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Pre-existing central nervous system ( CNS) involvement may influence referral for autologous haematopoietic cell transplantation ( AHCT) for patients with non-Hodgkin lymphoma ( NHL). The outcomes of 151 adult patients with NHL with prior secondary CNS involvement ( CNS+) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma ( CNS−). There were significant baseline differences between the cohorts. CNS+ patients were more likely to be younger, have lower performance scores, higher age-adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression-free survival ( PFS) and overall survival ( OS) at 5 years. A matched pair comparison of the CNS+ group with a subset of CNS− patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT ( n = 55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission ( n = 96) at the time of AHCT. CNS+ patients can achieve excellent long-term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis. [ABSTRACT FROM AUTHOR]