ESHAP+/− Rituximab as Salvage Therapy for Relapsed Lymphoma Prior to Stem Cell Transplant: Single Institution Experience.

OBJECTIVE: High dose chemotherapy with stem cell transplantation (ABMT) has become the standard treatment for relapsed aggressive non-Hodgkins and Hodgkins Lymphomas. However, there is no one salvage therapy accepted as a standard regimen prior to ABMT. ESHAP, as a combination chemotherapy regimen consisting of Etoposide, Methylprednisolone, Cytosine arabinoside, and infusional Cisplatin, has been shown to be an active regimen for the treatment of refractory Non-Hodgkins Lymphoma in previously published trials. The objective of this study was to determine the efficacy of ESHAP with and without Rituximab as a cytoreductive regimen in relapsed lymphomas prior to stem cell transplant.

METHODS: This retrospective study was approved by the Institutional Review Board. Patients with relapsed Hodgkins and Non-Hodgkins lymphoma who were treated at our institution between March 1997 and July 2004, with the intent of proceeding to ABMT after obtaining a complete remission and were treated with ESHAP containing salvage regimen, were included in this study. Data collection was done by review of all pertinent medical records.

RESULTS: Twenty four patients with relapsed lymphomas were identified that were treated with ESHAP +/− Rituximab during this period, with the intent to proceed with ABMT after achieving a maximal response. Histology included: large cell lymphoma (n=15), mantle cell lymphoma (n=3), and Hodgkin’s disease (n=6). Median age was 54 years and male-to-female ratio was 1.4:1. Staging of disease at the time of initial diagnosis was done by PET scan, CT scans, and bone marrow examination. Staging at time of salvage treatment for relapsed disease: stage I (n=1) stage II (n=2)), stage III (n=12), stage IV (n=9). Prior treatment consisted of CHOP, ABVD, TVC, MOPP/ABVD, CNOP, CVP, and CAV. The median disease free interval prior to salvage therapy was 12 months. Of 24 patients, 17 received ESHAP and 7 received ESHAP+ Rituximab as salvage therapy. The median time to transplant after initiation of salvage therapy was four months. Nineteen of twenty four patients (79%) proceeded to receive stem cell transplantation. Five patients did not proceed to ABMT secondary to failure to achieve a complete remission or had progressive disease. Patients treated with ESHAP + rituximab compared to ESHAP alone had no evidence of altered transplant related morbidity, as measured by time to engraftment, duration of hospitalization and the number of episodes of febrile neutropenia. No treatment related mortality occurred in all patients. Of the patients who underwent ABMT, 53% are disease free at a median follow up of 48 months. Among those who did not receive stem cell transplant, 4 died of progressive disease, and one has no evidence of disease in 12 months of follow up.

CONCLUSIONS: ESHAP with and without Rituximab is an effective and a feasible salvage therapy for patients with relapsed lymphomas when used as a cytoreductive regimen prior to stem cell transplantation and does not negatively impact on transplant treatment related morbidity and mortality. Further studies are necessary to compare its efficacy with other standard salvage regimens prior to ABMT.