LP-06. Conditioning regimen dose reduction in patients with lymphomas undergoing autologous hematopoietic stem cell transplantation: a retrospective-prospective matched cohort study
Polina V. Kotselyabina, Vladislav V. Kovalik, Artem S. Ivanov, Kirill V. Lepik, Andrey M. Chekalov, Liudmila V. Fedorova, Elena E. Lepik, Olesia G. Smykova, Vladislav V. Markelov, Evgenia S. Borzenkova, Elena V. Kondakova, Ivan S. Moiseev, Natalia B. Mikhailova, Alexander D. Kulagin
RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
Contact: Dr. Polina V. Kotselyabina, e-mail: firstname.lastname@example.org
Autologous hematopoietic stem cell transplantation (aHSCT) is the standard of care for patients with relapsed/refractory (r/r) lymphomas. Since high-dose chemotherapy (HDC) is the key therapeutic component of aHSCT, optimal dosing is critical. Currently, data regarding the impact of HDC dose reduction on aHSCT outcomes in lymphoma patients remains limited. In this study, we evaluated main aHSCT outcomes in patients with r/r lymphomas in HDC reduced-dose and full-dose groups.
Patients and methods
We conducted a single-center matched cohort study of 178 patients with r/r lymphomas who received aHSCT between 2013 and 2023. After excluding patients with missed data and those unmatched after matching was done (in total, 78 patients were excluded), we included 100 patients in the study, with retrospective part accounting for 94 and prospective making up to 6 patients. The patients with HDC dose reduction (group 1) were matched to the full-dose HDC patients (group 2) to 1:1 ratio, using the optimal pair matching method. The matching factors included age and disease status at the time of aHSCT, the number of CD34+ cells in transplant, and the type of lymphomas. The conditioning regimens included BeEAM (bendamustine, etoposide, cytarabine, melphalan) and BEAM (carmustine, etoposide, cytarabine, and melphalan) with or without rituximab. We hypothesized that patients in two groups may have similar 5-year overall survival (OS), progression-free survival (PFS) and median of neutrophil and platelets engraftment. To compare OS and PFS, we used a log-rank test. The other factors were compared using chi-square test for categorical variables and Mann-Whitney test for continuous variables. Analysis was performed in RStudio (v2022.07.2).
In total, 50 patients of the groups 1 and 50 of the group 2 were matched in a 1:1 ratio. Patients shared similar baseline characteristics between groups (Table 1). The majority of group 1 patients had dose reduction of multiple agents in 54% (n=27), with etoposide separately being reduced in 22% (n=11), cytarabine in 16% (n=8), bendamustine and melphalan in 4% (n=2) each. Median etoposide reduction rate was 50% (25-75%), bendamustine – 20% (15-25%), cytarabine – 50% (25-100%), melphalan – 29% (11-85%). The reasons behind dose reduction included low (2 millions and lower per kg) number of CD34+ cells (10%, n=5), renal (10%, n=5) and liver comorbidity (2%, n=1), other comorbidity (40%, n=20), including HIV, various types of cardiopulmonary, gastrointestinal diseases, and unknown reasons (38%, n=19). The median follow-up was 25 months (1-147) for both groups. The 5-year OS was similar between the groups 1 and the group 2: 84% (95% CI 73-97%) and 87% (95% CI 76-98%) respectively (p=0.69). There was no difference in 5-year PFS: 72% (95% CI 60-89%) and 79% (95% CI 65-96%) respectively (p=0.42). Additionally, the median time to neutrophil and platelet engraftment was similar between the dose-reduced and full-dose groups: 15 and 14 days for neutrophil, 13 and 16 days for platelets respectively (p=0.36 for the former, p=0.14, for the latter). As for adverse events, the study did not show any difference between group 1 and 2 in the frequency of grade 3/4 oral mucositis (34% and 34%) and gastrointestinal mucositis (24% and 16%, p=0.32), febrile neutropenia (92% and 86%, p=0.34) and sepsis (8% and 16%, p=0.22).
Among patients with r/r lymphomas who received aHSCT, HDC dosage reduction did not impact OS and PFS, neutrophil and platelets engraftment in the matched cohorts.
Hematopoietic stem cell transplantation, autologous, high-dose chemotherapy, lymphoma.
Table 1. Patient characteristics