Pilot Study of Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients With Life Threatening Hemophagocytic Disorders

PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Patients diagnosed with any of the following active but stable, or nonactive/quiescent, hemophagocytic disorders: Hemophagocytic lymphohistiocytosis (HLH) Fever greater than 38.5 degrees Celsius Splenomegaly (greater than 3 cm below costal margin) Hemophagocytosis in bone marrow or spleen or lymph nodes Disease may be confirmed by positive family history No evidence of malignancy Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides at least 2.0 mmol/L or at least 3 standard deviations above normal for age Fibrinogen no greater than 1.5 g/L or no greater than 3 standard deviations above normal Cytopenia (affecting at least 2 of 3 lineages in the peripheral blood) Hemoglobin less than 9.0 g/L Platelet count less than 100,000/mm3 X-linked lymphoproliferative disorder (XLP) Two or more maternally related males manifesting at least one of the following XLP phenotypes: Fulminant infectious mononucleosis Dysgammaglobulinemia Malignant lymphoma/lymphoproliferative disorder Aplastic anemia Lymphoid granulomatosis/vasculitis OR A maternally related male in an established XLP kindred who has strong genetic (RFLP) linkage to the XLP locus 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: Lymphadenopathy Pancytopenia Histiocytes with hemophagocytosis in bone marrow, lymph nodes, liver, or spleen 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: HLA A and B identical OR Single HLA A or B serologic mismatch with DRB1 identity OR HLA A or B serologic identity with a single DRB1 mismatch Patients 36 to 55 years of age must have a hematopoietic stem cell donor that is one of the following: HLA A and B and HLA DRB1 identical OR Single HLA A or B serologic mismatch with DRB1 identity 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: If symptomatic, DLCO greater than 45% predicted (corrected for hemoglobin) In children unable to perform pulmonary function testing, oxygen saturation must be greater than 95% Other: HIV negative No significant active infections