Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

A regiszterben nem jelölt feltételek

• 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.