History

The clinical manifestations of diffuse large B-cell lymphoma (DLBCL) are diverse and depend on the site of disease involvement. These tumors have a rapid growth rate and present as masses, causing symptoms when they infiltrate tissues or obstruct organs. Although lymphadenopathy may initially be painless, pain in an enlarged lymph node or affected organ may be noted if the lymphomatous mass enlarges rapidly.

As with other types of non-Hodgkin lymphoma (NHL), DLBCL can manifest with B symptoms: fever higher than 38°C, night sweats, and/or weight loss of more than 10% of body weight in the preceding 6 months. Generalized pruritus may also be present.

Other signs and symptoms can include the following:

Anorexia
Pedal edema - Caused by extensive pelvic lymphadenopathy
Fatigue
Chest discomfort or shortness of breath - Caused by mediastinal lymphadenopathy

Medical history should include inquiries about the following:

Duration/intensity of symptoms, with special attention to B symptoms
Neurological or gastrointestinal manifestations
History of environmental and/or infectious pathogens (eg, HIV, hepatitis B or C virus)
Exposure to certain viral organisms, which may affect treatment selection or outcome

Physical Examination

On physical examination, keep in mind that diffuse large B-cell lymphoma (DLBCL) appears most frequently in lymphoreticuloendothelial tissues, which include the lymph nodes, spleen, liver, and bone marrow. However, any extranodal site may be primarily or secondarily involved, including the central nervous system (CNS), lungs, gastrointestinal tract, genitourinary tract, and bones.

Involvement of sanctuary sites, including the CNS and testicles, occurs more commonly with the following disorders:

Burkitt and non-Burkitt lymphoma
HIV-associated lymphoma
Human T-cell leukemia virus (HTLV) type 1–associated lymphoma
Primary CNS lymphoma
Primary testicular diffuse large cell lymphoma

The following are common findings on physical examination in patients with DLBCL:

Lymphadenopathy - Ie, cervical, axillary, and inguinal
Splenomegaly
Low-grade fever
Pedal edema - Resulting from extensive pelvic lymphadenopathy

The clinical spectrum observed in lymphoma patients is diverse and is influenced by the subtype of lymphoma and its anatomical relationship with other organs and/or systems. Symptoms vary from painless lymph node enlargement to rapidly progressive lymphadenopathy and extranodal disease associated with end-organ damage (eg, superimposed infection, bone marrow, renal, hepatic or cardiac failure).

The clinical characteristics observed in lymphoma patients can be grouped in the following categories:

Structural dysfunction of anatomy such as, swelling, pain, organ obstruction, ulceration, or bleeding
Disruption of normal organ function as the result of extranodal involvement of liver, CNS, or kidney
Remote dysfunction of organ function (ie, paraneoplastic syndrome) such as hypercalcemia and B-symptoms (ie, night sweats, fever, itching, weight loss)

A complete physical examination should include evaluation of the following:

All lymph node chains
Cardiopulmonary system
Liver and spleen
Pelvis
Breasts
Testicles
Skin
Neurological aspects, to detect subtle signs of early CNS involvement or cord compression

