Role of Rituximab in the Treatment of Splenic Marginal Zone Lymphoma.
Authors: Shehadat Saaib Al , Bast Martin A. , Sehi Gene , Bociek Greory R. , Kessinger Anne , Armitage James O. 
Published: October 2019

Abstract
Background: Splenic marginal zone lymphoma (SMZL) is a rare malignancy accounting for less than 1% of all lymphomas. The tumor involves the spleen, splenic hilar lymph nodes, bone marrow, and often the peripheral blood. The peripheral lymph nodes are not typically enlarged. Patients typically have circulating neoplastic cells characterized by cytoplasmic projections, round or oval nuclei and clumped chromatin. The lymphoma cells express CD19, CD20, and CD22 but not usually CD5, CD10, CD23, CD25, CD43, CD103 or cyclin D1. The tumor may be surprisingly resistant to chemotherapy that would ordinarily be effective for chronic lymphocytic leukemia. For patients needing treatment, splenectomy is the usual first treatment, which may be followed by prolonged remission. The best approach for patients following splenectomy is not clear.
Methods: The characteristics of seven patients with SMZL who progressed after splenectomy are shown in the table. Six of the seven patients received rituximab therapy alone or in combination with other cytotoxic agents. One patient was ineligible for rituximab therapy due to hepatitis C.
Results: One patient who relapsed 16 months after splenectomy to diffuse large B cell lymphoma (DLBCL) achieved a complete remission after 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and then electively underwent autologous peripheral stem cell transplantation. His remission persisted 72+ months later. The two patients who received rituximab in combination with other cytotoxic agents 2 months after splenectomy (one had CNOP/cyclophosphamide, mitoxantrone, vincristine, and prednisone; and one had CVP/cyclophosphamide, vincristine, prednisone) remained in remission 52+ months. One patient with anemia refractory to splenectomy responded to 4 cycles of rituximab. One patient who developed anemia and monoclonal gammopathy post splenectomy received 8 weekly cycles of rituximab. Although anemia improved there was no objective response. One patient’s disease transformed to DLBCL 18 months post splenectomy, and did not respond to 8 cycles of rituximab.
Conclusion: These results suggest that SMZL in patients who relapsed after splenectomy transforms to aggressive lymphoma more commonly than several thought. Most patients respond to rituximab containing regimens and may achieve a prolonged remission. More studies are warranted to investigate whether rituximab therapy shortly after splenectomy provides better progression free survival than treatment after relapse.
Patients’ Characteristics
1 2 3 4 5 6* 7 F: female, CR: complete remission, M: male, P: progression, PR: partial remission, * Hepatitis C. Age 62 33 53 53 67 55 67 Sex M M F F F M F Year 1997 1998 2000 2001 2001 2001 2002 CD20 + + + + + + + DLBCL Transformation + - - - - - + Rituximab # of Cycles 6 8 4 4 6 0 8 Concurrent Chemotherapy CHOP CNOP - Fludarabine CVP CHOP - Response CR CR CR PR CR CR P Follow up (Months) 72+ 61+ 49+ 50+ 50+ 52+ 0