High-dose chemotherapy with autologousstem cells transplantation in the treatment ofpatients with diffuse large B-cell lym...
Epidemiology• DLBCL is the most common type of NHL, 30-40%• Bone marrow involvement- 10-20% of DLBCL• Mean age 60 years• A...
CHOP and high-dose therapy in 1st-linetreatment of NHLFisher R, Blood, 1993CHOP: the toxicity of grade 5or fatal 1% ! (Oth...
Concordant bone marrow involvement is predictorof poor response to chemotherapy.Chung, Blood, 20075-year overall survival ...
Bone marrow involvement in patientswith DLBCLConcordant DiscordantBoneBone marrowIntestineBone marrow
Intensification of induction therapyModified NHL-BFM-90• 86 patients with progressive adverse factors (bulkydisease, tumor...
DLBCL with bone marrow involvementMagomedova A.U., Ther. archive, 2008Overall survival of patients with DLBCLchemotherapy ...
Scheme modified NHL-BFM-90preparation dose dayIfosfamide 800 mgm2 1-5Methotrexate 1500 mgm2 1Vincristine 2 mg 1Doxorubicin...
ASCT in the treatment of relapsedchemosensitivity DLBCLPhilip T, N Engl J M, 1995N = 215 (109 patients responded to induct...
Nademanee A, Blood, 1992ASCT in first-line therapy in youngpatients with high IPIInductiontherapy:CHOP-likecourses (3-10)C...
Conditioning regimens beforeautologous stem cell transplantationregimen characteristicBEAM "Gold standard", the mortality ...
High-dose sequential chemotherapy:
Patients with bone marrow involvement.Treatment on the modified program NHL-BFM-90, high-dosesequential chemotherapy(HDSC)...
Patients with bone marrow involvement.Treatment on the modified program NHL-BFM-90, high-dose sequential chemotherapy(HDSC...
The results of treatment of DLBCL withbone marrow involvement0%25%50%75%100%Overallsurvival0 12 24 36 48 60 72 84Months af...
Acknowledgments:Director of National Research Center for Hematology, academician VG SavchenkoHead. Dep. VHL, MD Zvonkov EE...
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High-dose chemotherapy with autologous stem cells transplantation in the treatment of patients with diffuse large B-cell lymphoma with bone marrow involvement.

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Gavrilina Olga
National Research Center for Hematology, Moscow, Russian Federation
High-dose chemotherapy with autologous stem cells transplantation in the treatment of patients with diffuse large B-cell lymphoma with bone marrow involvement.

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High-dose chemotherapy with autologous stem cells transplantation in the treatment of patients with diffuse large B-cell lymphoma with bone marrow involvement.