Differential Diagnoses

Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19. 127 (20):2375-90. [QxMD MEDLINE Link]. [Full Text].
Howell JM, Auer-Grzesiak I, Zhang J, et al. Increasing incidence rates, distribution and histological characteristics of primary gastrointestinal non-Hodgkin lymphoma in a North American population. Can J Gastroenterol. Jul 2012. 26(7):452-6.
National Cancer Institute. National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer. 1982 May 15. 49(10):2112-35. [QxMD MEDLINE Link].
Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1. 84(5):1361-92. [QxMD MEDLINE Link].
Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010 Apr 15. 362(15):1417-29. [QxMD MEDLINE Link].
Nogai H, Dorken B, Lenz G. Pathogenesis of non-Hodgkin's lymphoma. J Clin Oncol. 2011 May 10. 29(14):1803-11. [QxMD MEDLINE Link].
Yoon N, Ahn S, Yong Yoo H, Jin Kim S, Seog Kim W, Hyeh Ko Y. Cell-of-origin of diffuse large B-cell lymphomas determined by the Lymph2Cx assay: better prognostic indicator than Hans algorithm. Oncotarget. 2017 Mar 28. 8 (13):22014-22022. [QxMD MEDLINE Link]. [Full Text].
Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000 Feb 3. 403(6769):503-11. [QxMD MEDLINE Link].
Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986 Dec 26. 47(6):921-8. [QxMD MEDLINE Link].
Shaffer AL 3rd, Young RM, Staudt LM. Pathogenesis of human B cell lymphomas. Annu Rev Immunol. 2012. 30:565-610. [QxMD MEDLINE Link].
Davis RE, Brown KD, Siebenlist U, Staudt LM. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med. 2001 Dec 17. 194(12):1861-74. [QxMD MEDLINE Link].
Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest. 2001 Feb. 107(3):241-6. [QxMD MEDLINE Link].
Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, Pileri SA, Malik F, Macon WR. Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer. 2011 Nov 15. 117(22):5058-66. [QxMD MEDLINE Link].
Dunleavy K, Pittaluga S, Czuczman MS, Dave SS, Wright G, Grant N. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood. 2009 Jun 11. 113(24):6069-76. [QxMD MEDLINE Link].
Ngo VN, Davis RE, Lamy L, Yu X, Zhao H, Lenz G. A loss-of-function RNA interference screen for molecular targets in cancer. Nature. 2006 May 4. 441(7089):106-10. [QxMD MEDLINE Link].
Thome M, Charton JE, Pelzer C, Hailfinger S. Antigen receptor signaling to NF-kappaB via CARMA1, BCL10, and MALT1. Cold Spring Harb Perspect Biol. 2010 Sep. 2(9):a003004. [QxMD MEDLINE Link].
Sommer K, Guo B, Pomerantz JL, Bandaranayake AD, Moreno-Garcia ME, Ovechkina YL. Phosphorylation of the CARMA1 linker controls NF-kappaB activation. Immunity. 2005 Dec. 23(6):561-74. [QxMD MEDLINE Link].
Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008 Mar 21. 319(5870):1676-9. [QxMD MEDLINE Link].
Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer. 2005 Apr. 5(4):251-62. [QxMD MEDLINE Link].
Clark MR, Tanaka A, Powers SE, Veselits M. Receptors, subcellular compartments and the regulation of peripheral B cell responses: the illuminating state of anergy. Mol Immunol. 2011 Jun. 48(11):1281-6. [QxMD MEDLINE Link].
Reth M. Antigen receptor tail clue. Nature. 1989 Mar 30. 338(6214):383-4. [QxMD MEDLINE Link].
Dal Porto JM, Gauld SB, Merrell KT, Mills D, Pugh-Bernard AE, Cambier J. B cell antigen receptor signaling 101. Mol Immunol. 2004 Jul. 41(6-7):599-613. [QxMD MEDLINE Link].
Scott DW. Cell-of-Origin in Diffuse Large B-Cell Lymphoma: Are the Assays Ready for the Clinic?. Am Soc Clin Oncol Educ Book. 2015. e458-66. [QxMD MEDLINE Link]. [Full Text].
Nakamura H, Said JW, Miller CW, Koeffler HP. Mutation and protein expression of p53 in acquired immunodeficiency syndrome-related lymphomas. Blood. 1993 Aug 1. 82(3):920-6. [QxMD MEDLINE Link].
Stein H, Dallenbach F. Diffuse Large cell lymphomas of B and T Cell type. Knowles DM, ed. Neoplastic Hematology. Baltimore, Md: Williams and Willkins; 1992. 675.
Hu CR, Wang JH, Wang R, Sun Q, Chen LB. Both FOXP1 and p65 expression are adverse risk factors in diffuse large B-cell lymphoma: a retrospective study in China. Acta Histochem. 2013 Mar. 115(2):137-43. [QxMD MEDLINE Link].
Pasqualucci L, Trifonov V, Fabbri G, et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011 Jul 31. 43(9):830-7. [QxMD MEDLINE Link]. [Full Text].
Alizadeh AA, Gentles AJ, Alencar AJ, et al. Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood. 2011 Aug 4. 118(5):1350-8. [QxMD MEDLINE Link]. [Full Text].
