URMC Related Haplo-identical Donor BMT

This study will be a single-center treatment protocol with five possible preparative
regimens, designed to validate the process of related donor haploidentical-SCT at the Wilmot
Cancer Institute Blood and Marrow Transplant Unit. Enrolled patients will receive
chemotherapy +/- radiation as a pre-transplant conditioning regimen. Patients will then
receive haploidentical stem cells, either bone marrow or mobilized peripheral blood, followed
by GvHD prophylaxis that will include cyclophosphamide. Multiple data points will be
collected prior to, during, and following transplantation to ensure safety of the process and
to evaluate the stated objectives.

Inclusion Criteria:

Patient Age:

- Pediatric (ages 6 months to 18 years)

- Adult (ages 18-75 years)

Disease:

Congenital and Other Non-malignant Disorders

- Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich
Syndrome)

- Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital
Osteopetrosis, Osteogenesis Imperfecta)

- Metabolic disorders (e.g. Hurler's Syndrome)

- Hemoglobinopathies (e.g. Sickle Cell Disease, Thalassemia)

- Severe aplastic anemia

High-Risk Leukemias

Acute Myelogenous Leukemia

- Refractory to standard induction therapy (more than 1 cycle required to achieve
remission)

- Recurrent (in CR≥2)

- Treatment-related AML or MDS

- Evolved from myelodysplastic syndrome

- Presence of Flt3 abnormalities

- FAB M6 or M7

- Adverse cytogenetics

Myelodysplastic Syndrome

Acute Lymphoblastic Leukemia including T lymphoblastic leukemia

- Refractory to standard induction therapy (time to CR >4 weeks)

- Recurrent (in CR ≥2)

- WBC count >30,000/mcL at diagnosis

- Age >30 at diagnosis

- Adverse cytogenetics, such as (t(9:22), t(1:19), t(4:11), other MLL rearrangements.

Chronic Myelogenous Leukemia in accelerated phase or blast crisis

Biphenotypic or undifferentiated leukemia

Burkitt's leukemia or lymphoma

Lymphoma:

- Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemosensitive, and
ineligible for an autologous stem cell transplant or previously treated with
autologous SCT

- Marginal zone or follicular lymphoma that is progressive after at least two prior
therapies

Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible
for an autologous HSCT

Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and
disease status

Graft failure following prior related donor, unrelated donor or UCB transplant

Myelofibrosis

Exclusion Criteria:

1. Patient Age below 6 months or over 75 years

2. Availability of a 10/10 HLA-matched related or unrelated donor within a reasonable
time-frame dictated by the clinical urgency of the transplant

3. Autologous HSCT < 6 months prior to proposed haplo-SCT

4. Pregnant or breast-feeding

5. Current uncontrolled infection

6. Evidence of HIV infection or positive HIV serology

7. Anti-donor HLA antibodies with positive crossmatch and unsuccessful -