Inferior Progression-Free Survival after Autotransplant for Relapsed or Refractory Aggressive Non-Hodgkin’s Lymphoma in Patients > 60 Versus ≤ 60 Years of Age.

INTRODUCTION: Results of the randomized Parma trial (Philip, NEJM 1995) demonstrated an overall survival (OS) advantage for patients aged ≤ 60 years who received an autotransplant for relapsed aggressive histology non-Hodgkin lymphoma (NHL). Autologous stem cell transplantation (ASCT) is the standard of care in this setting and trial results have been generalized to include patients up to age 65 years. Earlier results from our group (Gupta ASH 2003 abstract #2720) reported a treatment-related mortality (TRM) of 29% in a group of patients (pts) aged > 60 which included pts who had received bone marrow grafts and TBI-containing high dose therapy. We reviewed our results (overall [OS] and progression-free survival [PFS], TRM and non-relapse mortality (NRM) of ASCT in pts of age > 60 years (older group: OG) and compare these with patients aged ≤ 60 years (younger group: YG).

METHODS: We retrospectively reviewed our computerized database and charts between Jan 1^st 1986 until June 30^th 2006 and identified 289 pts with relapsed or refractory aggressive NHL who underwent ASCT. 30 pts were aged > 60 years and 259 were age ≤ 60. All pts had disease that did not respond to or relapsed after initial anthracycline-based chemotherapy. Responses have been retrospectively assessed using International Workshop Criteria. Pts typically received 2–3 cycles of platinum-based salvage therapy to assess chemotherapy sensitivity; responding pts proceeded to PBSC mobilization and subsequent ASCT. The intensive therapy regimen consisted of high-dose VP16 60 mg/kg day -4 and melphalan 180 mg/m2 day -3 with PBSC infusion day 0. Pts with bulky disease at relapse (> 5cm) received involved field radiation post-ASCT.

RESULTS: The median age at the time of transplant was 62 (range 61–66) in the OG vs. 50 (range 19–60) in the YG. Histology was similar in both groups: DLBCL and variants (OG: 63%; YG: 48%), transformed FL (OG: 10%; YG: 16%), MCL (OG: 7%; YG: 13%) (chi square 0.525). Prior chemotherapy was R-CHOP (OG: 23%; YG: 9%), CHOP or CHOP-like (OG: 69%; YG: 72%), chi-square p=0.10. There was no difference in prior radiotherapy (OG:40%;YG:38%, chi square 0.859). Advanced stage disease at relapse was seen in 56% (OG) vs. 44% (YG) (p=0.52 chi-square). Disease response [complete response (OG; 17%; YG:32%, p=0.09) and partial response rate (OG:67%, YG:68%, p=0.92)] pre-ASCT was not statistically different between groups. With a median follow-up of 41 months for OG and 81 months YG pts, the OS post-ASCT was 53% (OG) vs. 65% (YG), (p-value 0.06). Progression-free survival post-ASCT was 40% (OG) vs. 52% (YG), p-value 0.04. TRM was 7% (OG) vs. 3% (YG) (chi-square P=0.310) and NRM was 1% (OG) vs. 3% (YG) (chi square P=0.942).

CONCLUSIONS: While the OS between the OG and YG was not significantly different, PFS was inferior in the older pts. This difference was not expected based on available prognostic factors pre-ASCT although full IPI data is not available in all cases. This may suggest other factors related to tumour biology in patients age > 60 may be responsible for inferior PFS. TRM, NRM and OS were not statistically different and this may in part be due to small numbers in the OG. Well-designed prospective trials should address the role of salvage chemotherapy and ASCT in patients with aggressive NHL above the age of 60.