Korean J Gastroenterol.  2021 Dec;78(6):320-327. 10.4166/kjg.2021.082.

Clinical Features and Prognosis of Patients with Primary Intestinal B-cell Lymphoma Treated with Chemotherapy with or without Surgery

• Cha RR
• Baek DH
• Lee GW
• Park SJ
• Lee JH
• Park JH
• Kim TO
• Lee SH
• Kim HW
• Kim HJ
• Busan Ulsan Gyeongnam Intestinal Study Group Society (BIGS)

• KMID: 2523593
• DOI: http://doi.org/10.4166/kjg.2021.082

Abstract

Background/Aims
This multicenter study reviewed the clinical features and prognosis according to the primary site of involvement and the treatment modality in patients with B-cell primary intestinal lymphoma (PIL).
Methods
Among 125 consecutive patients diagnosed with PIL, 100 patients were analyzed.
Results
The median age was 59 years, and the male to female ratio was 1.86:1. Diffuse large B-cell lymphoma (66/100, 66.0%) was the most common histological subtype. The estimated 5-year survival rate (5-YSR) was 48.5%. The 5-YSR was similar regardless of the type of primary treatment (chemotherapy alone vs. surgery/chemotherapy, 50.7 vs. 45.3%, p=0.582). A comparison of the survival according to the primary site of involvement revealed a 5-YSR of 32.5% (p=0.027), 64.3% (reference), 46.5% (p=0.113), and 49.8% (p=0.024) for the small intestine, ileocecal region, large intestine, and multiple sites, respectively. Multivariate analysis, however, revealed a low hemoglobin level, advanced Ann Arbor stage, and aggressive histological type to be independent prognostic factors for shorter survival but not ileocecal region involvement.
Conclusions
The Ann Arbor stage, hemoglobin level, and histological type were independent prognostic factors for survival, while the primary site of involvement and treatment modality did not affect the prognosis in patients with B-cell PIL.

Keyword

Lymphoma; B-Cell; Intestines; Neoplasm staging; Hemoglobins; Surgery

Figure

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  Fig. 1 Kaplan-Meier estimates of the overall survival in all patients with primary intestinal B-cell lymphoma.

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  Fig. 2 Kaplan-Meier estimates of the overall survival according to (A) the primary site of involvement and (B) the type of primary treatment. ns, not significant.

Reference

1. d'Amore F, Brincker H, Grønbaek K, et al. 1994; Non-Hodgkin's lymphoma of the gastrointestinal tract: a population-based analysis of incidence, geographic distribution, clinicopathologic presentation features, and prognosis. Danish Lymphoma Study Group. J Clin Oncol. 12:1673–1684. DOI: 10.1200/JCO.1994.12.8.1673. PMID: 8040680.

2. Ko YH, Kim CW, Park CS, et al. 1998; REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma. Cancer. 83:806–812. DOI: 10.1002/(SICI)1097-0142(19980815)83:4<806::AID-CNCR26>3.0.CO;2-V. PMID: 9708949.

3. Lepage C, Bouvier AM, Manfredi S, Dancourt V, Faivre J. 2006; Incidence and management of primary malignant small bowel cancers: a well-defined French population study. Am J Gastroenterol. 101:2826–2832. DOI: 10.1111/j.1572-0241.2006.00854.x. PMID: 17026561.

4. Dragosics B, Bauer P, Radaszkiewicz T. 1985; Primary gastrointestinal non-Hodgkin's lymphomas. A retrospective clinicopathologic study of 150 cases. Cancer. 55:1060–1073. DOI: 10.1002/1097-0142(19850301)55:5<1060::AID-CNCR2820550523>3.0.CO;2-8.

5. Koch P, del Valle F, Berdel WE, et al. 2001; Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol. 19:3861–3873. DOI: 10.1200/JCO.2001.19.18.3861. PMID: 11559724.

6. Ruskoné-Fourmestraux A, Aegerter P, Delmer A, Brousse N, Galian A, Rambaud JC. 1993; Primary digestive tract lymphoma: a prospective multicentric study of 91 patients. Groupe d'Etude des Lymphomes Digestifs. Gastroenterology. 105:1662–1671. DOI: 10.1016/0016-5085(93)91061-L.

