Enisa Zaric, MD Montenegro Specialist

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Enisa Zaric, MD Montenegro Specialist Clinical Center of Montenegro, Center of Hematology Department of Internal Medicine Ljubljanska bb 81000 Podgorica, Montenegro Phone: +38-2-20412462, +38-2-67611800 Email 1: enisazaric@yahoo.com Email 2: enisazaric@gmail.com

Pregnancy after the treatment of the primary ovary Non Hodgkin lymphoma MSc Enisa Žarić Center for hematology,Clinical Center of Montenegro Montenegro

Clinical presentation and history 28-years-old-woman , without previous disease Patient presentation Complained of pain in both inguinal regions for six months, night sweats, irregular menstrual bleeding. (since november 2009.) Gynecology examinations: bimanual pelvic examination, ultrasound examination: showed a tumor mass in the right adnexa. Serum tumor markers were within reference range. Laparascopic right oophorectomy performed (december 2009.) Histopathology finding: Non Hodgkin follicular lymphoma (grade 3) Immunohistochemistry studies: CK-, LCA +, CD30-, CD20+++, CD79α+, anti LCA+, CD10+, EMA-, CD5 -, bcl2 +, bcl6+, CD43-, CD23-, CD21-, MUM 1 +/-, anti CD3 -, antiCD43+, CD23-, Ki 67 index 30-40%. References: 1. Johnston JB, Seftel M, Gibson SB. Chronic lymphocytic leukemia. In: Greer JP, Foerster J, Rodgers GM, et al, eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:2214-2255. 2. Dawson G. Prognostic factors in chronic lymphocytic leukemia associated with Agent Orange. J Natl Med Assoc. 2003;95:A21. 3. Chamie K, DeVere White RW, Leed D, et al. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer. 2008;113:2464-2470.

Clinical presentation and history Clinical examination, labarotory and imaging findings (march 2010.): Physical exam: no enlargement of lymph nodes, no organomegaly, no others abnormal findings Blood counts: normal Laboratory results: lactate dehydrogenase 139 ( upper limit 460) Imaging studies: ultrasound: no inguinal lymphadenopathy, and abdomen -ultrasound: no lymphadenopathy or other abnormal findings PET CT – negative , ( PET CT Center Linz, Austria, february 2010.) References: 1. Johnston JB, Seftel M, Gibson SB. Chronic lymphocytic leukemia. In: Greer JP, Foerster J, Rodgers GM, et al, eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:2214-2255. 2. Dawson G. Prognostic factors in chronic lymphocytic leukemia associated with Agent Orange. J Natl Med Assoc. 2003;95:A21. 3. Chamie K, DeVere White RW, Leed D, et al. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer. 2008;113:2464-2470.

Diagnosis, objectives of treatment, treatment Non Hodgkin lymphoma Clinical Stage IE, follicular grade 3 (ovary) FLIPI SCORE: 0 OBJECTIVES: Physician’s treatment objective: Complete remission of disease Patient’s objective: good quality of life allowing her to work and plan her family TREATMENT: first-line R-CHOP, 6 cycles, every 21 days ( Rituximab i.v.(375 mg/m2 d0), Cyclophosphamide i.v. ( 750 mg/ m² d1) , Adriablastin (50 mg/m2, d1), Oncovin 2 mg i.v. (d1), Pronison 40+40+20 mg p.o. (d1-d5). References: 1. Johnston JB, Seftel M, Gibson SB. Chronic lymphocytic leukemia. In: Greer JP, Foerster J, Rodgers GM, et al, eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:2214-2255. 2. Dawson G. Prognostic factors in chronic lymphocytic leukemia associated with Agent Orange. J Natl Med Assoc. 2003;95:A21. 3. Chamie K, DeVere White RW, Leed D, et al. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer. 2008;113:2464-2470.

Outcome After 4 cycles were administered: Patient without symptoms blood count and laboratory results were within normal limits Imaging studies (ultrasound of peripheral regions): without lymphadenopathy and other abnormal findings Bone marrow biopsy have not been done( technical reason) No infections or immuno-chemotherapy side effects 6 cycles were administered finally on 22.6.2010.: Previous results including PET-CT there is no appreciable evidence of abnormal lesion in regions, specially not related to the primary diagnosis References: 1. Johnston JB, Seftel M, Gibson SB. Chronic lymphocytic leukemia. In: Greer JP, Foerster J, Rodgers GM, et al, eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:2214-2255. 2. Dawson G. Prognostic factors in chronic lymphocytic leukemia associated with Agent Orange. J Natl Med Assoc. 2003;95:A21. 3. Chamie K, DeVere White RW, Leed D, et al. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer. 2008;113:2464-2470.

