The study experienced lower accrual rates after the onset of COVID. Upon review of the collected data it was deemed that an adequate amount of subjects has been enrolled to date to assess study aims.

This phase II trial studies how well donor peripheral blood stem cell (PBSC) transplant works in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of bone marrow from half-matched (haploidentical) donors. This approach has extended the transplant option to patients who do not have matched related or unrelated donors, especially for patients from ethnic minority groups. The graft contains cells of the donor's immune system which potentially can recognize and destroy the patient's cancer cells (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune system is prevented by giving low doses of chemotherapy (fludarabine phosphate and cyclophosphamide) and total-body irradiation before transplant. Patients can experience low blood cell counts after transplant. Using stem cells and immune cells collected from the donor's circulating blood may result in quicker recovery of blood counts and may be more effective in treating the patient's disease than using bone marrow.

PRIMARY OBJECTIVES:

I. To demonstrate that use of PBSC in place of marrow as the source of lymphocytes and stem cells for nonmyeloablative transplants from related, haploidentical donors will not result in unacceptable rates of high-grade acute or chronic GVHD, non-relapse mortality or relapse compared to historical data on nonmyeloablative transplants from unrelated donors.

SECONDARY OBJECTIVES:

I. Estimates of the rates of neutrophil and platelet recovery, number of red blood cell (RBC) and platelet transfusions, incidences of graft failure, transplant-related toxicities, disease-free survival and overall survival.

OUTLINE:

Patients receive fludarabine intravenously (IV) over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or orally (PO) twice daily (BID) on days 5-180 (may be continued if active GVHD is present), mycophenolate mofetil IV or PO thrice daily (TID) on days 5-35 (may be continued if GVHD present), and filgrastim IV beginning on day 5 until the absolute neutrophil count (ANC) is >= 1,000/mm^3 for three consecutive days.

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

Inclusion Criteria:

• Molecular based human leukocyte antigen (HLA) typing will be performed for the HLA-A, -B, -Cw, -DRB1 and -DQB1 loci to the resolution adequate to establish haplo-identity; a minimum match of 5/10 is required; an unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant; clinical urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched, unrelated donor

• Acute leukemias (includes T lymphoblastic lymphoma); remission is defined as < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer rods) in a bone marrow with > 20% cellularity, peripheral blood counts showing ANC > 1000/ul, including patients in complete remission with incomplete platelet recovery (CRp); if the marrow has < 20% cellularity due to treatment related cytotoxicity, but still has < 5% blasts, an exception may be made to include this patient up to principal investigator (PI) discretion

• Acute lymphoblastic leukemia in high risk first complete remission (CR1) as defined by at least one of the following:

  • Adverse cytogenetics including but not limited to t(9;22), t(1;19), t(4;11), mixed lineage leukemia (MLL) rearrangements
  • White blood cell counts > 30,000/mcL
  • Patients over 30 years of age
  • Time to complete remission > 4 weeks
  • Presence of extramedullary disease
  • Minimal residual disease
  • Other risk factors determined by the patient's attending physician to be high risk features requiring transplantation

• Acute myelogenous leukemia in high risk CR1 as defined by at least one of the following:

  • Greater than 1 cycle of induction therapy required to achieve remission

  • Preceding myelodysplastic syndrome (MDS)

  • Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities

  • French-American-British (FAB) M6 or M7 leukemia, or

  • Adverse cytogenetics for overall survival such as:

    • Those associated with MDS
    • Complex karyotype (>= 3 abnormalities); or
    • Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(11;19)(q23;p13.1)]

  • Other risk factors determined by the patient's attending physician to be high risk features requiring transplantation

• Acute leukemias in second (2nd) or subsequent remission

• Biphenotypic/undifferentiated leukemias in first (1st) or subsequent complete remission (CR)

• High-risk MDS status-post cytotoxic chemotherapy

• Burkitt's lymphoma: second or subsequent CR

• Chemotherapy-sensitive (at least stable disease) large cell, mantle cell or Hodgkin's lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are ineligible for an autologous transplant

• Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least two prior therapies (excluding single agent Rituxan)

• Multiple myeloma (MM) stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant

• Left ventricular ejection fraction at rest must be >= 35%

• Bilirubin =< 2.5 mg/dL

• Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) < 5 x ULN

• Alkaline phosphatase < 5 x ULN

• Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or glomerular filtration rate [GFR]) > 40 mL/min/1.73m^2

• Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO) (diffusion capacity) >= 40% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2) saturation > 92% on room air

• Karnofsky/Lansky score >= 60%

• Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active GVHD requiring immunosuppressive therapy

• Patients will undergo standard pre-transplant work-up as dictated by standard practice guidelines the results of which may be used for screening for this study

• DONOR: Donors must be HLA-haploidentical first-degree relatives of the patient; eligible donors include biological parents, siblings, or children, or half-siblings

• DONOR: Age >= 12 years

• DONOR: Weight >= 40 kg

• DONOR: Ability of donors < 18 years of age to undergo apheresis without use of a vascular access device; vein check must be performed and verified by an apheresis nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)

• DONOR: Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines

Exclusion Criteria:

• HLA-matched or single allele-mismatched donor able to donate
• Pregnancy or breast-feeding
• Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
• Patients with primary idiopathic myelofibrosis
• DONOR: Positive anti-donor HLA antibody