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 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:

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 first complete
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 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

3. Mantle Cell Lymphoma: in first or greater CR or PR

4. 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

1. 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.

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

2. 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:

1. fail to achieve complete remission with initial combination
chemotherapy

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., 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.

3. 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:

1. 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

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. Total
bilirubin ≤ 2.0 mg/dl, AST and alkaline phosphatase <5x upper limit of normal

4. 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%

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

6. 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

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

2. 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

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 test or
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