Auto Stem Cell Transplant for Lymphoma Patients

Inclusion Criteria:

• Eligible Diseases

1. Non-Hodgkin's Lymphoma (NHL)

• Patients with chemo-sensitive histologically confirmed NHL will beeligible for this treatment protocol contingent on histologicsub-classification.
• Patients in partial or complete remission following cell therapy will alsobe eligible.
• NHL patients with resistant or refractory lymphoma (no PR following up tothree cycles of combination chemotherapy) will not be eligible fortransplant in this trial.
• Lymphoblastic Lymphoma:

1. All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)
2. Patients with any high-risk features will be eligible in firstcomplete remission
3. High risk features include: Stage IV, LDH >2 x upper limit of normal, ≥ 2 extranodal sites

• Mature B-cell Lymphoma

1. Follicular Lymphoma and other indolent lymphoma in ≥ second CR2/PR2
2. Diffuse Large B-Cell Lymphoma: in ≥ CR2 or ≥ PR1; a high intermediateor high IPI (≥ 2 for age-adjusted IPI or ≥3 for IPI) at diagnosis anddouble-hit or triple-hit lymphoma will be eligible in first CR;transformed lymphoma from FL (or other indolent lymphoma) or chroniclymphocytic leukemia will be eligible if chemosensitive and bonemarrow is negative
3. Mantle Cell Lymphoma: in first or greater CR or PR
4. Burkitt's/Burkitt's like: all patients except localized lymphoma willbe eligible any time after initial therapy (after achievement offirst complete remission), or in partial remission if they fail toachieve CR; patients with localized (stage I or Ziegler stage A) willbe eligible only if they fail to achieve CR1 or after relapse

• Mature T-Cell Lymphoma

1. Chemosensitive T-cell lymphomas including Primary T-cell nototherwise specified angioimmunoblastic, and ALK-positive anaplasticlarge cell, will be eligible after initial therapy, whether or not CRis achieved.

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

3. Hodgkin Lymphoma (HL)

• Patients with histologically proven HL will be eligible fortransplantation after failing prior therapy.
• Patients with resistant disease (initial or at relapse): those who fail toachieve an objective partial response to three cycles of combinationnon-cross resistant chemotherapy will not be eligible for transplant inthis trial.
• For stage I/II patients treated with primary chemotherapy-radiation, theymust have failed (no CR or progression after CR) at least one salvagecombination chemotherapy treatment regimen
• For advanced (stage III/IV) Hodgkin disease, patients must have failed anAdriamycin containing regimen (ABVD) or an alternative non-cross resistantregimen (e.g. MOPP)
• Patients with any high-risk features will also be eligible, includingthose who:

1. fail to achieve complete remission with initial combinationchemotherapy
2. 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., PETscan positive; high LDH; enlarging on serial x-rays or biopsypositive) will be eligible - if feasible, persistent disease shouldbe proven by biopsy

• Patients should receive chemotherapy to attempt to achieve CR or minimaldisease state for all patients pre-transplantation. The use of up to threecycles of non-cross resistant combination chemotherapy is advised.
• Residual areas of limited disease should be considered for radiotherapyafter and not prior to transplantation.

3. HIV positive patients who are otherwise eligible for this study may be enrolledif they meet the following requirements:

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

• Are on maximally active anti-HIV regimen to control disease as determinedappropriate by the ID/HIV physicians. For the majority of patients, thiswill be a highly active anti-retroviral therapy (HAART)-type therapyincluding a protease inhibitor.

• CD4+ ≥ 50/µL

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

• Performance Status: Karnofsky Performance Status ≥ 80% for patients ≥ 16 years ofage or Lansky Play Score ≥ 80 for patients < 16 years of age. Note: if poorperformance 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 tumorincluding:

2. 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 10days or Neulasta for 21 days
• platelets > 100 x 109/L without transfusion
• bone marrow cellularity of > 20% with <5% involvement with tumor

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

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

4. Cardiac: free of symptoms of uncontrolled cardiac disease including unstableangina, decompensated congestive heart failure, or arrhythmia. The ejectionfraction by gated cardiac blood flow scan (MUGA) or Echocardiogram must be >40%

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

6. Central Nervous System: Patients with a history of CNS involvement by lymphomaor with relapsed primary CNS lymphoma will be eligible for Cy/TBI arm. Patientswith active CNS disease are eligible if they have completed a standardtreatment for CNS lymphoma and have no evidence of progressive CNS disease atthe time of enrollment

• Other Inclusion Criteria

1. At least 4 weeks from previous chemotherapy; 6 weeks from nitrosoureas

2. Women of child bearing potential and sexually active males with partners ofchild bearing potential must agree to use adequate birth control for theduration of treatment

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

4. Voluntary written consent

Exclusion Criteria:

• Pregnant or breastfeeding: Females of childbearing potential must have a blood testor urine study within 14 days prior to registration to rule out pregnancy

• Eligible for any higher priority transplant protocols

• Chemotherapy resistant disease

• Unrelated active infection