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Journal reading

Journal reading. Diffuse large B cell lymphoma in elderly patients(>80 years old). British Journal of Haematology, 2012, 157, 159–170 Annals of Oncology 23: 1280–1286, 2012. R4 簡聖軒 指導老師 : 蕭樑材大夫. Outline. Characteristic in elderly patient Evaluation of elderly patient Prognostic factor

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Journal reading

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  1. Journal reading Diffuse large B cell lymphoma in elderly patients(>80 years old) British Journal of Haematology, 2012, 157, 159–170 Annals of Oncology 23: 1280–1286, 2012 R4 簡聖軒 指導老師: 蕭樑材大夫

  2. Outline • Characteristic in elderly patient • Evaluation of elderly patient • Prognostic factor • Treatment strategy

  3. 100年國人零歲平均餘命,男性為76.0歲,女性為82.7歲100年國人零歲平均餘命,男性為76.0歲,女性為82.7歲

  4. 100年65歲以上死亡數占全體死亡數之68.5%

  5. Difficult in treatment • Multiple co-morbid illness • Decreased portal/renal perfusion flow • Altered pharmacokinetics • Decreased bone marrow hematopioetic reserve • Poor compliance and tolerance • Exclude in clinical trial, no available guideline

  6. Evaluation-cumulative illness score

  7. Charlson score

  8. IPI/AA-IPI,/R-IPI,/E-IPI

  9. NHL 3 hematology centers Israel 1984-2004 age 80 years or older at diagnosis.

  10. Annals of Oncology 17: 928–934, 2006

  11. Annals of Oncology 17: 928–934, 2006

  12. Annals of Oncology 17: 928–934, 2006

  13. Discussion • Aggressive lymphoma increase with age, especially in patient age > 85 years • Complete response : 50 %, • In aggressive lymphoma, short survival median survival : 18 months 3 year survival rate: 35%

  14. Discussion • Prognostic parameter: IPI and PS • Aggressive chemotherapy had a significantly longer median survival than no or mild therapy • For with aggressive lymphoma, age alone should not be a contraindication for treatment

  15. Five regional Dutch cancer registries From 1997-2004 (N:419)

  16. After adjustment other variable, age and performance was independently associated with receiving CHOP like chemotherapy

  17. Toxicities and response • Grade 3-4 toxicity occurred in 67 % in CHOP like therapy , 40 % in milder regimen

  18. Survival

  19. Influence survival After correction aaIPI, The effect of therapy (in four subgroups) was independently associated with survival

  20. N Engl J Med 2002; 346:235-242

  21. R-CHOP VS CHOP in elderly • 60 - 80 years of age with diffise large B cell lymphoma , randomization mainly in France • stage II, III, or IV disease • ECOG of 0 to 2 (good to fair) • No history of indolent lymphoma central nervous system involvement, active cancer • Excluded if cardiac contraindication to doxorubicin therapy • Excluded neurologic contraindication to vincristine

  22. R-CHOP VS CHOP in elderly • G-CSF in grade 4 neutropenia • C+H decreased 50 % in > 2 x grade 4 neutropenia • C+H decreased 50 % Grade 3- 4 thrombocytopenia • If neutrophil < 1500 or platelet < 10000, hold Tx • If hold Tx > 2 wks, DC treatment plan • The doses of rituximab were not modified, but rituximab was discontinued when CHOP was stopped. • Treatment was stopped if lymphoma progressed

  23. Lancet Oncol 2011; 12: 460–68

  24. Procedure • Prospective, multicentre, single-arm, phase 2 study • GELA ran the study in 38 centers in France and Belgium • Age > 80 years with diffuse large B-cell lymphoma. ECOG< 2 • Rituximab + CHOP (R-miniCHOP) at 3-week intervals. • 375 mg/m2 rituximab, • 400 mg/m2 cyclophosphamide, • 25 mg/m2 doxorubicin, • 1 mg vincristine • 40 mg/m2 prednisone on days 1–5.

  25. G-CSF or erythropoietin support was left to the discretion of the treating physician. • Recommend G-CSF SC used on day 6-day13 if severe neutropenic fever until neutrophil >1000 • Hold theray if neutrophil < 1000, if neutophil still < 1000 for more than 28 days, treatment DC

  26. Association of deaths with treatment during treatment phase

  27. Response 108/149 complete 6 X R-miniCHOP Median survival was 21 months 2 year prgoression free survival 47% 58 death report: 33 lymphoma progression 12 toxicities of treatment Most frequently side effeict : hematological toxicity >3 grade neutropenia : 59 Febrile neutropenia : 11

  28. Median overall survival was 29 months

  29. Conclusion • 29 months median survival • 62% complete response rate (CR+uCR) • The only parameter associated with poor outcome is low serum albumin • Death from toxicity in previous study: 9%-23%, but 5 death in first cycle in this study • Despite absence of a control arm. This study suggest selected patient older than 80 years with DLBCL in good performance, R-miniCHOP is considered

  30. Take home message • Treatment in very elderly patient is no more rare pratice • As age increased, aggressive lymphoma is more popular • Adequate evaluation is essential for treatment decision, suitable for elderly tool • Performance, LDH, albumin are most import prognostic factor

  31. Take home message • Age would not be contraindication for therapy • Median survival: 18-20 months and complete response: 50 % in treatment population • Treatment with Rituximab and reduced dose of chemotherapy would be acceptable strategy

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