Hartge P, Devesa SS, Fraumeni JF Jr. Hodgkin's and non-Hodgkin's lymphomas. Cancer Surv. 1994. 19-20:423-53. [QxMD MEDLINE Link].
De Roos AJ, Davis S, Colt JS, et al. Residential proximity to industrial facilities and risk of non-Hodgkin lymphoma. Environ Res. 2010 Jan. 110(1):70-8. [QxMD MEDLINE Link]. [Full Text].
Cancer Stat Facts: Non-Hodgkin Lymphoma. National Cancer Institute. Available at https://seer.cancer.gov/statfacts/html/nhl.html. Accessed: April 28, 2021.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan. 71 (1):7-33. [QxMD MEDLINE Link]. [Full Text].
Fisher SG, Fisher RI. The epidemiology of non-Hodgkin's lymphoma. Oncogene. 2004 Aug 23. 23(38):6524-34. [QxMD MEDLINE Link].
Hartge P, Devesa SS. Quantification of the impact of known risk factors on time trends in non-Hodgkin's lymphoma incidence. Cancer Res. 1992 Oct 1. 52(19 Suppl):5566s-5569s. [QxMD MEDLINE Link].
Wu XC, Andrews P, Chen VW, Groves FD. Incidence of extranodal non-Hodgkin lymphomas among whites, blacks, and Asians/Pacific Islanders in the United States: anatomic site and histology differences. Cancer Epidemiol. 2009 Nov. 33(5):337-46. [QxMD MEDLINE Link].
Ries LAG, Miller BA, Hankey BF. SEER Cancer Statistics Review 1973-1991: Tables and Graphs. Bethesda, Md: National Cancer Institute; 1994. 94-2789.
Flowers CR, Shenoy PJ, Borate U, et al. Examining racial differences in diffuse large B-cell lymphoma presentation and survival. Leuk Lymphoma. 2013 Feb. 54(2):268-76. [QxMD MEDLINE Link].
Lu Y, Prescott J, Sullivan-Halley J, et al. Body size, recreational physical activity, and B-cell non-Hodgkin lymphoma risk among women in the California teachers study. Am J Epidemiol. 2009 Nov 15. 170(10):1231-40. [QxMD MEDLINE Link]. [Full Text].
International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993 Sep 30. 329(14):987-94. [QxMD MEDLINE Link].
Blay J, Gomez F, Sebban C, Bachelot T, Biron P, Guglielmi C. The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial. Parma Group. Blood. 1998 Nov 15. 92(10):3562-8. [QxMD MEDLINE Link].
Alinari L, Gru A, Quinion C, Huang Y, Lozanski A, Lozanski G, et al. De novo CD5+ Diffuse Large B-cell Lymphoma: Adverse outcomes with and without stem cell transplantation in a large, multi-center, rituximab treated cohort. Am J Hematol. 2016 Jan 22. [QxMD MEDLINE Link].
Coltman CA, Dahlberg S, Jones SE, et al. Southwest Oncology Group Studies in diffuse large cell lymphoma: a subset analysis. Kimura K, ed. Cancer Chemotherapy: Challenges for the Future. Tokyo, Japan: Excerpta Medica; 1988. 194-202.
Horning SJ, Weller E, Kim KM, et al. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-hodgkin's lymphoma: Eastern Cooperative Oncology Group Study 1484 [abstract]. J Clin Oncol. 2004 Aug 1. 22(15):3032-8.
Sweetenham JW. Diffuse large B-cell lymphoma: risk stratification and management of relapsed disease. Hematology Am Soc Hematol Educ Program. 2005. 252-9. [QxMD MEDLINE Link].
Juweid ME, Cheson BD. Role of positron emission tomography in lymphoma. J Clin Oncol. 2005 Jul 20. 23(21):4577-80. [QxMD MEDLINE Link].
Martín-Subero JI, Kreuz M, Bibikova M, et al. New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling. Blood. 2009 Mar 12. 113(11):2488-97. [QxMD MEDLINE Link].
Zainuddin N, Berglund M, Wanders A, et al. TP53 mutations predict for poor survival in de novo diffuse large B-cell lymphoma of germinal center subtype. Leuk Res. 2009 Jan. 33(1):60-6. [QxMD MEDLINE Link].
Terasawa T, Nagai H. Current clinical evidence on interim fluorine-18 fluorodeoxy glucose positron emission tomography for advanced-stage Hodgkin lymphoma and diffuse large B-cell lymphoma to predict treatment outcomes. Leuk Lymphoma. 2009 Nov. 50(11):1750-2. [QxMD MEDLINE Link].
A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997 Jun 1. 89(11):3909-18. [QxMD MEDLINE Link].
Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood. 2008 Apr 15. 111(8):3941-67. [QxMD MEDLINE Link].
Lossos IS, Jones CD, Warnke R, et al. Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma. Blood. 2001 Aug 15. 98(4):945-51. [QxMD MEDLINE Link].
Winter JN, Weller EA, Horning SJ, Krajewska M, Variakojis D, Habermann TM. Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood. 2006 Jun 1. 107(11):4207-13. [QxMD MEDLINE Link].