7. Fischbach W, Dragosics B, Kolve-Goebeler ME, et al. 2000; Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group. Gastroenterology. 119:1191–1202. DOI: 10.1053/gast.2000.19579. PMID: 11054376.

8. Nakamura S, Matsumoto T, Iida M, Yao T, Tsuneyoshi M. 2003; Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends. Cancer. 97:2462–2473. DOI: 10.1002/cncr.11415. PMID: 12733145.

9. Ruskoné-Fourmestraux A, Fischbach W, Aleman BM, et al. 2011; EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT. Gut. 60:747–758. DOI: 10.1136/gut.2010.224949. PMID: 21317175.

10. Zucca E. ESMO Guidelines Working Group. 2007; Gastric marginal zone lymphoma of mucosa-associated lymphoid tissue type: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 18(Suppl 2):ii59–ii60. DOI: 10.1093/annonc/mdm039. PMID: 17491050.

11. Matysiak-Budnik T, Jamet P, Fabiani B, et al. 2013; Primary intestinal B-cell lymphoma: a prospective multicentre clinical study of 91 cases. Dig Liver Dis. 45:947–952. DOI: 10.1016/j.dld.2013.05.008. PMID: 23816692.

12. Kim SJ, Choi CW, Mun YC, et al. 2011; Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL). BMC Cancer. 11:321. DOI: 10.1186/1471-2407-11-321. PMID: 21798075. PMCID: PMC3160411.

13. Gurney KA, Cartwright RA, Gilman EA. 1999; Descriptive epidemiology of gastrointestinal non-Hodgkin's lymphoma in a population-based registry. Br J Cancer. 79:1929–1934. DOI: 10.1038/sj.bjc.6690307. PMID: 10206316. PMCID: PMC2362786.

14. Kim SJ, Kang HJ, Kim JS, et al. 2011; Comparison of treatment strategies for patients with intestinal diffuse large B-cell lymphoma: surgical resection followed by chemotherapy versus chemotherapy alone. Blood. 117:1958–1965. DOI: 10.1182/blood-2010-06-288480. PMID: 21148334.

15. Wang M, Ma S, Shi W, Zhang Y, Luo S, Hu Y. 2021; Surgery shows survival benefit in patients with primary intestinal diffuse large B-cell lymphoma: a population-based study. Cancer Med. 10:3474–3485. DOI: 10.1002/cam4.3882. PMID: 33931950. PMCID: PMC8124121.

16. Schemper M, Smith TL. 1996; A note on quantifying follow-up in studies of failure time. Control Clin Trials. 17:343–346. DOI: 10.1016/0197-2456(96)00075-X. PMID: 8889347.

17. Li B, Shi YK, He XH, et al. 2008; Primary non-Hodgkin lymphomas in the small and large intestine: clinicopathological characteristics and management of 40 patients. Int J Hematol. 87:375–381. DOI: 10.1007/s12185-008-0068-5. PMID: 18409078.

18. Nakamura S, Matsumoto T, Takeshita M, et al. 2000; A clinicopathologic study of primary small intestine lymphoma: prognostic significance of mucosa-associated lymphoid tissue-derived lymphoma. Cancer. 88:286–294. DOI: 10.1002/(SICI)1097-0142(20000115)88:2<286::AID-CNCR7>3.0.CO;2-Z. PMID: 10640959.

19. Wang GB, Xu GL, Luo GY, et al. 2011; Primary intestinal non-Hodgkin's lymphoma: a clinicopathologic analysis of 81 patients. World J Gastroenterol. 17:4625–4631. DOI: 10.3748/wjg.v17.i41.4625. PMID: 22147970. PMCID: PMC3226984.

20. Daum S, Ullrich R, Heise W, et al. 2003; Intestinal non-Hodgkin's lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin's Lymphoma. J Clin Oncol. 21:2740–2746. DOI: 10.1200/JCO.2003.06.026. PMID: 12860953.

