Prognostic value of the age-adjusted International Prognostic Index in chemosensitive recurrent or refractory non-Hodgkin's lymphomas treated with high-dose BEAM therapy and autologous stem cell transplantation

Abstract

High-dose therapy (HDT) is now recommended for patients under 60 years of age with chemosensitive relapsed aggressive non-Hodgkin's lymphoma. However, approximately half of these patients will be cured by HDT. Prognostic factors are needed to predict which patients with chemosensitive lymphoma to second-line therapy could benefit from HDT. We retrospectively investigated the prognostic value of the widely used age-adjusted International Prognostic Index (AA-IPI) calculated at the time of relapse (35 patients) or just before second-line salvage therapy for primary refractory disease (5 patients). The median age was 51 years (range 18-64 years). Thirty-six patients had diffuse large B-cell lymphoma. Salvage cytoreductive therapy before HDT was DHAP/ESHAP (cytarabine, cysplatin, etoposide, steroids) in 17 patients, VIM3-Ara-c/MAMI (high-dose cytarabine, ifosfamide, methyl-gag, amsacrine) in 17 patients, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or reinforced CHOP in 4 patients, high-dose cyclophosphamide and etoposide in 2 patients. The HDT regimen consisted of BEAM (carmusine, cytarabine, etoposide, melphalan) in all cases. Eleven patients were in partial remission and 29 in complete remission at the time of HDT. Ten patients had an IPI >1, 16 had relapsed early (<6 months after first-line therapy) or disease was refractory to first-line therapy (5 of the 16 patients). The median follow-up was 6.07 years (range 1.24-9.74 years). Overall survival was not statistically different in patients with refractory disease or in those who relapsed early compared with late failures (>6 months after first-line chemotherapy) (P=1), but the AA-IPI >1 was associated with a poor outcome (P=0.03). In conclusion, the AA-IPI could have a prognostic value in patients with chemosensitive recurrent lymphoma treated with BEAM HDT.

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.…”

“…16 The same institution later reported 98 patients with refractory or relapsed chemosensitive DLBCL (including 'transformed' cases) undergoing autologous SCT and identified aa-IPI at the time of initiation of second-line chemotherapy as a predictor of OS and DFS at 4 years. 19 Jabbour et al 18 in a series of 40 patients with aggressive NHL undergoing autologous transplantation also identified aa-IPI as being a predictor of OS and DFS. This study, however, found that TTR did not predict outcome.…”

R-CHOP chemoimmunotherapy followed by autologous transplantation for the treatment of diffuse large B-cell lymphoma

“…The IPI and its variants are the primary prognostic tools used in patients with DLBCL. In the pre-rituximab era, when the aaIPI was applied to patients with chemosensitive recurrent or refractory aggressive non-Hodgkin's lymphomas who had been treated with high-dose therapy followed by Auto-SCT, the scores were predictive of OS ( P =0.034) [14]. A recent prospective study reported a 2-year PFS and OS of 63% and 73%, respectively, in aaIPI high-intermediate- and high-risk patients with aggressive B-cell lymphoma who had been treated with R-CHOP alone [5].…”

The Role of Transplantation in Diffuse Large B-Cell Lymphoma: The Impact of Rituximab Plus Chemotherapy in First-line and Relapsed Settings

“…The International Prognostic Index (IPI) calculated at the time of relapse (IPI-R) or the age-adjusted IPI have also been used. Although the ageadjusted IPI did not influence the outcome in the Parma trial [26], in subsequent studies both the IPI-R and the ageadjusted IPI predicted survival after ASCT [27,28]. Costa et al [29] showed that IPI-R and the time from initial diagnosis to relapse (TTR) both influenced outcomes after ASCT for relapsed, chemosensitive disease.…”

“…Markers of poor prognosis at relapse include older age, advanced stage, chemorefractory disease, short remission duration, and the presence of significant comorbidities [26,28,69]. Outcome after recurrence is poor, with a median survival of less than 12 months [69].…”