reduced intensity (ric) conditioning and transplantation of hla-haplo-hct

Conditions: Hematologic Malignancies

Summary: this is a single institution phase ii study of a reduced intensity conditioning (ric) followed by a haploidentical hematopoietic cell transplant (haplo-hct) in persons with diagnosis of hematologic malignancy. conditioning will consists of fludarabine, cyclophosphamide, melphalan and total body irradiation (tbi) preparative regimen with a melphalan dose reduction for patients ≥55 years old and those with hct comorbidity index (ci) \>3. this study uses a two-stage phase ii design with accrual goal of 84 patients, using 28 patients separately for arms a, c and d


Eligibility criteria:
inclusion criteria: * karnofsky performance status of ≥70% or lansky play score ≥ 70% * a related haploidentical bone marrow donor with up to 2 or 3 hla locus-mismatches * the donor and recipient must be hla identical for at least one haplotype (using high resolution dna based typing) at the following genetic loci: hla-a, hla-b, hla-c, and hla-drb1. * adequate liver and renal function * absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 40% * diffusion capacity corrected (dlcocorr) \> 40% predicted, and absence of o2 requirements * \> 6 months after prior autologous transplant (if applicable) * agrees to use contraception during study treatment * voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate) * patients who are hiv+ must have undetectable viral load. all hiv+ patients must be evaluated by infectious disease (id) and a hiv management plan establish prior to transplantation exclusion criteria: * \< 70 years with an available 5-6/6 hla-a, b, drb1 matched sibling donor * pregnancy or breastfeeding * current active and uncontrolled serious infection * acute leukemia in morphologic relapse/persistent disease defined as \> 5% blasts in normocellular bone marrow or any % blasts if blasts have unique morphologic markers (e.g. auer rods). * cml in blast crisis * large cell lymphoma, mantle cell lymphoma and hodgkin disease that is progressive on salvage therapy. * stable non-bulky disease is acceptable. * active central nervous system malignancy criteria for donor selection: * donors must be hla-haploidentical relatives of the patient, defined as having a shared hla haplotype between donor and patient at hla-a, -b, -c, and -drb1. * eligible donors (14-70 years old) include biological children, siblings or half siblings, or parents, able and willing to undergo bone marrow harvesting. * for donors \<18 years, the maximum recipient weight (actual body weight) should not exceed 1.25 times the donor weight (actual body weight)1 in addition, bone marrow product volume should be limited to 20 ml/kg donor weight for donors \<18 years.

Keywords: acute leukemias acute myeloid leukemia (aml) acute lymphoblastic leukemia (all)/lymphoma biphenotypic/undifferentiated/prolymphocytic leukemias myelodysplastic syndrome chronic myelogenous leukemia minimal residual disease (mrd) positive leukemia leukemia or myelodysplastic syndromes (mds) in aplasia myeloproliferative neoplasms/myelofibrosis relapsed large-cell lymphoma, mantle-cell lymphoma and hodgkin lymphoma burkitt's lymphoma relapsed t-cell lymphoma natural killer cell malignancies relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (cll/sll), marginal zone b-cell lymphoma, follicular lymphoma lymphoplasmacytic lymphoma relapsed multiple myeloma bone marrow failure syndromes