Hartmann EM, Ott G, Rosenwald A. Molecular biology and genetics of lymphomas. Hematol Oncol Clin North Am. 2008 Oct. 22(5):807-23, vii. [QxMD MEDLINE Link].
Shipp MA, Ross KN, Tamayo P, Weng AP, Kutok JL, Aguiar RC. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002 Jan. 8(1):68-74. [QxMD MEDLINE Link].
Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jun 20. 346(25):1937-47. [QxMD MEDLINE Link].
Davies AJ, Caddy J, Maishman T, et al. A Prospective Randomised Trial of Targeted Therapy for Diffuse Large B-Cell Lymphoma (DLBCL) Based upon Real-Time Gene Expression Profiling: The Remodl-B Study of the UK NCRI and SAKK Lymphoma Groups (ISRCTN51837425). Blood. 2015. 126 (23):812. [Full Text].
Nowakowski GS, Feldman T, Rimsza LM, Westin JR, Witzig TE, Zinzani PL. Integrating precision medicine through evaluation of cell of origin in treatment planning for diffuse large B-cell lymphoma. Blood Cancer J. 2019 May 16. 9 (6):48. [QxMD MEDLINE Link]. [Full Text].
Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004 Jan 1. 103(1):275-82. [QxMD MEDLINE Link].
Muris JJ, Meijer CJ, Vos W, van Krieken JH, Jiwa NM, Ossenkoppele GJ. Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. J Pathol. 2006 Apr. 208(5):714-23. [QxMD MEDLINE Link].
Nyman H, Jerkeman M, Karjalainen-Lindsberg ML, Banham AH, Leppä S. Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP. Mod Pathol. 2009 Aug. 22(8):1094-101. [QxMD MEDLINE Link].
Colomo L, Lopez-Guillermo A, Perales M, Rives S, Martinez A, Bosch F. Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. Blood. 2003 Jan 1. 101(1):78-84. [QxMD MEDLINE Link].
Thieblemont C, Briere J, Mounier N, et al. The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol. 2011 Nov 1. 29(31):4079-87. [QxMD MEDLINE Link].
Lossos IS. Molecular pathogenesis of diffuse large B-cell lymphoma. J Clin Oncol. 2005 Sep 10. 23(26):6351-7. [QxMD MEDLINE Link].
Snuderl M, Kolman OK, Chen YB, Hsu JJ, Ackerman AM, Dal Cin P. B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma. Am J Surg Pathol. 2010 Mar. 34(3):327-40. [QxMD MEDLINE Link].
Li S, Lin P, Fayad LE, Lennon PA, Miranda RN, Yin CC. B-cell lymphomas with MYC/8q24 rearrangements and IGH@BCL2/t(14;18)(q32;q21): an aggressive disease with heterogeneous histology, germinal center B-cell immunophenotype and poor outcome. Mod Pathol. 2012 Jan. 25(1):145-56. [QxMD MEDLINE Link].
Aukema SM, Siebert R, Schuuring E, van Imhoff GW, Kluin-Nelemans HC, Boerma EJ. Double-hit B-cell lymphomas. Blood. 2011 Feb 24. 117(8):2319-31. [QxMD MEDLINE Link].
Kobayashi T, Tsutsumi Y, Sakamoto N, Nagoshi H, Yamamoto-Sugitani M, Shimura Y. Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab. Jpn J Clin Oncol. 2012 Nov. 42(11):1035-42. [QxMD MEDLINE Link].
Green TM, Young KH, Visco C, Xu-Monette ZY, Orazi A, Go RS. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012 Oct 1. 30(28):3460-7. [QxMD MEDLINE Link].
Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A. MYC/BCL2 protein co-expression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program Study. Blood. 2013 Feb 28. [QxMD MEDLINE Link].
Kim SJ, Kang HJ, Kim JS, et al. Comparison of treatment strategies for patients with intestinal diffuse large B-cell lymphoma: surgical resection followed by chemotherapy versus chemotherapy alone. Blood. 2011 Feb 10. 117(6):1958-65. [QxMD MEDLINE Link].
Pfreundschuh M, Truemper L, Gill D, et al. First analysis of the completed Mabthera International (Mint) Trial in young patients with low-risk diffuse large B-cell lymphoma (DLBCL): addition of rituximab to a CHOP-like regimen significantly improves outcome of all patients with the identification of a very favorable subgroup with IPI=O and no bulky disease [abstract 157]. Blood. 2004. 104:48a. [Full Text].
Sehn LH, Donaldson J, Chhanabhai M, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005 Aug 1. 23(22):5027-33. [QxMD MEDLINE Link].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas. Available at https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Version 3.2021 — March 16, 2021; Accessed: April 28, 2021.
Candelaria M, Dueñas-Gonzalez A. Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in diffuse large B-cell lymphoma. Ther Adv Hematol. 2021. 12:2040620721989579. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Tilly H, Gomes da Silva M, Vitolo U, Jack A, Meignan M, Lopez-Guillermo A, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep. 26 Suppl 5:v116-25. [QxMD MEDLINE Link]. [Full Text].
