Selection of CD34 Positive Stem Cells using CliniMACS Prodigy Device for the Prevention of Graft-versus-Host Disease

Inclusion Criteria

• Patients status post allogeneic hematopoietic stem cell transplantation for a neoplastic hematologic disorder (as defined below) with the need of a CD34 selected stem cell boost for * Graft failure. Graft failure is defined as primary graft failure = patient never engrafted after transplant or secondary graft failure (= persistent cytopenia regardless chimerism after initial engraftment). It is typically associated with thrombocytopenia [< 20,000/μL] and/or frequent [≤ 2 weeks] red blood cells [RBCs] transfusion) * Low graft function is defined as (e.g. marrow cellularity reduced per age and/or dropping donor chimerism with cytopenias and/or platelets or red blood cells transfusion requirement [≤ 2 weeks for at least 2 weeks without improvement]) * Dropping donor chimerism is defined as ≤ 5% full donor chimerism by myeloid markers (e.g. CD15 or CD33) and < 95% donor T cells
• Malignant hematologic conditions with transplant indication per National Comprehensive Cancer Network (NCCN) guidelines, such as: * Acute myeloid leukemia (AML) in morphologic remission with intermediate/high-risk features or relapsed disease * Acute lymphoblastic leukemia (ALL) in morphologic remission with high-risk features or relapsed disease 1 or 2 * Lymphoid malignancies in complete response (CR) or partial response (PR) according to Lugano’s criteria (e.g. non-Hodgkin’s lymphoma, prolymphocytic leukemia, chronic lymphocytic leukemia [CLL]) * Any diagnosis of myelodysplastic syndromes with ≤ 10% blasts * Chronic myeloid leukemia (CML) in morphologic remission after blast phase or accelerated phase * Primary myelofibrosis with ≤ 10% blasts * Morphologic remission is defined as < 5% blasts on the bone marrow biopsy * Negative test for donor-specific antibody within 28 days of starting conditioning regimen, or adequate for standard desensitization protocol
• Age criteria: 0-99 years
• PATIENTS RECEIVING CHEMOTHERAPY CONDITIONING PRIOR TO STEM CELL INFUSION: Normal left ventricular ejection fraction (LVEF) (40% or above) as measured by MUGA or echocardiogram
• PATIENTS RECEIVING CHEMOTHERAPY CONDITIONING PRIOR TO STEM CELL INFUSION: Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and diffuse capacity of the lung for carbon monoxide (DLCO) (corrected) should be 50% or above of expected
• PATIENTS RECEIVING CHEMOTHERAPY CONDITIONING PRIOR TO STEM CELL INFUSION: Serum creatinine level to be ≤ 2 mg/dl AND estimated (Cockcroft-Gault formula) or measured (takes priority if done) creatinine clearance (CrCl) must be equal or greater than 40 mL/min/1.73 m^2
• PATIENTS RECEIVING CHEMOTHERAPY CONDITIONING PRIOR TO STEM CELL INFUSION: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• PATIENTS RECEIVING CHEMOTHERAPY CONDITIONING PRIOR TO STEM CELL INFUSION: Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 x ULN
• PATIENTS RECEIVING CHEMOTHERAPY CONDITIONING PRIOR TO STEM CELL INFUSION: Alkaline phosphatase ≤ 2.5 x ULN
• PATIENTS NOT RECEIVING CONDITIONING PRIOR TO STEM CELL INFUSION: Serum creatinine level to be ≤ 4 mg/dl
• PATIENTS NOT RECEIVING CONDITIONING PRIOR TO STEM CELL INFUSION: Serum bilirubin < 3.1
• All patients must be given written informed consent in accordance with institutional and federal guidelines
• ALLOGENEIC DONOR: High resolution human leukocyte antigen (HLA) typing for HLA-A, B, C and DRB1
• ALLOGENEIC DONOR: Suitability assessment. At a minimum, donors will undergo a comprehensive history and physical examination, in addition to screening labs (complete blood count [CBC], renal and hepatic function tests) to determine their suitability to donate. Additional testing may be required based on the outcome of the clinical assessment
• ALLOGENEIC DONOR: All donors undergo testing through a Food and Drug Administration (FDA) licensed, cleared, or approved kits in a Clinical Laboratory Improvement Act (CLIA)-licensed donor testing facility. A donor stem cell panel is sent to Quest Laboratories (current contract). This includes testing for hepatitis B and C, syphilis, West Nile virus (WNV), Chagas disease, CMV, HIV I/II, human T-lymphotropic virus-1 (HTLV-1), and HTLV-2. HIV, hepatitis b and hepatitis C have both screening tests as well as nucleic acid amplification (NAT) testing utilizing the Procleix ® Ultrio ® Elite assay which is FDA approved to screen for human immunodeficiency virus (HIV), ribonucleic acid (RNA), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) in specimens from individual human donors, including donors of whole blood and blood components, source plasma, human cells and tissues and other living donors. In addition, all prospective donors complete the Be the Match Donor Health History Screening Questionnaire which addresses risk for other transmissible but non-testable conditions such as spongiform encephalopathies exposure to recent vaccinations including smallpox as well as other conditions that may be applicable based on travel, home location or exposure (malaria and zika virus for example). Testing is to be within 30 days of donation. The Foundation for the Accreditation of Cellular Therapy (FACT) requires additional testing of prospective donors including screening for hemoglobinopathies and pregnancy testing on female donors of child bearing potential. As an accredited transplant center we abide the additional requirements as outlined by FACT. Products from ineligible donors will require patient education and signature of the release of donor information form prior to donor’s mobilization, and exceptional release of the products signed by the primary physician and the cell therapy lab medical director, and communication to the FDA as request of approval for infusion
• ALLOGENEIC DONOR: Donor testing for lymphocyte collection is to be performed within 7 days before or after the collection
• ALLOGENEIC DONOR: Allogeneic donors must be at least 14 years of age to undergo evaluation and collection at University of Alabama at Birmingham (UAB) Hospital. Appropriate parental or guardian consent is obtained as applicable. Donors under the age of 14 must be evaluated and managed by Children’s of Alabama, our pediatric facility of UAB’s Blood and Marrow Transplant Program

Exclusion Criteria

• Non-compliant patients
• No appropriate caregivers identified
• Uncontrolled medical or psychiatric disorders which may preclude patients to undergo clinical studies (discretion of the attending physician)
• Pregnant or breastfeeding women
• Exclusion of infectious causes in particular viral infection cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and adenovirus, and parvovirus B19
• No GVHD or stable/improving acute or chronic GVHD less or equal grade 2 on ≤ 0.25 mg/kg prednisone for at least 7 days prior to the stem cell infusion and no change in other eventual medications to treat or prevent GVHD in the last 2 weeks preceding the infusion