Intrathecal Prophylaxis Might Be Required For Primary and Secondary Breast Lymphoma to prevent Central Nervous System Relapse
Authors: Kusano Yoshiharu , Nishimura Noriko , Ueda Kyoko , Yokoyama Masahiro , Terui Yasuhito , Hatake Kiyohiko 
Published: October 2019

Abstract

Background
Breast lymphomas is a rare type of malignant lymphoma. The major histopathological type of breast lymphoma is diffuse large B-cell lymphomas (DLBCL). Although conventional treatment regimen is cyclophosphamide, doxorubicin, vincristine, and predonisolone with rituximab (R-CHOP), the optimal cycles of chemotherapy, role of additional radiotherapy, and efficacy of intrathecal (IT) prophylaxis are still unclear.

Method
We retrospectively analyzed the clinical features and treatment outcomes of 22 patients with newly diagnosed primary breast lymphoma (PBL) of stage IE and IIE and secondary breast lymphoma of stage IIIE and IVE, and evaluated details of 20 DLBCL patients. All patients were treated at our institution between May 2002 and July 2013. Patients of stage IE were treated by 8 cycles of rituximab plus three cycles of CHOP-21 with radiotherapy, and patients of stage IIE-IVE were treated by 8 cycles of rituximab plus 6-8 cycles of CHOP-21 with or without radiotherapy. All patients were considered to receive intrathecal prophylaxis unless clinical study setting or patients’ denial. Patients were divided into three groups; primary breast lymphoma (PBL) of stage IE, PBL of stage IIE, and secondary breast lymphoma of stage IIIE and IVE.

Result
There were 22 malignant lymphoma patients of breast such as one follicular lymphoma patient, one Burkitt lymphoma patient, and 20 DLBCL patients with no bilateral breast involvement. In patients with DLBCL of the breast, the median age was 60 years (range 32–69 years), with all female. The median largest tumor diameter was 5 cm, and eight patients had bulky disease (>5 cm). Nine of 20 patients (45%) received at least once of IT prophylaxis during one to two cycles of R-CHOP therapy. Six patients were stage IE, nine patients were stage IIE, and five patients were stage III and IVE, who had another invasion including liver, bone, and bone marrow. CR rate after initial therapy was 90% (18/20). Five of 20 patients (25%) developed central nervous system (CNS) relapse with the median time to CNS relapse of 28 months. Although four of 11 (36.4%) patients without IT prophylaxis versus one of nine (11.1%) patients with IT prophylaxis developed CNS relapse with no significant difference between two groups (p=0.363), and IT prophylaxis tends to prevent CNS relapse. The median follow-up time was 48.5 months, and the 3-year progression free survival (PFS) and overall survival (OS) in each group were 75%, 87.5%, and 40.0% (p=0.154), and 100%, 85.7%, and 53.3% (p=0.244), respectively.

Conclusions
Primary and secondary breast lymphoma is still considered high-risk for CNS relapse in Rituximab era. IT prophylaxis might prevent CNS relapse in breast lymphoma patients, and, further study is needed to evaluate the efficacy of IT prophylaxis or another appropriate approach for CNS relapse.

Disclosures:
Nishimura: Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy.