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

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 \>4x the upper limit of normal
  * Renal: creatinine clearance \<50 cc/min (24 hour urine 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 non-melanoma 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 HLA-mismatched (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 mg/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.