Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

PRIMARY OBJECTIVES:

I. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation
(HSCT) from matched-related donors can improve the probability of survival 18 months after
treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate,
cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL)
beyond that observed in historical controls (30%).

SECONDARY OBJECTIVES:

I. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning for
patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with historical
data on autologous HSCT.

II. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic
GVHD in patients with CLL treated with low-dose TBI, fludarabine, peripheral blood stem cell
(PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.

III. To characterize the rate and types of infections with this regimen.

IV. To estimate the rate of transplant-related mortality in the first 200 days.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on
days -4 to -2 and TBI on day 0.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180
with taper beginning on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.

After completion of study treatment, patients are followed up at 12 and 18 months and then
annually for 5 years.

Inclusion Criteria:

- Patients with CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses
to prolymphocytic leukemia (PLL), or T-cell CLL or PLL

- Patients with B-Cell CLL or PLL who have at least one of the following:

- Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or
partial response after therapy with a regimen containing fludarabine (or another
nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse
within 12 months after completing therapy with a regimen containing fludarabine (or
another nucleoside analog)

- Failed FCR combination chemotherapy at any time point

- Had de novo of acquired "17p deletion" cytogenetic abnormality; patients should have
received induction chemotherapy but could be transplanted in first (1st) complete
response (CR)

- Patient has a suitable human leukocyte antigen (HLA)-matched related donor who is
willing to undergo leukapheresis initially for collection of PBSC and subsequently for
collection of peripheral blood mononuclear cells (PBMC) with filgrastim (G-CSF)
mobilization and willing to donate stem cells

- DONOR: Related donor who is HLA phenotypically or genotypically identical at the
allele level at HLA-A, -B, -C, -DRB1, and -DQB1

- DONOR: Donor must consent to G-CSF administration and leukapheresis

- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of
central venous catheter (femoral, subclavian)

Exclusion Criteria:

- Infection with human immunodeficiency virus (HIV), human T-lymphotropic virus
(HTLV)-1, or HTLV-2

- Active central nervous system (CNS) involvement with CLL

- Patients with active non-hematologic malignancies (except non-melanoma skin cancers)

- Patients with a history of non-hematologic malignancies (except non-melanoma skin
cancers) currently in a complete remission, who are less than 5 years from the time of
complete remission, and have a > 20% risk of disease recurrence

- Fertile men or women unwilling to use contraceptive techniques during and for 12
months following treatment

- Pregnant or breastfeeding women

- Karnofsky score =< 70

- Fungal infections with radiological progression after receipt of amphotericin B or
active triazole for greater than 1 month

- Cytotoxic agents for "cytoreduction" (with the exception of imatinib mesylate
[Gleevec], cytokine therapy, hydroxyurea, chlorambucil or Rituxan) within three weeks
of the initiation of conditioning

- Active bacterial or fungal infections unresponsive to medical therapy

- Cardiovascular: cardiac ejection fraction < 40%; patients with poorly controlled
hypertension despite multiple antihypertensives

- Pulmonary: diffusing capacity of carbon monoxide (DLCO) < 40%, total lung capacity
(TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or requiring
continuous supplementary oxygen, or severe deficits in pulmonary function testing as
defined by pulmonary consultant service

- Liver function abnormalities: patients with clinical or laboratory evidence of liver
disease would be evaluated for the cause of liver disease, its clinical severity in
terms of liver function, bridging fibrosis, and the degree of portal hypertension;
patients will be excluded if they are found to have fulminant liver failure, cirrhosis
of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal
varices, a history of bleeding esophageal varices, hepatic encephalopathy,
uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin
time, ascites related to portal hypertension, bacterial or fungal liver abscess,
biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or
symptomatic biliary disease

- DONOR: Age < 12 years

- DONOR: Identical twin

- DONOR: Pregnancy

- DONOR: Infection with HIV

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to filgrastim (G-CSF)

- DONOR: Current serious systemic illness