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Treatment of Familial Hemophagocytic Lymphohistiocytosis With Bone Marrow Transplantation From HLA Genetically Nonidentical Donors
Nada Jabado,
Elizabeth R. de Graeff-Meeder,
Marina Cavazzana-Calvo,
Elie Haddad,
Françoise Le Deist,
Malika Benkerrou,
Rémi Dufourcq,
Sophie Caillat,
Stephane Blanche, and
Alain Fischer
From the Unité d'Immuno-Hématologie Pédiatrique, Institut National pour la Santé et la Recherche Medicale U429, and Laboratoire d'immunologie, Hôpital Necker-Enfants Malades, Paris, France; and Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in patients with this disease. However, fewer than 20% of patients have a disease-free HLA-identical sibling. BMT from HLA-nonidentical related donors has previously met with poor results, with graft rejection a major obstacle in all cases. We describe BMTs from HLA-nonidentical related donors (n = 13) and from a matched unrelated donor (n = 1) performed in two centers in 14 consecutive cases of FHL. Remission of disease was achieved before BMT in 10 patients. Marrow was T-cell-depleted to minimize graft-versus-host disease (GVHD). Antiadhesion antibodies specific for the  chain of the leukocyte function-associated antigen-1 (LFA-1, CD11a) and the CD2 molecules were infused pre-BMT and post-BMT to help prevent graft rejection, in addition to a conditioning regimen of busulfan (BU), cyclophosphamide (CP), and etoposide (VP16) or antithymocyte globulin (ATG). Sustained engraftment was obtained in 11 of 17 transplants (3 patients had 2 transplants) and disease-free survival in 9 patients with a follow-up period of 8 to 69 months (mean, 33). Acute GVHD greater than stage I was not observed, and 1 patient had mild cutaneous chronic GVHD that resolved. Toxicity due to the BMT procedure was low. Results obtained using this protocol are promising in terms of engraftment and event-free survival within the limitations of the small sample. We conclude that an immunologic approach in terms of drugs used to obtain disease remission and a conditioning regimen that includes antiadhesion molecules in T-cell-depleted BMT from HLA genetically nonidentical donors is an alternative treatment that warrants further study in FHL patients who lack a suitable HLA genetically identical donor.
Blood, Vol. 90 No. 12 (December 15), 1997:
pp. 4743-4748
© 1997 by The American Society of Hematology.
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