Diffuse Large B-Cell Lymphoma (DLBCL)


Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma, a blood cancer originating primarily within the lymphatic system that is characterized by abnormally large white blood cells (B cells) and the formation of masses or tumors in lymph nodes; however, disease in extranodal sites is also possible. DLBCL primarily affects older individuals in their mid-60s to 70s.1

DLBCL presenting in extranodal sites causes complications within the affected organ systems, including the central nervous system (CNS), gastrointestinal system, liver, spleen, kidneys, reproductive system (especially the testicles), breasts, paranasal sinuses, pancreas, thorax, thyroid, bone tissues, bone marrow, salivary glands, and adrenal glands.2-5 Extranodal involvement often indicates a poor outcome in patients with DLBCL.2

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Gastrointestinal Complications Due to DLBCL

Gastrointestinal complications in patients with primary gastrointestinal DLBCL, such as bleeding, obstruction, perforation, abdominal pain or discomfort, hematemesis or melena, and changes in bowel habits, may occur before or following chemotherapy. The gastrointestinal system is the most common extranodal site of involvement in DLBCL.6 

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Neurological Complications Due to DLBCL

Patients with DLBCL may present with CNS complications, with an incidence rate between 5% to 20%.7 Complications from brain lesions include focal neurological deficits, such as asymmetric muscle weakness or paresis, altered mental status, behavioral changes, seizures, and symptoms of increased intracranial pressure, including headache, nausea, vomiting, and papilledema. Ocular involvement may cause blurry vision and floaters. Brainstem involvement may cause ataxia, intractable vomiting, vertigo, and problems coordinating eye movements. Rarely, spinal cord compression occurs, resulting in motor and sensory deficits, and bowel and bladder dysfunction.8,9 Extranodal involvement of the adrenal glands, kidneys, nasopharynx, bone marrow, breasts, or testes increases the risk for CNS involvement in DLBCL.7

Hepatic Complications Due to DLBCL

Hepatic complications due to DLBCL may be related to hepatitis C virus (HCV) or to chemotherapy. Patients who tested positive for HCV demonstrated poor performance status, more advanced stages of DLBCL, lower platelet counts, a decreased number of chemotherapy cycles, and liver toxicity, all resulting in shorter overall survival.10 Additionally, chemotherapy may cause drug-induced liver injury and liver failure.11

Renal Complications Due to DLBCL

Renal failure is a possible complication when DLBCL affects the kidneys.5 One study reported a higher incidence of CNS relapse in patients with DLBCL and renal involvement; however, renal involvement is uncommon in DLBCL.4

Orthopedic Complications Due to DLBCL

Bone lesions, especially lesions in the long bones, may occur in DLBCL, with osteolytic bone destruction evident on radiographic imaging.5 

The side effects of chemotherapy can cause complications.

Hematological side effects include febrile neutropenia (fever and low white blood cell counts increasing the risk for infection), anemia (weakness and fatigue), and thrombocytopenia (increased bruising/risk for bleeding).12  

Gastrointestinal side effects of chemotherapy include nausea and vomiting in 30% to 90% of patients with DLBCL.12 In one study, gastrointestinal bleeding, obstruction, and perforation occurred following chemotherapy in 22.6% of patients with primary gastrointestinal DLBCL.6 

Another study found that patients receiving R-CHOP (which stands for Rituxan® [rituximab] combined with cyclophosphamide, hydroxydaunorubicin [sold as Lipodox® or Doxil®], Oncovin® [vincristine], and prednisone) chemotherapy in whom gastric symptoms developed were less likely to complete treatment and less likely to experience a complete remission of DLBCL. Low serum albumin levels at the time of diagnosis predicted a risk for gastric complications.13

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Patients with DLBCL receiving chemotherapy are at increased risk for infection because the immune system is compromised. Infections caused the majority (75%) of respiratory complications following chemotherapy, including pneumonia.14 Patients with DLBCL undergoing immunochemotherapy are at increased risk for infection-related death for up to 5 years following treatment, particularly older patients.15 

