Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma

Abstract

Second-line chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Prognostic models capable of predicting outcome are essential. In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease. We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy (sAAIPI) as a predictor of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 4 years, the PFS and OS are 28% and 34% by intention to treat and 39% and 45% for only those patients with chemosensitive disease. Three risk groups with different PFS and OS were identified by the sAAIPI: low risk (0 factors), 70% and 74%; intermediate risk (1 factor), 39% and 49%; and high risk (2 or 3 factors), 16% and 18% (P < .001 for both PFS and OS). The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease: low risk, 69% and 83%; intermediate risk, 46% and 55%; and high risk, 25% and 26% (P < .001 PFS and OS). The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive populations. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regi-

R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study

“…The most significant adverse prognostic factors for response in both the whole series and the R+ group were the presence of bulky disease, primary refractory disease, an aaIPI higher than 1 at the time of R-ESHAP, as well as the administration of fewer than three cycles of R-ESHAP. Moreover, the presence of primary refractory disease and high-risk aaIPI at the time of R-ESHAP were also independent adverse prognostic factors for survival, in accordance with reports from other authors, 9,13,14,[23][24][25][26] but in contrast to the data published by Kewalramani et al, 13 who observed that the addition of rituximab to the ICE regimen seemed to overcome the adverse effects of an unfavorable IPI score. The dismal outcome of patients with primary refractory disease or with an unfavorable aaIPI at the time of relapse underlines the need for the evaluation of alternative treatments.…”

Time of relapse after initial therapy significantly adds to the prognostic value of the IPI-R in patients with relapsed DLBCL undergoing autologous stem cell transplantation

“…An adaptation of the IPI, the age-adjusted IPI (aa-IPI, excludes age and extent of extra nodal disease) has been proposed as a better prognostic system in patients undergoing transplantation, reflecting the uniformly young population included in early series. Although aa-IPI at relapse did not predict the outcome of patients undergoing transplantation in the Parma trial, 15 this finding conflicts with subsequent series where IPI-R 16,17 or aa-IPI 18,19 were able to predict survival after transplantation. These series, although very informative, included multiple histologies of lymphoma, broad variety of conditioning regimens (some using TBI), heterogeneous source of stem cells and often restricted inclusion to younger patients.…”

Prognostic value of comorbidity for auto-SCT eligibility and outcome in relapsed or refractory aggressive non-Hodgkin's lymphoma

“…[6][7][8] Recently, the influence of comorbidity on outcome after autologous transplantation has also been reported by others. [13][14][15] However, none of these studies have compared comorbidity directly with sAAIPI scores or analyzed its predictive value for eligibility for transplantation.…”

“…The sAAIPI has extensively proved its value in predicting response to reinduction therapy and final outcome in patients with relapsed aggressive NHL. [7][8][9] In our cohort, high-risk sAAIPI was highly predictive for both not receiving auto-SCT and survival. Probably because of the fact that only 5 out of 22 patients with sAAIPI scores of 3 ultimately received transplantation, the sAAIPI was no longer predictive for survival among the transplanted patients.…”

“…6,7 The so-coined secondary age-adjusted IPI (sAAIPI) has extensively shown its predictive value for response to salvage therapy and survival in relapsed or refractory aggressive NHL. 8,9 Age is left out of this sAAIPI as most patients treated with high-dose chemotherapy (HDCT) are below 60 years. Comorbidity, however, is not included in this prognostic index and has received little attention as a prognostic factor in the auto-SCT setting.…”