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Haploidentical Transplants with Post-Transplant Cyclophosphamide for Relapsed or Refractory Hodgkin Lymphoma: The Role of Comorbidity Index and Pretransplant Positron Emission Tomography
Authors:Carlo Marani  Anna Maria Raiola  Silvia Morbelli  Alida Dominietto  Giulia Ferrarazzo  Daniele Avenoso  Livia Giannoni  Riccardo Varaldo  Francesca Gualandi  Di Grazia  Teresa Lamparelli  Stefania Bregante  Maria Teresa Van Lint  Adalberto Ibatici  Francesca Bovis  Roberto Massimo Lemoli  Marco Gobbi  Andrea Bacigalupo  Emanuele Angelucci
Affiliation:1. Division of Haematology and Bone Marrow Transplantation, Policlinico San Martino, IRCCS Ospedale Policlinico San Martino, Genoa, Italy per l''Oncologia, Genoa, Italy;2. Haematology Clinic, Department of Internal Medicine, University of Genoa, Policlinico San Martino, IRCCS Ospedale Policlinico San Martino, Genoa, Italy per l''Oncologia, Genoa, Italy;3. Nuclear Medicine Unit, Department of Health Sciences, Policlinico San Martino, IRCCS Ospedale Policlinico San Martino, Genoa, Italy per l''Oncologia, Genoa, Italy;4. Biostatistics Unit, Department of Health Sciences, University of Genoa, Italy;5. Haematology Institute, Policlinico Universitario A Gemelli, Cattolica University, Rome, Italy
Abstract:Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P?=?.03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P = .01; HR, 3.3; 95% CI, 1.2 to 9.0; P?=?.02; and HR, 4.2; 95% CI, 1.7 to 9.9; P?=?.001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P?=?.005, HR, 3.8; 95% CI, 1.5 to 9.7; P?=?.005; and 3.2; 95% CI, 1.3 to 7.9; P?=?.01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS.
Keywords:Hodgkin lymphoma  Allogeneic transplant  Hematopoietic cell transplantation  Post-transplant cyclophosphamide  Positron emission tomography
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