Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation.

By J. Henter, AnnaCarin Samuelsson-Horne, M. Aricò, R. Egeler, G. Elinder, A. Filipovich, H. Gadner, S. Imashuku, D. Komp, S. Ladisch and 2 more. Blood, 2002

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Hemophagocytic lymphohistiocytosis (HLH) comprises familial (primary) hemophagocytic lymphohistiocytosis (FHL) and secondary HLH (SHLH), both clinically characterized by fever, hepatosplenomegaly, and cytopenia. FHL, an autosomal recessive disease invariably fatal when untreated, is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages. In 1994 the Histiocyte Society initiated a prospective international collaborative therapeutic study (HLH-94), aiming at improved survival. It combined chemotherapy and immunotherapy (etoposide, corticosteroids, cyclosporin A, and, in selected patients, intrathecal methotrexate), followed by bone marrow transplantation (BMT) in persistent, recurring, and/or familial disease. Between July 1, 1994, and June 30, 1998, 113 eligible patients aged no more than 15 years from 21 countries started HLH-94. All had either an affected sibling (n = 25) and/or fulfilled the Histiocyte Society diagnostic criteria. At a median follow-up of 3.1 years, the estimated 3-year probability of survival overall was 55% (95% confidence interval +/- 9%), and in the familial cases, 51% (+/- 20%). Twenty enrolled children were alive and off therapy for more than 12 months without BMT. For patients who received transplants (n = 65), died prior to BMT (n = 25), or were still on therapy (n = 3), the 3-year survival was 45% (+/- 10%). The 3-year probability of survival after BMT was 62% (+/- 12%). HLH-94 is very effective, allowing BMT in most patients. Survival of children with HLH has been greatly improved.

Subfields: Hematology, Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/680ba1272eea7d8e2a504a6180f53c040318f5ae

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C. Allen
Helena Trottestam
Xiaoying Yu
D. Webb
R. M. Egeler
J. Winiarski
C. Kozinetz
S. Imashuku

Citations in the corpus

Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. (2011, background): “Patient characteristics in history, clinical findings, and laboratory parameters before start of therapy in all patients, as well as in 4 different subgroups: (1) patients with an affected sibling; (2) patients who died within the first 8 weeks of therapy; (3) patients who underwent HSCT; and (4) pa”
Familial and acquired hemophagocytic lymphohistiocytosis (2006, background): “Of the 35 patients with CNS symptoms at diagnosis, an equal percentage had normalization of symptoms with or without intrathecal therapy [43].”
How I treat hemophagocytic lymphohistiocytosis. (2011, neutral): “PRF1 20 (27) 41 (71) 44 (98) 8 (36) 22 (88)”
HLH‐2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis (2007, methodology): “It proposes including etoposide, in addition to busulfan and cyclophosphamide, in the conditioning regimen, in accordance with previous experiences [48,53].”
Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis (2008, background): “Patients treated on the lastopenHistiocyteSocietyprotocol (HLH-94)hadanestimated3-year survival of 55% (þ/ 9%) [3].”