Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

PRIMARY OBJECTIVES:

I. To demonstrate efficacy of this approach over the historical 2 step reduced intensity conditioning (RIC) approaches in the "vulnerable" population defined as: patients with hematopoietic cell transplant (HCT)-co-morbidity index (CI)/age scores >= 2, but no more than a score of 5 as based on the Sorror et al. data.

SECONDARY OBJECTIVES:

I. To compare the non-relapse mortality (NRM) and relapse related mortality (RRM) rates at 1 year for patients treated on this study to the that of patients undergoing haploidentical RIC hematopoietic stem cell transplantation (HSCT) as reported in the literature and as observed in the 2 step RIC trials.

II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the Thomas Jefferson University (TJU) RIC 2 step approach.

III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU RIC 2 step approach.

OUTLINE:

RIC: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -10 to -8 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total body irradiation (TBI) followed by a donor lymphocyte infusion (DLI) on day -6.

TRANSPLANT: Patients undergo cluster of differentiation (CD)34+ peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus orally (PO) beginning day -1 with a taper initiated on day 42 and mycophenolate mofetil IV twice daily (BID) on days -1 to 28 in the absence of GVHD.

After completion of study treatment, patients are followed up for 1 year.

Inclusion criteria

• Patients treated on this study will have:

• Acute myeloid leukemia in morphologic complete remission (CR) not requiring treatment for their disease for 4 weeks
• A history of acute myeloid leukemia (AML) with < 10% residual blasts (use highest count on staging studies) after induction therapy and persisting with < 10% blasts for at least 8 weeks without reinduction and at the time of HSCT
• Refractory anemia (RA) or refractory anemia with ring sideroblasts (RARS) or isolated 5q-
• Refractory anemia with excess blasts (RAEB)-1, refractory cytopenia with multilineage dysplasia (RCMD)+/-ringed sideroblasts (RS), or myelodysplastic syndrome (MDS) not otherwise specified (NOS) with stable disease for at least 3 months
• RAEB-2 must demonstrate chemo-responsiveness; chemo-responsiveness is defined as a persistent blast percentage decrease by at least 5 percentage points to therapy and there must be =< 10% blasts (use highest count on staging studies) after treatment and at the time of transplant
• Hodgkin or Indolent non-Hodgkin's lymphoma
• Myeloma with < 5% plasma cells in the marrow
• Myeloproliferative disorders (excludes chronic myelomonocytic leukemia [CMML])
• Aplastic anemia
• A hematological or oncological disease (not listed) in which allogeneic HSCT is thought to be beneficial, and the disease is chemoresponsive
• Patients without clear manifestation of their disease status in terms of stage and/or responsiveness should be discussed with the principal investigator (PI) and enrollment analysis should be documented in the study records
• Patients must have a related donor who is human leukocyte antigen (HLA) mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the graft-versus-host disease (GVHD) direction; (patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study); the HLA matched related category includes patients with a syngeneic donor
• Patients must have had front line therapy for their disease
• LVEF (left ventricular end diastolic function) of >= 45%
• DLCO (diffusing capacity of the lung for carbon monoxide) >= 45% of predicted corrected for hemoglobin, FEV-1 (forced expiratory volume at 1 second) >= 50% of predicted
• Serum bilirubin =< 1.8
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 X upper limit of normal
• Creatinine clearance of >= 60 mL/min
• HCT-CI/age score =< 5 points (patients with greater than 5 points will be allowed for trial with approval of the PI and the co-PI or his designee; this is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points; an example is a patient with a solid tumor malignancy in their remote history [adds 3 points to HCT-CI total] where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities)
• Karnofsky performance status (KPS) >= 90% patients older than 70 years, KPS >= 80% patients younger than 70 years
• Patients must be willing to use contraception if they have childbearing potential

Exclusion criteria

• Performance status < 90% in patients 70 years old or greater, < 80% in patients less than age 70 years
• HCT-CI/age score > 5 points (patients with greater than 5 points will be allowed for trial with approval of the principal investigator and the co-principal investigator or his designee; this is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points; an example is a patient with a solid tumor malignancy in their remote history [adds 3 points to HCT-CI total] where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities)
• A diagnosis of chronic myelomonocytic leukemia (CMML), unless in morphologic CR
• Human immunodeficiency virus (HIV) positive
• Active involvement of the central nervous system with malignancy
• Inability to obtain informed consent from patient or surrogate
• Pregnancy
• Patients with life expectancy of =< 6 months for reasons other than their underlying hematologic/oncologic disorder
• Patients who have received alemtuzumab or antithymocyte globulin within 8 weeks of the transplant admission; the absence of these therapies in the medical record will serve as documentation that they were not given
• Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol