Bone marrow involvement in patients with diffuse large B-cell lymphoma.

Compromiso de médula ósea en pacientes con linfoma B difuso de célula grande.

Main Article Content

Milton Alberto Lombana
Juan Felipe Combariza
Ana Milena Torre
Javier Segovia
Andrés Acevedo
Luis Eduardo Pino
Abstract

Introduction: bone marrow involvement in patients with diffuse large B-cell lymphoma is associated with a worse prognosis; however, the use of rituximab appears to improve it. It is unknown whether myelophthisis is a predictor of response or a prognostic factor for survival in Latin America during the rituximab era. Design and Methods: The aim of this multicenter dynamic prognostic cohort study was to determine the role of lymphoma bone marrow involvement to predict response to treatment and its usefulness as an independent prognostic factor for event free survival and overall survival. The survival analysis was performed by the nonparametric Kaplan-Meier method. Comparison of probability of survival between groups was made using the log-rank test. Results: 163 patients with diffuse large cell B lymphoma were included. The prevalence of myelophthisis was 11%. Complete response was 77% versus 38% in patients with and without bone marrow involvement respectively (P < 0.0001 Fisher). Multivariate analysis showed that bone marrow involvement was significantly associated with less likelihood of treatment response. Treatment response and low IPI score reduced the risk of relapse. Multivariate analysis by Cox regression showed that only treatment response and high IPI significantly affect overall survival. In patients with low-risk IPI and objective response and in those with high IPI and no response the two-year survival was 99% and 17% respectively. The Kaplan-Meier analysis showed that treatment response was the only variable that influenced survival. Conclusions: Our study confirms the significant predictive value of bone marrow involvement for poor response treatment. Overall survival was only modified by the IPI score and treatment response. Bone marrow involvement seems to be a predictor of response and no an independent prognostic factor for overall survival.

Keywords

Downloads

Download data is not yet available.

Article Details

Author Biographies (SEE)

Milton Alberto Lombana, Universidad El Bosque

Oncólogos Asociados de Imbanaco (Cali, Colombia). Facultad de Medicina, Departamento de Epidemiología, Universidad El Bosque (Bogotá, Colombia).

Juan Felipe Combariza, Hospital Pablo Tobón Uribe

Servicio de Hematología y Trasplante de Médula Ósea, Hospital Pablo Tobón Uribe (Medellín, Colombia).

Ana Milena Torre, Universidad El Bosque

Facultad de Medicina, Departamento de Epidemiología, Universidad El Bosque (Bogotá, Colombia).

Javier Segovia, Universidad Militar Nueva Granada

Servicio de Hematología y Oncología, Hospital Militar Central, Universidad Militar Nueva Granada (Bogotá, Colombia).

Andrés Acevedo, Hospital Pablo Tobón Uribe

Servicio de Hematología y Trasplante de Médula Ósea, Hospital Pablo Tobón Uribe (Medellín, Colombia).

Luis Eduardo Pino, Universidad Militar Nueva Granada

Servicio de Hematología y Oncología, Hospital Militar Central, Universidad Militar Nueva Granada (Bogotá, Colombia).

References

Globocan. Cancer incidence, mortality and prevalence worldwide in 2008. Lyon: International Agency for Research on Cancer. 2008 [cited 2011 oct 1º]. Available from: http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=170.

Ziepert M, Hasenclever D, Kuhnt E, Glass B, Schmitz N, Pfreundschuh M, et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(14):2373-80.

A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329(14):987-94.

Gallamini A, Stelitano C, Calvi R, Bellei M, Mattei D, Vitolo U, et al. Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study. Blood. 2004;103(7):2474-9.

Sehn LH, Scott DW, Chhanabhai M, Berry B, Ruskova A, Berkahn L, et al. Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2011;29(11):1452-7.

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(4):1278-82.

Bennett JM, Cain KC, Glick JH, Johnson GJ, Ezdinli E, O’Connell MJ. The significance of bone marrow involvement in nonHodgkin’s lymphoma: the Eastern Cooperative Oncology Group experience. J Clin Oncol. 1986;4(10):1462-9.

Hodges GF, Lenhardt TM, Cotelingam JD. Bone marrow involvement in large-cell lymphoma. Prognostic implications of discordant disease. Am J Clin Pathol. 1994;101(3):305-11.

