Abstract
In 27% of diffuse large B cell lymphoma (DLBCL) cases, bone marrow (BM), assessed by BM biopsy, is involved. BM involvement, an extranodal site involvement, affects the International Prognostic Index (IPI) score adversely. However, chromosomal abnormalities are neither included as a prognostic factor nor are they considered in the IPI risk classification category. We retrospectively analyzed 600 DLBCL patients at diagnosis for BM involvement (by both BM biopsy immunohistochemistry [BMI] with karyotyping and 18-fluorodeoxyglucose-positron emission tomography [FDG-PET] high uptake [BMP]). The BM-involved DLBCL patients identified by both BMI and BMP showed significantly inferior survival outcomes. Chromosomal abnormalities, especially complex karyotype (CK) of the involved BM, are related to much worse survival outcomes due to the inadequate treatment response including frontline auto-hematopoietic stem cell transplantation (HSCT). Therefore, CK population should either be considered for more aggressive treatment modalities, such as frontline allo-HSCT, or those further clinical trials are explored for alternative or novel treatment approaches. Furthermore, if the FDG-PET shows high possibility of marrow involvement, bilateral BM biopsy with cytogenetic evaluation should be incorporated into the routine workup for newly diagnosed DLBCL patients. This is to look for other markers of poor-risk factors, such as CK or further genetic mutations.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Campbell J, Seymour JF, Matthews J, Wolf M, Stone J, Juneja S (2006) The prognostic impact of bone marrow involvement in patients with diffuse large cell lymphoma varies according to the degree of infiltration and presence of discordant marrow involvement. Eur J Haematol 76:473–480. https://doi.org/10.1111/j.1600-0609.2006.00644.x
Morra E, Lazzarino M, Castello A, Inverardi D, Coci A, Pagnucco G, Orlandi E, Merante S, Magrini U, Zei G, Bernasconi C (1989) Bone marrow and blood involvement by non-Hodgkin's lymphoma: a study of clinicopathologic correlations and prognostic significance in relationship to the working formulation. Eur J Haematol 42:445–453. https://doi.org/10.1111/j.1600-0609.1989.tb01469.x
Lister TA, Crowther D, Sutcliffe SB, Glatstein E, Canellos GP, Young RC, Rosenberg SA, Coltman CA, Tubiana M (1989) Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 7:1630–1636. https://doi.org/10.1200/JCO.1989.7.11.1630
Sehn LH, Scott DW, Chhanabhai M, Berry B, Ruskova A, Berkahn L, Connors JM, Gascoyne RD (2011) Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 29:1452–1457. https://doi.org/10.1200/JCO.2010.33.3419
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA, Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organization for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Español de Médula Ósea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphoma Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32:3059–3068. https://doi.org/10.1200/JCO.2013.54.8800
Hodges GF, Lenhardt TM, Cotelingam JD (1994) Bone marrow involvement in large-cell lymphoma. Prognostic implications of discordant disease. Am J Clin Pathol 101:305–311. https://doi.org/10.1093/ajcp/101.3.305
Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282
Shaffer LG, Slovak ML, Campbell LJ (2009) ISCN 2009: an international system for human cytogenetic nomenclature. Karger, Basel
El-Galaly TC, d'Amore F, Mylam KJ, de Nully BP, Bøgsted M, Bukh A, Specht L, Loft A, Iyer V, Hjorthaug K, Nielsen AL, Christiansen I, Madsen C, Johnsen HE, Hutchings M (2012) Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography-staged treatment-naive patients with Hodgkin lymphoma. J Clin Oncol 30:4508–4514. https://doi.org/10.1200/JCO.2012.42.4036
Jardin F, Jais JP, Molina TJ, Parmentier F, Picquenot JM, Ruminy P, Tilly H, Bastard C, Salles GA, Feugier P, Thieblemont C, Gisselbrecht C, de Reynies A, Coiffier B, Haioun C, Leroy K (2010) Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood 116:1092–1104. https://doi.org/10.1182/blood-2009-10-247122
Yoon JH, Min GJ, Park SS, Jeon YW, Lee SE, Cho BS, Eom KS, Kim YJ, Lee S, Kim HJ, Min CK, Lee JW, Cho SG (2019) Autologous hematopoietic cell transplantation using dose-reduced intravenous busulfan, melphalan, and thiotepa for high-risk or relapsed lymphomas. Bone Marrow Transplant 54:330–333. https://doi.org/10.1038/s41409-018-0289-z
Lee JL, Gooley T, Bensinger W, Schiffman K, McDonald GB (1999) Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome. Biol Blood Marrow Transplant 5:306–315
Lee SC, Kim SJ, Lee DH, Kim WS, Suh C, Won JH (2010) Excessive toxicity of once daily i.v. BU, melphalan and thiotepa followed by auto SCT on patients with non-Hodgkin's lymphoma. Bone Marrow Transplant 45:801–802. https://doi.org/10.1038/bmt.2009.240
Blay J, Gomez F, Sebban C, Bachelot T, Biron P, Guglielmi C, Hagenbeek A, Somers R, Chauvin F, Philip T (1998) The international prognostic index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial. Parma Group Blood 92:3562–3568
Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M (1987) High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med 316:1493–1498. https://doi.org/10.1056/NEJM198706113162401
Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N (2010) Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 28:4184–4190. https://doi.org/10.1200/JCO.2010.28.1618
Yoon JH, Kim JW, Jeon YW, Lee SE, Eom KS, Kim YJ, Lee S, Kim HJ, Min CK, Lee JW, Min WS, Park CW, Cho SG (2015) Role of frontline autologous stem cell transplantation in young, high-risk diffuse large B-cell lymphoma patients. Korean J Intern Med 30:362–371. https://doi.org/10.3904/kjim.2015.30.3.362
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405. https://doi.org/10.1182/blood-2016-03-643544
Kwee TC, Kwee RM, Nievelstein RA (2008) Imaging in staging of malignant lymphoma: a systematic review. Blood 111:504–516. https://doi.org/10.1182/blood-2007-07-101899
Zinzani PL, Fanti S, Battista G, Tani M, Castellucci P, Stefoni V, Alinari L, Farsad M, Musuraca G, Gabriele A, Marchi E, Nanni C, Canini R, Monetti N, Baccarani M (2004) Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients. Br J Cancer 91:850–854. https://doi.org/10.1038/sj.bjc.6602040
Khan AB, Barrington SF, Mikhaeel NG, Hunt AA, Cameron L, Morris T, Carr R (2013) PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement. Blood 122:61–67. https://doi.org/10.1182/blood-2012-12-473389
Funding
This study was funded by the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (grant number HI14C3417) and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (grant number HI14C3417).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of Seoul St. Mary’s Hematology Hospital of the Catholic University of Korea (reference number KC19RESI0308) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Min, GJ., Jeon, YW., Park, SS. et al. Poor prognosis in patients with diffuse large B cell lymphomas with bone marrow involvement possessing chromosomal abnormalities, despite aggressive treatment. Ann Hematol 99, 557–570 (2020). https://doi.org/10.1007/s00277-020-03929-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-020-03929-3