Phan J, Mazloom A, Medeiros LJ, et al. Benefit of consolidative radiation therapy in patients with diffuse large B-cell lymphoma treated with R-CHOP chemotherapy. J Clin Oncol. 2010 Sep 20. 28(27):4170-6. [QxMD MEDLINE Link].
Moccia AA, Schaff K, Freeman C, Hoskins PJ, Klasa RJ, Savage KJ, et al. Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines. Blood Adv. 2021 Mar 9. 5 (5):1483-1489. [QxMD MEDLINE Link]. [Full Text].
Persky DO, Miller TP. Localized large cell lymphoma: is there any need for radiation therapy?. Curr Opin Oncol. 2009 Sep. 21(5):401-6. [QxMD MEDLINE Link].
Friedberg JW, Fisher RI. Diffuse large B-cell lymphoma. Hematol Oncol Clin North Am. 2008 Oct. 22(5):941-52, ix. [QxMD MEDLINE Link].
Miller TP, Dahlberg S, Cassady JR, et al. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2. 339(1):21-6. [QxMD MEDLINE Link].
Alas S, Emmanouilides C, Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. Clin Cancer Res. 2001 Mar. 7(3):709-23. [QxMD MEDLINE Link].
Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May. 7(5):379-91. [QxMD MEDLINE Link].
Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10. 26(14):2258-63. [QxMD MEDLINE Link].
Peyrade F, Jardin F, Gisselbrecht C, et al. Rituximab and Reduced Dose CHOP (R-mini-CHOP) for Patients Over 80 Years with Diffuse Large B-Cell Lymphoma (DLBCL) – Groupe d'Etude Des Lymphomes De l'Adulte (GELA) Study LNH03-7B. Blood. 2010. 116 (21):853. [Full Text].
Tomita N, Takasaki H, Miyashita K, Fujisawa S, Ogusa E, Matsuura S. R-CHOP therapy alone in limited stage diffuse large B-cell lymphoma. Br J Haematol. 2013 May. 161(3):383-8. [QxMD MEDLINE Link].
Persky DO, Li H, Stephens DM, Park SI, Bartlett NL, Swinnen LJ, et al. Positron Emission Tomography-Directed Therapy for Patients With Limited-Stage Diffuse Large B-Cell Lymphoma: Results of Intergroup National Clinical Trials Network Study S1001. J Clin Oncol. 2020 Sep 10. 38 (26):3003-3011. [QxMD MEDLINE Link]. [Full Text].
Levitt M, Marsh JC, DeConti RC, Mitchell MS, Skeel RT, Farber LR. Combination sequential chemotherapy in advanced reticulum cell sarcoma. Cancer. 1972 Mar. 29(3):630-6. [QxMD MEDLINE Link].
DeVita VT Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1. 1(7901):248-50. [QxMD MEDLINE Link].
Czuczman MS, Grillo-Lopez AJ, White CA, Saleh M, Gordon L, LoBuglio AF. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan. 17(1):268-76. [QxMD MEDLINE Link].
Vose JM, Link BK, Grossbard ML, et al. Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2001 Jan 15. 19(2):389-97. [QxMD MEDLINE Link].
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24. 346(4):235-42. [QxMD MEDLINE Link].
Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20. 23(18):4117-26. [QxMD MEDLINE Link].
Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23. 116(12):2040-5. [QxMD MEDLINE Link].
Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1. 24(19):3121-7. [QxMD MEDLINE Link].
Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb. 9(2):105-16. [QxMD MEDLINE Link].
Delarue R, Tilly H, Mounier N, et al. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May. 14(6):525-33. [QxMD MEDLINE Link].
Kühnl A, Cunningham D, Counsell N, et al. Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial. Ann Oncol. 2017 Jul 1. 28 (7):1540-1546. [QxMD MEDLINE Link]. [Full Text].
Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15. 99(8):2685-93. [QxMD MEDLINE Link].
Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1. 26(16):2717-24. [QxMD MEDLINE Link].
Bartlett NL, Wilson WH, Jung SH, et al. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20. 37 (21):1790-1799. [QxMD MEDLINE Link]. [Full Text].
Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7. 333(23):1540-5. [QxMD MEDLINE Link].
Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Maertens J, Bormans G. Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood. 2003 Jul 1. 102(1):53-9. [QxMD MEDLINE Link].
Derenzini E, Musuraca G, Fanti S, Stefoni V, Tani M, Alinari L. Pretransplantation positron emission tomography scan is the main predictor of autologous stem cell transplantation outcome in aggressive B-cell non-Hodgkin lymphoma. Cancer. 2008 Nov 1. 113(9):2496-503. [QxMD MEDLINE Link].
