Safety and Efficacy of Abatacept for Treating Chronic Cytopenia in Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Haploinsufficiency

INCLUSION CRITERIA:

Individuals must meet all of the following criteria to be eligible for study participation:

1. Age 8-65 years.
2. Documented CTLA4 mutation (requires documentation of confirmed mutation via Sanger sequencing at a laboratory approved by the Clinical Laboratory Improvement Amendments [CLIA]).

At least one of the following established hematologic abnormalities during the past 6 months (including results from outside CLIA-certified laboratories) prior to screening:

1. ANC < 750 cells/microL.
2. Platelet count < 75,000 cells/microL.
3. Hemoglobin < 7.5 g/dL.
4. The above mentioned hematologic abnormalities should require active treatment with steroids, immunomodulatory agents (e.g., mycophenolate mofetil, cyclosporine, tacrolimus, mercaptopurine, methotrexate, sirolimus, high dose intravenous immunoglobulin [IVIG]), and/or other agents (e.g., TPO agonists) for at least 60 days prior to screening.

The dose of any concomitant medication(s) aimed at treating cytopenia should be stable in the 60 days prior to screening. Stable is defined as:

1. No new concomitant medications for cytopenia were initiated.
2. No dose increase of the medication was required.
3. Did not receive blood product transfusions within 30 days prior to screening.
4. Did not receive abatacept within 60 days prior to screening.
5. Did not receive rituximab within 3060 days of screening.
6. Did not receive alemtuzumab at any time.
7. Has access to healthcare provider at home.
8. Able to provide informed consent.
9. Willing to allow storage of biological specimens for future use in medical research.

Females of childbearing potential must agree to use appropriate birth control methods when engaging in sexual activities that can result in pregnancy, beginning Day -30 through 30 days after the last dose of study agent. Appropriate methods should include 2 forms of contraception, one from each of the following categories:

1. Hormonal contraception or placement of an intrauterine device or intrauterine system.
2. Barrier method: Condom or occlusive cap (diaphragm or cervical/vault cap) with a spermicide.

EXCLUSION CRITERIA:

Patients meeting any of the following criteria are not eligible for this study:

1. History of hypersensitivity to abatacept.
2. Any live vaccines (including attenuated live vaccines) within 6 weeks of screening.
3. History of acquired immunodeficiency diseases, including a positive HIV polymerase chain reaction (PCR) test result.
4. Untreated chronic hepatitis B (positive PCR) or hepatitis C (positive PCR) infection. Patients with chronic hepatitis must be on medical treatment for at least 3 months before screening and have evidence of decreased viral loads after starting treatment.
5. EBV viral load > 4log on 2 or more laboratory checks greater than 1 month apart and within 6 months of screening.
6. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of evidence of local recurrence or metastases.
7. Current active infectious disease (bacterial or fungal) including evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON TB-Gold test. Test results within the past 6 months will be accepted. If presence of latent TB is established, then treatment must be completed before the patient can be considered for enrollment. The patient may also be considered for enrollment after completing treatment of any other active bacterial or fungal infection.
8. Contraindication to PFT or CT scan.
9. Pregnancy or breastfeeding.
10. Any condition that, in the opinion of the investigator, contraindicates participation in this study.