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Experience With Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome at a Single Institution

Gupta, Abha A. MD, MSc, FRCP(C)*; Tyrrell, Pascal MSc; Valani, Rahim MD; Benseler, Susanne MD; Abdelhaleem, Mohamed MD, PhD, FRCP(C)§; Weitzman, Sheila MB, BCh, FRCP(C)*

Journal of Pediatric Hematology/Oncology: February 2009 - Volume 31 - Issue 2 - p 81-84
doi: 10.1097/MPH.0b013e3181923cb4
Original Articles

Background Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) is a serious and potentially life threatening histiocytic disorder in children and adults. The most commonly used protocol-based therapy includes corticosteroids, cyclosporine-A, and etoposide. However, patients are often started on corticosteroid alone with or without the addition of intravenous γ-globulin. The role of the various therapies in HLH/MAS remains undefined.

Objective To identify patient-related factors that led to the use of full protocol therapy (HLH 1994/2004) and to determine treatment-related factors that were associated with adverse outcome including relapse and death.

Design/Methods Patients who were diagnosed with HLH/MAS between January 1998 and December 2005 were included in this study.

Results Thirty-eight patients had a median age of 9.1 years at diagnosis. Underlying diagnoses were: viral/other 42%; rheumatologic 37%; and malignancy 21%. Initial treatment included corticosteroids 29%; intravenous immunoglobulin (IVIG) 18%; steroids+IVIG 8%; cyclosporine 5%; etoposide 5%; HLH protocol 32%. Etoposide was eventually used in 21% (3/14) of rheumatology and 75% (18/25) viral/other patients. In all, 5/14 (36%) rheumatology and 12/16 (75%) viral/other patients required intensive care unit admission, and 1/14 (7.1%) rheumatology, and 6/16 (38%) viral/other patients died. Three children received a bone marrow transplant. Eleven of 38 (29%) patients died, despite 8 having received etoposide therapy. Three deaths were secondary to underlying malignancy and one from transplant-related complication for malignancy.

Conclusions Patients with HLH are at high risk for death early in their disease course. However, corticosteroids and/or IVIG may be sufficient as first-line therapy for patients with underlying rheumatologic disease who present with HLH/MAS. Further prospective studies are required to more precisely define early risk factors for poor outcomes in this often fatal disease.

*Division of Hematology/Oncology

Division of Rheumatology

Department of Emergency Medicine

§Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada

Reprints: Abha A. Gupta, MD, MSc, FRCP(C), Division of Hematology/Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1×8 (e-mail:

Received for publication October 26, 2007; accepted October 15, 2008

© 2009 Lippincott Williams & Wilkins, Inc.