Lerner RE, Thomas W, Defor TE, Weisdorf DJ, Burns LJ. The International Prognostic Index assessed at relapse predicts outcomes of autologous transplantation for diffuse large-cell non-Hodgkin's lymphoma in second complete or partial remission. Biol Blood Marrow Transplant. 2007 Apr. 13(4):486-92. [QxMD MEDLINE Link].
Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM. R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica. 2008 Dec. 93(12):1829-36. [QxMD MEDLINE Link].
Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15. 111(2):537-43. [QxMD MEDLINE Link].
Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15. 103(10):3684-8. [QxMD MEDLINE Link].
Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20. 28 (27):4184-90. [QxMD MEDLINE Link]. [Full Text].
Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20. 30 (36):4462-9. [QxMD MEDLINE Link]. [Full Text].
Velasquez WS, Cabanillas F, Salvador P, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan. 71(1):117-22. [QxMD MEDLINE Link].
Hagberg H, Gisselbrecht C. Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol. 2006 May. 17 Suppl 4:iv31-2. [QxMD MEDLINE Link].
Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec. 17(12):3776-85. [QxMD MEDLINE Link].
Josting A, Sieniawski M, Glossmann JP, et al. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug. 16(8):1359-65. [QxMD MEDLINE Link].
Witzig TE, Geyer SM, Kurtin PJ, Colgan JP, Inwards DJ, Micallef IN. Salvage chemotherapy with rituximab DHAP for relapsed non-Hodgkin lymphoma: a phase II trial in the North Central Cancer Treatment Group. Leuk Lymphoma. 2008 Jun. 49(6):1074-80. [QxMD MEDLINE Link].
Mey UJ, Orlopp KS, Flieger D, et al. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Cancer Invest. 2006 Oct. 24(6):593-600. [QxMD MEDLINE Link].
Olivieri A, Brunori M, Capelli D, Montanari M, Massidda D, Gini G. Salvage therapy with an outpatient DHAP schedule followed by PBSC transplantation in 79 lymphoma patients: an intention to mobilize and transplant analysis. Eur J Haematol. 2004 Jan. 72(1):10-7. [QxMD MEDLINE Link].
Soussain C, Souleau B, Gabarre J, et al. Intensive chemotherapy with hematopoietic cell transplantation after ESHAP therapy for relapsed or refractory non-Hodgkin's lymphoma. Results of a single-centre study of 65 patients. Leuk Lymphoma. 1999 May. 33(5-6):543-50. [QxMD MEDLINE Link].
Lopez A, Gutierrez A, Palacios A, Blancas I, Navarrete M, Morey M. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008 Feb. 80(2):127-32. [QxMD MEDLINE Link].
Crump M, Baetz T, Couban S, Belch A, Marcellus D, Howson-Jan K. Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer. 2004 Oct 15. 101(8):1835-42. [QxMD MEDLINE Link].
Chau I, Harries M, Cunningham D, Hill M, Ross PJ, Archer CD. Gemcitabine, cisplatin and methylprednisolone chemotherapy (GEM-P) is an effective regimen in patients with poor prognostic primary progressive or multiply relapsed Hodgkin's and non-Hodgkin's lymphoma. Br J Haematol. 2003 Mar. 120(6):970-7. [QxMD MEDLINE Link].
Ng M, Waters J, Cunningham D, Chau I, Horwich A, Hill M. Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma. Br J Cancer. 2005 Apr 25. 92(8):1352-7. [QxMD MEDLINE Link].
van Besien K, Rodriguez A, Tomany S, et al. Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival. Bone Marrow Transplant. 2001 Feb. 27(4):397-404. [QxMD MEDLINE Link].
Pocali B, De Simone M, Annunziata M, Palmieri S, D'Amico MR, Copia C. Ifosfamide, epirubicin and etoposide (IEV) regimen as salvage and mobilization therapy for refractory or early relapsing patients with aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2004 Aug. 45(8):1605-9. [QxMD MEDLINE Link].
Schütt P, Passon J, Ebeling P, Welt A, Müller S, Metz K. Ifosfamide, etoposide, cytarabine, and dexamethasone as salvage treatment followed by high-dose cyclophosphamide, melphalan, and etoposide with autologous peripheral blood stem cell transplantation for relapsed or refractory lymphomas. Eur J Haematol. 2007 Feb. 78(2):93-101. [QxMD MEDLINE Link].
Girouard C, Dufresne J, Imrie K, Stewart AK, Brandwein J, Prince HM. Salvage chemotherapy with mini-BEAM for relapsed or refractory non-Hodgkin's lymphoma prior to autologous bone marrow transplantation. Ann Oncol. 1997 Jul. 8(7):675-80. [QxMD MEDLINE Link].
