The purpose of this trial is to determine if administration of rituximab after allogeneic stem cell transplantation can reduce the incidence of chronic GVHD. Chronic GVHD is a medical condition that can occur after bone marrow or stem cells are transplanted form one individual to another. After the transplant, the donor immune system may recognize the recipient body as foreign and may attempt to "reject" the body. Rituximab is a drug that interferes with the immune system function by specifically targeting B cells and killing them.

Study Design: The study is designed as a Phase II, open label trial of Rituximab as chronic GVHD prophylaxis after HLA-matched, related or unrelated peripheral blood stem cell transplantation after ablative or non-ablative conditioning.

Primary Objective: To determine the incidence of clinically extensive chronic GVHD at one and two years after allogeneic stem cell transplantation after a single dose of Rituximab administered at 100 days, 6 months, 9 months and 1 year from transplantation as chronic GVHD prophylaxis.

Secondary Objectives: To determine the incidence of adverse hematological events, the incidence of infectious complications, the rate of malignant relapse, and the effects on donor hematopoietic chimerism after Rituximab administration.

Eligibility Criteria: Eligible patients will be 18 years of age or greater and will have undergone a non-myeloablative or fully ablative transplantation from an HLA-matched (6/6 loci) or single antigen/allele mismatched (5/6) donor approximately 100 days ago. Adequate performance status and organ function will be confirmed prior to enrollment. No ongoing infection or acute GVHD will be present at the time of enrollment. Evidence of sustained donor chimerism will be confirmed prior to study entry.

Treatment Description: Chronic GVHD prophylaxis will consist of Rituximab 375 mg/m2 administered 100 days, 6, 9 and 12 months after transplantation.

Accrual Objective: 68 patients will be accrued over 12 months.

Study Duration: Patients will be evaluated for two years after the time of transplantation for evaluation of the primary and secondary endpoints. Subjects will be followed longitudinally after completion of the study period for determination of clinical status.

Inclusion Criteria:

• Patients who have undergone either ablative or non-myeloablative allogeneic stem cell transplantation
• Peripheral blood stem cells must have been used as the stem cell source
• Patients must have received transplantation from donors who are identical at 6 HLA loci, or mismatched at no more than 1 locus.
• Patients who have undergone a non-myeloablative stem cell transplant must have > 80% donor hematopoiesis within 30 days of study enrollment
• 18 years of age or older
• Performance Status 0-2
• Life expectancy of > 100 days
• Subjects with CLL are eligible, if there is no more than 20% residual leukemia in the bone marrow at the time of study entry

Exclusion Criteria:

• Evidence of relapsed or residual malignancy within 30 days of trial entry
• Highly aggressive B cell malignancy, such as Burkitt's lymphoma or Burkitt's-like lymphoma
• Allogeneic stem cell transplantation using a single or multiple umbilical cord blood units or using bone marrow
• Evidence of any active uncontrolled infection, or evidence of natural exposure to Hepatitis B, Hepatitis C or HIV
• Evidence of ongoing gastrointestinal or hepatic acute GVHD, or evidence of greater than ongoing Stage I cutaneous acute GVHD
• GVHD with chronic features diagnosed prior to day +100 or prior to enrollment
• Participation in a clinical trial evaluating another preventative strategy for chronic GVHD, or ongoing participation in a clinical trial for therapy of acute GVHD
• No Donor Lymphocyte Infusion (DLI) prior to day 100 and not plans for a DLI in the upcoming 30 days
• Heart failure uncontrolled by medications
• Pregnancy or lactation

Reported Adverse Events (AEs) inlcude events starting on or after day 0 and on or before day 540.

If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once in that SOC.