Total Body Irradiation and Astatine-211-Labeled BC8-B10 Monoclonal Antibody for the Treatment of Nonmalignant Diseases

Inclusion Criteria:

• Age >= 18 years and < 50 years

• Nonmalignant disease treatable by allogeneic hematopoietic cell transplantation (HCT). Patients with a nonmalignant disease that is not clearly defined must beapproved by the principal investigator (PI)

• Karnofsky score >= 70

• Patients must have normal elastography

• If ferritin is elevated, patient must have less than 7 mg/g liver iron concentrationon liver T2 magnetic resonance imaging (MRI)

• Patients should have an official gastrointestinal (GI) consult prior to thetransplant for full evaluation

• DONOR INCLUSION

• HLA matched related donor that is genotypically or phenotypically identical forHLA-A, -B, -C, -DRB1, -DQB1. Phenotypic identity must be confirmed byhigh-resolution typing. Sibling donors are preferred over other relationships

• Unrelated donor.

• Matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing; OR

• Mismatched for a single HLA-class 1 allele or HLA-DQB1 antigen or allele byhigh-resolution typing.

Note: A donor homozygous for one allele only at HLA-A, B, C, DRB1, or DQB1 is allowed (1 antigen mismatch for graft versus host disease [GVHD], 0 antigen mismatch for graft-rejection). In the case of a recipient who is homozygous at one locus, the mismatch is not allowed to be at that locus (0 antigen mismatch for GVHD, 1 antigen mismatch for graft-rejection)

• HLA haploidentical donor. There must be one shared HLA-haplotype based oninheritance. The noninherited haplotype is allowed to be mismatched at any or all ofthese loci: HLA-A, B, C, DRB1 or DQB1.

• Donor selection guideline recommendations: in the case where there are multipledonor options, donors should be selected based on the following priority numberedbelow:

• Related donor genotypically HLA-matched

• Related donor phenotypically HLA-matched

• Unrelated donor HLA-matched

• Unrelated donor with single allele level mismatch at class 1 (HLA-A, -B, or -C). For example, HLA-A02:01 versus HLA-A 02:02

• Unrelated donor with single allele level mismatch at DQB1

• HLA-haploidentical donor Note: We require that the donor testing be performedby a United States Clinical Laboratory Improvement Amendment (CLIA) approvedlaboratory. In the very rare case where the donor testing is not able to beperformed in a CLIA approved laboratory, or there is confirmatory testing thatneeds to be performed, or for any donor identified from Europe and at risk forCreutzfeldt-Jakob Disease (CJD), we note this on the donor screening form andrequire that the unrelated donor medical director or the attending physicianapproves the use of the donor HPC-A product under urgent medical need

Exclusion Criteria:

• Patients with Fanconi Anemia

• Impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable toobtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiencyrequiring treatment or symptomatic coronary artery disease. Patients with ashortening fraction of < 26% may be enrolled if approved by a cardiologist. Inaddition, patients with poorly controlled hypertension on multiple anti-hypertensivemedications, symptomatic coronary artery disease, or patients on cardiac medicationsfor antiarrhythmic or inotropic effects are excluded

• Impaired pulmonary function as evidenced by carbon monoxide diffusing capabilitytest (DLCO) < 35% of predicted or receiving supplemental continuous oxygen. Inaddition, if patients are unable to perform pulmonary function tests, then O2saturation < 92% on room air

• Impaired renal function as evidenced by estimated creatinine clearance less than 50ml/min or serum creatinine > 2 x upper normal limit or dialysis-dependent. Serumcreatinine value must be within 28 days prior to start of conditioning

• The creatinine clearance may be estimated by the Cockcroft-Gault formula

• Impaired liver function as evidenced by abnormal hepatic function within 2 monthsprior to the astatine-211 infusion date defined as a total bilirubin, aspartateaminotransferase (AST), and alanine aminotransferase (ALT) > 2 times the upper limitof normal (with the exception of elevated total bilirubin level, predominantlyindirect bilirubin, in patients with hemoglobinopathy due to acute and/or chronichemolysis). In addition, patients with the following liver abnormalities areexcluded: fulminant liver failure, cirrhosis of the liver with evidence of portalhypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy,uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of theprothrombin time, ascites related to portal hypertension, bacterial or fungal liverabscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliarydisease

• An uncontrolled infection requiring deferral of conditioning as recommended by aninfectious disease specialist. A viral upper respiratory tract infection does notconstitute an uncontrolled infection in this context

• Patients who are known to be positive for HIV (human immunodeficiency virus)

• Women of childbearing potential who are pregnant or breast-feeding

• Fertile men or women unwilling to use contraceptive techniques during and for 12months following treatment

• Allergy to murine-based monoclonal antibodies

• Known contraindication to radiotherapy

• DONOR EXCLUSION

• Donors are excluded when preexisting immunoreactivity is identified that wouldjeopardize donor hematopoietic cell engraftment. The recommended procedure forpatients with 10 of 10 HLA allele level (phenotypic) match is to obtain panelreactive antibody (PRA) screens to class I and class II antigens for all patientsbefore hematopoietic cell transplantation (HCT). If the PRA shows > 10% activity,then flow cytometric or B and T cell cytotoxic cross matches should be obtained. Thedonor should be excluded if any of the cytotoxic cross match assays are positive.For those patients with an HLA class I allele or class II allele or antigen mismatchor haploidentical donors, flow cytometric or B and T cell cytotoxic cross matchesshould be obtained regardless of the PRA results. A positive anti-donor cytotoxiccrossmatch is an absolute donor exclusion