Papageorgiou ES, Tsirigotis P, Dimopoulos M, Pavlidis N, Fountzilas G, Papageorgiou S. Combination chemotherapy with gemcitabine and vinorelbine in the treatment of relapsed or refractory diffuse large B-cell lymphoma: a phase-II trial by the Hellenic Cooperative Oncology Group. Eur J Haematol. 2005 Aug. 75(2):124-9. [QxMD MEDLINE Link].
Müller-Beissenhirtz H, Kasper C, Nückel H, Duhrsen U. Gemcitabine, vinorelbine and prednisone for refractory or relapsed aggressive lymphoma, results of a phase II single center study. Ann Hematol. 2005 Nov. 84(12):796-801. [QxMD MEDLINE Link].
Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug. 11(8):1573-82. [QxMD MEDLINE Link].
Gutierrez M, Chabner BA, Pearson D, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8-year follow-up study of EPOCH. J Clin Oncol. 2000 Nov 1. 18(21):3633-42. [QxMD MEDLINE Link].
Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar. 15(3):511-6. [QxMD MEDLINE Link].
FDA approves polatuzumab vedotin-piiq for diffuse large B-cell lymphoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-diffuse-large-b-cell-lymphoma. June 10, 2019; Accessed: June 30, 2020.
Sehn LH, Herrera AF, Matasar MJ, et al. Addition of polatuzumab vedotin to bendamustine and rituximab (BR) improves outcomes in transplant-ineligible patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) versus BR alone: Results from a randomized phase 2 study. Blood. 2017. 130:2821. [Full Text].
FDA approves selinexor for relapsed/refractory diffuse large B-cell lymphoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selinexor-relapsedrefractory-diffuse-large-b-cell-lymphoma. June 22, 2020; Accessed: June 30, 2020.
Salles G, Duell J, González Barca E, Tournilhac O, Jurczak W, Liberati AM, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul. 21 (7):978-988. [QxMD MEDLINE Link]. [Full Text].
Spira AI, Chen L, Zhou X, Gnanasakthy A, Wang L, Ungar D, et al. Symptoms, health-related quality of life, and tolerability of loncastuximab tesirine in patients with relapsed or refractory diffuse large B cell lymphoma. Blood 2020;136(suppl 1):3-4. [Full Text].
Boehme V, Zeynalova S, Kloess M, et al. Incidence and risk factors of central nervous system recurrence in aggressive lymphoma--a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol. 2007 Jan. 18(1):149-57. [QxMD MEDLINE Link].
van Besien K, Ha CS, Murphy S, McLaughlin P, Rodriguez A, Amin K. Risk factors, treatment, and outcome of central nervous system recurrence in adults with intermediate-grade and immunoblastic lymphoma. Blood. 1998 Feb 15. 91(4):1178-84. [QxMD MEDLINE Link].
Boehme V, Schmitz N, Zeynalova S, Loeffler M, Pfreundschuh M. CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood. 2009 Apr 23. 113(17):3896-902. [QxMD MEDLINE Link].
Savage KJ. Secondary CNS relapse in diffuse large B-cell lymphoma: defining high-risk patients and optimization of prophylaxis strategies. Hematology Am Soc Hematol Educ Program. 2017 Dec 8. 2017 (1):578-586. [QxMD MEDLINE Link]. [Full Text].
Abramson JS, Hellmann M, Barnes JA, Hammerman P, Toomey C, Takvorian T, et al. Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma. Cancer. 2010 Sep 15. 116 (18):4283-90. [QxMD MEDLINE Link]. [Full Text].
FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm. October 18, 2017; Accessed: October 21, 2017.
Frederick L, et al. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axicel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL) [abstract]. Proceedings of the American Association for Cancer Research Annual Meeting 2017. 2017 Apr 1-5. Available at http://cancerres.aacrjournals.org/content/77/13_Supplement/CT019.
U.S. Food and Drug Administration. FDA approves tisagenlecleucel for adults with relapsed or refractory large B-cell lymphoma. 2018 May 03. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisagenlecleucel-adults-relapsed-or-refractory-large-b-cell-lymphoma.
Schuster SJ, et al; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3. 380 (1):45-56. [QxMD MEDLINE Link]. [Full Text].
Breyanzi (lisocabtagene maraleucel) [package insert]. Bothell, WA: Bristol Myers Squibb. February 2021. Available at [Full Text].
Leonard JP, Kolibaba KS, Reeves JA, Tulpule A, Flinn IW, Kolevska T, et al. Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2017 Nov 1. 35 (31):3538-3546. [QxMD MEDLINE Link].
Pfreundschuh M, et al; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct. 12 (11):1013-22. [QxMD MEDLINE Link].

