donor stem cell transplantation using α/β+ t-lymphocyte depleted grafts from hla mismatched donors

Conditions: Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML); Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia

Summary: this study is being done to learn whether a new method to prevent rejection between the donor immune system and the patient's body is effective.


Eligibility criteria:
subject inclusion criteria: * patients with any of the following hematologic malignancies who are considered to be eligible for allogeneic transplantation: * acute lymphoid leukemia (all) in first complete remission (cr1) with high risk for relapse including: * detectable minimal residual disease by either multicolor flow cytometry or by genomic assay after initial induction therapy * t(9;22) or detected bcr-abl1 translocation by genomic methodologies * bcr-abl1-like b-all \[23\] including mutations of ikzf1 or crlf2 * translocations or mutations involving 11q23 (mll) gene. * hypodiploid karyotype * deletion of 9p * loss of 17p or tp53 mutation * t-lymphocyte lineage antigen expression (t-all) * prior cns or other extramedullary involvement * wbc count ≥ 100,000 cells/μl at diagnosis * acute biphenotypic or bilineal leukemia in cr1 * acute myeloid leukemia (aml) in cr1 with * detectable minimal residual disease (mrd) by either multicolor flow cytometry or by genomic assay after initial induction therapy * in the absence of mrd any intermediate or high risk features according to the european leukemianet 2017 guidelines indlucing: * mutated fl t3-itd or fl t3-tkd * cytogenetic abnormalities not classified as favorable * cytogenetic abnormalities associated with myelodysplastic syndrome including abnormalities of chromosome 5, 7, or 17p * complex karyotype or monosomal karyotype * t(9;11)(p21.1;q23.3); mll-kmt2a or other rearrangements of kmt2a * t(9;11); bcr-abl1 * inversions or translocations of chromosome 3 * t(6;9)(p23;q34.1); dek-nup214 * somatic mutation of runx1, asx1 or tp53 * extramedullary involvement * wbc count ≥100,000 cells/μl at diagnosis * relapsed acute leukemia with ≤ 5% blasts in the bone marrow prior to transplantation (i.e. cr2 or greater). * myelodysplastic syndrome, myeloproliferative neoplasms, or mds/mpn overlap syndrome with ≤ 10% blasts and at least one of the following: * revised international prognostic scoring system risk score of int, high, or very high at the time of transplant evaluation. * life-threatening cytopenias * 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. * chronic myelomonocytic leukemia (cmml) with ≤ 10% blasts prior to transplantation. * chronic myeloid leukemia (cml) meeting one of the following criteria: * failed or are intolerant to bcr-abl tyrosine kinase inhibitors. * cml with bcr-abl mutation consistent with poor response to tyrosine kinase inhibition (e.g. t351i mutation). * cml with accelerated or blast phase with \<10% blasts after therapy. * chronic lymphocytic leukemia (cll) with high risk disease as defined by the ebmt consensus criteria * hodgkin lymphoma meeting both of the following criteria: * responding to therapy prior to enrollment * relapse after autologous bone marrow transplant or are ineligible for autologous bone marrow transplant. °non-hodgkin lymphoma meeting both of the following criteria: * responding to therapy prior to enrollment. * relapse after prior autologous bone marrow transplant or are ineligible for autologous bone marrow transplant. * patients aged from birth through 65 years old are eligible. * patients must have karnofsky/lanksy performance status ≥70%. * cardiac left ventricular ejection fraction ≥50% at rest. * serum bilirubin ≤ 2 mg/dl. patients with gilbert's disease or ongoing hemolytic anemia are acceptable if the direct bilirubin is ≤ 2 mg/dl. * ast and alt ≤ 2.5 x uln unless thought to be disease related * estimated or measured creatinine clearance \> 50 ml/min/1.73 m\^2 body surface area. * adult patients and pediatric patients capable of performing pulmonary function studies must have hemoglobin adjusted pulmonary dlco ≥50% of predicted. subject exclusion criteria: * persons with a hla matched sibling donor or a 8/8 allele level hla-matched unrelated donor. * female patients who are pregnant or breast-feeding. * persons with an infection that is not responding to antimicrobial therapy. * persons who are seropositive for hiv. * persons with active/detectable central nervous system malignancy. * persons who do not meet the age and organ function criteria specified above. * presence of psychiatric or neurologic disease, or lack of social support that limits the patient's ability to comply with the treatment protocol including supportive care, followup, and research tests. * prior allogeneic hematopoietic cell transplantation are ineligible. * patients with history of other malignancy within 5 years of study therapy are ineligible with the following exceptions: low grade prostate cancer (gleason's ≤6) treated with curative intent, breast ductal carcinoma in situ treated with curative intent, or nonmelanomatous skin carcinomas. donor inclusion and exclusion criteria: * partially hla-matched unrelated volunteers (allele level matched at 6-7 of 8 hla loci: -a, -b, -c, and -drb1) are eligible. * related, haploidentical donors are eligible. * able to provide informed consent to the donation process * meet standard criteria for donor collection as defined by the national marrow donor program guidelines.

Keywords: allogeneic hematopoietic cell transplantation α/β+ t-lymphocyte 18-224