URMC Related Haplo-identical Donor BMT

This study will be a single-center treatment protocol, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit.

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.

Eligibility Criteria:
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 -