• Eligible Diseases

‣ Non-Hodgkin's Lymphoma (NHL)

• Patients with chemo-sensitive histologically confirmed NHL will be eligible for this treatment protocol contingent on histologic sub-classification.

∙ Patients in partial or complete remission following cell therapy will also be eligible.

∙ NHL patients with resistant or refractory lymphoma (no PR following up to three cycles of combination chemotherapy) will not be eligible for transplant in this trial.

∙ Lymphoblastic Lymphoma:

‣ All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)

⁃ Patients with any high-risk features will be eligible in first complete remission

⁃ High risk features include: Stage IV, LDH \>2 x upper limit of normal, ≥ 2 extranodal sites

∙ Mature B-cell Lymphoma

‣ Follicular Lymphoma and other indolent lymphoma in ≥ second CR2/PR2

⁃ Diffuse Large B-Cell Lymphoma: in ≥ CR2 or ≥ PR1; a high intermediate or high IPI (≥ 2 for age-adjusted IPI or ≥3 for IPI) at diagnosis and double-hit or triple-hit lymphoma will be eligible in first CR; transformed lymphoma from FL (or other indolent lymphoma) or chronic lymphocytic leukemia will be eligible if chemosensitive and bone marrow is negative

⁃ Mantle Cell Lymphoma: in first or greater CR or PR

⁃ Burkitt's/Burkitt's like: all patients except localized lymphoma will be eligible any time after initial therapy (after achievement of first complete remission), or in partial remission if they fail to achieve CR; patients with localized (stage I or Ziegler stage A) will be eligible only if they fail to achieve CR1 or after relapse

∙ Mature T-Cell Lymphoma

‣ Chemosensitive T-cell lymphomas including Primary T-cell not otherwise specified angioimmunoblastic, and ALK-positive anaplastic large cell, will be eligible after initial therapy, whether or not CR is achieved.

⁃ Mycosis fungoides/Sezary syndrome will be eligible in ≥CR2/PR2

⁃ Hodgkin Lymphoma (HL)

• Patients with histologically proven HL will be eligible for transplantation after failing prior therapy.

∙ Patients with resistant disease (initial or at relapse): those who fail to achieve an objective partial response to three cycles of combination non-cross resistant chemotherapy will not be eligible for transplant in this trial.

∙ For stage I/II patients treated with primary chemotherapy-radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen

∙ For advanced (stage III/IV) Hodgkin disease, patients must have failed an Adriamycin containing regimen (ABVD) or an alternative non-cross resistant regimen (e.g. MOPP)

∙ Patients with any high-risk features will also be eligible, including those who:

‣ fail to achieve complete remission with initial combination chemotherapy

⁃ have bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass ≥ 5 cm or other residual mass ≥ 10 cm accompanied by other features of persisting disease (e.g., PET scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible - if feasible, persistent disease should be proven by biopsy

∙ Patients should receive chemotherapy to attempt to achieve CR or minimal disease state for all patients pre-transplantation. The use of up to three cycles of non-cross resistant combination chemotherapy is advised.

∙ Residual areas of limited disease should be considered for radiotherapy after and not prior to transplantation.

⁃ HIV positive patients who are otherwise eligible for this study may be enrolled if they meet the following requirements:

• Are seen in the infectious disease (ID)/HIV clinic prior to enrollment on study for the purpose of determining eligibility and for local coordination of HIV care during the peri-transplant period.

∙ Are on maximally active anti-HIV regimen to control disease as determined appropriate by the ID/HIV physicians. For the majority of patients, this will be a highly active anti-retroviral therapy (HAART)-type therapy including a protease inhibitor.

∙ CD4+ ≥ 50/µL

∙ HIV RNA viral load ≤ 100,000 copies per mL on each of samples 4 weeks apart. The most recent level must be within 30 days of enrollment.

• Performance Status: Karnofsky Performance Status ≥ 80% for patients ≥ 16 years of age or Lansky Play Score ≥ 80 for patients \< 16 years of age. Note: if poor performance status is due to lymphoma - KPS ≥ 60% or LPS ≥ 60 is acceptable

• Organ Function

• 1\. No evidence of serious organ dysfunction that is not attributable to tumor including:

⁃ Hematologic:

• hemoglobin \> 8 gm/dL

∙ WBC \> 2.5 x 109/L with an ANC \> 1.5 x 109/L off G-CSF or GM-CSF for 10 days or Neulasta for 21 days

∙ platelets \> 100 x 109/L without transfusion

∙ bone marrow cellularity of \> 20% with \<5% involvement with tumor

⁃ Renal: GFR \> 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age

⁃ Hepatic: no history of severe prior or ongoing chronic liver disease. Total bilirubin ≤ 2.0 mg/dl, AST and alkaline phosphatase \<5x upper limit of normal

⁃ Cardiac: free of symptoms of uncontrolled cardiac disease including unstable angina, decompensated congestive heart failure, or arrhythmia. The ejection fraction by gated cardiac blood flow scan (MUGA) or Echocardiogram must be \>40%

⁃ Pulmonary: no significant obstructive airways disease (FEV1 must be ≥ 50%) and must have acceptable diffusion capacity (corrected DLCO \> 50% of predicted)

⁃ Central Nervous System: Patients with a history of CNS involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible for Cy/TBI arm. Patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollment

• Other Inclusion Criteria

‣ At least 4 weeks from previous chemotherapy; 6 weeks from nitrosoureas

⁃ Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment

⁃ Patients who are carriers of Hepatitis B will be included in this study

⁃ Voluntary written consent