Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders.

Busulfan / therapeutic use Cyclophosphamide / therapeutic use Graft vs Host Disease / etiology Hematopoietic Stem Cell Transplantation / adverse effects Humans Lymphohistiocytosis, Hemophagocytic / therapy Melphalan / therapeutic use Thiotepa Transplantation Conditioning / adverse effects Vidarabine / therapeutic use
BMT HCT HLH HSCT Hemophagocytic lymphohistiocytosis allogeneic hematopoietic cell transplantation bone marrow transplantation hematopoietic stem cell transplantation

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
03 2022
Historique:
received: 11 02 2021
revised: 29 07 2021
accepted: 30 07 2021
pubmed: 11 8 2021
medline: 26 4 2022
entrez: 10 8 2021
Statut: ppublish

Résumé

Allogeneic hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis (HLH) disorders is associated with substantial morbidity and mortality. The effect of conditioning regimen groups of varying intensity on outcomes after transplantation was examined to identify an optimal regimen or regimens for HLH disorders. We studied 261 patients with HLH disorders transplanted between 2005 and 2018. Risk factors for transplantation outcomes by conditioning regimen groups were studied by Cox regression models. Four regimen groups were studied: (1) fludarabine (Flu) and melphalan (Mel) in 123 subjects; (2) Flu, Mel, and thiotepa (TT) in 28 subjects; (3) Flu and busulfan (Bu) in 14 subjects; and (4) Bu and cyclophosphamide (Cy) in 96 subjects. The day 100 incidence of veno-occlusive disease was lower with Flu/Mel (4%) and Flu/Mel/TT (0%) compared to Flu/Bu (14%) and Bu/Cy (22%) (P < .001). The 6-month incidence of viral infections was highest after Flu/Mel (72%) and Flu/Mel/TT (64%) compared to Flu/Bu (39%) and Bu/Cy (38%) (P < .001). Five-year event-free survival (alive and engrafted without additional cell product administration) was lower with Flu/Mel (44%) compared to Flu/Mel/TT (70%), Flu/Bu (79%), and Bu/Cy (61%) (P = .002). The corresponding 5-year overall survival values were 68%, 75%, 86%, and 64%, and did not differ by conditioning regimen (P = .19). Low event-free survival with Flu/Mel is attributed to high graft failure (42%) compared to Flu/Mel/TT (15%), Flu/Bu (7%), and Bu/Cy (18%) (P < .001). Given the high rate of graft failure with Flu/Mel and the high rate of veno-occlusive disease with Bu/Cy and Flu/Bu, Flu/Mel/TT may be preferred for HLH disorders. Prospective studies are warranted.

Sections du résumé

BACKGROUND
Allogeneic hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis (HLH) disorders is associated with substantial morbidity and mortality.
OBJECTIVE
The effect of conditioning regimen groups of varying intensity on outcomes after transplantation was examined to identify an optimal regimen or regimens for HLH disorders.
METHODS
We studied 261 patients with HLH disorders transplanted between 2005 and 2018. Risk factors for transplantation outcomes by conditioning regimen groups were studied by Cox regression models.
RESULTS
Four regimen groups were studied: (1) fludarabine (Flu) and melphalan (Mel) in 123 subjects; (2) Flu, Mel, and thiotepa (TT) in 28 subjects; (3) Flu and busulfan (Bu) in 14 subjects; and (4) Bu and cyclophosphamide (Cy) in 96 subjects. The day 100 incidence of veno-occlusive disease was lower with Flu/Mel (4%) and Flu/Mel/TT (0%) compared to Flu/Bu (14%) and Bu/Cy (22%) (P < .001). The 6-month incidence of viral infections was highest after Flu/Mel (72%) and Flu/Mel/TT (64%) compared to Flu/Bu (39%) and Bu/Cy (38%) (P < .001). Five-year event-free survival (alive and engrafted without additional cell product administration) was lower with Flu/Mel (44%) compared to Flu/Mel/TT (70%), Flu/Bu (79%), and Bu/Cy (61%) (P = .002). The corresponding 5-year overall survival values were 68%, 75%, 86%, and 64%, and did not differ by conditioning regimen (P = .19). Low event-free survival with Flu/Mel is attributed to high graft failure (42%) compared to Flu/Mel/TT (15%), Flu/Bu (7%), and Bu/Cy (18%) (P < .001).
CONCLUSIONS
Given the high rate of graft failure with Flu/Mel and the high rate of veno-occlusive disease with Bu/Cy and Flu/Bu, Flu/Mel/TT may be preferred for HLH disorders. Prospective studies are warranted.

