Statistics from Altmetric.com
Editor,—Familial haemophagocytic lymphohistiocytosis (FHL) is a lethal disease with an uncontrolled activation of T lymphocytes and macrophages due to a perforin gene defect.1 The only current curative treatment is bone marrow transplantation. However, favourable outcome is associated with clinical remission status at the time of the procedure.2 3 Unfortunately, the use of steroids, etoposide (VP16), cyclosporin A, and antithymocyte globulins alone or in association frequently fails to control recurrent active phases.
BL, a 2 month old boy, was admitted in June 1999 for an active phase of FHL. His elder brother had died of FHL. The diagnosis was established on clinical (vomiting, fever, pallor, hepatosplenomegaly) and biological features (pancytopenia, hypertriglyceridaemia (3.82 mmol/l), haemodilution, hypofibrinaemia (0.65g/l), a moderate elevation of aspartate transamineses (2N) and haemophagocytosis on bone marrow aspirates). No central nervous system abnormality was observed on cerebrospinal fluid analysis and cerebral magnetic resonance imaging.
A first remission was obtained with the combination of steroids: prednisolone (2 mg/kg/day), VP16-phosphate (150 mg/kg/day, d1–d3), cyclosporin A (4 mg/kg/day, continuous infusion), and antithymocyte globulins (10 mg/kg/day, d1–d5) three weeks after diagnosis. Despite maintenance treatment, relapse occurred one month later with severe pancytopenia. No remission was obtained with a second course of steroids, VP16-phosphate, and antithymocyte globulins. Two and a half months (day 76) after diagnosis, a course of fludarabine (30 mg/m2/day for four days) was initiated and dramatically improved our patient's condition regarding the clinical and all biological criteria of FHL. An additional course was given on day 92. Transient neutropenia and a noticeable lymphopenia were observed. After a busulfan (120 mg/m2/day for four days) and cyclophosphamide (50 mg/kg/day for four days) conditioning regimen, one month after the last course of fludarabine, we performed a haematopoietic stem cell transplant with the father's CD34+ HLA-half-identical peripheral cells (Miltenyi, Germany). Haematological reconstitution was observed from day 24 post transplant. There was transient grade II acute graft versus host disease (skin, liver). No relapse of FHL has occurred to this date (day 330 post transplant).
Treatment of active phases of FHL is based on drugs killing immunocompetent cells. Fludarabine is a purine antimetabolite with a strong immunosuppressive action.4 During treatment with fludarabine for B cell malignancies, an important decrease in the T cell subpopulations, particularly of the natural killer phenotype (CD16/56+), was observed. Our patient's response to the first course of this drug was dramatic and allowed bone marrow transplant when in good clinical condition. Nevertheless a series of patients is needed to assess the efficacy of fludarabine for the treatment of active phases of FHL.
We thank Dr JL Stephan for his helpful clinical advice.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.