Reduced Intensity Flu/Mel/TBI Conditioning for HAPLO HCT Patients With Hematologic Malignancies

Inclusion Criteria:

Age ≥ 55 years or HCT Co-Morbidity score (HCT-CI) >/=3
Lack of a suitable 8/8 HLA-matched sibling donor
Adequate performance status is defined as Karnofsky score ≥ 70%
Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors must be HLA-haploidentical relatives including, but not limited to, children, siblings, or parents, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1.
Acute Myeloid Leukemia (AML): Must be in remission with morphology (<5% blasts)
Acute Lymphoblastic Leukemia (ALL)/lymphoma second or greater complete remission (CR) first CR unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities, first CR high-risk ALL
Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR
Myelodysplastic syndrome: any subtype including refractory anemia (RA) if severe pancytopenia or complex cytogenetics. Blasts must be less than 5%. If 5% of more requires chemotherapy for cytoreduction to Chronic Myelogenous leukemia in accelerated phase: patient must have failed at least two different Tyrosine Kinase Inhibitor (TKI)s, been intolerant to all TKIs, or have T315l mutation
Myeloproliferative neoplasms/myelofibrosis: Blasts must be less than 5%. If 5% or more requires chemotherapy for cytoreduction to Relapsed large-cell lymphoma, mantle-cell lymphoma or Hodgkin lymphoma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant
Burkitt's lymphoma in second CR or subsequent CR
Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/Partial Response (PR) that has failed or ineligible for an autologous transplant
Natural killer cell malignancies
Relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma with any of the following:
Progressed within 12 months of achieving a partial or complete remission Patients who had remissions lasting up
Patients who had remission lasting > 12 months are eligible after at least two prior therapies
Patients with primary, refractory disease. Bulky disease and an estimated tumor doubling time of less than one month require debulking therapy prior to transplant.
Lymphoplasmacytic lymphoma is eligible after initial therapy if chemotherapy sensitive
Adequate organ function as defined per protocol
Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use adequate birth control during study treatment

Exclusion Criteria:

Pregnant or breastfeeding
Untreated active infection
Active HIV infection
Prior allogenic transplant at any time prior or less than 6 months since prior autologous transplant (if applicable)
Active central nervous system malignancy
Favorable risk AML defined as per protocol
Active central nervous system malignancy
Favorable risk AML defined as having one of the following:
t(8,21) without cKIT mutation or evidence of immunophenotypic, cytogenetic or molecular minimal residual disease (MRD)
inv(16) or t(16;16) without cKIT mutation or evidence of MRD
Normal karyotype with mutated NPM1 but FLT3-ITD wild type without evidence of MRD
Normal karyatype with double mutated CEBPA without evidence of MRD