21. Kodama T, Ohshima K, Nomura K, et al. 2005; Lymphomatous polyposis of the gastrointestinal tract, including mantle cell lymphoma, follicular lymphoma and mucosa-associated lymphoid tissue lymphoma. Histopathology. 47:467–478. DOI: 10.1111/j.1365-2559.2005.02225.x. PMID: 16241994.

22. Salar A, Juanpere N, Bellosillo B, et al. 2006; Gastrointestinal involvement in mantle cell lymphoma: a prospective clinic, endoscopic, and pathologic study. Am J Surg Pathol. 30:1274–1280. DOI: 10.1097/01.pas.0000208899.15859.cb. PMID: 17001159.

23. Lee J, Kim WS, Kim K, et al. 2004; Intestinal lymphoma: exploration of the prognostic factors and the optimal treatment. Leuk Lymphoma. 45:339–344. DOI: 10.1080/10428190310001593111. PMID: 15101721.

24. Troppan KT, Melchardt T, Deutsch A, et al. 2015; The significance of pretreatment anemia in the era of R-IPI and NCCN-IPI prognostic risk assessment tools: a dual-center study in diffuse large B-cell lymphoma patients. Eur J Haematol. 95:538–544. DOI: 10.1111/ejh.12529. PMID: 25677782.

25. Tisi MC, Bozzoli V, Giachelia M, et al. 2014; Anemia in diffuse large B-cell non-Hodgkin lymphoma: the role of interleukin-6, hepcidin and erythropoietin. Leuk Lymphoma. 55:270–275. DOI: 10.3109/10428194.2013.802314. PMID: 23647063.

26. Giachelia M, Voso MT, Tisi MC, et al. 2012; Interleukin-6 plasma levels are modulated by a polymorphism in the NF-κB1 gene and are associated with outcome following rituximab-combined chemotherapy in diffuse large B-cell non-Hodgkin lymphoma. Leuk Lymphoma. 53:411–416. DOI: 10.3109/10428194.2011.621566. PMID: 21902578.

27. Suzuki K, Terui Y, Nishimura N, et al. 2013; Prognostic value of C-reactive protein, lactase dehydrogenase and anemia in recurrent or refractory aggressive lymphoma. Jpn J Clin Oncol. 43:37–44. DOI: 10.1093/jjco/hys194. PMID: 23166385.

28. Hong J, Woo HS, Kim H, et al. 2014; Anemia as a useful biomarker in patients with diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy. Cancer Sci. 105:1569–1575. DOI: 10.1111/cas.12544. PMID: 25263825. PMCID: PMC4317957.

29. Gobbi PG, Ghirardelli ML, Cavalli C, et al. 2000; The role of surgery in the treatment of gastrointestinal lymphomas other than low-grade MALT lymphomas. Haematologica. 85:372–380. PMID: 10756362.

30. Ibrahim EM, Ezzat AA, El-Weshi AN, et al. 2001; Primary intestinal diffuse large B-cell non-Hodgkin's lymphoma: clinical features, management, and prognosis of 66 patients. Ann Oncol. 12:53–58. DOI: 10.1023/A:1008389001990. PMID: 11249049.

31. Zinzani PL, Magagnoli M, Pagliani G, et al. 1997; Primary intestinal lymphoma: clinical and therapeutic features of 32 patients. Haematologica. 82:305–308. PMID: 9234576.

32. Kobayashi H, Nagai T, Omine K, et al. 2013; Clinical outcome of non-surgical treatment for primary small intestinal lymphoma diagnosed with double-balloon endoscopy. Leuk Lymphoma. 54:731–736. DOI: 10.3109/10428194.2012.725850. PMID: 22946663.

33. Shawky H, Tawfik H. 2008; Primary gastrointestinal non-Hodgkin's lymphoma: a retrospective study with emphasis on prognostic factors and treatment outcome. J Egypt Natl Canc Inst. 20:330–341.

34. Lee HS, Park LC, Lee EM, et al. 2014; Comparison of therapeutic outcomes between surgical resection followed by R-CHOP and R-CHOP alone for localized primary intestinal diffuse large B-cell lymphoma. Am J Clin Oncol. 37:182–187. DOI: 10.1097/COC.0b013e318271b125. PMID: 23211226.