Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient's immune system from rejecting the donor's stem cells. Healthy stem cells from a donor that are infused into the patient help the patient's bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body's normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe.

PRIMARY OBJECTIVES:

I. The primary objective of this study is to assess outcomes when high-dose cyclophosphamide (CY) is administered on days 3 and 4 followed by cyclosporine (CSP) after human leukocyte antigen (HLA)-matched related or unrelated mobilized blood cell transplantation with total-body irradiation (TBI) or busulfan (BU)-based conditioning.

SECONDARY OBJECTIVES:

I. The secondary objective of this study is to assess hematopoietic cell transplantation (HCT) outcomes when withdrawal of CSP is accelerated in patients without acute graft-versus-host disease (GVHD).

OUTLINE: Patients' conditioning regimens are determined by the Clinical Coordinator after consultation with the attending physician. Based on disease, patients receive either TBI or fludarabine and busulfan.

PREPARATIVE REGIMEN: Patients receive TBI twice daily (BID) on days -4 or -3 to -1. Some patients also receive fludarabine intravenously (IV) daily on days -5 to -2 and busulfan IV over 3 hours once daily (QD) or over 2 hours every 6 hours on days -5 to -2. Patients may also undergo central nervous system (CNS) prophylaxis, testicular irradiation, and/or involved field irradiation as per standard practice.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0 per standard practice.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4. Patients also receive cyclosporine IV every 12 hours or every 8 hours beginning on day 5 with taper on days 56-126.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at day 180 and then annually for 5 years.

Eligibility Criteria:
Inclusion Criteria:

* Acute lymphocytic leukemia (ALL) in morphologic first complete remission (CR1) with high risk features defined as, but not limited to: evidence of adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or mixed-lineage leukemia (MLL) rearrangements; presence of minimal residual disease; progenitor B-cell immunophenotype; high white blood cells (WBC) at diagnosis (\> 30,000/ul in B-ALL; \> 100,000/ul in T-ALL); or delayed attainment of CR (\> 4 weeks) after induction therapy; additional clinical characteristics deemed to confer a high relapse risk may be discussed with and approved by the Principal Investigator (PI)
* Acute myeloid leukemia (AML) in CR1 EXCEPT patients with low-risk features defined as:

  * Inv 16 or t(8;21) in the absence of c-kit mutations
  * Normal karyotype who are FLT3-ITD-negative and NPM1-positive in the absence of c-kit mutations
  * Patients with respective "low-risk" features are eligible, however, if (i) more than 1 cycle of induction therapy was required to achieve CR1 (ii) the patient had a preceding myelodysplastic syndrome (MDS) other than myelofibrosis, or (iii) secondary AML
* Acute leukemia in 2nd or greater CR (CR \>= 2)
* Refractory or relapsed AML with =\< 10% bone marrow blasts and no circulating blasts or proven extramedullary disease
* AML transformed from myelodysplastic syndrome (MDS) with \< 10% bone marrow blasts
* MDS with following high risk features:

  * High risk cytogenetics (including, but not limited to: 7q--, inv\[3\], t\[3q\], del\[3q\] or complex karyotype)
  * International Prognostic Scoring System (IPSS) intermediate (INT)-2 or greater
  * Treatment-related MDS
  * Any phase of MDS if patient is \< 21 years of age
* Chronic myelogenous leukemia (CML) beyond 1st chronic phase or resistant or intolerant to tyrosine kinase inhibitors (adults) or any phase (pediatric \< 21 years)
* Chronic myelomonocytic leukemia
* Philadelphia-negative myeloproliferative disorder
* Lymphoma: relapsed chemotherapy-sensitive (complete or partial response) Hodgkin or non-Hodgkin lymphoma
* Multiple myeloma-stage III
* The patient or legal representative must be able to understand and give written informed consent
* DONORS: The donor must be a genotypically HLA-identical sibling, a phenotypically HLA-matched first-degree relative, or an unrelated donor who is molecularly matched with the patient at HLA-A, B, C, DRB1
* DONORS: Donors must meet the selection criteria for administration of G-CSF (filgrastim) and apheresis defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB)
* DONORS: Donors must be capable of giving informed consent

Exclusion Criteria:

* Prior autologous or allogeneic stem cell transplant
* Performance status \> 2 (Eastern Cooperative Oncology Group \[ECOG\]) or \< 50 (Lansky; for patients \< 16 years old)
* Uncontrolled infection; the protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is under adequate control to allow enrollment in the study
* Positive serology for human immunodeficiency virus (HIV)-1, 2 or human T cell lymphotropic virus (HTLV)-1, 2
* Left ventricular ejection fraction \< 45% or shortening fraction \< 25%; no uncontrolled arrhythmias or symptomatic cardiac disease
* Symptomatic pulmonary disease; forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO) =\< 50% of predicted (corrected for hemoglobin); if pulmonary function tests cannot be performed, an oxygen saturation \< 92% on room air
* Calculated (Cockcroft-Gault or appropriate calculation for pediatric patients) serum creatinine clearance =\< 60 mL/min; if the calculated CrCl is 50-60 mL/min, but a measured CrCl by 24 hour urine collection is \> 60 mL/min, this measurement is acceptable
* Total serum bilirubin more than twice upper normal limit
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3-fold higher than laboratory upper normal limits
* Female patient must have negative serum pregnancy test (all women of child bearing-potential must have test performed)
* DONORS: Potential donors who for psychological, physiological, or medical reasons cannot tolerate administration of G-CSF or apheresis
* DONORS: Donors who are allergic to filgrastim or Escherichia (E.) coli-derived proteins
* DONORS: Donor-related risks to recipients
* DONORS: Positive anti-donor lymphocytotoxic crossmatch
* DONORS: Donors who are positive for HIV