Cancer Res Treat.  2013 Jun;45(2):112-117.

Clinical Outcome of Rituximab-Based Therapy (RCHOP) in Diffuse Large B-Cell Lymphoma Patients with Bone Marrow Involvement

• Kang BW
• Moon JH
• Chae YS
• Lee SJ
• Kim JG
• Kim YK
• Lee JJ
• Yang DH
• Kim HJ
• Kim JY
• Do YR
• Park KU
• Song HS
• Kwon KY
• Kim MK
• Lee KH
• Hyun MS
• Ryoo HM
• Bae SH
• Kim H
• Sohn SK

Abstract

PURPOSE
We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy.
MATERIALS AND METHODS
A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively.
RESULTS
The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p<0.001) was statistically higher than that in patients with BM involvement (44.3% and 40.1%, p<0.001). In multivariate analysis, among total patients, BM involvement showed a significant association with OS and EFS. In univariate and multivariate analyses, even among stage IV patients, a significant association with worse EFS was observed in the BM involvement group.
CONCLUSION
BM involvement at diagnosis affected the survival of patients with DLBCL who received RCHOP. Although use of RCHOP can result in significant improvement of the therapeutic effect of DLBCL, BM involvement is still a negative prognostic factor of DLBCL patients in the era of rituximab.

Keyword

Diffuse large B-cell lymphoma; Bone marrow; Rituximab

MeSH Terms

Antibodies, Monoclonal, Murine-Derived
B-Lymphocytes
Bone Marrow
Cohort Studies
Disease-Free Survival
Follow-Up Studies
Humans
Incidence
Lymphoma, B-Cell
Multivariate Analysis
Prognosis
Rituximab
Antibodies, Monoclonal, Murine-Derived

Figure

• 

  Fig. 1 Kaplan-Meier analysis of overall survival (A) and event-free survival (B) for patients with and without bone marrow (BM) involvement.

• 

  Fig. 2 Kaplan-Meier analysis of overall survival (A) and event-free survival (B) for stage IV patients with and without bone marrow (BM) involvement.

Reference

1. Zhang QY, Foucar K. Bone marrow involvement by hodgkin and non-hodgkin lymphomas. Hematol Oncol Clin North Am. 2009; 23:873–902. PMID: 19577173.

2. Arber DA, George TI. Bone marrow biopsy involvement by non-Hodgkin's lymphoma: frequency of lymphoma types, patterns, blood involvement, and discordance with other sites in 450 specimens. Am J Surg Pathol. 2005; 29:1549–1557. PMID: 16327427.

3. Kajiura D, Yamashita Y, Mori N. Diffuse large B-cell lymphoma initially manifesting in the bone marrow. Am J Clin Pathol. 2007; 127:762–769. PMID: 17439835.

4. Conlan MG, Bast M, Armitage JO, Weisenburger DD. Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group. J Clin Oncol. 1990; 8:1163–1172. PMID: 1694234.

5. Zwick C, Murawski N, Pfreundschuh M. German High-Grade Non-Hodgkin Lymphoma Study Group. Rituximab in high-grade lymphoma. Semin Hematol. 2010; 47:148–155. PMID: 20350662.

6. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002; 346:235–242. PMID: 11807147.

7. Yi SH, Xu Y, Zou DH, An G, Zhao YZ, Qi JY, et al. Prognostic impact of bone marrow involvement (BMI) and therapies in diffuse large B cell lymphoma. Zhonghua Xue Ye Xue Za Zhi. 2009; 30:307–312. PMID: 19799125.

8. Li QC, Yuan XL, Wang YF, Zou DH, Zhao YZ, Qiu LG. Clinical outcomes of different regimens for non-Hodgkin's lymphoma with bone marrow involvement: analysis of 148 cases. Zhonghua Yi Xue Za Zhi. 2008; 88:254–257. PMID: 18361837.

9. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkins Lymphoma Prognostic Factors Project. N Engl J Med. 1993; 329:987–994. PMID: 8141877.

10. Armitage JO. Staging non-Hodgkin lymphoma. CA Cancer J Clin. 2005; 55:368–376. PMID: 16282281.

11. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007; 25:579–586. PMID: 17242396.

12. Chung R, Lai R, Wei P, Lee J, Hanson J, Belch AR, et al. Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index. Blood. 2007; 110:1278–1282. PMID: 17475910.

13. Chang H, Hung YS, Lin TL, Wang PN, Kuo MC, Tang TC, et al. Primary bone marrow diffuse large B cell lymphoma: a case series and review. Ann Hematol. 2011; 90:791–796. PMID: 21181164.

14. Gaudio F, Giordano A, Perrone T, Pastore D, Curci P, Delia M, et al. High Ki67 index and bulky disease remain significant adverse prognostic factors in patients with diffuse large B cell lymphoma before and after the introduction of rituximab. Acta Haematol. 2011; 126:44–51. PMID: 21430371.

15. Abe T, Kitajima T, Honma K, Kurasaki T, Okazuka K, Shibasaki Y, et al. Effective combination chemotherapy with rituximab for acute lymphoblastic leukemia with bone relapse after bone marrow transplantation. Rinsho Ketsueki. 2008; 49:1556–1561. PMID: 19047788.

16. Jardin F, Callonnec F, Contentin N, Picquenot JM, Gueit I, Heron F, et al. Intravascular large B-Cell lymphoma with bone marrow involvement and superior sagittal sinus thrombosis: report of a case successfully treated with a CHOP/rituximab combination regimen. Clin Lymphoma. 2005; 6:46–49. PMID: 15989707.

17. Takahashi T, Minato M, Tsukuda H, Yoshimoto M, Tsujisaki M. Successful treatment of intravascular large B-cell lymphoma diagnosed by bone marrow biopsy and FDG-PET scan. Intern Med. 2008; 47:975–979. PMID: 18480585.

18. Quartuccio L, Salvin S, Fabris M, Sacco S, De Vita S. Disappearance of bone marrow B cell clonal expansion in patients with type II hepatitis C virus-related cryoglobulinemic glomerulonephritis after clinical efficient rituximab therapy. Ann Rheum Dis. 2008; 67:1494–1495. PMID: 18791058.

19. Sieniawski M, Bhartia S, Wilkinson J, Proctor SJ. Incidence and outcome of patients with diffuse large B cell lymphoma with marrow involvement and preliminary experience of an adult acute lympho-blastic leukemia protocol (NEALL VI) in cyclophosphamide, doxorubicin, vincristine, and prednisolone: rituximab refractory patients. Leuk Lymphoma. 2009; 50:1726–1730. PMID: 19639513.

20. Sweetenham JW. Treatment of lymphoblastic lymphoma in adults. Oncology (Williston Park). 2009; 23:1015–1020. PMID: 20017283.