Thiotepa, Busulfan and Fludarabin for pt With Refractory/Early Relapsed Aggressive B-cell Non Hodgkin Lymphomas

In the present study, it is hypothesised that patients with aggressive B cell lymphomas refractory to or relapsed early (within 12 months) after the completion of standard first-line immunoProtocol TBF2012 Version 1, 20 Nov 2012 9 chemotherapy can benefit from de-bulking salvage therapy (i.e. R-DHAP + bortezomib) followed by an allograft to improve progression-free survival. Patient inclusion criteria * Patients with refractory/relapsed aggressive B-cell non Hodgkin lymphomas after frontline therapy. * Patients with stable disease or partial or complete remission (PET-negative) after salvage therapy * Patients younger than 65 years old * A fully HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered * Patient must be competent to give consent Patient exclusion criteria * Patients treated with an autologous transplant as salvage therapy * Patients with progressive lymphomas despite conventional therapies * Patients with progressive lymphomas despite conventional therapies * Uncontrolled CNS involvement with disease * Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment * Females who are pregnant or breastfeeding * Organ dysfunction defined as follows: * Cardiac function: ejection fraction \<30% or uncontrolled cardiac failure * Pulmonary: DLCO \<40% predicted * Liver function abnormalities: elevation of bilirubin to \> 3 mg/dl and/or transaminases \>4 the upper limit of normal * Renal: creatinine clearance \<50 cc/min (24 hour urine Protocol TBF2012 Version 1, 20 Nov 2012 6 collection) * Karnofsky performance score \< 60% * Patients with poorly controlled hypertension despite multiple antihypertensives * Documented fungal disease that is progressive despite treatment * Viral infections: HIV positive patients. * Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded. * Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result * Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen. * Patients with active non-hematologic malignancies (except nonmelanoma skin cancers). * Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a \>20% risk of disease recurrence. Donor inclusion criteria: * Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered. * No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight. * Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria: * Age \< 18 years. * Identical twin. * Pregnancy. * Infection with HIV. * Inability to achieve adequate venous access. * Known allergy to filgrastin (G-CSF). * Current serious systemic illness. Donor inclusion criteria: * Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered. * No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight. * Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria: * Age \< 18 years. * Identical twin. * Pregnancy. * Infection with HIV. * Inability to achieve adequate venous access. * Known allergy to filgrastin (G-CSF). * Current serious systemic illness. Donor inclusion criteria: * Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered. * No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight. * Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria: * Age \< 18 years. * Identical twin. * Pregnancy. * Infection with HIV. * Inability to achieve adequate venous access. * Known allergy to filgrastin (G-CSF). * Current serious systemic illness.