The risk for immunodeficiency, infection, and autoimmune disease secondary to immunochemotherapy, especially immunochemotherapy incorporating rituximab, may be higher for up to 10 years in survivors of DLBCL than in survivors of other cancers.16

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Patients with DLBCL undergoing chemotherapy may sustain permanent damage to the reproductive system, making it difficult to have children. The preservation of reproductive capacity involves gamete cryopreservation techniques, and it may be important to discuss this complication with patients of reproductive age before they start chemotherapy.12,17

In addition to hepatotoxicity, chemotherapy for DLBCL may cause cardiotoxicity and neurotoxicity. Hydroxydaunorubicin, one of the medications in R-CHOP, is an anthracycline derivative known to cause cardiotoxicity in patients with DLBCL.18,19 

Before they start chemotherapy, patients with DLBCL must undergo multigated acquisition (MUGA) scanning to assess the left ventricular ejection fraction and determine whether they are candidates for R-CHOP chemotherapy. In high-risk patients with cardiovascular disease, an alternative to anthracyclines is required to prevent cardiotoxicity. In one study, researchers questioned the utility of cardiac screening before the initiation of chemotherapy in patients with DLBCL. They observed that the incidence of congestive heart failure did not differ significantly after chemotherapy between patients who received hydroxydaunorubicin and those who did not, regardless of their left ventricular ejection fraction.20

Chimeric antigen receptor T-cell (CAR-T) therapy, an alternative to R-CHOP therapy for patients with refractory or relapsed DLBCL, is known to cause neurotoxicity and cytokine release syndrome. Inflammation due to the treatment disrupts the blood-brain barrier and causes neurotoxicity, also known as immune effector cell-associated neurotoxicity syndrome (ICANS).21

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Tumor lysis syndrome is a serious, sometimes fatal condition that occurs after the initiation of chemotherapy, when tumor cells release toxic by-products into the circulatory system following cell death. Symptoms of tumor lysis syndrome include nausea, vomiting, diarrhea, lethargy, decreased appetite, muscle cramping, seizures, hematuria, and heart problems.12 Rarely, it may lead to multiple organ failure.22

Patients receiving chemotherapy must be monitored for tumor lysis syndrome with blood tests before and following each treatment.12   

Patients with DLBCL receiving their first chemotherapy cycle may experience a hypersensitivity reaction to the medications. Symptoms include itching, flushing, fever, nausea, dizziness, and pain in the abdomen, chest, or back. Steroids, antihistamines, and acetaminophen may reduce hypersensitivity reactions during later treatments.12

