Destiny of Elderly Patients with Lymphoma Indicated for Autologous Stem Cell Transplantation (ASCT)

Background. Autologous stem cell transplantation is the standard method of treatment of relapsed/refractory lymphoma patients (pts) and is a part of first-line therapy in certain diagnoses. ASCT in elderly pts (≥60 years) is much less studied than in younger ones and usually, only pts who actually undergone ASCT are included. This is a retrospective analysis of all subsequent patients ≥60 years indicated for ASCT at 1st Department of Medicine, General University Hospital, Prague, during 2008-2016.

Methods. Subsequent pts ≥60 years with any type of lymphoma who proceeded to mobilization of peripheral blood progenitor cells (PBPC) in the given period were included. All histologies were reviewed by expert hematopathologist. Demographic, prognostic and treatment data were collected from clinical documentation at diagnosis (pts transplanted as a part of 1^st line treatment) or at progression (relapsed/refractory pts) and compared by Pearson´s chi square, Fischer's exact and Mann-Whitney U tests. Overall survival (OS) and progression-free survival (PFS) were calculated from the beginning of mobilization of PBPC. Survival curves were estimated via Kaplan-Meier method and compared by log-rank test. Multivariate analyses were performed by Cox proportional hazard test.

Results. In total, 155 patients were included. Median age was 64 years (60-72) and 61% of them were males. 135 pts (87%) had B-NHL, 16 (10%) T-NHL and 4 (3%) Hodgkin´s lymphoma. Most common diagnoses were mantle cell lymphoma (MCL, 29%), diffuse large B-cell lymphoma (DLBCL, 28%) and follicular lymphoma (FL, 19%). Median number of previous treatment lines was 2 (1-6). 67 patients (43%) were scheduled for ASCT as a part of the 1^st line treatment and 88 (57%) for relapsed/refractory (R/R) disease. Collection of PBPC (≥2x10⁶ CD34+/kg) was successful in 143 pts (92%). Twenty-seven pts (17%) received plerixafor because of low number of CD34+ cells in peripheral blood, and 18 of them had successful harvest (66%).

The OS and PFS for the whole cohort were 71% and 60% at 2 years with median follow-up of 41 months for living patients, with no difference between 1^st line ASCT and R/R patients (p = 0.58 for OS and p = 0.33 for PFS, respectively). However, there was imbalance in indication for ASCT for different diagnoses (91% of MCL were transplanted in 1st line setting compared to 24% of others, p <0.0001), which also disabled comparison of outcomes according to diagnosis. On multivariate analysis of the whole cohort, ECOG performance status >2 was the most powerful prognostic factor (HR, 3.1 for OS and 2.8 for PFS, p = 0.0009 for both), followed by high LDH (HR, 2.9 for OS and 2.5 for PFS, p = 0.002 both), and age >65 years (HR, 2.3 for OS and 1.8 for PFS, p = 0.003 and 0.015 respectively). Sex, clinical stage, number of extranodal sites involved and number of lines of chemotherapy (1-2 v. >2) before indication for mobilization were not statistically significant.

117 patients (75%) were actually transplanted. The main reasons of dropout were progressive disease and mobilization failure (9% and 8% of the whole cohort, respectively). Age >65 years was statistically significant for non-proceeding to ASCT (33% v. 19%, p = 0.03). For transplanted pts, OS and PFS was 80% and 69%. Only performance status retained statistical significance both for OS and PFS, while age was a prognostic factor for OS only and diagnosis was a prognostic factor for PFS only. Four pts (3.5%) died before day +100 because of treatment-related toxicity. There were no difference in toxicities or engraftment between pts 60-65 and >65 years old.

Conclusion. In our cohort of elderly patients scheduled for collection of PBSC, 92% collected enough PBPC and 75% were actually transplanted. OS and PFS for the whole cohort are encouraging and peritransplantation mortality was acceptable. Inclusion of pts who did not proceed to ASCT provides a better estimate of the destiny of elderly pts scheduled for this procedure than studies, where only actually transplanted patients were included. Limitation of our results are different settings, in which were patients with different diagnoses indicated for ASCT.

Financial support: grants AZV16-310092A and AZV 17-28980A from Czech Ministry of Public Health.