119) months and median year of UCBT was 2010 (2003-2015). Ninety pts had received a previous autologous transplantation (ASCT), while 19 had received 2 ASCT before UCBT; median time from ASCT to UCBT was 15 (2-281) months. Disease status at UCBT was complete remission (CR) in 45%, partial remission (PR) in 28% and relapse or refractory disease in 27% of the pts. Sixty percent of pts were male and 54% had a positive cytomegalovirus serology. Fifty-one percent (n=68) received a single UCBT and 49% (n=65) a double UCBT; 58% of pts received a graft with 2 or more HLA mismatch. The majority of the pts (n=104, 77%) underwent a reduced intensity conditioning regimen, the most frequent conditioning regimen (n=69) being Cyclophosphamide + Fludarabine + Total Body Irradiation (TBI) (2 Gy). Forty percent (n=46) of pts received anti-thymocyte globulin and Cyclosporine A + mycophenolate mofetil prophylaxis was given to 60% (n=80) of the pts. Median total nucleated cell (TNC) dose at cryopreservation was 3.99 (1.5-12.2) x10⁷/Kg.

The cumulative incidence (CI) of neutrophil engraftment at 60 days was 87% (81%-93%). The 100-day CI of acute grade II-IV GVHD was 26% (19%-35%). At 3 years, chronic GVHD was 30% (21%-41%). Relapse incidence (RI) and non-relapse mortality (NRM) were 40% (32%-50%) and 30% (23%-40%) at 3 years, respectively. The overall survival (OS) was 48% (39%-57%) and progression free survival (PFS) was 28% (21%-37%) at 3 years. Sixty-nine patients died: 27 of relapse and 39 of transplant related causes (infections, n=13, GVHD, n=7, idiopathic pneumonia syndrome n=6, EBV-PTLD n=2, VOD n=2 and others causes, n=9). According to disease status at UCBT, OS at 3 years was 68% (55%-79%) for pts in CR, 31% (18%-50%) for pts in PR and 26% (14%-44%) for pts in relapsed or refractory disease.

In multivariate analysis, adjusted for median year of UCBT, Cyclophosphamide + Fludarabine + low dose TBI conditioning regimen, disease status at UCBT, conditioning intensity and type of UCBT, none of these factors were found to be associated with acute or chronic GVHD. 3-year RI and NRM were higher for pts in relapse or refractory disease at UCBT compared to pts in CR (HR=2.62, 95%CI 1.12-6.11, p=0.03 and HR=3.66, 95%CI 1.52-8.80, p=0.004, respectively). The use of Cyclophosphamide + Fludarabine + low dose TBI conditioning regimen was associated with a lower risk of NRM (HR=0.38, 95%CI 0.15-0.95, p=0.04) and also with a better OS (HR=0.37, 95%CI 0.18-0.76, p=0.006). OS was significantly worse for pts who underwent UCBT in PR (HR=1.97, 95%CI 1.02-3.80, p=0.04) and for those in relapse or refractory disease at transplant (HR=2.86, 95%CI 1.41-5.81, p=0.004). Pts transplanted in relapse or refractory disease have also a lower PFS (HR=3.12, 95%CI 1.71-5.71, p<0.001).

In conclusion, UCBT is feasible in heavily pretreated pts with HL, if there are no other alternative donors. Conditioning with Cyclophosphamide + Fludarabine + low dose TBI is associated with a better OS and NRM. However, outcomes are poor for patients not in CR at the time of UCBT and one might consider the use of new therapeutic agents earlier before UCBT in this setting.