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

This clinical trial studies the use of reduced intensity chemotherapy and radiation therapy before donor stem cell transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine phosphate, before a donor stem cell transplant may help stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Reducing the intensity of the chemotherapy and radiation may also reduce the side effects of the donor stem cell transplant.

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.

Eligibility Criteria:
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