HLA-Mismatched Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematological Malignancies

Date de début de l'étude : 1 juin 1998

Patient: Ages 10-45 years. Chronic myelogenous leukemia, any of these categories: accelerated phase or blast transformation. Acute lymphoblastic leukemia, any of these categories: Adults (greater than 18 years) in any remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia). All second remissions, primary induction failure including partial remission, partially responding or untreated relapse. Acute myelogenous leukemia (AML): All AML in second or subsequent remission, primary induction failure or partial remission and resistant relapse. Myelodysplastic syndromes, any of these categories: refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia. Myeloproliferative disorders undergoing transformation to terminal stages. Chronic lymphocytic leukemia (CLL) in Richter transformation. High-grade lymphoma, refractory to standard treatment approaches, mantle cell lymphoma. No major organ dysfunction precluding transplantation. DLCO greater than 65% predicted. Left ventricular ejection fraction: greater than 40% predicted. ECOG performance status of 0 or 1. Informed consent given. Informed consent from parents for minors. Women of childbearing age with a negative pregnancy test may participate. Donor: Partially HLA matched family donor (3-5/6 matches). Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, and no history of stroke). Informed consent given. Patients or donors must not be pregnant or nursing. Must not have ECOG performance status of 2 or more. No severe psychiatric illness in patient or donor: Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely and making informed consent impossible. No major anticipated illness or organ failure incompatible with survival from BMT. DLCO must not be less than 65% predicted. No left ventricular ejection fraction: less than 40% predicted. Must not have serum creatinine greater than 3 mg/dl. Must not have serum bilirubin greater than 4 mg/dl, Transaminases greater than 3 times the upper limit of normal. Donor or patient must not be HIV positive. Must not have history of other malignancies except basal cell or squamous carcinoma of the skin, positive PAP smear and subsequent negative follow up. Donor must be fit to receive G-CSF and undergo apheresis. Must not fail to mobilize adequate numbers of CD34+ cells after two cycles of G-CSF.