‘Relative’ chemotherapy sensitivity: the impact of number of salvage regimens prior to autologous stem cell transplant for relapsed and refractory aggressive non-Hodgkin's lymphoma

Abstract

Summary:The purpose of the study was to assess the impact of number of salvage regimens needed to demonstrate chemotherapy sensitivity on relapse rates, survival, and toxicity following high-dose therapy and autologous bone marrow transplantation (ABMT) in relapsed or refractory non-Hodgkin's lymphoma. We retrospectively reviewed 136 patients with intermediate-grade lymphoma who underwent ABMT. All patients were treated with salvage therapy to maximum tumor reduction. Three quarters (102/136) of the patients received one salvage regimen, while 31 (23%) patients received two or more regimens. When compared to patients requiring у two regimens, patients requiring only one salvage regimen to demonstrate chemosensitivity were more likely to have a longer previous CR from initial therapy (CR у12 months in 47% vs 26%; P = 0.04) and to have attained CR with salvage (54% vs 16%; P = 0.001). Both median relapse-free survival (RFS) and overall survival (OS) have not yet been reached in patients receiving one salvage regimen (median follow-up 50.6 months). This is superior to the median RFS of 9.1 months (P = 0.004) and OS of 11.1 months in patients requiring уtwo regimens to demonstrate chemosensitivity (P = 0.002). Time to engraftment, toxic deaths and incidence of myelodysplasia were similar in the groups. The survival rate observed in patients requiring уtwo salvage regimens, although inferior to that of patients receiving a single salvage regimen, are still generally superior to results in the literature for patients treated with chemotherapy alone without ABMT. We conclude that high-dose therapy with ABMT is appropriate for lymphoma patients even when disease reduction requires repeated numbers of salvage regimens. Keywords: lymphoma; transplant; salvage; chemotherapy; chemosensitivity Sensitivity to salvage chemotherapy is one of the strongest predictors of outcome after high-dose therapy with autologous bone marrow or peripheral blood stem cell transplantation (ABMT) in relapsed or refractory non-Hodgkin's lymphoma. [1][2][3][4][5][6] Numerous salvage chemotherapy regimens have been used to reduce disease bulk and test chemosensitivity, but no single regimen appears superior. In general, initial response rates of 30-50% with salvage therapy are attainable. 7-16 Those who do not respond or have disease progression with first-line salvage tend to fare poorly with high-dose therapy and may proceed to second-or even third-line salvage treatment with the hope of qualifying for high-dose therapy and ABMT. This approach may seem reasonable, particularly in young patients with good performance status, but has not been validated in the literature. Requiring more than one salvage regimen to attain an adequate response may reflect greater intrinsic drug resistance or may identify patients with a less favorable natural history predicting for transplant failure, regardless of the disease status ultimately achieved. Hence, the use of multiple salvage regimens pre-ABMT raises concerns of greater risk-to-benefit ratio and poor uti...

Primary refractory diffuse large B cell lymphoma in the rituximab era

“…Disease status and a low number of salvage regimens at the time of transplant are important prognostic markers [43,44] and nonresponding patients to second-line strategy have a very poor OS (4 months in retrospective analysis) [44]. Nevertheless, late-responding patients (i.e., after more than two salvages) might still benefit from an ASCT and intensification consolidation [45], although this is not universally reported in different retrospective series with a 3-year PFS and OS of only 4% for progressive patients after first salvage [46].…”

Salvage chemotherapy with rituximab DHAP for relapsed non-Hodgkin lymphoma: A phase II trial in the North Central Cancer Treatment Group

“…For patients under the age of 75 years who are otherwise in good health, the standard of care is to provide high-dose therapy with autologous stem cell transplant (SCT) [5] for patients with chemotherapy sensitive relapsed disease or patients with chemotherapy sensitive disease who achieve less than a complete response to initial therapy. The efficacy of autologous SCT is greater when performed after a first relapse rather than after multiple relapses [6].…”

Prognostic impact of pre-transplantation computed tomography and 67gallium scanning in chemosensitive diffuse large B cell lymphoma patients undergoing hematopoietic stem-cell transplantation

“…Although CT scan is the gold standard for the restaging of patients with DLBCL before transplantation, the assessment of response and consequently the disease status often represent a problem considering the common fi nding of persistent masses on the CT scan after treatment. In this sense, although a great variety of patients, disease-and transplant-related factors have been shown to infl uence the outcome of DLBCL patients undergoing ASCT, including age [16], number of previous cycles of chemotherapy [17][18][19], extra-nodal involvement [20], tumoral mass before transplantation [17], or IPI during transplantation [21], with continuous disease status, seen by several authors as the most important prognostic factors [21][22][23].…”