Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab

Marsh, Rebecca A.; Allen, Carl E.; McClain, Kenneth L.; Weinstein, Joanna L.; Kanter, Julie; Skiles, Jodi; Lee, Nadine D.; Khan, Shakila P.; Lawrence, Julia; Mo, Jun Q.; Bleesing, Jack J.; Filipovich, Alexandra H.; Jordan, Michael B.

doi:10.1002/pbc.24188

Cited by 310Autoimmune and Inflammatory Disorders ResearchKawasaki Disease and Coronary ComplicationsImmunodeficiency and Autoimmune Disorders

Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab

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Marsh, Rebecca A., Allen, Carl E., McClain, Kenneth L., Weinstein, Joanna L., Kanter, Julie, Skiles, Jodi, Lee, Nadine D., Khan, Shakila P. +5 more·2013·Pediatric Blood & Cancer

DOI 10.1002/pbc.24188PMC PMC3410971

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Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome that remains difficult to treat. Even with current standard HLH therapy, only approximately half of patients will experience complete resolution of disease, and early mortality remains a significant problem. Salvage therapies have been described only in limited case reports, and there are no large studies of second‐line therapies. Procedure: We reviewed the charts of 22 pediatric and adult patients who received alemtuzumab for the treatment of refractory HLH at our center or in consultation with our group. Results: Patients had received conventional therapies for a median of 8 weeks (range: 2–70) prior to alemtuzumab, and treatment immediately prior to alemtuzumab included dexamethasone (100%), etoposide (77%), cyclosporine (36%), intrathecal hydrocortisone ± methotrexate (23%), methylprednisolone (9%), and rituximab (14%). Patients received a median dose of 1 mg/kg alemtuzumab (range: 0.1–8.9 mg/kg) divided over a median of 4 days (range: 2–10). Fourteen patients experienced an overall partial response, defined as at least a 25% improvement in two or more quantifiable symptoms or laboratory markers of HLH 2 weeks following alemtuzumab (64%). Five additional patients had a 25% or greater improvement in a single quantifiable symptom or laboratory marker of HLH (23%). Seventy‐seven percent of patients survived to undergo allogeneic hematopoietic cell transplantation. Patients experienced an acceptable spectrum of complications, including CMV and adenovirus viremia. Conclusion: Alemtuzumab appears to be an effective salvage agent for refractory HLH, leading to improvement and survival to HCT in many patients. Prospective trials to define optimal dosing levels, schedules, and responses are needed. Pediatr Blood Cancer 2013; 60: 101–109. © 2012 Wiley Periodicals, Inc.

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Generalized T-cell and B-cell ablation with alemtuzumab and T-cell ablation with antithymocyte globulin have been reported, and ablation most likely works by depleting pathogenic CD8+ T cells among other cell types.
“Generalized T-cell and B-cell ablation with alemtuzumab and T-cell ablation with antithymocyte globulin have been reported; ablation most likely works by depleting the pathogenic CD8+ T cells, among other cell types.76”
From Cytokine storm (2020) · cites this paper as [76]

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Alemtuzumab Is an Effective Salvage Agent for Refractory Hemophagocytic Lymphohistiocytosis
Marsh, R. A., Filipovich, A. H., Allen, C. E., McClain, K. L., Weinstein, J. L., Kanter-Washko, J., Skiles, J. L., Lee, N. D., Khan, S. P., Lawrence, J., et al. (2012) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2011.12.262
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Reduced Cumulative Dosing of Alemtuzumab in Patients with Hemophagocytic Lymphohistiocytosis (HLH) Is Associated with Improved Long Term Survival
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Alemtuzumab as First Line Treatment in Children with Familial Lymphohistiocytosis
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Authors: Marsh, R. A., Allen, C. E., McClain, K. L., Weinstein, J. L., Kanter, J., Skiles, J., Lee, N. D., Khan, S. P., Lawrence, J., Mo, J. Q., Bleesing, J. J., Filipovich, A. H., & Jordan, M. B.
Affiliations: Cincinnati Children's Hospital Medical Center (US)
Baylor College of Medicine (US)
Northwestern University (US)
Tulane Medical Center (US)
Riley Hospital for Children (US)
Mayo Clinic (US)
Corresponding author: Marsh, Rebecca A.
Jordan, Michael B.
ORCID: Marsh, Rebecca A.
Allen, Carl E.
McClain, Kenneth L.
Weinstein, Joanna L.
Kanter, Julie
Skiles, Jodi
Khan, Shakila P.
Mo, Jun Q.
Bleesing, Jack J.
Jordan, Michael B.
Venue: Pediatric Blood & Cancer
Publisher: Wiley
Published: 2012-04-22
Volume: 60
Issue: 1
Pages: 101-109
ISSN: 1545-5009 (ISSN-L)
1545-5017
DOI: 10.1002/pbc.24188
PMC: PMC3410971
OpenAlex: W2064037171
Cited by: 310
References: 21
Citations by year: 2026: 18 · 2025: 12 · 2024: 26 · 2023: 28 · 2022: 24 · 2021: 22 · 2020: 39 · 2019: 24 · 2018: 22 · 2017: 31 · 2016: 21 · 2015: 14 · 2014: 17 · 2013: 9 · 2012: 1
FWCI: 8.74
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Pediatric Blood & Cancer (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (R01HL091769)
Clinical Immunology Society
Topics: Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Health Sciences › Medicine › Surgery › Kawasaki Disease and Coronary Complications
Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Keywords: hemophagocytic lymphohistiocytosis, alemtuzumab, salvage therapy, refractory disease, hyperinflammatory syndrome, allogeneic hematopoietic stem cell transplantation, cytomegalovirus viremia, treatment response
MeSH terms: Alemtuzumab, Alanine Transaminase, Humans, Retrospective Studies, Salvage Therapy, Lymphohistiocytosis, Hemophagocytic, Antibodies, Monoclonal, Humanized

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Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab

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