  1. 1. High-dose chemotherapy with autologousstem cells transplantation in the treatment ofpatients with diffuse large B-cell lymphomawith bone marrow involvement.Rapporteur: Gavrilina OlgaNational Research Center forHematology, Moscow, Russian Federation.Moscow, 2013
  2. 2. Epidemiology• DLBCL is the most common type of NHL, 30-40%• Bone marrow involvement- 10-20% of DLBCL• Mean age 60 years• About 2,500 new cases of DLBCL in the year inRussia• OS (10 y) <50%, RFS (10y) ~ 40% with standardchemotherapy (CHOP +-R)• OS (5 y) DLBCL with bone marrow involvementdoes not exceed 10% (* concordant)Coiffier B, Blood, 2010
  3. 3. CHOP and high-dose therapy in 1st-linetreatment of NHLFisher R, Blood, 1993CHOP: the toxicity of grade 5or fatal 1% ! (Other courses:3, 5, 6%)
  4. 4. Concordant bone marrow involvement is predictorof poor response to chemotherapy.Chung, Blood, 20075-year overall survival rate in the group with bone marrow involvement(34.5%) and without BM involvement (46.9%)5-year overall survival rate in the group with discordantbone marrow involvement (61.5%), with concordantbone marrow involvement (10.3%) and without BMinvolvement (46.9%)489 DLBCL patients, of which 55 with bone marrow(29 - concordant, 26 - discordant).
  5. 5. Bone marrow involvement in patientswith DLBCLConcordant DiscordantBoneBone marrowIntestineBone marrow
  6. 6. Intensification of induction therapyModified NHL-BFM-90• 86 patients with progressive adverse factors (bulkydisease, tumor invasion into adjacent organs / tissues in allits dimensions, III-IV stage of the disease at Ann -Arborclassification, and LDH above normal)• OR 64 patients (86%)• OS and 5y PFS 74.4% and 65%, respectively.• Patients without bone marrow involvement with III-IVstage (5y OS 84%)• Patients with bone marrow involvement 5y OS 12%Magomedova A.U., Ther. archive, 2011
  7. 7. DLBCL with bone marrow involvementMagomedova A.U., Ther. archive, 2008Overall survival of patients with DLBCLchemotherapy with CHOP-21 ± ROverall survival of patients with DLBCLwith bone marrow involvementWithout BMIBMImonth month
  8. 8. Scheme modified NHL-BFM-90preparation dose dayIfosfamide 800 mgm2 1-5Methotrexate 1500 mgm2 1Vincristine 2 mg 1Doxorubicin 25 mgm2 1-2Ara-C 100 mgm2twice a day4-5Etoposide 100 mgm2 4-5Dexamethasone 10 mgm2 1-5preparation dose dayCyclophosphamide 200 mgm2 1-5Methotrexate 1500 mgm2 1Vincristine 2 mg 1Doxorubicin 25 mgm2 4-5Dexamethasone 10 mgm2 1-5preparation dose dayMethotrexate 1500 mgm2 1Vinblastine 10 mg 1Ara-C 2000 mgm2twice a day2-3Etoposide 100 mgm2 3-5Dexamethasone 20 mg 1-5Block A Block B Block C
  9. 9. ASCT in the treatment of relapsedchemosensitivity DLBCLPhilip T, N Engl J M, 1995N = 215 (109 patients responded to induction therapy were separated by arm with ASCT (n = 55) andstandard 2-line chemotherapy (n = 54).Event-free survival in groups with ASCT (46%)and standard chemotherapy (12%)Overall survival in groups ASCT (53%) andstandard chemotherapy (32%)
  10. 10. Nademanee A, Blood, 1992ASCT in first-line therapy in youngpatients with high IPIInductiontherapy:CHOP-likecourses (3-10)Conditioning:Vp16 + Cycl +TBI or BCNU
  11. 11. Conditioning regimens beforeautologous stem cell transplantationregimen characteristicBEAM "Gold standard", the mortality rate of 3-5%131 I Tositumomab +BEAM Toxicity does not exceed BEAM, perhapsmore effectively90 Y Ibritumomab tiuxetan+ BEAM Toxicity does not exceed BEAM, perhapsmore effectiveBusulfan+ Cyclophosphomide+ Vp-16 Most of the toxicity, no "+" compared withBEAMTBI containing regimens Most of the early and delayed toxicity,there is no difference in survivalBeEAM Toxicity does not exceed BEAM,? efficiencyGascoyne R, Biology of Blood and Marrow Transplantation, 2012
  12. 12. High-dose sequential chemotherapy:
  13. 13. Patients with bone marrow involvement.Treatment on the modified program NHL-BFM-90, high-dosesequential chemotherapy(HDSC) and ASCT.IPI Bone marrowinvolvementInductiontherapyResponse toinductiontherapyResponseto HDSCOS,monthEFS,monthR., 38 HI Discordant А-С-А-С CR CR 45 6G., 48 H Concordant А-С-А-С с R PR CR 63+ 50+А., 23 LI Discordant А-С-А-С PR CR 56+ 44+Т., 41 H Concordant А-С-А-С PR CR 49+ 40+B., 52 LI Discordant А-С-А-С-А-В с R PR CR 18+ 4+S., 57 HI Discordant А-В-А-В-А-В с R CR - 25+ 12+All patients were treated at the National Research Center for Hematology at the Department Chemotherapyhematological diseases and intensive care from 2007 to 2012.Mean observation time: 46 months (18-65 months)Mean overall survival: 42 months (18-63 months)Mean event-free survival: 26 months (4-50 months)
  14. 14. Patients with bone marrow involvement.Treatment on the modified program NHL-BFM-90, high-dose sequential chemotherapy(HDSC) without ASCT.IPI Bone marrowinvolvementInduction therapy Response toinductiontherapyResponse toHDSCOS EFSS., 31г HI Discordant А-С-А-С CR CR + Dexa-BEAM 38+ 32+SH., 55 л HI Concordant А-С-А-С PR CR 26+ 19+S., 33 л LI Discordant А-С-А-С+R CR CR 24+ 17+S., 48 л H Discordant А-С-А-С-А PR CR 58+ 50+D., 54 г HI Discordant А-С-А-С CR CR+ Dexa-BEAM 44+ 34+К., 40 л HI Concordant А-С-А-С+R PR CR 32 6К ., 36 г H Concordant А-С-А-А PR CR+ Dexa-BEAM 43+ 36+D., 73 г HI Discordant А-В-А-В CR CR 27 20S., 67 л H Discordant В-А-С-А PR PR 21+ 8YA., 55 л HI Discordant А-С PR CR+ Dexa-BEAM 92+ 87+Mean observation time and overall survival: 40 months (21-92 months)Mean event-free survival: 30 months (6-87 months)
  15. 15. The results of treatment of DLBCL withbone marrow involvement0%25%50%75%100%Overallsurvival0 12 24 36 48 60 72 84Months after start of treatment0%25%50%75%100%Relapse-freesurvival0 12 24 36 48 60 72 84Months after start of treatment5-year overall survival rate is 72% ± 14%. 5-year disease-free survival rate is80% ± 10%.
  16. 16. Acknowledgments:Director of National Research Center for Hematology, academician VG SavchenkoHead. Dep. VHL, MD Zvonkov EEHead. Dep. HGZiIT, MD Kravchenko, SKMD Magomedova AUMD Lorie YYk.m.n Gabeeva NGK.m.n Mangasarova JKVI VorobievEmployees department VHL and HGZiIT National Research Center forHematology Russian Ministry of Health

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