Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Bone marrow transplantation (BMT) is the treatment of choice for patients whose lymphoma has relapsed.[1] Preliminary studies indicate that approximately 20% to 40% of patients will have a long-term disease-free status, but the precise percentage depends on patient selection and the specific treatment used. Preparative drug regimens have varied; some investigators also use total-body irradiation. Similar success has been achieved using autologous marrow, with or without marrow purging, and allogeneic marrow.[2,3,4,5,6]

In a prospective randomized study known as the PARMA trial, 215 patients in first or second relapse of aggressive lymphoma, younger than 60 years, and with no bone marrow or central nervous system involvement, were given two cycles of intensive combination chemotherapy. The 109 patients who responded were randomly assigned to receive four more cycles of chemotherapy and involved-field radiation therapy (IF-XRT) versus autologous BMT followed by IF-XRT. With a 5-year median follow-up, the event-free survival was significantly improved with transplantation (46% vs. 12%). Overall survival (OS) was also significantly better with transplantation (53% vs. 32%).[7][Level of evidence: 1iiA] Salvage BMT was unsuccessful for patients on the nontransplant arm whose disease relapsed.

In general, patients who responded to initial therapy and who have responded to conventional therapy for relapse prior to the BMT have had the best results. In a prospective trial, patients who relapsed late (more than 12 months after diagnosis) had better OS than patients who relapsed earlier (8-year survival was 29% vs. 13%, P = .001).[8][Level of evidence: 3iiiA] Peripheral stem cell transplantation has yielded results equivalent to standard autologous transplantation.[9,10] Even patients who never experienced complete remission with conventional chemotherapy may have prolonged progression-free survival (31% at 5 years) after high-dose chemotherapy and hematopoietic stem cell transplantation if they retain chemosensitivity to reinduction therapy.[11][Level of evidence: 3iiiDiii] Some patients who relapse after a previous autologous transplantation can have durable remissions after myeloablative or nonmyeloablative allogeneic stem cell transplantation.[12,13][Level of evidence: 3iiiDiv] Since toxic effects can be severe, and patients require specialized team management, BMT should be done at institutions that have the appropriate expertise and resources available.

In general, retreatment with standard agents rarely produces a cure in patients whose lymphomas relapse. Patients who relapse with aggressive lymphoma after 3 years in remission have similar prognoses to de novo lymphoma using curative therapy.[14] Several salvage chemotherapy regimens are available.[15,16,17] Rituximab, an anti-CD20 monoclonal antibody, can induce responses in 33% of patients with relapsing aggressive lymphoma of appropriate phenotype (CD20-positive).[18,19][Level of evidence: 3iiiDiv] Radiolabeled anti-CD20 monoclonal antibodies, such as iodine-131 tositumomab and yttrium-90 ibritumomab, induce 60% to 80% response rates in patients with relapsed or refractory B-cell lymphoma.[20,21,22][Level of evidence: 3iiiDiv] Denileukin difitox, a fusion protein combining diptheria toxin and interleukin-2, resulted in a 25% objective response rate in 45 heavily pretreated patients as evidenced in E-1497, for example, with aggressive B-cell non-Hodgkin lymphoma (CD25, i.e., interleukin-2 receptor, expression was not correlated with response).[23][Level of evidence: 3iiiDiv]