Outcomes of Advanced Hodgkin Lymphoma after Umbilical Cord Blood Transplantation: A Eurocord and EBMT Lymphoma and Cellular Therapy & Immunobiology Working Party Study

Abstract

Allogeneic stem cell transplantation is an alternative for patients with relapsed or refractory Hodgkin lymphoma (HL), but only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 131 adults with HL who underwent UCBT in European Society for Blood and Marrow Transplantation centers from 2003 to 2015. Disease status at UCBT was complete remission (CR) in 59 patients (47%), and almost all patients had received a previous autologous stem cell transplantation. The 4-year progression-free survival (PFS) and overall survival (OS) were 26% (95% confidence interval [CI], 19% to 34%) and 46% (95% CI, 37% to 55%), respectively. Relapse incidence was 44% (95% CI, 36% to 54%), and nonrelapse mortality (NRM) was 31% (95% CI, 23% to 40%) at 4 years. In multivariate analysis refractory/relapsed disease status at UCBT was associated with increased relapse incidence (hazard ratio [HR], 3.14 [95% CI, 1.41 to 7.00], P = .005) and NRM (HR, 3.61 [95% CI, 1.58 to 8.27], P = .002) and lower PFS (HR, 3.45 [95% CI, 1.95 to 6.10], P < .001) and OS (HR, 3.10 [95% CI, 1.60 to 5.99], P = .001). Conditioning regimen with cyclophosphamide + fludarabine + 2 Gy total body irradiation (Cy+Flu+2GyTBI) was associated with decreased risk of NRM (HR, .26 [95% CI, .10 to .64], P = .004). Moreover, Cy+Flu+2GyTBI conditioning regimen was associated with a better OS (HR, .25 [95% CI, .12 to .50], P < .001) and PFS (HR, .51 [95% CI, .27 to .96], P = .04). UCBT is feasible in heavily pretreated patients with HL. The reduced-intensity conditioning regimen with Cy+Flu+2GyTBI is associated with a better OS and NRM. However, outcomes are poor in patients not in CR at UCBT.

Nonmyeloablative Alternative Donor Transplantation for Hodgkin and Non-Hodgkin Lymphoma: From the LWP-EBMT, Eurocord, and CIBMTR

“…The recorded high incidence of transplantation-related mortality after UCB transplantation is consistent with other reports. [3][4][5]10 Several factors may have contributed to the higher transplantation-related mortality, including higher grade 3-4 acute and chronic GVHD, higher incidence of bacterial and viral infections, 21 and HLA disparity. 22 Most UCB transplantations were mismatched at 2 HLA loci considering lower resolution HLA match and, therefore, likely to be mismatched at $ 3 HLA loci considering allelelevel match.…”

“…Both donor sources are readily available, tolerance has been demonstrated for donorrecipient HLA disparity, and reports suggest comparable outcomes between the 2 donor types for hematologic malignancy. [2][3][4][5][6][7][8][9][10][11] Donor selection (UCB or haploidentical relative) is often based on transplantation center experience, donor availability, and the cost associated with transplantation, although there are no comparative economic analyses to date. However, several reports included heterogenous conditioning regimens and graft-versus-host disease (GVHD) prophylaxis.…”

Reappraising the Role of Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed and Refractory Hodgkin’s Lymphoma: Recent Advances and Outcomes

“…The 4-year relapse rate, NRM, PFS and OS were 44%, 31%, 26%, and 46%, respectively. Having residual disease at the time of transplant was associated with worse outcomes, while receiving RIC regimen of cyclophosphamide, fludarabine, and low dose total body irradiation was associated with better PFS and OS in multivariate analysis [45].…”

Filling the Gap: The Immune Therapeutic Armamentarium for Relapsed/Refractory Hodgkin Lymphoma

“…The retained hypothesis is that the long half-life of nivolumab and pembrolizumab in the plasma would induce a persistent T cell activation of donor-derived immune cells increasing the risk of severe acute and chronic GvHD, immune-mediated pneumonia and other organ-related immune alterations in the recipient. Some translational data have attempted to explain the pathophysiology of these complications and biological analyses of a multicenter retrospective study conducted on 39 patients who received PD-1 blockade before allo-HCT have shown a significant reduction in PD-1 T cells and decreased Tregs as compared with the historical cohort of patients who did not receive checkpoint inhibitors [ 138 ]. An interesting study conducted by the Spanish group from the University of Barcelona, showed that nivolumab may persist in the blood until 56 days after transplant and that while patients receiving only calcineurin inhibitors had an increased incidence of severe acute GvHD and a more effector T cell profile, patients undergoing PT-Cy had a similar risk of GVHD and similar T cell profile to those without previous nivolumab exposure [ 139 ].…”