T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia

Inclusion criteria

• Patients with one of the high risk myeloid diseases as outlined below. Patients must have ≤ 5% blasts on the last BM evaluation prior to starting the conditioning regimen. Diseases included on this protocol include:

• Acute Myeloid Leukemia (AML) in CR1 with intermediate or high risk features as defined below:

°Cytogenetic abnormalities which are not considered "good risk" cytogenetic features (i.e t(8:21), t(15:17), inv 16 without c-kit mutations.

And/or

• Therapy related AML with history of antineoplastic therapy (radiation and/or chemotherapy) And/or
• Normal karyotype with mutations of FLT3, RUNX1, TP53 mutation, ASXL1 or any others that are considered to be high risk
• AML in ≥ 2nd remission
• Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap syndrome with:

°International prognostic scoring system risk score INT-2 or high risk at the time of transplant evaluation.

And/or

• Any risk category if life-threatening cytopenia exists And/or
• Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
• Chronic myelomonocytic leukemia (CMML)
• Chronic myeloid leukemia (CML) with the following features:

°Patients who have failed or are intolerant to BCR-ABL tyrosine kinase inhibitors.

And/or

°CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g T351l mutation)

• Patients with severe aplastic anemia
• Chronic lymphocytic leukemia (CLL) with high risk disease as defined by the EBMT consensus criteria.
• Non-Hodgkin lymphoma meeting both of the following criteria:

• Responding to therapy prior to enrollment.
• Relapse after prior autologous bone marrow transplant or are ineligible for autologous bone marrow transplant.
• Multiple Myeloma with disease in the following categories:

• Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy
• Patients with high risk cytogenetics at diagnosis must have achieved at least a partial response following autologous stem cell transplantation. Patients must have complex karyotype, del17p, t4;14, and/or t14;16 by FISH and/or del13 by karyotyping.
• Each patient must be willing to participate as a research participant and must sign an informed consent form.
• Organ Function and Performance Status Criteria:

• Patients be ≥ 18 years old.
• Patients must have a Karnofsky (adult) or Performance Status ≥ 70%.
• Patients must have adequate organ function measured by:

• Cardiac: asymptomatic or if symptomatic, then LVEF at rest must be ≥ 40% and must improve with exercise.
• Hepatic: < 5x ULN ALT and < 2x ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
• Renal: CrCl >30ml/min (measured or calculated/estimated).
• Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)

Exclusion criteria

• Prior allogenic hematopoietic stem cell transplantation
• Prior radiation therapy with 400cGY or more of TBI
• BM with increased fibrosis (Reticulin stain > 1/3)
• Active and uncontrolled infection at time of transplantation
• HIV infection
• Seropositivity for HTLV-1
• Inadequate performance status/ organ function
• Pregnancy or breast feeding
• Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests.

Donor Inclusion and Exclusion Criteria:

• Must be a 10/10 HLA genotypically match related or unrelated donor at all A, B, C, DRB1, and DQB1 loci, as tested by DNA analysis
• Able to provide informed consent for the donation process per institutional standards
• Meet standard criteria for donor collection as defined by the National Marrow Donor Program Guidelines