References

  1. Diffuse large B-cell lymphoma (DLBCL). Cancer Support Community. Accessed August 17, 2022.
  2. Yao S, Li J, Yao Z, et al. Extranodal involvement in young patients with diffuse large B-cell lymphoma: distribution, prognostic value and treatment options. Chin J Cancer Res. 2017;29(1):57-65. doi:10.21147/j.issn.1000-9604.2017.01.07
  3. Vitolo U, Seymour JF, Martelli M, et al. Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2016;27:v91-v102. doi:10.1093/annonc/mdw175
  4. Villa D, Connors JM, Sehn LH, Gascoyne RD, Savage KJ. Diffuse large B-cell lymphoma with involvement of the kidney: outcome and risk of central nervous system relapse. Haematologica. 2011;96(7):1002-1007. doi:10.3324/haematol.2011.041277
  5. Ben Abdelghani K, Rouached L, Mourad Dali K, et al. Diffuse large B cell lymphoma presenting with renal failure and bone lesions in a 46-year-old woman: a case report and review of literature. CEN Case Rep. 2020;10(2):165-171. doi:10.1007/s13730-020-00537-y
  6. Shen Y, Ou J, Wang B, Wang L, Xu J, Cen X. Influence of severe gastrointestinal complications in primary gastrointestinal diffuse large B-cell lymphoma. Cancer Manag Res. 2021;13:1041-1052. doi:10.2147/CMAR.S295671
  7. Ma J, Li Q, Shao J, et al. Central nervous system involvement in patients with diffuse large B cell lymphoma: analysis of the risk factors and prognosis from a single-center retrospective cohort study. Cancer Manag Res. 2019;11:10175-10185. doi:10.2147/CMAR.S225372
  8. Grommes C, DeAngelis LM. Primary CNS lymphoma. J Clin Oncol. 2017;35(21):2410-2418. doi:10.1200/JCO.2017.72.7602
  9. Primary central nervous system lymphoma: Signs and symptoms. NORD. Accessed August 23, 2022.
  10. Tsai YF, Liu YC, Yang CI, et al. Poor prognosis of diffuse large B-cell lymphoma with hepatitis C infection. J Pers Med. 2021;11(9):844. doi:10.3390/jpm11090844
  11. Shimazu Y, Nohgawa M. DLBCL developed into fatal liver failure during rituximab-containing chemotherapy. J Clin Exp Hematop. 2019;59(2):93-95. doi:10.3960/jslrt.19004
  12. Diffuse large B-cell lymphoma in adults. UpToDate. Updated July 22, 2022. Accessed August 17, 2022.
  13. Kadota T, Seo S, Fuse H, et al. Complications and outcomes in diffuse large B‐cell lymphoma with gastric lesions treated with R‐CHOP. Cancer Med. 2019;8(3):982-989. doi:10.1002/cam4.1982
  14. Wang J, Liu F, Tang X. Incidence and risk factors of pneumonia in diffuse large B-cell lymphoma patients receiving first line R-CHOP/R-CHOP-like immunochemotherapy: a retrospective study of 287 patients in single center. Ann Palliat Med. 2021;10(11):119311938-119311938. doi:10.21037/apm-21-3280
  15. Eyre TA, Wilson W, Kirkwood AA, et al. Infection-related morbidity and mortality among older patients with DLBCL treated with full- or attenuated-dose R-CHOP. Blood Advances. 2021;5(8):2229-2236. doi:10.1182/bloodadvances.2021004286
  16. Shree T, Li Q, Glaser SL, et al. Impaired immune health in survivors of diffuse large B-cell lymphoma. J Clin Oncol. 2020;38(15):1664-1675. doi:10.1200/JCO.19.01937
  17. Viviani S, Caccavari V, Gerardi C, et al. Male and female fertility: prevention and monitoring Hodgkin’ lymphoma and diffuse large B-cell lymphoma adult survivors. A systematic review by the Fondazione Italiana Linfomi. Cancers (Basel). 2021;13(12):2881. doi:10.3390/cancers13122881
  18. Mörth C, Sabaa AA, Freyhult E, et al. Plasma proteome profiling of cardiotoxicity in patients with diffuse large B-cell lymphoma. Cardiooncology. 2021;7:6. doi:10.1186/s40959-021-00092-0
  19. Ferraro MP, Gimeno-Vazquez E, Subirana I, et al. Anthracycline-induced cardiotoxicity in diffuse large B-cell lymphoma: NT-proBNP and cardiovascular score for risk stratification. Eur J Haematol. 2019;102(6):509-515. doi:10.1111/ejh.13234
  20. Enns DL, Mandelson MT, Aboulafia DM. Utility of left ventricular ejection fraction measurements before the administration of doxorubicin-based chemotherapy in patients with diffuse large B-cell lymphoma. Mayo Clin Proc Innov Qual Outcomes. 2018;2(3):277-285. doi:10.1016/j.mayocpiqo.2018.06.004
  21. Castaneda-Puglianini O, Chavez JC. Assessing and management of neurotoxicity after CAR-T therapy in diffuse large B-cell lymphoma. J Blood Med. 2021;12:775-783. doi:10.2147/JBM.S281247
  22. Guan X, He F, Wang Y, et al. Rare multiple organ failure caused by tumor lysis and subsequent fatal sepsis after novel salvaged chemotherapy of rituximab in a diffuse large B-cell lymphoma patient: a case report. Research Square Preprint. 2020. doi:10.21203/rs.3.rs-78233/v1 

Reviewed by Harshi Dhingra, MD, on 8/23/2022.

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