Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source

Inclusion Criteria

• •Subject
• •1. Age\< 70.
• •2. Molecular based HLA typing will be performed for the HLA-A, -B, -Cw, DRB1 and -DQB1 loci to the resolution adequate to establish haplo identity. A minimum match of 5/10 is required. An unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched, unrelated donor.
• •3. Subjects must meet one of the disease classifications listed below:
• •Acute leukemias (includes T lymphoblastic lymphoma). Remission is defined as \< 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with \> 20% cellularity, peripheral blood counts showing ANC \>1000/ul, including patients in CRp.
• •Acute Lymphoblastic Leukemia in high risk CR1 as defined by at least one of the following:
• •Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), MLL rearrangements White blood cell counts \>30,000/mcL Patients over 30 years of age Time to complete remission \>4 weeks Presence of extramedullary disease
• •Acute Myelogeneous Leukemia in high risk CR1 as defined by at least one of the following:
• •Greater than 1 cycle of induction therapy required to achieve remission Preceding myelodysplastic syndrome (MDS) Presence of Flt3 abnormalities FAB M6 or M7 leukemia or
• •Adverse cytogenetics for overall survival such as:
• •those associated with MDS Complex karyotype (≥ 3 abnormalities) Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 \[alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)\], t(11;19)(q23;p13.1)
• •Acute Leukemias in 2nd or subsequent remission
• •Biphenotypic/Undifferentiated Leukemias in 1st or subsequent CR.
• •High-risk MDS status-post cytotoxic chemotherapy
• •Myelofibrosis
• •Burkitt's lymphoma: second or subsequent CR.
• •Lymphoma.
• •Chemotherapy-sensitive (complete or partial response; see response criteria Appendix C) large cell, Mantle Cell or Hodgkin's lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are ineligible for an autologous transplant or relapsed/progressed after autologous stem cell transplant.
• •Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least two prior therapies (excluding single agent Rituxan) and are ineligible for an autologous transplant or relapsed/progressed after autologous stem cell transplant..
• •4. Patients with adequate physical function as measured by:
• •Cardiac: left ventricular ejection fraction at rest must be ≥ 35%.
• •Hepatic: bilirubin ≤ 2.5 mg/dL; and ALT, AST, and Alkaline Phosphatase \< 5 x ULN.
• •Renal: serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function(creatinine clearance or GFR) \> 40 mL/min/1.73m2.
• •Pulmonary: FEV1, FVC, DLCO (diffusion capacity) ≥ 40% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation \> 92% on room air.
• •Performance status: Karnofsky/Lansky score ≥ 60%.
• •5. Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active GVHD requiring immunosuppressive therapy.
• •Donor
• •1. Donors must be HLA-haploidentical first-degree or second degree relatives of the patient.
• •2. Age ≥ 18 years
• •3. Weight ≥ 40 kg