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