Hematopoietic Stem Cell Mobilization in Idiopathic CD4 Lymphocytopenia Patients and Healthy Controls for the Study of T Cell Maturation and Trafficking in Murine Models

This is an interventional basic science trial for Idiopathic CD4-Positive focused on measuring Leukapheresis, Progenitor Cells Read More

• INCLUSION CRITERIA

ICL patients:

1. Documented history of idiopathic CD4 lymphocytopenia as defined by CD4 T cell count <300 cells/microL or <20% of total T lymphocytes on 2 occasions at least 6 weeks apart in the absence of any illness or medications accounting for CD4 lymphocytopenia. Although the protocol will primarily enroll ICL patients who are lymphopenic at the time of enrollment, up to three patients who had clear documentation of ICL in the past and are currently not lymphopenic may still be enrolled for comparative purposes.
2. Hemoglobin greater than or equal to 9 g/dL
3. Human T-lymphotropic virus Type 1 (HTLV-1) and HTLV-2 seronegative
4. Persons with documented history of ICL in whom genetic analysis revealed inherited defects that are either known or suspected to be involved in development, maturation, or homeostasis of hematopoietic cells.

Healthy volunteers: white blood cell count >2500/microL and hemoglobin greater than or equal to 12.5 g/dL

ICL patients and healthy volunteers:

1. Age 18-65 years
2. Weight at least 50 kg but less than 167 kg and <175% ideal body weight (due to lack of data regarding appropriate dosing of plerixafor)
3. Ability to give informed consent
4. Capacity and willingness to adhere to study procedures, including scheduled follow-up visits
5. Willingness to have blood samples stored for future research
6. Willingness to undergo HLA testing
7. Willingness to be hospitalized for approximately 24 hours
8. Established primary care provider
9. HIV-1 and HIV-2 seronegativity and plasma HIV-1 RNA polymerase chain reaction (PCR) below the limit of detection
10. Adequate venous access to allow leukapheresis without use of a central line or a large volume blood draw
11. Participant agrees to be heterosexually inactive or consistently use effective birth control (e.g., barrier methods, oral contraceptives, intrauterine devices, vasesctomy) for the duration of study participation and for approximately 8 weeks after the last dose of G-CSF. This is necessary for both male and female participants.

12. For women of childbearing potential:

    1. Negative serum or urine pregnancy test

EXCLUSION CRITERIA

1. Active uncontrolled infection at the time of enrollment
2. Current autoimmune conditions requiring systemic (oral, injection, or other parenteral) therapy
3. History of vasculitis
4. Current or history of hematologic or lymphoid malignancy (leukemia)
5. History of splenomegaly or current splenomegaly on exam or ultrasound (for ICL patients)
6. History of hypersensitivity to plerixafor and/or G-CSF
7. Systemic immune-modulatory agent within the past 6 months
8. Thrombocytopenia (platelets <100,000 cells/microL)
9. Hepatitis B and C seropositivity (HBsAg positive and anti-HCV positive) Need for anticoagulant medication (e.g., warfarin, heparin), other than aspirin, clopidogrel, or other antiplatelet agent
10. Creatinine clearance <50 mL/min including end-stage renal disease requiring hemodialysis
11. Symptomatic coronary artery disease
12. Uncontrolled hypertension (i.e., resting systolic blood pressure >160 mmHg or resting diastolic blood pressure >90 mmHg) despite pharmacologic antihypertensive treatment confirmed with a second blood pressure measurement done later on the same day
13. Cardiac, pulmonary, thyroid, renal, hepatic, neurological (central or peripheral) disease or disorder of hemostasis requiring therapy and considered to be significant by the protocol team
14. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
15. Currently receiving lithium due to contraindication of co-administration of G-CSF with lithium
16. Past or current psychiatric illness that, in the opinion of the investigator, would interfere with protocol adherence or the ability to give written informed consent
17. Any illness or condition that, in the opinion of the investigator, may substantially increase the risk associated with participation in the study or compromise the scientific objectives
18. Participation in a clinical protocol which includes an intervention that, in the opinion of the investigator, may affect the results of the current study
19. Previous history of anaphylactic reaction to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
20. Female of child-bearing potential who is breast-feeding.