ex-vivo expanded donor regulatory t cells for prevention of acute graft-versus-host disease

Conditions: Graft Versus Host Disease

Summary: clinical trial of allospecific regulatory t cells (tregs) for prevention of acute graft-versus-host disease (gvhd) in human leukocyte antigen (hla) identical sibling transplants.

to evaluate the safety of sirolimus based immune suppression and ex-vivo expanded donor regulatory t cells for the prevention of acute graft-versus-host disease following allogeneic hematopoietic cell transplantation.

Eligibility criteria:
inclusion criteria: * signed informed consent * diagnoses: a. hematologic malignancies - acute myelogenous leukemia (aml), acute lymphoblastic leukemia (all), myelodysplastic syndrome (mds), chronic lymphocytic leukemia (cll), non-hodgkin lymphoma (nhl), hodgkin lymphoma (hl), multiple myeloma (mm) - in complete remission (cr). complete remission is defined per morphologic, cytogenetic, fish, molecular, and radiographic imaging studies appropriate for each condition listed. * aml, all: normal values for absolute neutrophil count (\>1000/microl) and platelet count (\>100,000/microl); absence of extramedullary leukemia; less than 5 percent blast cells present in the bone marrow * mds: bone marrow with ≤5 percent myeloblasts with normal maturation of all cell lines; peripheral blood demonstrates hemoglobin ≥11 g/dl, platelets ≥100 x 10\^9/l, neutrophils ≥1 x 10\^9/l, and no circulating blasts * cll: absence of constitutional symptoms attributable to cll; no lymph nodes \>1.5 cm in diameter on computed tomography; no hepatomegaly or splenomegaly by computed tomography; absolute neutrophil count \>1500/microl; platelet count \>100,000/microl; no clonal lymphocytes in the peripheral blood by immunophenotyping; bone marrow with no evidence of clonal cll (by flow cytometry and/or immunohistochemistry * nhl: no clinical evidence of disease or disease-related symptoms; typically fdg-avid lymphomas: a post-treatment residual mass of any size is permitted as long as it is pet negative; variably fdg-avid lymphoma/fdg avidity unknown: all lymph nodes normal size by ct; spleen and liver non-palpable and without nodules; if pretreatment bone marrow biopsy was positive, repeat bone marrow biopsy must be negative; if morphologically indeterminate, immunohistochemistry should be negative if pretreatment bone marrow biopsy was positive, repeat bone marrow biopsy must be negative; if morphologically indeterminate, immunohistochemistry should be negative * hl: no clinical evidence of disease or disease-related symptoms; a post-treatment residual mass of any size is permitted as long as it is pet negative; spleen and liver must be non-palpable and without nodules; if a pre-treatment bone marrow biopsy was positive, an adequate bone marrow biopsy from the same site must be cleared of infiltrate; if this is indeterminate by morphology, immunohistochemistry should be negative * mm: absence of monoclonal protein in serum and urine by immunofixation with no current evidence of soft tissue plasmacytoma; bone marrow aspirate and biopsy must demonstrate less than 5 percent clonal plasma cells; in patients who lack measurable m proteins in the serum and urine being monitored using the flc levels, the definition of cr requires a normalization of the free light chain (flc) ratio in addition to the above criteria * mds: may have achieved cr through either hypomethylating agent therapy, induction chemotherapy, or other therapy * mds: low/intermediate-1 ipss risk category patients are eligible only if they have failed prior therapy or are transfusion-dependent * peripheral blood white blood count (wbc) greater than 2,000 per microliter (required for collection of dendritic cell precursors) * adequate vital organ function: left ventricular ejection fraction (lvef) ≥ 45% by multigated acquisition (muga) scan or echocardiogram; forced expiratory volume in one second (fev1), forced vital capacity (fvc), and diffusing lung capacity oxygenation (dlco) ≥ 50% of predicted values on pulmonary function tests; transaminases (ast, alt) \< 3 times upper limit of normal values; creatinine clearance ≥ 50cc/min * infectious disease criteria: * no active infection; infection controlled with antimicrobial therapy is not excluded * hiv negative by elisa or reverse transcription polymerase chain reaction (rt-pcr) \[if elisa is positive and rt-pcr is negative, the elisa is considered false positive\] * hepatitis b and c negative by serology or rt-pcr * must complete full screening panel: hiv 1, 2 serology and rt-pcr; human t cell lymphotropic virus types 1/2 (htlv-1/2) serology; rapid plasma reagin (rpr) serology; epstein-barr virus (ebv) serology; cytomegalovirus (cmv) serology; herpes simplex virus (hsv) serology; varicella-. zoster virus (vzv) serology * performance status: karnofsky performance status score ≥ 60%. * agreement to utilize effective contraceptive methods during the study (for one year) * eligible donors will include siblings age ≥ 18 matched with the recipient at hla-a, b, c, and drb1 exclusion criteria: * antithymocyte globulin (atg) as part of the conditioning regimen

Keywords: gvhd aml all mds cll nhl hl mm