INCLUSION CRITERIA:
Inclusion Criteria-Patient (Recipient):
Patients with hematologic malignancies, myelodysplasia, or myeloproliferative disorders, as summarized below:
Disease: Chronic Lymphocytic Leukemia; Disease Status: (a) Relapse post-fludarabine, (b) Non-CR after salvage regimen; Age: 18 to 75.
Disease: Hodgkin's and Non-Hodgkin's Lymphoma (all types, including Mantle Cell Lymphoma); Disease Status: (a) Primary treatment failure, (b) Relapse after autologous SCT, (c) Hepatosplenic gamma/delta T cell lymphoma; Age: 18 to 75.
Disease: Multiple Myeloma; Disease Status: (a) Primary treatment failure, (b) Relapse after autologous SCT, (c) Non-CR after salvage regimen; Age: 18 to 75.
Disease: Acute Myelogenous Leukemia; Disease Status: (a) In Complete Remission #1, with high-risk cytogenetics [abnormalities other than t(8;21), t(15;17), or inv(16)], (b) In Complete Remission #2 or greater; Age: 18 to 75.
Disease: Acute Lymphocytic Leukemia; Disease Status: (a) In Complete Remission #1, with high-risk cytogenetics [t(9;22) or bcr-abl rearrangement; t(4;11), 1(1;19), t(8;14)], (b) In Complete Remission #2 or greater; Age: 18 to 75.
Disease: Myelodysplastic Syndrome; Disease Status: (a) RAEB, (b) RAEB-T (if blasts are less than 10% in marrow and blood after induction chemotherapy); Age: 18 to 75.
Disease: Myeloproliferative disorders; Disease Status: (a) Idiopathic myelofibrosis, (b) Polycythemia vera, (c) Essential thrombocytosis, (d) Chronic myelomonocytic leukemia; Age: 18 to 75.
Disease: Chronic Myelogenous Leukemia; Disease Status: (a) Chronic phase CML, (b) Accelerated phase CML; Age 50 to 75; (c) Not eligible for myeloablative allogeneic HSCT; Age: 18 to 50.
Patients 18-75 years of age. Patients older than 75 years of age will be considered on an individual basis.
Consenting first degree relative matched at 6/6 HLA antigens (A, B, and DR).
Patient or legal guardian must be able to give informed consent.
All previous therapy must be completed at least 2 weeks prior to study entry, and any grade 3 or 4 non-hematologic toxicity of previous therapy must be resolved to grade 2 or less, unless specified elsewhere.
ECOG performance status equal to 0 or 1.
Life expectancy of at least 3 months.
Patients with acute leukemia must be in hematologic remission, defined as less than 5% blasts present in blood or bone marrow.
Left ventricular ejection fraction greater than 45% by either MUGA or 2-D echo, obtained within 28 days of enrollment. The cumulative dose of doxorubicin received by patients will not be considered, as the cardiac ejection fraction appears to indicate the safe cumulative doxorubicin dose in the setting of EPOCH-based chemotherapy.
DLCO greater than 50% of the expected value when correlated for Hb, obtained within 28 days of enrollment.
Creatinine less than or equal to 1.5 mg/dl and creatinine clearance greater than or equal to 50 ml/min/1.73 m(2).
Serum total bilirubin less than 2.5 mg/dl, and serum ALT and AST values less than or equal to 2.5 times the upper limit of normal. Values above these levels may be accepted, at the discretion of the PI or study chairman, if such elevations are thought to be due to liver involvement by malignancy. If these values do not normalize during induction chemotherapy, such patients will not be eligible for the transplant phase of the protocol, and will thus be taken off study.
Minimum absolute neutrophil count of 1,000 cells/microliter and minimum platelet count (without transfusion) of 20,000/mm(3).
Inclusion Criteria-Donor:
First-degree relative with genotypic identity at 6/6 HLA loci (HLA-A, B and DR).
Ability to give informed consent. For donors under 18 years of age, the donor must complete an assent form, and the donor's legal guardian must complete an informed consent form.
Age 12-75 years. As the potential cerebrovascular and cardiac complications may potentially increase with age, age 75 has been chosen arbitrarily as the upper age limit. However, if it is determined after initial accrual of patients in this upper age range that this procedure is relatively safe, the age range may be extended.
Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis.
Donors must be HIV negative, hepatitis B surface antigen negative, and hepatitis C antibody negative. This is to prevent the possible transmission of these infections to the recipient.
A donor who is lactating must substitute formula feeding for her infant during the period of cytokine administration. Filgrastim may be secreted in human milk, although its bioavailability from this source is not known. Limited clinical data suggest that short-term administration of filgrastim or sargramostim to neonates is not associated with adverse outcomes.
EXLCUSION CRITERIA:
Exclusion Criteria-Patient:
Active infection that is not responding to antimicrobial therapy.
Active CNS involvement by malignancy.
HIV infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
Chronic active hepatitis B. Patients may be hepatitis B core antibody positive but must be surface antigen negative and without evidence of active infection.
Hepatitis C infection.
Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant.
History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent (as determined by principal investigator or study chairman).
Exclusion Criteria-Donor:
History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
History of hypertension that is not controlled by medication, stroke, or severe heart disease. Individuals with symptomatic angina will be considered to have severe heart disease will not be eligible to be a donor.
No other medical contraindications to stem cell donation (i.e. severe atherosclerosis, autoimmune disease, cerebrovascular accident, prior malignancy). Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis. Persons with a history of non-hematologic malignancy must have undergone potentially curative therapy for that malignancy and (1) have had no evidence of that disease for 5 years, and/or (2) be deemed at low risk for recurrence (less than or equal to 20% at 5 years). Such persons will be considered eligible for stem cell donation at the discretion of the principal investigator. Prospective donors with a history of non-hematologic malignancy who have received potentially curative therapy and are in remission, but whose estimated risk of recurrence is greater than 20% at 5 years, will be considered on an individual basis in consultation with the NCI IRB.
Donors must not be pregnant. The effects of cytokine administration on a fetus are unknown. Donors of childbearing potential must use an effective method of contraception.
Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000 per microliter).
Warren Grant Magnuson Clinical Center (CC)