Autologous Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma

OBJECTIVES:

Primary

- Determine the disease-free survival and overall survival of patients with non-Hodgkin's
or Hodgkin's lymphoma treated with autologous peripheral blood stem cell transplantation
(PBSCT).

- Verify the safety and efficacy of autologous PBSCT in patients with HIV disease and
relapsed lymphoma.

Secondary

- Evaluate immune reconstitution in HIV-positive patients undergoing autologous PBSCT and
compare to immune reconstitution in HIV-negative patients.

- Predict the adequacy of peripheral blood stem cell (PBSC) harvest prior to flow analysis
of a PBSC yield.

- Determine the time to engraftment for neutrophils and platelets.

OUTLINE:

- Peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF) alone: Patients
not requiring further disease reduction receive G-CSF subcutaneously (SC) once daily on
days 1-8. Patients undergo PBSC collection by leukapheresis on days 5-8. Patients who do
not adequately mobilize with G-CSF alone proceed to chemo-mobilization.

- Chemo-mobilization: Patients requiring further disease reduction receive 1 of 2
chemo-mobilization regimens.

- Patients with CD20+ non-Hodgkin's lymphoma (NHL) or lymphocyte predominant
Hodgkin's lymphoma: Patients receive rituximab intravenously (IV) over 6-8 hours on
day 1, ifosfamide IV over 2 hours and etoposide IV over 30 minutes on days 2-4, and
carboplatin IV over 1 hour on day 2. Patients receive G-CSF SC once daily beginning
on day 5 and continuing until leukapheresis is completed. Patients undergo PBSC
collection by leukapheresis on days 12-15.

- All other patients: Patients receive ifosfamide IV over 2 hours and etoposide IV
over 30 minutes on days 1-3 and carboplatin IV over 1 hour on day 1. Patients
receive G-CSF SC once daily beginning on day 4 and continuing until leukapheresis
is completed. Patients undergo PBSC collection by leukapheresis on days 12-15.

- Autologous PBSC transplantation (PBSCT) (Patients with NHL undergoing irradiation):
Patients receive cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo
total body irradiation (TBI) twice daily on days -4 to -1. Patients undergo autologous
PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day 5 and continuing
until blood counts recover.

- Autologous PBSCT (Patients with Hodgkin's lymphoma or NHL not undergoing irradiation and
cyclophosphamide): Patients receive camustine IV over 2 hours on days -6, etoposide IV
over 2 hours twice daily on days -5 to -2, and melphalan over 1 hour on day -1. Patients
undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day
5 and continuing until blood counts recover.

- Autologous PBSC transplantation (PBSCT) (Patients with HL not undergoing irradiation):
Patients receive cyclophosphamide IV over 2 hours on days -6 to -3, camustine IV over 2
hours on day -6, and etoposide IV over 4 hours twice daily on days -6 to -4. Patients
undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day
5 and continuing until blood counts recover.

- Post-transplant irradiation: Patients undergo post-transplant irradiation beginning on
day 28. Persisting nodal masses ≥ 2 cm are treated with additional localized external
beam irradiation.

- Post-transplant Rituximab therapy: patients with CD20+ NHL may undergo Rituximab
maintenance starting between day +45 and +90 and being repeated at day +180 ± 14 days.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.

Inclusion Criteria:

- Karnofsky performance status: >80% (>60% if poor performance status is related to
lymphoma)

- No evidence of serious organ dysfunction that is not attributable to tumor

- Central nervous system: Patients with a history of CNS involvement by lymphoma or
with relapsed primary lymphoma will be eligible.

- Infection: Patients with serious uncontrolled infections at the time of
transplant will be excluded.

- Hepatitis B: Patients who are carriers of Hepatitis B will be included in this study.
These patients are not eligible to receive rituximab as a component of their
chemotherapy mobilization.

- HIV disease. Patients with HIV disease are eligible for this study provided that:

- Patients will be 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.

- Must be on a maximally active anti-HIV regimen

- 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 one month of enrollment.

- Non-Hodgkin's lymphoma (NHL). Patients with chemo-sensitive histologically confirmed
NHL.

- Precursor B-cell or Precursor T-cell NHL

- Lymphoblastic lymphoma

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

- Mature B-cell Lymphomas:

- Small lymphocytic lymphoma (SLL) or Chronic Lymphocytic Leukemia (CLL)

- Follicular Lymphoma

- Diffuse Large B-cell Lymphoma

- Mantle Cell Lymphoma

- Burkitt's/Burkitt's like

- Mature T-cell lymphoma

- Hodgkin's lymphoma (HL)

- patients with histologically proven HL will be eligible for transplantation after
failing prior therapy.

Exclusion Criteria:

- Patients eligible for any higher priority transplant protocols

- Women who are pregnant or breast feeding

- Patients with chemotherapy resistant disease