Abstract
Introduction: Autologous Stem Cell Transplantation (ASCT) has become the cornerstone of managing relapsed lymphomas. However, its use in elderly patients or those with comorbidities is limited because of high regimen related toxicities (RRT). Several chemotherapy regimens have been suggested to minimize RRT while maintaining the antitumor effect. TECAM (Thiotepa 160 mg/m2 over 4 days , Etoposide and Cytarabine 800mg/m2 over 4 days, Cytoxan 60 mg/kg, and Melphalan 120 mg/m2 over 2 days) is a reduced toxicity modification for the commonly used BEAM protocol.
Aim: This study aimed to compare the safety and efficacy or the TECAM regimen with that of its more intense BEAM counterpart.
Methods: A retrospective cohort study of all patients who underwent ASCT for treatment of lymphoma with either BEAM or TECAM conditioning regimens at the Tel Aviv Medical Center between October 1999 and January 2014. We compared early (≤100 days) mortality, RRT rate, time to engraftment and length of hospitalization as well as overall and progression free survival.
Results: A total of 146 patients (76 BEAM, 70 TECAM) were included in the analysis. Median follow up was 47 months. Patient treated with TECAM were older (54.5 vs. 45.5, p=0.001), and nearly 20% (n=13) of them had dose reductions (average 17±7%), as opposed to a single patient in the BEAM arm. Conversely, TECAM patients had a longer time interval from first diagnosis to transplant (22 vs. 13 months, p<0.001), and had a higher rate of CR at transplantation, though not statistically significant (57% vs. 49%, p=0.39). At 100 days there was no difference in mortality rates between the groups (5 vs. 7 deaths, TECAM vs. BEAM, p=0.63). There was no difference in the median time to engraftment of neutrophils (11 days) or platelets (13 days), nor in the median length of hospitalization (25 days TECAM vs. 24 days BEAM, p=0.28). Similarly, there was no difference in the transfusion requirements, rate of severe mucositis, bacteremia or ARDS.
There was no statistically significant difference in PFS (26 months vs. not reached, TECAM vs. BEAM, p=0.16), nor in OS (not reached for both, p=0.55). In multivariable analysis the only factor associated with PFS was not entering transplantation in CR (HR 2.4, 95% CI 1.4-4.0, p=0.001). Similarly, factors associated with OS were older age (HR 1.023, 95% CI 1.004-1.043 per year, p=0.016) and non-CR at transplantation (HR 2.4, 95% CI 1.4-4.4, p=0.003).
Discussion: We found comparable results for BEAM and its low toxicity counterpart TECAM. There were no differences in early mortality, RRT, time to engraftment, PFS, or OS. This was despite the fact that patients treated with TECAM were, on average, nine years older, and probably perceived to be frailer as indicated by a considerably higher rate of dose reductions. This study has several limitations that extend beyond its retrospective single institution nature. It encompasses a heterogeneous group of lymphomas, and there was possibly a selection bias allocating patients with a more severe disease to BAEM. Regardless, it suggests that TECAM could provide a lower toxicity alternative for ASCT conditioning in a selected group of patients.
Table 1. Baseline characteristics BEAM (n=76) TECAM (n=70) p vlaue Age* 45.5 [29.5-54.0] 54.5 [41.3-65.0] 0.001 Sex (female) 31 (40.8%) 32 (45.7%) 0.67 Lymphoma type 0.09 Diffuse large B cell 32 (42.1%) 35 (50.7%) Hodgkin's 15 (19.7%) 15 (21.7%) T Cell 16 (21.1%) 4 (5.80%) Follicular 3 (3.95%) 6 (8.70%) Mantle cell 7 (9.21%) 8 (11.6%) Other 3 (3.95%) 1 (1.45%) Months from diagnosis* 13 [9-22] 22 [12-37] <0.001 Comorbidity index 1.5 [0-2] 1.0 [0-2] 0.58 CR at transplantation 37 (48.7%) 40 (57.1%) 0.39 Dose reduction 1 (1.32%) 13 (18.6%) 0.001 CD34 < 2X106/kg: 2 (2.63%) 11 (15.7%) 0.01 *(median [IQR])
Figure 1. Overall and progression free survival Figure 1. Overall and progression free survival
Disclosures
Rozovski: Novartis: Other: Advisory board.
Autologous Stem Cell Transplantation Added to Standard Chemotherapy, Hipec Surgery, and Whole Abdominal Radiation is Well Tolerated and May Increases Progression Free Survival in Patients with Desmoplastic Small Round Cell Tumors