Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders

Rebecca A. Marsh; Kyle Hebert; Soyoung Kim; Christopher C. Dvorak; Victor M. Aquino; K. Scott Baker; Deepak Chellapandian; Blachy Dávila Saldaña; Christine N. Duncan; Michael J. Eckrich; George E. Georges; Timothy S. Olson; Michael A. Pulsipher; Shalini Shenoy; Elizabeth Stenger; Mark Vander Lugt; Lolie C. Yu; Andrew R. Gennery; Mary Eapen

doi:10.1016/j.jaci.2021.07.031

Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders

Rebecca A. Marsh^*, Kyle Hebert, Soyoung Kim, Christopher C. Dvorak, Victor M. Aquino, K. Scott Baker, Deepak Chellapandian, Blachy Dávila Saldaña, Christine N. Duncan, Michael J. Eckrich, George E. Georges, Timothy S. Olson, Michael A. Pulsipher, Shalini Shenoy, Elizabeth Stenger, Mark Vander Lugt, Lolie C. Yu, Andrew R. Gennery, Mary Eapen

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1097-1104.e2
Journal	Journal of Allergy and Clinical Immunology
Volume	149
Issue number	3
DOIs	https://doi.org/10.1016/j.jaci.2021.07.031
State	Published - Mar 2022

Funding

The CIBMTR is supported primarily by Public Health Service grant agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID), and contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS). The views expressed in this article do not reflect the official policy or position of the National Institute of Health, Health Resources and Services Administration, or any other agency of the US government. The CIBMTR is supported primarily by Public Health Service grant agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID), and contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS). The views expressed in this article do not reflect the official policy or position of the National Institute of Health, Health Resources and Services Administration, or any other agency of the US government.

Keywords

BMT
HCT
HLH
HSCT
Hemophagocytic lymphohistiocytosis
allogeneic hematopoietic cell transplantation
bone marrow transplantation
hematopoietic stem cell transplantation

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.jaci.2021.07.031

Cite this

Marsh, R. A., Hebert, K., Kim, S., Dvorak, C. C., Aquino, V. M., Baker, K. S., Chellapandian, D., Dávila Saldaña, B., Duncan, C. N., Eckrich, M. J., Georges, G. E., Olson, T. S., Pulsipher, M. A., Shenoy, S., Stenger, E., Lugt, M. V., Yu, L. C., Gennery, A. R., & Eapen, M. (2022). Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders. Journal of Allergy and Clinical Immunology, 149(3), 1097-1104.e2. https://doi.org/10.1016/j.jaci.2021.07.031

@article{a0ffab6ab06740aab1e2e87de3ad63a2,

title = "Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders",

abstract = "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.",

keywords = "BMT, HCT, HLH, HSCT, Hemophagocytic lymphohistiocytosis, allogeneic hematopoietic cell transplantation, bone marrow transplantation, hematopoietic stem cell transplantation",

author = "Marsh, {Rebecca A.} and Kyle Hebert and Soyoung Kim and Dvorak, {Christopher C.} and Aquino, {Victor M.} and Baker, {K. Scott} and Deepak Chellapandian and {D{\'a}vila Salda{\~n}a}, Blachy and Duncan, {Christine N.} and Eckrich, {Michael J.} and Georges, {George E.} and Olson, {Timothy S.} and Pulsipher, {Michael A.} and Shalini Shenoy and Elizabeth Stenger and Lugt, {Mark Vander} and Yu, {Lolie C.} and Gennery, {Andrew R.} and Mary Eapen",

note = "Publisher Copyright: {\textcopyright} 2021 American Academy of Allergy, Asthma & Immunology",

year = "2022",

month = mar,

doi = "10.1016/j.jaci.2021.07.031",

language = "English (US)",

volume = "149",

pages = "1097--1104.e2",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "3",

}

Marsh, RA, Hebert, K, Kim, S, Dvorak, CC, Aquino, VM, Baker, KS, Chellapandian, D, Dávila Saldaña, B, Duncan, CN, Eckrich, MJ, Georges, GE, Olson, TS, Pulsipher, MA, Shenoy, S, Stenger, E, Lugt, MV, Yu, LC, Gennery, AR & Eapen, M 2022, 'Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders', Journal of Allergy and Clinical Immunology, vol. 149, no. 3, pp. 1097-1104.e2. https://doi.org/10.1016/j.jaci.2021.07.031

TY - JOUR

T1 - Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders

AU - Marsh, Rebecca A.

AU - Hebert, Kyle

AU - Kim, Soyoung

AU - Dvorak, Christopher C.

AU - Aquino, Victor M.

AU - Baker, K. Scott

AU - Chellapandian, Deepak

AU - Dávila Saldaña, Blachy

AU - Duncan, Christine N.

AU - Eckrich, Michael J.

AU - Georges, George E.

AU - Olson, Timothy S.

AU - Pulsipher, Michael A.

AU - Shenoy, Shalini

AU - Stenger, Elizabeth

AU - Lugt, Mark Vander

AU - Yu, Lolie C.

AU - Gennery, Andrew R.

AU - Eapen, Mary

PY - 2022/3

Y1 - 2022/3

N2 - 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.

AB - 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.

KW - BMT

KW - HCT

KW - HLH

KW - HSCT

KW - Hemophagocytic lymphohistiocytosis

KW - allogeneic hematopoietic cell transplantation

KW - bone marrow transplantation

KW - hematopoietic stem cell transplantation

UR - http://www.scopus.com/inward/record.url?scp=85114615522&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85114615522&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2021.07.031

DO - 10.1016/j.jaci.2021.07.031

M3 - Article

C2 - 34375618

AN - SCOPUS:85114615522

SN - 0091-6749

VL - 149

SP - 1097-1104.e2

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -

Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this