High-Dose Therapy (HDT) with Hematopoietic Stem Cell Transplantation (HSCT) Is Effective Therapy for Patients with Non-Hodgkin Lymphoma (NHL) and Central Nervous System (CNS) Involvement

Abstract 1358

Patients with NHL and CNS involvement have a poor prognosis when treated with conventional therapy. We performed a retrospective review of the Nebraska Lymphoma Study Group database to identify patients with NHL and CNS involvement who underwent HSCT. CNS involvement was defined as the presence of lymphomatous cells in cerebrospinal fluid, clear evidence of leptomeningeal disease by imaging studies, or biopsy proven parenchymal disease. Between January 1991 and December 2006, 24 such patients underwent HDT/HSCT. The median age at transplantation was 43 years (range 20–61). Fifty four percent of patients had diffuse large B-cell lymphoma. Sixty three percent of patients had parenchymal CNS involvement. CNS directed therapy as part of salvage prior to transplantation included intrathecal chemotherapy in 19 patients, high-dose methotrexate in 15 patients, and cranial irradiation in 10 patients. All but one patient achieved CNS remission prior to transplant. Twenty patients underwent autologous HSCT and four underwent allogeneic HSCT. The majority of patients were conditioned with carmustine, etoposide, cytarabine and melphalan (BEAM). At a median follow-up of 67 months for surviving patients (range 35–224 mo) the 1-year progression-free survival (PFS) is 50% (95% confidence interval [CI] 30–67) and the 5-year PFS is 38% (95% CI 20–56). The 1-year overall survival (OS) is 65% (95% CI 44–80) and the 5-year overall survival is 52% (95% CI 31–70). Eleven patients have relapsed and all relapses occurred within 13 months of HSCT. Thirteen patients remain alive and in remission. There have been 9 deaths due to disease recurrence and one death with no evidence of relapse. Among 15 patients who received high-dose methotrexate as part of CNS directed therapy the 5-year probability of PFS was 47% (95% CI 23–68) compared with 22% (95% CI, 3–51) in 9 patients not receiving high-dose methotrexate (p = 0.24). For patients transplanted as consolidation of initial therapy (n = 9) the 3-year probability of PFS was 63% (95% CI 29–96) compared with 36% (95% CI 0–71) for 12 patients transplanted in sensitive relapse (p = 0.36). Those same 9 patients had an 88% probability of survival at three years post transplant (95% CI 65%-100%) compared with 33% (95% CI 0–68) for the 12 patients with sensitive relapse (p = 0.046). In conclusion patients with NHL and CNS involvement who undergo HDT/HSCT appear to have similar outcomes to patients transplanted without CNS involvement. Patients destined to relapse appear to do so relatively soon after transplantation. Patients who received high-dose methotrexate as CNS directed therapy prior to transplant had a trend toward superior PFS compared with those receiving only intrathecal methotrexate, CNS irradiation, or both.