Seneviratne L, Espina BM, Nathwani BN, Chan JA, Brynes RK, Levine AM. Clinical, immunologic, and pathologic correlates of bone marrow involvement in 291 patients with acquired immunodeficiency syndrome-related lymphoma. Blood. 2001;98(8):2358-63.

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(5):307-12.

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(1):44-51.

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(4):235-42.

Jäger U, Fridrik M, Zeitlinger M, Heintel D, Hopfinger G, Burgstaller S, et al. Rituximab serum concentrations during immunochemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Haematologica. 2012;97(9):1431-8.

Johnson NA, Boyle M, Bashashati A, Leach S, Brooks-Wilson A, Sehn LH, et al. Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival. Blood. 2009;113(16):3773-80.

Gronich N, Radnay J, Shapiro H, Manor Y, Lahav M, Lishner M. Clinical outcome of low-grade NHL patients with bone marrow involvement. Eur J Clin Invest. 2007;37(4):305-9.

Terasawa T, Lau J, Bardet S, Couturier O, Hotta T, Hutchings M, et al. Fluorine-18-fluorodeoxyglucose positron emission tomography for interim response assessment of advanced-stage Hodgkin’s lymphoma and diffuse large B-cell lymphoma: a systematic review. J Clin Oncol. 2009;27(11):1906-14.

Yang DH, Min JJ, Song HC, Jeong YY, Chung WK, Bae SY, et al. Prognostic significance of interim (1)(8)F-FDG PET/CT after three or four cycles of R-CHOP chemotherapy in the treatment of diffuse large B-cell lymphoma. Eur J Cancer. 2011;47(9):1312-8.

Safar V, Dupuis J, Itti E, Jardin F, Fruchart C, Bardet S, et al. Interim [18F]fluorodeoxyglucose positron emission tomography scan in diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy plus rituximab. J Clin Oncol. 2012;30(2):184-90.

Park S, Moon SH, Park LC, Hwang DW, Ji JH, Maeng CH, et al. The impact of baseline and interim PET/CT parameters on clinical outcome in patients with diffuse large B cell lymphoma. Am J Hematol. 2012;87(9):937-40.

Lanic H, Mareschal S, Mechken F, Picquenot JM, Cornic M, Maingonnat C, et al. Interim positron emission tomography scan associated with international prognostic index and germinal center B cell-like signature as prognostic index in diffuse large B-cell lymphoma. Leuk Lymphoma. 2012;53(1):34-42.

Pregno P, Chiappella A, Bello M, Botto B, Ferrero S, Franceschetti S, et al. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood. 2012;119(9):2066-73.

Cox MC, Ambrogi V, Lanni V, Cavalieri E, Pelliccia S, Scopinaro F, et al. Use of interim [18F]fluorodeoxyglucose-positron emission tomography is not justified in diffuse large B-cell lymphoma during first-line immunochemotherapy. Leuk Lymphoma. 2012;53(2):263-9.

Yoo C, Lee DH, Kim JE, Jo J, Yoon DH, Sohn BS, et al. Limited role of interim PET/CT in patients with diffuse large B-cell lymphoma treated with R-CHOP. Ann Hematol. 2011;90(7):797-802.

Mato AR, Svoboda J, Feldman T, Zielonka T, Agress H, Panush D, et al. Post-treatment (not interim) positron emission tomography-computed tomography scan status is highly predictive of outcome in mantle cell lymphoma patients treated with RHyperCVAD. Cancer. 2012;118(14):3565-70.

Cabanillas F. Non-Hodgkin’s lymphoma: the old and the new. Clin Lymphoma Myeloma Leuk. 2011;11 Suppl 1:S87-90.

Wada N, Zaki MA, Hori Y, Hashimoto K, Tsukaguchi M, Tatsumi Y, et al. Tumour-associated macrophages in diffuse large Bcell lymphoma: a study of the Osaka Lymphoma Study Group. Histopathology. 2012;60(2):313-9.

Seki R, Ohshima K, Fujisaki T, Uike N, Kawano F, Gondo H, et al. Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. Cancer Sci. 2009;100(10):1842-7.

Zanoni L, Cerci JJ, Fanti S. Use of PET/CT to evaluate response to therapy in lymphoma. Q J Nucl Med Mol Imaging. 2011;55(6):633-47.

Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011;378(9806):1858-67.

Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, et al. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011;29(6):690-7.

OJS System - Metabiblioteca |