Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

Inclusion criteria

• Presence of a suitable related HLA-haploidentical bone marrow donor.a. The donor and recipient must be identical at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype. 1 year-50 years Patients must have a confirmed histopathologic diagnosis and be classified as high risk defined by having an expected survival of \< 10%. Examples include:
• Neuroblastoma or ganglioneuroblastoma
• Failure to achieve at least a PR after induction therapy with COG ANBL0532 or standard chemotherapy
• Refractory to induction chemotherapy with COG ANBL0532 or standard chemotherapy
• Patients with high risk disease as defined in Appendix 1 whose autologous peripheral blood stem cell product is contaminated with neuroblastoma or who do not have an autologous product available
• Patients with high risk disease as defined in Appendix 1 who do not meet eligibility requirements/organ function requirements for myeloablative conditioning. Patients with \>5 identified lesions on the end of induction (COG ANBL0532 or standard chemotherapy) MIBG scan
• Stage 4 rhabdomyosarcoma
• Metastatic Ewing Sarcoma
• Osteosarcoma with metastatic disease beyond the lungs and/or with lung metastases not amenable to resection
• Desmoplastic small round cell tumor
• Any other solid tumor and soft tissue sarcoma with an estimated \<10% chance of survival will be considered on a case by case basis at the departmental tumor board and/or sarcoma meeting Previous therapy:
• It is expected that patients will have received upfront standard of care therapy for their respected disease
• Patients who relapse after either single or tandem autologous BMT are eligible (\> 6 months must have elapsed from start of last BMT).
• Patients must be recovered from the acute toxicities of any prior chemo/radio/immunotherapy or BMT Patients do not need to have measurable disease at time of enrollment. Patients with measurable disease must have stable disease by RECIST criteria on two scans at least 6 weeks apart. Patients with adequate organ function as measured by
• Cardiac: Left ventricular ejection fraction at rest must be ≥ 35%, or shortening fraction \> 25%.
• Hepatic: Bilirubin ≤ 3.0 mg/dL; and ALT, AST, and Alkaline Phosphatase \< 5 x ULN.
• Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) \> 40 mL/min/1.73m2.
• Pulmonary: FEV1, FVC, DLCO (diffusion capacity) \> 50% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation \> 92% on room air. Good performance status (Karnofsky/Lansky 60-100) Patients (Parents/guardians for those \<18) and donors must be able to sign consent forms. Patients must be willing to participate in all stages of treatment Criteria for recipient ineligibility Patients will not be excluded on the basis of sex, racial or ethnic background. HIV-positive Donor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is available. Positive leukocytotoxic crossmatch Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception Uncontrolled viral, bacterial, or fungal infections. Criteria for donor eligibility Age \>0.5 years Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT). Lack of recipient anti-donor HLA antibody Note: In some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if they are found to be at a level well below that detectable by flow cytometry. This will be decided on a case-by-case basis by the PI and one of the immunogenetics directors. In the event that two or more eligible donors are identified, the following order of priority will be used to determine the preferred donor:
• Medically and psychologically fit and willing to donate
• Killer Immunoglobulin Receptor (KIR) Haplotype B Donor
• Red blood-cell compatibility (in order of preference)
• RBC cross-match compatible
• Minor ABO incompatibility
• Major ABO incompatibility
• For CMV seronegative recipients, a CMV seronegative donor. For CMV seropositive recipients, a CMV seropositive donor is preferred.
• When possible, HLA-mismatched donors will be prioritized over HLA-matched to maximize an allogeneic benefit. If more than one preferred donor is identified from the above list and there is no medical reason to prefer one of them, then the following guidelines are recommended:
• If the patient is male, choose a male donor
• Choose the youngest preferred donor
• If the patient and family express a strong preference for a particular donor, use that one.