Partially-Matched Donor Stem Cell Transplant in Treating Younger Patients with High-Risk Hematologic Malignancies

Inclusion Criteria

• Patients must have histo-pathologically confirmed diagnosis of hematologic malignancy (leukemia or lymphoma); patients to be considered will either have resistant/refractory hematologic malignancies (disease exceeding 5% by morphology or with measurable extramedullary diseases: e.g. nodal disease or chloroma) or have relapsed following an initial allogeneic HSCT; alternatively, they will have a hematologic malignancy where allogeneic HSCT is indicated and their disease is in a state of remission, but they lack a well matched donor: related, unrelated donor (URD) or umbilical cord blood (UCB) HSC source (less than 7 of 8 URD match, less than 4 of 6 UCB match and/or less than 2 x10^5 CD 34+ HSC/kg in a matched UCB product); patients between 19 and 24 years of age will have been previously diagnosed and cared for by a Pediatric Oncologist
• Fractional shortening (FS) > 27%
• Diffusing capacity of the lungs for carbon monoxide (DLCO) > 50% corrected for hemoglobin
• Creatinine clearance > 50 ml/min/1.73 m^2 (Schwartz formula)
• Serum bilirubin < 2x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 4x ULN, unless secondary to disease
• For children who are unable to perform pulmonary function tests but have no evidence of dyspnea at rest nor exercise intolerance nor abnormal chest X-ray (CXR), a pulse oximetry > 94% on room air is acceptable
• Central vascular access device(s) (e.g. infusaport, tunneled central veinous catheter [CVC] &/or peripherally inserted central catheter [PICC] line) providing a combined 3 access ports is advised for all patients
• The recipient and/or the recipient's legal guardian must have been informed of the investigational nature of this study and have signed a consent form which is in accordance with Federal guidelines
• Haploidentical Related Donor Selection Criteria: the recipient must have a related donor haploidentical for HLA A, B, C, and DR (i.e. matched at one locus); they may be partially matched on the other haplotype; if a matched sibling donor is available but disease status (poor disease control, recurrence after allogeneic HSCT) precludes treatment on other protocols, a haplo-identical relative is preferred as the HSC (cluster of differentiation [CD]34+ cell) source
• Concomitant administration of investigational drugs is not allowed; if investigational drugs were given, their use should be completed as guided by that protocol prior to initiation of cytoreduction on this protocol; if the patient is being treated for secondary (treatment related) myelodysplasia after treatment for a non-hematologic malignancy (e.g. Sarcoma), the primary disease should be in remission for at least 6 months after completing primary therapy; patients with secondary myelodysplasia after treatment of a lymphoma, may proceed with treatment with the lymphoma responding or stable but not progressing
• DONOR: Medical history and physical examination confirm good health status as defined by institutional standards (see Lurie Children’s Hospital of Chicago Stem Cell Transplant Program policy VII-B entitled Allogeneic Donor Identification, Evaluation, Education, Consent and Management)
• DONOR: Donor is to be negative for human immunodeficiency virus (HIV) antigen (Ag), HIV 1+2 antibody (Ab), human T-lymphotropic virus (HTLV) I/II Ab, hepatitis B surface antigen (HbsAg), hepatitis B core antibody (HbcAb) (immunoglobulin [Ig]M [combination screening test] and IgG), hepatitis C virus (HCV), and rapid plasma reagin (RPR) for syphilis within 30 days of apheresis collection; if the only donor is positive for Hepatitis B or C or syphilis, the recipient must be notified - the recipient may proceed if Principal Investigator (PI), recipient and donor agree and there is no alternative related donor
• DONOR: Haploidentical-(related) donor’s age should be 4-60 years and weigh > than 20 kg; general preference of related haplo-identical marrow HSC donors prioritizes male relatives over female relatives and younger age balanced with size and ease/safety of marrow collection
• DONOR: HLA matching criteria
• DONOR: Female donors of child-bearing potential (> 7 yo) must have a negative serum or urine beta-HCG test within three weeks of marrow donation and agree to utilize contraception if sexually active
• DONOR: Cell yield goal (post CD34 determination): > 1-6 x10^6 CD34+ cells/kg recipient
• DONOR: The donor, or legal guardian, must have been informed of the investigational nature of this study and have signed a consent form in accordance with Federal Guidelines

Exclusion Criteria

• Females of childbearing potential (> 7 years old [yo]) must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test prior to initiation of cytoreductive therapy; sexually active patients will be informed of the risk of not using adequate contraception
• Patients excluded from this protocol are those with high risk hematologic malignancies in remission (and no prior allogeneic HSCT), where allogeneic HSCT is indicated but an appropriately matched HSC source (sibling, unrelated adult or UCB) is available
• Patients with systemic infections and/or organ dysfunction mandating a reduced intensity conditioning regimen are also excluded