Further case information / follow-up Maintenance therapy with Rutiximab, 4 cycles every 2 months, (finally with 22.02.2011.) Further follow up: at 3-month intervals for the two year, twice a year for the third and fourth years Follow-up visits include interval history, careful physical examination, laboratory studies including a complete blood count, chemistry screen, and serum lactate dehydrogenase level, image studies including at times NMR of abdomen and pelvis, also PET CT 4 years follow up- no signs of disease March 2015. delivery of a healthy female child Good course of the pregnancy, vaginal delivery Physician’s objective met: Complete remission of disease Patient’s objectivemet : to be healthy, allowing her to work and plan her family References: 1. Johnston JB, Seftel M, Gibson SB. Chronic lymphocytic leukemia. In: Greer JP, Foerster J, Rodgers GM, et al, eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:2214-2255. 2. Dawson G. Prognostic factors in chronic lymphocytic leukemia associated with Agent Orange. J Natl Med Assoc. 2003;95:A21. 3. Chamie K, DeVere White RW, Leed D, et al. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer. 2008;113:2464-2470.

Literature data Primary ovarian NHL is an extremely rare disease as other primary lymphomas of the genital tract, accounting for 0.5% of all NHLs and 1.5% of all malignant ovarian neoplasms. [1] The most common type of lymphoma involving the ovary is diffuse large B-cell lymphoma. [2] The initial clinical manifestation of an occult nodal lymphoma as an ovarian mass is known as having a poor outcome with a survival rate ranging from 7% to 38% at 5 years. But primary ovarian lymphoma has better prognosis. [3] The histologic type of ovary lymphoma is probably the most important prognostic factor being associated with longer survival. [4] In our case R-CHOP regimen, also according literature, was useful and well tolerated by the patient. [5,6] 1.Y. Yildirim, “Primary ovarian large B-cell lymphoma in patient with juvenile rheumatoid arthritis treated with low dose Methotrexate,” Gynecologic Oncology, vol. 97, no. 1, pp. 249–252, 2005. 2.R. Vang, et all, “Ovarian non-Hodgkin's lymphoma: a clinicopathologic study of eight primary cases,” Modern Pathology, vol. 14, no. 11, pp. 1093–1099, 2001. 3. S. Weingertner, et all, “Non-Hodgkin malignant lymphoma revealed by an ovarian tumor: case report and review of the literature,” Gynecologic Oncology, vol. 95, no. 3, pp. 750–754, 2004. 4.T. Yamada, et all, “A case of malignant lymphoma of the ovary manifesting like an advanced ovarian cancer,” Gynecologic Oncology, vol. 90, no. 1, pp. 215–219, 2003 5. Taylan Senol, et all, “ Five cases of Non-Hodgkin B-Cell Lymphoma of the Ovary ”Case Reports in Obstetrics and Gynecology, Volume 2014 (2014), Article ID 392758, 5 pages 6.T. Yamada, et all, “A case of malignant lymphoma of the ovary manifesting like an advanced ovarian cancer,” Gynecologic Oncology, vol. 90, no. 1, pp. 215–219, 2003. References: 1. Johnston JB, Seftel M, Gibson SB. Chronic lymphocytic leukemia. In: Greer JP, Foerster J, Rodgers GM, et al, eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:2214-2255. 2. Dawson G. Prognostic factors in chronic lymphocytic leukemia associated with Agent Orange. J Natl Med Assoc. 2003;95:A21. 3. Chamie K, DeVere White RW, Leed D, et al. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer. 2008;113:2464-2470.

Dillemas and questions Was it good choice of therapy? How many cycles of therapy were optimal and what about maintenance therapy? What is proposal for shortest period of time free of therapy for safe pregnancy planning, and should it be counted related to immuno-chemotherapy or end of maintenance therapy? . References: 1. Johnston JB, Seftel M, Gibson SB. Chronic lymphocytic leukemia. In: Greer JP, Foerster J, Rodgers GM, et al, eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:2214-2255. 2. Dawson G. Prognostic factors in chronic lymphocytic leukemia associated with Agent Orange. J Natl Med Assoc. 2003;95:A21. 3. Chamie K, DeVere White RW, Leed D, et al. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer. 2008;113:2464-2470.