a modified dose of rabbit anti-thymocyte globulin (ratg) in children and adults receiving treatment to help prepare their bodies for a bone marrow transplant

Conditions: Acute Myeloid Leukemia (AML); Acute Lymphoid Leukemia (ALL); Myelodysplastic Syndromes (MDS)

Summary: the purpose of this study is to see if conditioning regimens that include personalized rabbit atg (p-ratg) help the immune system recover sooner and decrease the chances of transplant-related side effects. participants in this study will be children and adults who have acute leukemia or myelodysplastic syndrome (mds), and will receive a standard conditioning regimen to prepare the body for an allogeneic hematopoietic cell transplant (allo-hct). the conditioning regimen will include r-atg, one of two combinations of chemotherapy, and possibly total body irradiation (tbi).


Eligibility criteria:
inclusion criteria: * patients receiving first peripheral blood mobilized ex-vivo cd34-selected t cell depleted allo-hct for the following hematologic malignant conditions: * acute myeloid leukemia (aml) with intermediate or high-risk features in cr1 or relapse aml in ≥ cr2. * must have mrd \<5% (flow cytometry, molecular and/or cytogenetics accepted). * acute leukemias of ambiguous lineage in ≥ cr1. * must have mrd \<5% (flow cytometry, molecular and/or cytogenetics accepted). * acute lymphoid leukemia (all) in cr1 with clinical, flow cytometric, or molecular features indicating a high risk for relapse, or all in ≥ cr2. * adult patients - recommended but not required to be mrdnegative (by flow cytometry, molecular and/or cytogenetics). * pediatric patients - must be mrd-negative by flow cytometry, molecular and/or cytogenetics. * myelodysplastic syndromes (mds) with least one of the following: * revised international prognostic scoring system risk score of intermediate or higher at the time of transplant evaluation. * life-threatening cytopenia. * karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of tp53, or complex or monosomal karyotype. * therapy related disease or disease evolving from other malignant processes. * able to tolerate cytoreduction * patients age: * regimen a: 4 - 60 years * regimen b - no age restriction * adequate organ function is required, defined as follows: * hepatic: serum bilirubin ≤ 2 mg/dl, unless benign congenital hyperbilirubinemia. patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders are eligible with pi approval. * hepatic: ast, alt, and alkaline phosphatase \< 2.5 times the upper limit of normal unless thought to be disease-related. * renal: serum creatinine \ 50 ml/min/1.73m2 (calculated or estimated) or gfr (ml/min/1.72m2) \>30% of predicted normal for age. * normal gfr by age * 1 week 40.6 + / - 14.8 * 2 - 8 weeks 65.8 + / - 24.8 °\> 8 weeks 95.7 +/- 21.7 * 2 - 12 years 133 +/- 27 * 13 - 21 years (males) 140 +/- 30 * 13 - 21 years (females) 126.0 + / - 22.0 * cardiac: lvef ≥ 50% by muga or resting echocardiogram. * pulmonary: pulmonary function testing (fev1 and corrected dlco) ≥ 50% predicted (pediatric patients unable to complete pfts will need oxygen saturation as recorded by pulse oximetry of ≥92% on room air). * adequate performance status: * age ≥ 16 years: ecog ≤ 1 or karnofsky 70% * age \< 16 years: lansky 70% * each patient must be willing to participate as a research subject and must sign an informed consent form or legal guardian with assent as appropriate. exclusion criteria: * patients with active extramedullary disease. * patients with active central nervous system malignancy. * uncontrolled infection at the time of allo-hct. * patients who have undergone previous allo-hct. * patient seropositivity for hiv i/ii and/or htlv i/ii. * females who are pregnant or breastfeeding. * patients unwilling to use contraception during the study period. * patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests. donor inclusion criteria: * related or unrelated donors: °8/8 hla matched at a, b, c, and drb1 loci, as tested by dna analysis. * able to provide informed consent for the donation process per institutional standards. * meet standard criteria for donor collection (e.g. national marrow donor program guidelines or collecting center guidelines as approved by treating physician). * provide gscf mobilized peripheral blood stem cells

Keywords: personalized rabbit atg (p-ratg) ex-vivo cd34+ t cell depleted total body irradiation thiotepa cyclophosphamide busulfan melphalan fludarabine 21-193