Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells, Mononuclear Cells and Granulocytes
The research goal of this study is to obtain CD34+ hematopoietic stem cells (HSC) from peripheral blood and/or bone marrow, and Mononuclear Cells (lymphocytes and monocytes), and granulocytes (grans) from peripheral blood that will be used in the laboratory and/or in the clinic to develop new cell therapies for patients with inherited or acquired disorders of immunity or blood cells. Development of novel cellular therapies requires access to HSC, Mononuclear Cells and/or granulocytes as the essential starting materials for the pre-clinical laboratory development of gene therapies and other engineered cell products. HSC or blood cells from healthy adult volunteers serve both as necessary experimental controls and also as surrogates for patient cells for clinical scale-up development. HSC or blood cells from patients serve both as the necessary experimental substrate for novel gene therapy and cellular engineering development for specific disorders and as pre-clinical scale up of cellular therapies. Collection of cells from adult patients collected in the NIH Department of Transfusion Medicine (DTM) under conditions conforming to accepted blood banking clinical practice may also be used directly in or cryopreserved for future use in other NIH protocols that have all required regulatory approvals allowing such use. In summary, the research goal of this protocol is the collection of HSC or blood cells that may be used for both laboratory research and/or for clinical treatment in other approved protocols.
• ELIGIBILITY CRITERIA:
‣ Patients (Patients with a genetically defined PID or other blood disorder or clinical history consistent with PID or other blood disorder)
⁃ Patients will have a genetically defined PID or have a clinical history of recurrent infections or other problems suggestive of PID or other blood disorder, must be 18-70 years of age,
⁃ Some patients may have active bacterial or fungal infection at the time of study entry.
⁃ Preserved renal function (creatinine less than or equal to 2.5 mg/dL; less than or equal to 3+ proteinuria); preserved hepatic function (bilirubin less than or equal to 2.0 mg/dl); preserved hematologic function (WBC greater than or equal to1000/mm\^3;granulocytes greater than or equal to 500/mm\^3; platelets greater than or equal to 100,000; hematocrit greater than or equal to 25). Of note, patients with PID often have associated chronic thrombocytopenia. Patients with stable chronic thrombocytopenia will be eligible for collection, at the investigator s discretion, with the caveat that patients with platelet count \<40,000 the day prior to collection will be transfused with platelets on the morning of collection. Platelets may also be given to these patients following the collection if medically indicated..
⁃ Patients of childbearing potential may be entered if using effective contraception and having a negative serum or urine pregnancy test within one week of beginning G-CSF administration.
⁃ Patients may remain on their regimen of prophylactic treatments as deemed necessary by the investigator.
⁃ Willingness to allow blood cell samples to be stored
⁃ Willingness to allow blood and/or bone marrow samples to be modified to iPS cells
‣ Healthy Adult Volunteers
⁃ Healthy adults aged 18-65 without active current infection or history of recurrent infection,
⁃ Weighs at least 50kg.
⁃ Normal renal function (creatinine less than or equal to 1.5 mg/dL; less than or equal to 1+ proteinuria); normal hepatic function (bilirubin less than or equal to 1.5 mg/dL); normal hematologic function (WBC greater than or equal to 2500/mm\^3; granulocytes greater than or equal to 1200/mm\^3; platelets greater than or equal to 120,000; hematocrit greater than or equal to 38).
⁃ Normal female volunteers of childbearing potential may be entered if using effective contraception and having a negative serum or urine pregnancy test within one week of beginning GCSF administration.
⁃ Willingness to allow blood cell samples to be stored
⁃ Willingness to allow blood and/or bone marrow samples to be modified to iPS cells
‣ For PBMCs and grans collections, adult subjects with known genetic mutations may participate as healthy volunteers for research purposes as long as the other criteria listed above are fulfilled.