Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol

• Published in: Blood Vol. 118; no. 17; pp. 4577 - 4584
• Main Authors: Trottestam, Helena, Horne, AnnaCarin, Aricò, Maurizio, Egeler, R. Maarten, Filipovich, Alexandra H., Gadner, Helmut, Imashuku, Shinsaku, Ladisch, Stephan, Webb, David, Janka, Gritta, Henter, Jan-Inge
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 27.10.2011; Americain Society of Hematology; American Society of Hematology
• Subjects: Adolescent; Biological and medical sciences; Child; Child, Preschool; Clinical Protocols; Clinical Trials and Observations; Combined Modality Therapy; Cytotoxins - administration & dosage; Cytotoxins - adverse effects; Drug Combinations; Female; Follow-Up Studies; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunotherapy - adverse effects; Immunotherapy - methods; Infant; Infant, Newborn; Lymphohistiocytosis, Hemophagocytic - diagnosis; Lymphohistiocytosis, Hemophagocytic - drug therapy; Lymphohistiocytosis, Hemophagocytic - mortality; Lymphohistiocytosis, Hemophagocytic - therapy; Lymphoid Neoplasia; Maintenance Chemotherapy; Male; Medical sciences; Medicin och hälsovetenskap; Phagocytes, Granulocytes, and Myelopoiesis; Survival Analysis; Time Factors; Immunopathology; Hemophagocytic lymphohistiocytosis; Treatment; Hematology; Long term
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2011-06-356261

Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis. We report the final results of HLH-94, the largest prospective diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients with familial, persistent, or recurrent disease. Altogether, 249 patients fulfilled inclusion criteria and started HLH-94 therapy (July 1994-December 2003); 227 (91%) were followed-up for ≥ 5 years. At 6.2 years median follow-up, estimated 5-year probability of survival was 54% ± 6%. Seventy-two patients (29%) died before HSCT, 64 within 1 year, 97% of whom had active disease. In 124 patients who underwent HSCT, 5-year survival was 66 ± 8%; tendency to increased survival (P = .064) in patients with nonactive disease at HSCT. Patients with familial disease had a 5-year survival of 50% ± 13%; none survived without HSCT. Patients deceased during the first 2 months more often had jaundice, edema, and elevated creatinine. Forty-nine patients (20%) were alive without signs of HLH activity and off-therapy > 1-year without HSCT; they presented at older age (P < .001), were more often female (P = .011), and less often had CNS disease (P < .001) or hepatomegaly (P = .007). To conclude, HLH-94 chemoimmunotherapy has considerably improved outcome in HLH. Collaborative efforts are needed to further reduce early mortality, HSCT-related mortality, and neurologic late effects.