Article

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

Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Blood (Impact Factor: 10.43). 09/2011; 118(17):4577-84. DOI: 10.1182/blood-2011-06-356261
Source: PubMed

ABSTRACT 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.

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    • "The onset of FHL is often at a very young age and it is almost invariably fatal without treatment; some studies also suggested that younger HLH patients have poor outcome [10] [24]. In addition, Trottestam et al. [10] reported that patients who did not need the hematopoietic stem-cell transplantation were older at onset and more likely to be female . In this study, however, neither age nor sex was related to the fatal outcome. "
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    • "Only 14% of patients had a tri-lineage cytopenia, the most common feature of FHLH (Kaito et al, 1997; Trottestam et al, 2011). Neurological involvement, a prominent feature in about 50% of patients with FHLH (Trottestam et al, 2011), was found only in the 9% of our patients as seizures, somnolence or rigour nucalis. Of note, liquor examination was always negative . "
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    • "Genetically defined, or primary, HLH is generally fatal unless treated with immune suppression and ultimately bone marrow transplant (Jordan and Filipovich, 2008; Trottestam et al., 2011). The pathophysiology of HLH has been modeled in Prf1- deficient and Unc13d deficient mice (Jordan et al., 2004; Crozat et al., 2007). "
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