Media Gallery

Biopsy of a cervical lymph node showing infiltration with a population of large cells (B cells) consistent with diffuse large cell lymphoma.
Computed tomography (CT) scan of the abdomen showing mesenteric and retroperitoneal adenopathy in a patient with diffuse large cell lymphoma.
Diffuse large B-cell lymphoma. Hematoxylin and eosin stain of a lymph node biopsy sample showing a mixture of large and small cells. The architecture of the node is lost, with a diffuse pattern of involvement.
Patient with diffuse large B-cell lymphoma with extranodal involvement. This computed tomography (CT) scan shows an enlarged spleen and liver as a result of lymphomatous involvement.
Patient with diffuse large B-cell lymphoma with extranodal involvement (same patient as in the previous image). This patient has an enlarged spleen and liver as a result of lymphomatous involvement. Extensive retroperitoneal lymphadenopathy is also present.
This image depicts gallium scans performed as part of a staging workup for a patient with diffuse large B-cell lymphoma. The scans show extensive hepatosplenic and multiple sites of nodal involvement with a gallium-avid tumor.
Role of B-cell receptor signaling in promoting proliferation and survival of DLBCL. BCR is the main factor in B-cell biology, playing a key role in B-cell development, antigen-driven clonal selection, and humoral immunity. B-cell receptor signaling activates PI3K-mediated activation of the kinase AKT, which activates many downstream signaling pathways. All these downstream pathways are essential for the survival of B cells. PIP3 is generated as a result of BCR-dependent PI3K activation. BTK also hydrolyzes PIP2 into DAG and IP3. IP3 induces release of calcium stores from the endoplasmic reticulum. Ca and DAG activate PKC, which leads to activation of NF-k B pathyway. PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol-4,5-trisphosphate; IKK, IkB kinase; mTOR, mammalian target of rapamycin; FoxO, Forkhead box transcription factors; GSK3b, glycogen synthase 3-beta; p21, inhibitor of cyclin-dependent kinases.

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Author

Shipra Gandhi, MBBS Resident Physician, Department of Internal Medicine, University of Buffalo, State University of New York School of Medicine and Biomedical Sciences

Shipra Gandhi, MBBS is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Andre M Kallab, MD Clinical Associate Professor of Oncology, Medical College of Georgia; Consulting Staff, Department of Oncology, Northeast Georgia Diagnostic Clinic

Andre M Kallab, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology

Disclosure: Nothing to disclose.

Francisco J Hernandez-Ilizaliturri, MD Professor of Medicine, Department of Medical Oncology, Associate Professor of Immunology, Department of Immunology, Chief, Lymphoma and Myeloma Section, Director, The Lymphoma Translational Research Program, Roswell Park Cancer Institute, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Asher A Chanan-Khan, MD Assistant Professor, Department of Medicine, Division of Lymphoma and Bone Marrow Transplantation, Roswell Park Cancer Institute, State University of New York at Buffalo

Disclosure: Nothing to disclose.

Wendy Hu, MD Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center

Disclosure: Nothing to disclose.

Michael Paul Kosty, MD Associate Director, Associate Professor, Department of Internal Medicine, Divisions of Supportive Care Services and Hematology and Oncology, Ida M and Cecil H Green Cancer Center, Scripps Clinic

Disclosure: Nothing to disclose.

Clifford H Pemberton, MD Instructor in Medicine, Jefferson Medical College; Medical Director, Jefferson Hospice and Palliative Care Program; Consulting Staff, Department of Medicine, Division of Hematology/Oncology, Lankenau Hospital

Clifford H Pemberton, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians, American Medical Association, American Society of Hematology, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment