Treatment of hemophagocytic lymphohistiocytosis with chemotherapy and bone marrow transplantation: a single-center study of 22 cases

Abstract

Twenty-two children with hemophagocytic lymphohistiocytosis were treated with a chemotherapy regimen consisting of VP16–213, corticosteroids, and intrathecal methotrexate. A sustained clinical and biologic complete remission was obtained in 15 children and a partial remission in one child; six children died early of opportunistic infection (n = 4) or of disease progression (n = 2). Of the 16 children who were placed in first remission, 10 received maintenance chemotherapy alone, while six underwent bone marrow transplantation (HLA matched in five, HLA mismatched in one). Of the children who received chemotherapy alone, only two are in long-term remission after cessation of treatment. The remaining eight patients relapsed after a mean period of 5.4 months (range 2 to 8 months). Further treatment using the same regimen induced second remissions of short duration; death occurred after a median period of 2.3 months (range 0.5 to 6 months). A total of nine patients received allogeneic bone marrow transplantation (BMT). Among the six children transplanted in remission, four are in long-term unmaintained remission, 1 to 6 years after HLA-matched BMT. However, the relapse that occurred in one patient 1 year post BMT is difficult to interpret because the donor, the patient's 5-year-old sister, also developed the disease 1 year later. An HLA-nonidentical BMT resulted in unmaintained remission for 1 year, with autologous hematologic reconstitution followed by disease relapse. HLA-nonidentical BMT failed in three other patients with active disease at time of transplant. The poor long-term results of chemotherapy alone justify the use of related HLA-matched BMT in complete remission.

Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis

“…(5) Persistent disease activity at 2 months after start of HLH treatment appears to suggest a worse long-term prognosis. Fischer et al (1986) were the first to show that a cure for FHL could be achieved by SCT, as later confirmed by others (Todo et al, 1990;Blanche et al, 1991;Nespoli et al, 1991;Bolme et al, 1995;Baker et al, 1997;Jabado et al, 1997;Dürken et al, 1999;Imashuku et al, 1999b). Initially, only matched donors were used but, since the outcome of FHL is invariably fatal without a successful SCT, HLA non-identical donors are now used more often and represent a third of the donors in this analysis.…”

Hemophagocytic lymphohistiocytosis: review of etiologies and management

“…252 Several studies have demonstrated that HSCT is the only true hope for permanent control of the disease or essentially a cure. [253][254][255][256][257] A study of 86 children treated with HLH-94 followed by HSCT demonstrated similar long-term disease-free survival (70% at 3 years) with matched unrelated donor transplants as with matched sibling transplants. Survival with family haploidentical donor transplants or mismatched unrelated transplants showed much less favorable results with long-term disease-free survival of only 50%.…”

Longitudinal observation and outcome of nonfamilial childhood haemophagocytic syndrome receiving etoposide‐containing regimens

“…Although initial results appeared to be satisfactory , the current long-term observation has revealed frequent relapses and only 22·7% of patients enjoyed continuous disease-free survival, a result similar to that observed in FHL (Ambruso et al, 1980;Fisher et al, 1985). This experience suggests that a more intensive therapy, or bone marrow transplantation, as adopted currently in FHL treatment (Blanche et al, 1991;Jabado et al, 1996), should be applied to those relapsed patients or partial responders.…”