Recommended Repeated Intrathecal Ara-C/MTX/PDN Injections during Rituximab-Based Therapy for B-Cell Lymphoma.

Rituximab-based chemotherapy for B-cell lymphoma is available in Japan since ‘01. We have treated twenty-eight B-cell lymphoma patients with rituximab and found four patients relapsed with posterior radiculopathy of the spinal cord due to lymphoma involvement. Because frequency of CNS lymphoma is reported to be 1~2%, we are surprised at the high incidence (14.2%) and thereafter we routinely repeat intrathecal cytarabine (Ara-C), methotrexate (MTX), and prednisolone (PDN) administrations during rituximab-based chemotherapy. Up to now, there is no new spinal cord relapse. The followings are the four spinal cord relapse cases we have experienced, which are characterized by severe back pain. (Case 1) A 46-years-old male with follicular lymphoma. Clinical stage (CS) was IIIB. He had cervical lymphadenopathy and breast involvement. He was treated with three courses of CHOP chemotherapy and achieved CR. Then he was treated with 1 course of rituximab alone and relapsed with severe neck and back pain five-days later. MRI imaging revealed posterior radiculopathy of the spinal cord between C2 and C4. (Case 2) A 48-years-old female with diffuse large B-cell lymphoma, CS IIIA. She had uterine cervix lymphoma and cervical lymphadenopathy four-years after acute lymphocytic leukemia (ALL) therapy. She was treated with 8 courses of biweekly R-CHOP and achieved CR. She relapsed with severe back and left arm pain with double vision six-months later. MRI imaging revealed posterior radiculopathy of the spinal cord between C5 and C6, and Th2 and Th3. She also had trigeminal radiculopathy and facial nerve oppression. The involved nerves were swollen like dumbbell. (Case 3) An 83-years-old female with MALToma, CSIIA. She had cervical lymphadenopathy. She was treated with 5 courses of rituximab alone and relapsed with severe back and lumbar pain one-month later. MRI imaging revealed posterior radiculopathy of the spinal cord between Th6 and Th7, and, Th12 and L1. (Case 4) A 63-years-old male with mantle cell lymphoma, CSIIIB. He had general lymphadenopathy. He was treated with 8 courses of CHOP, achieved CR, and relapsed with general lymphadenopathy and breast involvement thirteen-months later. He was treated with additional 7 courses of R-CHOP and relapsed again with severe oral, bilateral leg, and back pain seven-days later. MRI imaging revealed posterior radiculopathy of C2 and sacrum. All the patients except case 3 died due to lymphomas. When we treated the four patients with rituximab-based therapy, we did not repeat intrathecal Ara-C/MTX/PDN injections. Our data suggest that rituximab possibly induce posterior radiculopathy of spinal cord lymphoma involvement via some unknown pathway. In conclusion, we recommend repeated intra-thecal injections during rituximab administration.