Haploidentical Transplants with Post-Transplant Cyclophosphamide for Relapsed or Refractory Hodgkin Lymphoma: The Role of Comorbidity Index and Pretransplant Positron Emission Tomography

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2501-2508
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number12
DOIs
Publication statusPublished - Dec 2018

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Hodgkin Disease
Positron-Emission Tomography
Cyclophosphamide
Comorbidity
Cell Transplantation
Confidence Intervals
Transplants
Recurrence
Graft vs Host Disease
Survival
Stem Cell Transplantation
Tumor Burden
Neutrophils
Blood Platelets
Multivariate Analysis

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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. / Marani, Carlo; Raiola, Anna Maria; Morbelli, Silvia; Dominietto, Alida; Ferrarazzo, Giulia; Avenoso, Daniele; Giannoni, Livia; Varaldo, Riccardo; Gualandi, Francesca; Grazia, Di; Lamparelli, Teresa; Bregante, Stefania; Van Lint, Maria Teresa; Ibatici, Adalberto; Bovis, Francesca; Lemoli, Roberto Massimo; Gobbi, Marco; Bacigalupo, Andrea; Angelucci, Emanuele.

In: Biology of Blood and Marrow Transplantation, Vol. 24, No. 12, 12.2018, p. 2501-2508.

Research output: Contribution to journalArticle

Marani, C, Raiola, AM, Morbelli, S, Dominietto, A, Ferrarazzo, G, Avenoso, D, Giannoni, L, Varaldo, R, Gualandi, F, Grazia, D, Lamparelli, T, Bregante, S, Van Lint, MT, Ibatici, A, Bovis, F, Lemoli, RM, Gobbi, M, Bacigalupo, A & Angelucci, E 2018, 'Haploidentical Transplants with Post-Transplant Cyclophosphamide for Relapsed or Refractory Hodgkin Lymphoma: The Role of Comorbidity Index and Pretransplant Positron Emission Tomography', Biology of Blood and Marrow Transplantation, vol. 24, no. 12, pp. 2501-2508. https://doi.org/10.1016/j.bbmt.2018.07.025
Marani, Carlo ; Raiola, Anna Maria ; Morbelli, Silvia ; Dominietto, Alida ; Ferrarazzo, Giulia ; Avenoso, Daniele ; Giannoni, Livia ; Varaldo, Riccardo ; Gualandi, Francesca ; Grazia, Di ; Lamparelli, Teresa ; Bregante, Stefania ; Van Lint, Maria Teresa ; Ibatici, Adalberto ; Bovis, Francesca ; Lemoli, Roberto Massimo ; Gobbi, Marco ; Bacigalupo, Andrea ; Angelucci, Emanuele. / Haploidentical Transplants with Post-Transplant Cyclophosphamide for Relapsed or Refractory Hodgkin Lymphoma : The Role of Comorbidity Index and Pretransplant Positron Emission Tomography. In: Biology of Blood and Marrow Transplantation. 2018 ; Vol. 24, No. 12. pp. 2501-2508.
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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.",
author = "Carlo Marani and Raiola, {Anna Maria} and Silvia Morbelli and Alida Dominietto and Giulia Ferrarazzo and Daniele Avenoso and Livia Giannoni and Riccardo Varaldo and Francesca Gualandi and Di Grazia and Teresa Lamparelli and Stefania Bregante and {Van Lint}, {Maria Teresa} and Adalberto Ibatici and Francesca Bovis and Lemoli, {Roberto Massimo} and Marco Gobbi and Andrea Bacigalupo and Emanuele Angelucci",
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TY - JOUR

T1 - Haploidentical Transplants with Post-Transplant Cyclophosphamide for Relapsed or Refractory Hodgkin Lymphoma

T2 - The Role of Comorbidity Index and Pretransplant Positron Emission Tomography

AU - Marani, Carlo

AU - Raiola, Anna Maria

AU - Morbelli, Silvia

AU - Dominietto, Alida

AU - Ferrarazzo, Giulia

AU - Avenoso, Daniele

AU - Giannoni, Livia

AU - Varaldo, Riccardo

AU - Gualandi, Francesca

AU - Grazia, Di

AU - Lamparelli, Teresa

AU - Bregante, Stefania

AU - Van Lint, Maria Teresa

AU - Ibatici, Adalberto

AU - Bovis, Francesca

AU - Lemoli, Roberto Massimo

AU - Gobbi, Marco

AU - Bacigalupo, Andrea

AU - Angelucci, Emanuele

N1 - Copyright © 2018. Published by Elsevier Inc.

PY - 2018/12

Y1 - 2018/12

N2 - 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.

AB - 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.

U2 - 10.1016/j.bbmt.2018.07.025

DO - 10.1016/j.bbmt.2018.07.025

M3 - Article

C2 - 30041010

VL - 24

SP - 2501

EP - 2508

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 12

ER -