Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy

Chiara Messina, Marco Zecca, Franca Fagioli, Attilio Rovelli, Stefano Giardino, Pietro Merli, Fulvio Porta, Maurizio Aricò, Elena Sieni, Giuseppe Basso, Mimmo Ripaldi, Claudio Favre, Marta Pillon, Antonio Marzollo, Marco Rabusin, Simone Cesaro, Mattia Algeri, Maurizio Caniglia, Paolo Di Bartolomeo, Ottavio ZiinoFrancesco Saglio, Arcangelo Prete, Franco Locatelli

Research output: Contribution to journalArticle

Abstract

We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34+ cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft.

Original languageEnglish
Pages (from-to)1223-1231
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number6
DOIs
Publication statusPublished - Jun 2018

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Hemophagocytic Lymphohistiocytosis
Hematopoietic Stem Cell Transplantation
Italy
Tissue Donors
Transplants
treosulfan
Disease-Free Survival
Transplantation
Recurrence
Busulfan
Unrelated Donors
Survival
Graft Rejection
Hematology
Allografts
Siblings
Pediatrics

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Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy. / Messina, Chiara; Zecca, Marco; Fagioli, Franca; Rovelli, Attilio; Giardino, Stefano; Merli, Pietro; Porta, Fulvio; Aricò, Maurizio; Sieni, Elena; Basso, Giuseppe; Ripaldi, Mimmo; Favre, Claudio; Pillon, Marta; Marzollo, Antonio; Rabusin, Marco; Cesaro, Simone; Algeri, Mattia; Caniglia, Maurizio; Di Bartolomeo, Paolo; Ziino, Ottavio; Saglio, Francesco; Prete, Arcangelo; Locatelli, Franco.

In: Biology of Blood and Marrow Transplantation, Vol. 24, No. 6, 06.2018, p. 1223-1231.

Research output: Contribution to journalArticle

Messina, C, Zecca, M, Fagioli, F, Rovelli, A, Giardino, S, Merli, P, Porta, F, Aricò, M, Sieni, E, Basso, G, Ripaldi, M, Favre, C, Pillon, M, Marzollo, A, Rabusin, M, Cesaro, S, Algeri, M, Caniglia, M, Di Bartolomeo, P, Ziino, O, Saglio, F, Prete, A & Locatelli, F 2018, 'Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy', Biology of Blood and Marrow Transplantation, vol. 24, no. 6, pp. 1223-1231. https://doi.org/10.1016/j.bbmt.2018.01.022
Messina, Chiara ; Zecca, Marco ; Fagioli, Franca ; Rovelli, Attilio ; Giardino, Stefano ; Merli, Pietro ; Porta, Fulvio ; Aricò, Maurizio ; Sieni, Elena ; Basso, Giuseppe ; Ripaldi, Mimmo ; Favre, Claudio ; Pillon, Marta ; Marzollo, Antonio ; Rabusin, Marco ; Cesaro, Simone ; Algeri, Mattia ; Caniglia, Maurizio ; Di Bartolomeo, Paolo ; Ziino, Ottavio ; Saglio, Francesco ; Prete, Arcangelo ; Locatelli, Franco. / Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy. In: Biology of Blood and Marrow Transplantation. 2018 ; Vol. 24, No. 6. pp. 1223-1231.
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T1 - Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy

AU - Messina, Chiara

AU - Zecca, Marco

AU - Fagioli, Franca

AU - Rovelli, Attilio

AU - Giardino, Stefano

AU - Merli, Pietro

AU - Porta, Fulvio

AU - Aricò, Maurizio

AU - Sieni, Elena

AU - Basso, Giuseppe

AU - Ripaldi, Mimmo

AU - Favre, Claudio

AU - Pillon, Marta

AU - Marzollo, Antonio

AU - Rabusin, Marco

AU - Cesaro, Simone

AU - Algeri, Mattia

AU - Caniglia, Maurizio

AU - Di Bartolomeo, Paolo

AU - Ziino, Ottavio

AU - Saglio, Francesco

AU - Prete, Arcangelo

AU - Locatelli, Franco

N1 - Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

PY - 2018/6

Y1 - 2018/6

N2 - We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34+ cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft.

AB - We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34+ cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft.

U2 - 10.1016/j.bbmt.2018.01.022

DO - 10.1016/j.bbmt.2018.01.022

M3 - Article

C2 - 29410181

VL - 24

SP - 1223

EP - 1231

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

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