A Two-Step Approach to Bone Marrow Transplant Using Cells From Two Partially-Matched Relatives

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PRIMARY OBJECTIVES: I. To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach using 2 donors. SECONDARY OBJECTIVES: I. To assess the consistency and pace of engraftment. II. To assess the pac...

PRIMARY OBJECTIVES: I. To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach using 2 donors. SECONDARY OBJECTIVES: I. To assess the consistency and pace of engraftment. II. To assess the pace of T cell and B cell immune recovery in patients in each arm. III. To assess regimen related toxicity, graft-versus-host disease (GVHD) incidence and severity, and overall survival. IV. To assess the tolerance of the period of fever, diarrhea, and rash after the introduction of second donor and qualitatively compare it to prior patient groups or concurrent patient groups. V. To assess chimerism to ascertain whether one donor is emerging as dominant at regular intervals beginning at the time of engraftment. VI. If dominance is observed, to compare the donors with regard to degree of human leukocyte antigen (HLA) mismatch, killer Ig-like receptor (KIR) types, cluster of differentiation (CD)34+ cell doses, infusion order, donor age, and donor alloreactivity points in an effort to identify potential biologic factors that predict for dominance. To determine if trends toward dominance occur in T cell, natural killer (NK) cell, or other cellular subsets prior to emerging in the graft as a whole. VII. To assess if establishment of a dominant donor versus persistent chimerism of both donors is associated with a lower relapse rate. VIII. To collect leukemia samples prior to transplant and after relapse whenever possible. To assess the overall degree of HLA-class I and class II expression on these paired samples. To test for loss of one or both HLA haplotypes in the relapsed tumor specimens. When observed, to correlate loss of one HLA haplotype with: a) receipt of a transplant capable of targeting only that haplotype; b) establishment of dominance in a 2 haplotype transplant such that the lost haplotype would be the primary target of the dominant donor; c) being the target of the donor predicted to be more alloreactive in a 2 haplotype transplant. OUTLINE: CONDITIONING: Patients undergo total-body irradiation (TBI) twice daily (BID) on days -9 to -6, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28. After completion of study treatment, patients are followed up for 1 year, and then periodically thereafter.

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