yttrium-90 anti-cd45 monoclonal antibody bc8 followed by donor stem cell transplant in treating patients with high-risk aml, all, or mds

Conditions: Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

Summary: this phase i trial studies the side effects and maximum tolerated dose of yttrium y 90 anti-cluster of differentiation 45 (cd45) monoclonal antibody bc8 (90y-bc8) followed by donor stem cell transplant in treating patients with acute myeloid leukemia (aml), acute lymphoblastic leukemia (all), or myelodysplastic syndrome (mds) that is likely to come back or spread. giving chemotherapy drugs, such as fludarabine phosphate (flu), and total-body irradiation (tbi) before a donor peripheral blood stem cell (pbsc) or bone marrow transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. radiolabeled monoclonal antibodies, such as 90y-bc8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. when the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. giving flu, 90y-bc8, and tbi before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

primary objectives: i. to estimate the maximum tolerated dose (mtd) of radiation delivered via 90y-dota-bc8 (90y-bc8) when combined with flu and 2 gy tbi as a preparative regimen for patients aged \>= 18 with advanced aml, all, and high-risk mds. secondary objectives: i. to determine disease response and duration of remission. ii. to determine the rates of engraftment and donor chimerism resulting from this combined preparative regimen, and to correlate level of donor chimerism with estimated radiation doses delivered to hematopoietic tissues via antibody. outline: preparative regimen: patients receive 90y-bc8 via central line on approximately day -12 and flu intravenously (iv) over 30 minutes on days -4 to -2. transplantation: patients undergo tbi followed by allogeneic pbsc or bone marrow transplant on day 0. graft-vs-host disease (gvhd) prophylaxis: patients receive mycophenolate mofetil orally (po) or iv every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on days 0-40 with taper to day 96 (for patients with unrelated donors). patients also receive cyclosporine po or iv every 12 hours on days -3 to 56 (for patients with related donors) or 100 (for patients with unrelated donors) with taper to day 180. after completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24 months, and then annually thereafter.

Eligibility criteria:
inclusion criteria: * patients must have advanced aml, all or high-risk mds meeting one of the following descriptions: * aml or all beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen) * aml or all representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens) * aml evolved from myelodysplastic or myeloproliferative syndromes; or * mds expressed as refractory anemia with excess blasts (raeb) or chronic myelomonocytic leukemia (cmml) by french-american-british (fab) criteria * patients not in remission must have cd45-expressing leukemic blasts; patients in remission do not require phenotyping and may have leukemia previously documented to be cd45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up \>= 95% of nucleated cells in the marrow) * patients should have a circulating blast count of less than 10,000/mm\^3 (control with hydroxyurea or similar agent is allowed) * patients must have an estimated creatinine clearance greater than 50/ml per minute (serum creatinine value must be within 28 days prior to registration) * bilirubin \< 2 times the upper limit of normal * aspartate aminotransferase (ast) and alanine transaminase (alt) \< 2 times the upper limit of normal * eastern cooperative oncology group (ecog) =\ = 70 * patients must have an expected survival of \> 60 days and must be free of active infection * patients must have an human leukocyte antigen (hla)-identical sibling donor or an hla-matched unrelated donor who meets standard seattle cancer care alliance (scca) and/or national marrow donor program (nmdp) or other donor center criteria for pbsc or bone marrow donation, as follows: * related donor: related to the patient and genotypically or phenotypically identical for hla-a, b, c, drb1 and dqb1; phenotypic identity must be confirmed by high-resolution typing * unrelated donor: * matched for hla-a, b, c, drb1 and dqb1 by high resolution typing; or mismatched for a single allele without antigen mismatching at hla-a, b or c as defined by high resolution typing but otherwise matched for hla-a, b, c, drb1 and dqb1 by high resolution typing * doors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 hla allele level (phenotypic) match is to obtain panel reactive antibody (pra) screens to class i and class ii antigens for all patients before hematopoietic cell transplant (hct); if the pra shows \> 10% activity, then flow cytometric or b and t cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with and hla class i allele mismatch, flow cytometric or b and t cell cytotoxic cross matches should be obtained regardless of the pra results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion * patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch; i.e., the patient is a\*0101 and the donor is a\*0102, and this type of mismatch is not allowed * donor: donors must meet hla matching criteria and standard scca and/or national marrow donor program (nmdp) or other donor center criteria for pbsc or bone marrow donation exclusion criteria: * circulating human anti-mouse antibody (hama) * prior radiation to maximally tolerated levels to any critical normal organ, or \> 20 gy prior radiation to large areas of the bone marrow (e.g., external radiation therapy to whole pelvis) * patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects * left ventricular ejection fraction \< 35% * corrected diffusion lung capacity of carbon monoxide (dlco) \< 35% or receiving supplemental continuous oxygen * liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease * patients who are known to be seropositive for human immunodeficiency virus (hiv) * perceived inability to tolerate diagnostic or therapeutic procedures * active central nervous system (cns) leukemia at time of treatment * women of childbearing potential who are pregnant (beta-human chorionic gonadotropin positive \[hcg+\]) or breast feeding * fertile men and women unwilling to use contraceptives during and for 12 months post-transplant * inability to understand or give an informed consent