Page 1482 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 82 Diagnosis and Treatment of Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma 1317

ischemic heart disease, anthracycline-related cardiotoxicity, and based on the molecular phenotype. Clin Cancer Res 20(20):5182–5193,
radiation- or bleomycin-induced pulmonary toxicity. The risk of 2014.
developing myelodysplastic disorders and acute myeloid leukemia is 6. Zhou Z, Sehn LH, Rademaker AW, et al: An enhanced International
related to alkylator and topoisomerase inhibitor use and is enhanced Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell
by radiation. Radiation therapy increases the risk of malignancy in lymphoma treated in the rituximab era. Blood 123(6):837–842, 2014.
the treatment region, particularly breast cancer in women and lung 7. Dunleavy K, Pittaluga S, Maeda LS, et al: Dose-adjusted EPOCH-
cancer in smokers. Indeed, it is imperative to consider late-term rituximab therapy in primary mediastinal B-cell lymphoma. New Engl J
toxicity when selecting treatment. Med 368(15):1408–1416, 2013.
A general guideline for follow-up after initial therapy involves 8. Martelli M, Ceriani L, Zucca E, et al: [18F]fluorodeoxyglucose positron
visits every 3 or 4 months for 2 years, and every 6 months or annually emission tomography predicts survival after chemoimmunotherapy for
thereafter. During these visits, examination of the LN areas, abdomen, primary mediastinal large B-cell lymphoma: results of the International
thyroid, and skin is important. CT scans are recommended in early Extranodal Lymphoma Study Group IELSG-26 Study. J Clin Oncol
follow-up but it is important to note that they are associated with a 32(17):1769–1775, 2014.
relatively high radiation exposure and projected risks and should not 9. Cunningham D, Hawkes EA, Jack A, et al: Rituximab plus cyclophos-
be used unnecessarily or for a prolonged amount of time. PET scans phamide, doxorubicin, vincristine, and prednisolone in patients with
are not recommended for routine follow-up because the high rate of newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase
false-positive scans is unlikely to offset the value of early detection. 3 comparison of dose intensification with 14-day versus 21-day cycles.
Routine laboratory studies with blood counts, liver function tests, Lancet 381(9880):1817–1826, 2013.
and LD should be performed. Thyroid-stimulating hormone levels 10. Delarue R, Tilly H, Mounier N, et al: Dose-dense rituximab-CHOP
should be monitored annually in patients who received neck radio- compared with standard rituximab-CHOP in elderly patients with
therapy. Mammography for women should begin 10 years from the diffuse large B-cell lymphoma (the LNH03-6B study): a randomised
diagnosis of lymphoma or at age 40 years, whichever comes first. phase 3 trial. Lancet Oncol 14(6):525–533, 2013.
11. Récher C, Coiffier B, Haioun C, et al: Intensified chemotherapy with
ACVBP plus rituximab versus standard CHOP plus rituximab for the
FUTURE DIRECTIONS treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label
randomised phase 3 trial. Lancet 378(9806):1858–1867, 2011.
Over recent years, we have made significant advances in elucidating 12. Holte H, Leppa S, Bjorkholm M, et al: Dose-densified chemoim-
the molecular biology of DLBCL and BL, and this has led to an era munotherapy followed by systemic central nervous system prophylaxis
of enhanced and exciting drug discovery. In DLBCL in particular, for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma
many critical pathways and novel mutations have been identified, and patients: results of a phase II Nordic Lymphoma Group study. Ann
many small molecule inhibitors are being investigated and in develop- Oncol 2012.
ment as a result of these advances. For example, in the ABC subtype 13. Wilson WH, Grossbard ML, Pittaluga S, et al: Dose-adjusted EPOCH
of DLBCL, recent work has identified that chronic active B-cell chemotherapy for untreated large B-cell lymphomas: a pharmacody-
receptor signaling is an important mechanism of ABC tumor cell namic approach with high efficacy. Blood 99(8):2685–2693, 2002.
survival; to test this clinically, studies in patients with ABC DLBCL 14. Wilson WH, Dunleavy K, Pittaluga S, et al: Phase II study of dose-
are in progress targeting specific components of this pathway. In BL, adjusted EPOCH and rituximab in untreated diffuse large B-cell
cure rates are very high with conventional approaches, and the chal- lymphoma with analysis of germinal center and post-germinal center
lenge for the future is to further develop strategies that maintain the biomarkers. J Clin Oncol 26(16):2717–2724, 2008.
efficacy of “standard” treatment but with much less toxicity. Recently, 15. Davis RE, Ngo VN, Lenz G, et al: Chronic active B-cell-receptor signal-
the discovery of novel mutations in BL has set the stage for the ling in diffuse large B-cell lymphoma. Nature 463(7277):88–92, 2010.
21
investigation of small molecule inhibitors in this disease also. To 16. Rubenstein JL, Hsi ED, Johnson JL, et al: Intensive chemotherapy
advance the therapeutics of these diseases, it is critical to wisely choose and immunotherapy in patients with newly diagnosed primary CNS
which drugs should be developed and incorporated into upfront lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol 31(25):3061–
clinical trials and to pair drug development with understanding of 3068, 2013.
tumor biology. 17. Gerrard M, Cairo MS, Weston C, et al: Excellent survival following
two courses of COPAD chemotherapy in children and adolescents with
resected localized B-cell non-Hodgkin’s lymphoma: results of the FAB/
REFERENCES LMB 96 international study. Br J Haematol 141(6):840–847, 2008.
18. Dunleavy K, Pittaluga S, Shovlin M, et al: Low-intensity therapy in
1. Sehn LH, Gascoyne RD: Diffuse large B-cell lymphoma: optimizing adults with Burkitt’s lymphoma. N Engl J Med 369(20):1915–1925,
outcome in the context of clinical and biologic heterogeneity. Blood 2013.
125:22, 2015. 19. Noy A, Lee JY, Cesarman E, et al: AMC 048: modified CODOX-M/
2. Scott DW, Wright GW, Williams PM, et al: Determining cell-of-origin IVAC-rituximab is safe and effective for HIV-associated Burkitt lym-
subtypes of diffuse large B-cell lymphoma using gene expression in phoma. Blood 126(2):160–166, 2015.
formalin-fixed paraffin-embedded tissue. Blood 123(8):1214–1217, 20. Kochenderfer JN, Dudley ME, Kassim SH, et al: Chemotherapy-
2014. refractory diffuse large B-cell lymphoma and indolent B-cell malignan-
3. Lenz G, Wright G, Dave SS, et al: Stromal gene signatures in large-B-cell cies can be effectively treated with autologous T cells expressing an
lymphomas. N Engl J Med 359(22):2313–2323, 2008. anti-CD19 chimeric antigen receptor. J Clin Oncol 33(6):540–549,
4. Wilson WH, Bromberg JE, Stetler-Stevenson M, et al: Detection and 2015.
outcome of occult leptomeningeal disease in diffuse large B-cell lym- 21. Basso K, Dalla-Favera R: Germinal centres and B cell lymphomagenesis.
phoma and Burkitt lymphoma. Haematologica 99(7):1228–1235, 2014. Nat Rev Immunol 15(3):172–184, 2015.
5. Dunleavy K, Roschewski M, Wilson WH: Precision treatment of distinct
molecular subtypes of diffuse large B-cell lymphoma: ascribing treatment