Risk Factors for Central Nervous System (CNS) Relapse after Autologous Stem Cell Transplant (ASCT) in Diffuse Large B-Cell Lymphoma (DLBCL)

Background:Although the addition of rituximab to CHOP regimen improved prognosis in DLBCL patients with more than 80% of a long-term survival rate, CNS relapse did not decrease and 5 to 10% of patients experienced CNS relapse after rituximab-containing chemotherapy. Risk factors for CNS relapse after standard chemotherapy have been aggressively investigated, and a risk model, CNS-international prognostic index (IPI), has been widely used. However, risk factors for CNS relapse after high-dose chemotherapy following ASCT, which is recognized as an important treatment option for high-risk DLBCL patients, have not been elucidated. So, we performed this retrospective analysis to address this unsolved issue. Patients and methods:This study analyzed 87 adult patients who underwent ASCT against chemo-sensitive DLBCL including intravascular large B-cell lymphoma (IVLBCL) between 1997 and 2015 at the four institutions in Gunma, Japan. There was no restriction on the type of conditioning regimens. CNS-directed regimens were defined as chemotherapy or conditioning regimens containing high dose cytarabin, high dose methotrexate, busulfan, ranimustine, or total body irradiation. Only the first relapse after ASCT was assessed in this study. Fisher's exact test was used to compare binary variables. Cumulative incidences (CIs) of CNS relapse were compared using the stratified Gray test, considering relapse without CNS lesions and death without the event as a competing risk. The Fine-Gray proportional hazard model was used for multivariate analysis of risk factors for CNS relapse. The potential risk factors evaluated in this analysis were age at transplant, gender, clinical stage, IPI (high-intermediate/high or not), and CNS-IPI (high or not) at diagnosis, CD5 positivity, CNS involvement prior to ASCT, CNS-directed chemotherapy prior to ASCT, and CNS-directed conditioning regimen. Values of p < 0.05 were considered significant. Results:Of the 87 patients assessed in this study, 48 were male and 39 were female, and the median age was 57 years (range: 23 to 66 years). CD5 was expressed in 19% of the patients, and 10% were diagnosed as IVLBCL. CNS-IPI at diagnosis was high in 53%, and rituximab and CNS-directed chemotherapy was administered prior to ASCT in 83% and 16%, respectively. CNS involvement was observed prior to ASCT and at the time of ASCT in 9% and 0%, respectively. Disease status at the time of transplant was first complete remission (CR) in 47%, advanced CR in 23%