Autologous and Allogeneic Transplant for Relapsed Lymphoma

The sequential combination of myeloablative therapy and autologous stem cell transplantation (APBSCT) followed by a reduced intensity allogeneic stem cell transplant (Allo SCT) and post SCT adoptive cellular immunotherapy will be well tolerated in patients with refractory or recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).

Lymphomas are the third most common group of cancers in children and adolescents in the United States. While Hodgkin's Disease (HD) has been described for many years, some subtypes of the non-Hodgkin's Lymphomas (NHL) have only recently been described. Non-Hodgkin's lymphomas traditionally have been classified as low, intermediate or high grade based on their clinical aggressiveness. More recently they have been divided into two major subgroups indolent and aggressive lymphomas by the current National Cancer Institute (NCI/PDQ) reference. Among children, aggressive histologies are prevalent including small non-cleaved cell lymphoma, lymphoblastic lymphoma, and diffuse large cell lymphoma. The most common histologic classifications of childhood non-Hodgkin's lymphoma over the past 30 years has included the morphological schema developed by Rappaport, the morphologically and immunologically based schema of Lukes and Collins, the Kiel classifications, the prognostic sub-groupings of the National Cancer Institute's Working Formulation, and the most recently developed classification that utilizes morphological, immunophenotypic and genetic information in the Revised European-American Lymphoma (REAL) classification.

Eligibility Criteria:
Inclusion Criteria:

Patient must have adequate organ function as below

* Adequate renal function defined as:

  1. Serum creatinine less than or equal to 2.0 x normal, or
  2. Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 40 ml/min/m2 or \>60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
* Adequate liver function defined as:

  1. Total bilirubin \<2.0 x normal; or
  2. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SPGT) (alanine aminotransferase (ALT)) \<5.0 x normal
* Adequate cardiac function defined as:

  1. Shortening fraction of \>27% by echocardiogram, or
  2. Ejection fraction of \>47% by radionuclide angiogram or echocardiogram
* Adequate pulmonary function defined as:

  1. Diffusing capacity of the lungs for carbon monoxide (DLCO) \>50% by pulmonary function test for autologous transplant
  2. DLCO \> 40% by pulmonary function test for reduced intensity allogeneic transplant
  3. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \>94% in room air.

Disease Status (Eligibility)

* Patients with Non-Hodgkin's Lymphoma with either of the following:

  1. Primary induction failure (failure to achieve initial CR) who have a partial response (PR) or stable disease (SD) with reinduction chemotherapy. \*All patients are required to have a biopsy regardless of positron emission tomography (PET)/Gallium results.
  2. Patients with 1st PR, 2nd CR, 2nd PR, or 2nd SD following reinduction chemotherapy
  3. Patients with 3rd CR, 3rd PR, 3rd SD following reinduction chemotherapy
* Patients with Hodgkin's Disease with either of the following:

  1. Primary induction failure (failure to achieve initial CR) and/or primary refractory disease.
  2. First relapse

     1. Early relapse (within 12 months off therapy) (excluding those who received no therapy or radiation therapy only for initial therapy)
     2. Late relapse (greater than 12 months off therapy). Only patients with recurrent Stage III or IV disease and/or those with B symptoms at relapse (all other late relapses are excluded).
     3. Second relapse.
     4. Third relapse.
* Patients must achieve a CR, PR or SD after reinduction chemotherapy.

Exclusion Criteria:

* Patients with NHL or HD with 4th or greater CR, PR, and/or SD
* Patients with progressive disease (PD) unresponsive to reinduction chemo, radio, or immunotherapy
* Hodgkin's Disease in late relapse (other than those discussed above).
* Patients with post-transplant lymphoproliferative disease following a solid organ transplantation or AIDS associated NHL
* Patients who don't have an eligible donor
* Women who are pregnant