Non-Myeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in High Risk Patients and in Patients With Debilitating Hematologic Diseases

Inclusion Criteria

- INCLUSION CRITERIA - Recipients:

Group A: Subjects at high risk for transplant related complications and mortality as
defined below:

Ages 10 to 75 (both inclusive) with a history of one of the following:

- Treatment with dose intensive chemotherapy and/or radiotherapy

- Previous history of allo/auto transplant

- History of multiple myeloma or extramedullary plasmacytoma

- Chronic disease or co-morbid medical condition including subjects with symptoms or
signs of significant pulmonary disease, hepatic disease, kidney disease, cardiac
disease or disease of other organ systems which would result in increased risk of
morbidity or death from a standard myeloablative transplant.

Diseases to be included:

- Chronic myelogenous leukemia (CML) chronic phase

- Acute lymphoblastic leukemia (ALL), all subjects in complete or partial remission.

- Acute myelogenous leukemia (AML): AML in first complete or partial remission
Exceptions: AML with good risk karyotypes: AML M3 t(15:17), AML M4Eo (inv. 16), AML
t(8;21). All AML in second or subsequent complete remission.

- Myelodysplastic syndromes: refractory anemia with excess blasts (RAEB), or chronic
myelomonocyte leukemia (CMML).

- Myeloproliferative diseases associated with either cytopenia or uncontrolled
proliferation.

- Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with bulky or
progressive disease despite prior treatment with chemotherapy which includes purine
analogs.

- Non-Hodgkin's lymphoma (NHL)

A) Intermediate or high grade relapsed or progressive despite treatment with standard
therapy ineligible for autologous PBSC transplant.

B) Non-Hodgkin's intermediate or high grade relapsing despite prior autologous transplant.

C) Low grade follicular or small lymphocytic lymphoma (1) high risk patients who have
relapsed following conventional chemotherapy, (2) relapsed following autologous marrow or
PBSC transplant, or (3) chemo resistant disease.

D) Mantle cell lymphoma

E) Non-Hodgkin's lymphoma intermediate or high grade with concurrent BCL2 and MYC
translocations who are at high risk for relapsed and who have low survival with
conventional chemotherapy.

- Hodgkin's disease, relapsed after prior autologous transplant or after 2 or more
combination chemotherapy regimens and ineligible for autologous PBSC transplant.

- EBV driven lymphoproliferative disorders progressing despite standard therapies.

Group B: (Closed to enrollment Oct 2010) Subjects with hematologic diseases associated
with reasonable longevity, shown to be curable by allogeneic BMT but where concern for a
high procedural mortality with conventional BMT may delay or prevent such treatment.

Ages 8 to 80 (both inclusive) with a history of one of the following

- Paroxysmal nocturnal hemoglobinuria (PNH) associated with either life-threatening
thrombosis, cytopenia, transfusion dependence or recurrent and debilitating hemolytic
crisis.

- Aplastic anemia or pure red cell aplasia (acquired or congenital) in subjects
associated with transfusion dependence and/or neutropenia who are not candidates for
or who have failed immunosuppressive therapy

- Refractory anemia (RA) or RARS MDS subjects who have associated transfusion
dependence and/or neutropenia.

Ability to comprehend the investigational nature of the study and provide informed
consent. The procedure will be explained to subjects age 8-17 years with formal consent
being obtained from parents or legal guardian.

Availability of HLA identical or single HLA locus mismatched family donor

INCLUSION CRITERIA - Donor:

HLA identical or single HLA mismatched family donor

Age greater than or equal to 2 up to 80 years old

Weight greater than or equal to 18 kg

Ability of donor or guardian of donor to comprehend the investigational nature of the
study and provide informed consent.

EXCLUSION CRITERIA - Recipient - any of the following:

Pregnant or lactating

Group A: age less than 10 or greater than 75 (multiple myeloma age less than 10 or greater
than 65); Group B: Age less than 8 or greater than 80 years.

ECOG performance status of 3 or more. Psychiatric disorder or mental deficiency severe as
to make compliance with the BMT treatment unlikely and making informed consent impossible.

Major anticipated illness or organ failure incompatible with survival from PBSC transplant

Diffusion capacity of carbon monoxide (DLCO) less than 40% predicted.

Left ventricular ejection fraction: less than 30%.

Serum creatinine greater than 2.5 mg/dl or creatinine clearance less than 50 cc/min by 24
hr urine collection

Serum bilirubin greater than 4 mg/dl, transaminases greater than 5x upper limit of
normal,

Other malignant diseases liable to relapse or progress within 5 years.

EXCLUSION CRITERIA - Donor - any of the following:

Pregnant or lactating

Donor unfit to receive G-CSF and undergo apheresis (uncontrolled hypertension, history of
congestive heart failure or unstable angina, thrombocytopenia)

HIV positive donor. Donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or
human T-cell lymphotropic virus (HTLV I/II) will be used at the discretion of the
investigator following counseling and approval from the recipient