Pilot and Feasibility Study of Reduced-Intensity Hematopoietic Stem Cell Transplant for MonoMAC

• INCLUSION CRITERIA RECIPIENT:
• Patient age of 12-60 years
• GATA2 Mutation Syndrome
• Clinical history of at least two episodes of life-threatening infection with opportunistic organisms, one of which is a MAC infection.
• Mutation in the GATA2 gene performed by the CLIA certified laboratory of Dr. Steven Holland of the NIAID Institute of the NIH.
• Available 10/10 HLA-matched related or 8/8 matched unrelated donor, or 4/6 (or greater) matched UCB unit(s) with a total dose of greater than or equal to 3.5 times 10(7) TNC/kg.
• Patients may have evidence of MDS with one or more peripheral blood cytopenias and greater than 5% blasts but less than 10% blasts in the bone marrow in the absence of GCSF.

Patients previously treated for acute myelogenous leukemia are eligible if they have less than or equal to 10% blasts in the bone marrow in the absence of G-CSF.

Subjects 12-17 years of age are required to have MDS with chromosomal abnormalities in addition to mutation in the GATA2 gene for enrollment on this protocol.

• Left ventricular ejection fraction > 50%, preferably by 2-D echo, or by MUGA, or shortening fraction > 28% by ECHO, obtained within 28 days of enrollment.
• Pulmonary Function Tests: Adult patients: DLCO diffusion capacity and FEV1 greater than 10% of expected value obtained within 28 days of enrollment. Pediatric patients: DLCO corrected for hemoglobin and alveolar volume greater than or equal to 20% of predicted.
• Creatinine: Adult patients: less than or equal to 2.0 mg/dl and creatinine clearance greater than or equal to 30 ml/min; Pediatric patients: age-adjusted normal serum creatinine OR a creatinine clearance > 60 mL/min/1.73m(2).
• Serum total bilirubin less than 2.5 mg/dl; ALT and AST less than or equal to 5 times upper limit of normal .
• Adequate central venous access potential.
• Written informed consent/assent obtained from patient/parent or legal guardian.
• Life expectancy of at least 3 months but less than 24 months.
• Disease status: Patients are to be referred in remission for evaluation. Should a patient have progressive disease or a donor not be available after enrollment, the patient will be referred back to their primary hematologist-oncologist for treatment. If this course of action is not in the best interest of the patient according to the clinical judgment of the PI/LAI, then the patient may receive standard treatment for the malignant disease under the current study. If under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off study. Recipient-Subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol.

EXCLUSION CRITERIA- RECIPIENT:

• HIV infection.
• Chronic active hepatitis B. Patient may be hepatitis B core antibody positive. For patients with a concomitant positive hepatitis B surface antigen, patients will require a hepatology consultation. The risk-benefit profile of transplant and hepatitis B will be discussed with the patient, and eligibility determined by the PI and the protocol chairperson.
• History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
• Active infection that is not responding to antimicrobial therapy.
• Active CNS involvement by malignancy (patients with known positive CSF cytology or parenchymal lesions visible by CT or MRI.
• Pregnant or lactating.
• Sexually active individuals capable of becoming pregnant who are unable or unwilling to use effective form(s) of contraception during time enrolled on study and for 1 year post-transplant. Effective forms of contraception include one or more of the following: intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligatio