Contributions
Abstract: PB2161
Type: Publication Only
Background
High-dose chemotherapy before ASCT has been established as an effective treatment option for high-risk patients with chemo-sensitive ML. Although the therapeutic efficacy of this strategy highly depends on the conditioning regimens before ASCT, the appropriate regimen has been controversial. Thus, we performed a multi-center retrospective study of ASCT recipients with ML to compare the safety and efficacy of the conditioning regimens LEED and MCEC, which are widely used in Japan.
Aims
The primary objective was to determine the preferable conditioning regimen before ASCT: LEED or MCEC.
Methods
This study analyzed 127 adult patients who underwent ASCT following LEED or MCEC as the conditioning regimen against chemo-sensitive ML at four institutions in Japan between 1997 and 2015. Any type of pathological diagnosis was considered. The LEED regimen consisted of 140 mg/m2 L-PAM (day −1), 500 mg/m2 etoposide (days −4 to −2), 60 mg/kg cyclophosphamide (days −4 to −3), and 40 mg/body dexamethasone (days −4 to −1). The MCEC regimen consisted of 200 mg/m2 MCNU (days −8 and -3), 300 mg/m2 carboplatin (days −7 to −4), 500 mg/m2 etoposide (days −6 to −4), and 50 mg/kg cyclophosphamide (days −3 to −2). Fisher’s exact test was used to compare binary variables. OS rates were estimated by the Kaplan-Meier method and compared using the log-rank test. Cumulative incidences (CIs) of relapse and non-relapse mortality (NRM) were compared using the stratified Gray test. The Cox proportional hazards regression model was used for multivariate analysis of OS. Values of p < 0.05 were considered significant.
Results
Of the 127 patients, 76 were male and 51 were female, and the median age was 56 years (range: 18 to 68 years). Underlying diseases were DLBCL in 74 patients, mantle cell lymphoma in 16, other B-cell lymphoma in 14, Hodgkin lymphoma in 9, and T-NK-cell lymphoma in 14. The disease status at the time of transplant was first complete remission (CR) in 68, advanced CR in 27, and partial remission in 32. As the conditioning regimens before ASCT, 81 patients (64%) received the LEED regimen, and 46 (36%) received the MCEC regimen. No significant differences in patient characteristics, disease features, or transplant procedures were present between the two groups except for the following three factors: (1) ASCT in the later period (2007–2015) in the LEED group compared with the MCEC group (72% vs. 13%; p < 0.01); (2) more frequent administration of rituximab before ASCT in the LEED group (84% vs. 59%; p < 0.01); and (3) less frequent radiation therapy before ASCT in the LEED group (17% vs. 37%; p = 0.02). The 5-year OS rates were not significantly different between the LEED and MCEC groups (77% vs. 68%; p = 0.35). Likewise, both the 5-year CIs of relapse and NRM were similar in the two groups (relapse: 39% vs. 33%; p = 0.61, NRM: 1% vs. 5%; p = 0.71). In multivariate analysis that included the transplant periods, rituximab administration, and radiation therapy as independent variables, two or more prior regimens was extracted as an independent unfavorable prognostic factor for OS, but not conditioning regimens. Regimen-related toxicities within 100 days after ASCT were assessed. The incidences of grade 3-4 nausea (36% vs. 78%; p < 0.01), vomiting (4% vs. 28%; p < 0.01), diarrhea (36% vs. 56%; p = 0.02), and liver dysfunction (4% vs. 36%; p < 0.01) were significantly decreased in the LEED group. The 5-year CIs of secondary MDS/AML were similar between the two groups (4% vs. 3%; p = 0.62).
Conclusion
Our findings demonstrated that both the LEED and MCEC regimens showed sufficient anti-lymphoma effect as conditioning regimens before ASCT, with a 5-year OS rate of more than 70% in patients with chemo-sensitive ML. However, the LEED regimen is considered more preferable in comparison with the MCEC regimen based on the low frequency of severe regimen-related toxicities. A large-scale prospective study is warranted to confirm these findings.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Malignant lymphoma, Conditioning, Autologous hematopoietic stem cell transplantation
Abstract: PB2161
Type: Publication Only
Background
High-dose chemotherapy before ASCT has been established as an effective treatment option for high-risk patients with chemo-sensitive ML. Although the therapeutic efficacy of this strategy highly depends on the conditioning regimens before ASCT, the appropriate regimen has been controversial. Thus, we performed a multi-center retrospective study of ASCT recipients with ML to compare the safety and efficacy of the conditioning regimens LEED and MCEC, which are widely used in Japan.
Aims
The primary objective was to determine the preferable conditioning regimen before ASCT: LEED or MCEC.
Methods
This study analyzed 127 adult patients who underwent ASCT following LEED or MCEC as the conditioning regimen against chemo-sensitive ML at four institutions in Japan between 1997 and 2015. Any type of pathological diagnosis was considered. The LEED regimen consisted of 140 mg/m2 L-PAM (day −1), 500 mg/m2 etoposide (days −4 to −2), 60 mg/kg cyclophosphamide (days −4 to −3), and 40 mg/body dexamethasone (days −4 to −1). The MCEC regimen consisted of 200 mg/m2 MCNU (days −8 and -3), 300 mg/m2 carboplatin (days −7 to −4), 500 mg/m2 etoposide (days −6 to −4), and 50 mg/kg cyclophosphamide (days −3 to −2). Fisher’s exact test was used to compare binary variables. OS rates were estimated by the Kaplan-Meier method and compared using the log-rank test. Cumulative incidences (CIs) of relapse and non-relapse mortality (NRM) were compared using the stratified Gray test. The Cox proportional hazards regression model was used for multivariate analysis of OS. Values of p < 0.05 were considered significant.
Results
Of the 127 patients, 76 were male and 51 were female, and the median age was 56 years (range: 18 to 68 years). Underlying diseases were DLBCL in 74 patients, mantle cell lymphoma in 16, other B-cell lymphoma in 14, Hodgkin lymphoma in 9, and T-NK-cell lymphoma in 14. The disease status at the time of transplant was first complete remission (CR) in 68, advanced CR in 27, and partial remission in 32. As the conditioning regimens before ASCT, 81 patients (64%) received the LEED regimen, and 46 (36%) received the MCEC regimen. No significant differences in patient characteristics, disease features, or transplant procedures were present between the two groups except for the following three factors: (1) ASCT in the later period (2007–2015) in the LEED group compared with the MCEC group (72% vs. 13%; p < 0.01); (2) more frequent administration of rituximab before ASCT in the LEED group (84% vs. 59%; p < 0.01); and (3) less frequent radiation therapy before ASCT in the LEED group (17% vs. 37%; p = 0.02). The 5-year OS rates were not significantly different between the LEED and MCEC groups (77% vs. 68%; p = 0.35). Likewise, both the 5-year CIs of relapse and NRM were similar in the two groups (relapse: 39% vs. 33%; p = 0.61, NRM: 1% vs. 5%; p = 0.71). In multivariate analysis that included the transplant periods, rituximab administration, and radiation therapy as independent variables, two or more prior regimens was extracted as an independent unfavorable prognostic factor for OS, but not conditioning regimens. Regimen-related toxicities within 100 days after ASCT were assessed. The incidences of grade 3-4 nausea (36% vs. 78%; p < 0.01), vomiting (4% vs. 28%; p < 0.01), diarrhea (36% vs. 56%; p = 0.02), and liver dysfunction (4% vs. 36%; p < 0.01) were significantly decreased in the LEED group. The 5-year CIs of secondary MDS/AML were similar between the two groups (4% vs. 3%; p = 0.62).
Conclusion
Our findings demonstrated that both the LEED and MCEC regimens showed sufficient anti-lymphoma effect as conditioning regimens before ASCT, with a 5-year OS rate of more than 70% in patients with chemo-sensitive ML. However, the LEED regimen is considered more preferable in comparison with the MCEC regimen based on the low frequency of severe regimen-related toxicities. A large-scale prospective study is warranted to confirm these findings.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Malignant lymphoma, Conditioning, Autologous hematopoietic stem cell transplantation