Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

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