OBJECTIVES: I. Determine the efficacy of unrelated donor hematopoietic stem cell transplantation in the treatment of patients with life threatening hemophagocytic disorders.
II. Determine the rate of disease free survival, incidence of graft failure, and incidence of graft versus host disease in these patients after undergoing this treatment regimen.
PROTOCOL OUTLINE: Patients receive oral busulfan twice a day on days -9 to -6; cyclophosphamide IV over 1 hour on days -5 to -2; etoposide IV over 4 hours on days -5 to -3; and anti-thymocyte globulin IV twice a day on days -2 and -1 and days 1 and 2. Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. Filgrastim (G-CSF) is administered subcutaneously beginning on day 1 and continuing until blood counts recover. Patients receive graft versus host disease prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1-4 hours (orally once the patients resumes eating) every 12 hours (every 8 hours for pediatric patients) starting on or prior to day -3 and continuing up to 1 year.
Patients are followed at days 28 and 100, at 6 months and 1 year, and then annually for 5 years.
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics--
Patients diagnosed with any of the following active but stable, or nonactive/quiescent, hemophagocytic disorders:
X-linked lymphoproliferative disorder (XLP)
Two or more maternally related males manifesting at least one of the following XLP phenotypes:
Chediak-Higashi syndrome
Partial oculocutaneous albinism (hair, skin, eyes)
Frequent bacterial infections
Large peroxidase positive granules in leukocytes of peripheral blood or bone marrow
Positive family history or parental consanguinity is supportive of the diagnosis
May not have entered accelerated phase as defined by any of the following:
Viral associated hemophagocytic syndrome (VAHS)
Relapsed after prior therapy or supportive care
Diagnostic criteria as for HLH
No hemophagocytic disorders secondary to underlying malignancy
Patients 35 years of age and under must have a hematopoietic stem cell donor that is one of the following:
Patients 36 to 55 years of age must have a hematopoietic stem cell donor that is one of the following:
Patients receiving umbilical cord blood must have an unrelated donor with no more than two antigen HLA A, B, or DRB1 mismatches
--Patient Characteristics--
Performance status: Karnofsky 70-100% OR Age less than 16 years: Lansky 50-100%
Life expectancy: Not severly limited by another disease
Hepatic: SGOT less than 3 times normal Bilirubin less than 2.5 mg/dL
Renal: Creatinine normal OR Creatinine clearance or glomerular filtration rate greater than 50% normal
Cardiovascular: If symptomatic, ventricular ejection fraction must be greater than 40% and must improve with exercise OR Shortening fraction normal on echocardiogram
Pulmonary:
Other: HIV negative No significant active infections