phase 2 poor risk dlbcl of tli and atg followed by matched allogeneic ht as consolidation to autologous hct

Conditions: Lymphoma, B-cell; Lymphoma, Non-Hodgkin; Diffuse Large B-cell Lymphoma (DLBCL); Malignant Lymphoma, Non-Hodgkin

Summary: the purpose of this study is to determine if double autologous then allogeneic hematopoietic cell transplant may offer an improved treatment option for patients with relapsed diffuse large b-cell lymphoma (dlbcl) who are not likely to be cured by the conventional transplantation regimen.

this study tests a tandem transplant approach that starts with transplantation of the participant's own hematopoietic (blood) cells, eg, autologous hematopoietic cell transplant (auto-hct) as preparation for an subsequent matched-donor allogeneic hct (allo-hct). participants will be have progenitor cells (stem cells) mobilized into the peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim (g-csf); undergo apheresis to collect autologous peripheral blood stem cells (pbsc, aka hematopoietic cells); and be re-infused with ≥ 3 x 10e6 cd34+ cells/kg (auto-hct). subsequently, participants will receive therapeutic, non-myeloablative chemotherapy (carmustine + cyclophosphamide + etoposide), then transplant conditioning \[total lymphoid irradiation (tli) + anti-thymocyte globulin (atg)\] followed by ≥ 2 x 10e6 cd34+ cells/kg allogeneic pbsc obtained from a human leukocyte antigen (hla)-matched or hla single allele / antigen-mismatched donor (allo-hct). donors will be mobilized with 16 µg/kg filgrastim. participant allo-hct transplant is to occur within 150 days of auto-hct. post-allo-hct infusion treatment includes cyclosporine and mycophenolate mofetil (mmf) subject's participation ends if a suitable matched donor is not identified within the 150 days. pre-medication treatments administered during this study may include acetaminophen; diphenhydramine; hydrocortisone; and methylprednisolone.

Eligibility criteria:
inclusion criteria * age 18 to 70 years. * histologically-proven diffuse large b-cell lymphoma (dlbcl) by the world health organization (who) classification. * relapse after achieving initial remission or failure to achieve initial remission. patients with residual radiographic abnormalities after primary therapy are eligible if abnormalities are postive by fluorodeoxyglucose (fdg)-positron emission tomography (pet) (fdg-pet). * receipt of 2 cycles of second-line therapy and fdg-pet positive per stanford (central) review. fdg-pet to be done 2 weeks after cycle 2 of second line chemotherapy. * eastern cooperative oncology group (ecog) performance status \< 2 * matched related or unrelated donor identified and available * bone marrow biopsy and cytogenetic analysis within 8 weeks of registration * pretreatment serum bilirubin \< 2 x the institutional upper limit of normal (uln) * serum creatinine \ 60 ml/min by the following formula (all tests must be performed within 28 days prior to registration): * estimated creatinine clearance = (140 age) x weight (kg) x 0.85 if female 72 x serum creatinine (mg/dl). * ekg within 42 days prior to registration with no significant abnormalities suggestive of active cardiac disease * patients must have a radionuclide ejection fraction within 42 days of registration. if the ejection fraction is \< 40%, the patient will not be eligible. if the ejection fraction is 40-50%, the patient will have a cardiology consult. * corrected diffusion capacity \> 55%. * sexually active males are advised to use an accepted and effective method of birth control * women of child-bearing potential are advised to use an accepted and effective method of birth control * patients must sign and give written informed consent in accordance with institutional and federal guidelines. patients must be informed of the investigational nature of this study. exclusion criteria * known allergy to etoposide or a history of grade 3 hemorrhagic cystitis with cyclophosphamide * greater than grade 2 sensory or motor peripheral neuropathy from prior vinca alkaloid use * requiring therapy for coronary artery disease, cardiomyopathy, dysrhythmia, or congestive heart failure * known to be human immunodeficiency virus (hiv)-positive. the antibody test for hiv must be performed within 42 days of registration. * prior chemotherapy other than corticosteroids administered within 2 weeks of the initiation of protocol therapy. * prior malignancy, except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the patients has been disease-free for five years. * prior diagnosis of non-hodgkin's lymphoma * active infection requiring oral or intravenous antibiotics * prior autologous or allogeneic hematopoietic cell transplantation * prior radioimmunotherapy * pregnant * lactating donor eligibility * related or unrelated hla-identical donors who are in good health and have no contra-indication to donation * no contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by g-csf at a dose of 16 µg/kg of body weight. * donors will be evaluated with a full history and physical examination. * virology testing including hiv; cytomegalovirus (cmv); epstein-barr virus (ebv); human t-lymphotropic virus (htlv); rapid plasma reagin (rpr); hepatitis a, b and c be performed within 30 days of donation. * prospective donors will be screened for cmv seroreactivity and seronegative donors will be utilized if available. * if more than one human leukocyte antigen (hla)-matched related donor exists, then the donor will be selected on the basis of cd31 allotype.