Identifiants

DOI: 10.1016/j.jaci.2021.07.031 PMID: 34375618 PMC: PMC8821728
pubmed: 34375618
pii: S0091-6749(21)01205-7
doi: 10.1016/j.jaci.2021.07.031
pmc: PMC8821728
mid: NIHMS1731505
pii:
doi:

Substances chimiques

Cyclophosphamide 8N3DW7272P
Thiotepa 905Z5W3GKH
Vidarabine FA2DM6879K
Busulfan G1LN9045DK
Melphalan Q41OR9510P

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1097-1104.e2

Subventions

Organisme : NCI NIH HHS
ID : U24 CA076518
Pays : United States

Informations de copyright

Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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Auteurs

Rebecca A Marsh (RA)

University of Cincinnati and Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Rebecca.marsh@cchmc.org.

Kyle Hebert (K)

Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisc.

Soyoung Kim (S)

Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisc.

Christopher C Dvorak (CC)

Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, Calif.

Victor M Aquino (VM)

UT Southwestern Medical Center, Dallas, Tex.

K Scott Baker (KS)

Fred Hutchinson Cancer Research Center, Seattle, Wash.

Deepak Chellapandian (D)

Center for Cell and Gene Therapy for Non-Malignant Conditions, Johns Hopkins All Children's Hospital, St Petersburg, Fla.

Blachy Dávila Saldaña (B)

Division of Bone Marrow Transplant, Children's National Hospital, Washington, DC.

Christine N Duncan (CN)

Dana-Farber Cancer Institute, Boston, Mass.

Michael J Eckrich (MJ)

Sarah Cannon Pediatric Transplant and Cellular Therapy Program, Methodist Children's Hospital, San Antonio, Tex.

George E Georges (GE)

Fred Hutchinson Cancer Research Center, Seattle, Wash.

Timothy S Olson (TS)

Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pa.

Michael A Pulsipher (MA)

Children's Hospital Los Angeles, Los Angeles, Calif.

Shalini Shenoy (S)

Department of Pediatrics, Washington University School of Medicine, St Louis, Mo.

Elizabeth Stenger (E)

Children's Hospital of Pittsburgh, Pittsburgh, Pa.

Mark Vander Lugt (MV)

The University of Michigan, Ann Arbor, Mich.

Lolie C Yu (LC)

Children's Hospital, New Orleans, La.

Andrew R Gennery (AR)

Newcastle University, Newcastle Upon Tyne, United Kingdom.

Mary Eapen (M)

Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisc.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Composés du soufre › Acides du soufre › Acides sulfoniques › Acides alcanesulfoniques › Alcanesulfonates › Méthanesulfonates › Busulfan › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Composés chimiques organiques › Composés organiques du phosphore › Phosphoramides › Moutardes phosphoramide › Cyclophosphamide › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Maladies du système immunitaire › Maladie du greffon contre l'hôte › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches hématopoïétiques › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Maladies lymphatiques › Histiocytose › Histiocytose non langerhansienne › Lymphohistiocytose hémophagocytaire › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés cycliques › Acides aminés aromatiques › Melphalan › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azirines › Aziridines › 1,1',1''-Phosphoryltriaziridine › Thiotépa › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunosuppression thérapeutique › Conditionnement pour greffe › Comparison of hematopoietic cell transplant...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Nucléoside purique › Vidarabine › Comparison of hematopoietic cell transplant...