Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

oligoblastic AML

1,160 views

Published on

Should patients with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation?
Yes: Suporn Chancharunee, MD
No: Nina Shah, MD

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

oligoblastic AML

  1. 1. Should patient with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation?
  2. 2. Should patient with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation? My answer is“Yes”
  3. 3. Should patient with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation? My answer is “Yes” What is the evidence-based data? No randomized trials and retrospective studies are subject to selection bias
  4. 4. Outline • Terminology: RAEB-t , Oligoblastic AML • Type of induction therapy prior to HSCT • Does the disease burden at the time of HSCT matter? • Will pre-transplantation therapy lead to lower relapse rate and superior longer survival? • Pre-HSCT therapy with induction chemotherapy • Pre-HSCT therapy with DNA hypomethylating agents • Strategies in preperation for HSCT and Recommendations from the experts
  5. 5. Terminology • Smoldering acute leukemia: blast 3-20% • Pauciblastic myeloid leukemia • Oligoblastic myelogenous leukemia • Refractory anemia with excess blasts - Myelodysplastic syndrome: high risk • Acute leukemia with blast 20-30%
  6. 6. IPSS-Revised: Prognostic Variables Greenberg et al Blood 2012
  7. 7. Outline • Terminology: RAEB-t , Oligoblastic AML • Type of induction therapy prior to HSCT • Does the disease burden at the time of HSCT matter? • Will pre-transplantation therapy lead to lower relapse rate and superior longer survival? • Pre-HSCT therapy with induction chemotherapy • Pre-HSCT therapy with DNA hypomethylating agents • Strategies in preperation for HSCT and Recommendations from the experts
  8. 8. The only curative treatment modality for high risk MDS is allogeneic hematopoietic cell transplantation(HSCT) Rational for Pre-HSCT therapy • Tumor debulking to reduce the risk of post- HSCT relapse • Slow leukemic transformation • Reduce transfusion needs during the time of donor search
  9. 9. Outline • Terminology: RAEB-t , Oligoblastic AML • Type of induction therapy prior to HSCT • Does the disease burden at the time of HSCT matter? • Will pre-transplantation therapy lead to lower relapse rate and superior longer survival? • Pre-HSCT therapy with induction chemotherapy • Pre-HSCT therapy with DNA hypomethylating agents • Strategies in preperation for HSCT and Recommendations from the experts
  10. 10. Type of treatment prior to transplantation • AML induction-type chemotherapy • Hypomethylating agent(HMA) therapy
  11. 11. Does the disease burden matter? • Outcomes are improved with lower disease burden at the time of HSCT. • Retrospective analyses from EBMT and NMDP showed an improved outcome in patients with lower disease burden at the time of HSCT. - De Witte T, Suciu S, Verhoef G, et al. Blood 2001;98: 2326-31 - Castro-Malaspina H, Jabubowski AA, Papadopoulos EB, et al. Biol Blood Marrow Transplant 2008; 14: 458-68
  12. 12. Outline • Terminology: RAEB-t , Oligoblastic AML • Type of induction therapy prior to HSCT • Does the disease burden at the time of HSCT matter? • Pre-HSCT therapy with induction chemotherapy • Pre-HSCT therapy with DNA hypomethylating agents • Will pre-transplantation therapy lead to lower relapse rate and superior longer survival? • Strategies in preperation for HSCT and Recommendations from the experts
  13. 13. Pre-HSCT therapy with induction chemotherapy • Selection bias for patients with chemosensitive disease, favorable prognosis. Higher treatment-related toxicity. - They might have favorable outcomes if not exposed to cytotoxic chemotherapy. Value is not cleared in the absence of RCT. Good option in young and fit AML patients with high tumor burden.
  14. 14. Pre-HSCT therapy with DNA hypomethylating agents • Widely used to prevent disease progression and to reduce transfusion needs while the process of donor selection is performed. • Engraft graft-versus-MDS effects: increased expression of KIR and minor histocompatibility antigens . • Patients who did not respond to HMA have very poor prognosis. • Good outcome in TET-2 mutation
  15. 15. Pre-HSCT therapy with DNA hypomethylating agents • Feasible, even in patients with comorbidities and or poor performance status • Azacytidine: less toxicity than induction chemotherapy • Lower response rates compare to induction chemotherapy • no negative impact on HSCT outcome Gerts AT et al : Biol Blood Marrow Transplant 2008; 14: 458-68 Damaj G, et al: J Clin Oncol 2012; 30:4533-40
  16. 16. Type of treatment prior to transplantation: IC vs Aza • 163 patients who underwent HCT after azacytidine(Aza), after AML-type induction chmeotherapy(IC), or after both. • No differences in relapse rates, nonrelapse mortality, EFS, or overall survival comparing Aza and IC Damaj et al J Clin Oncol 2012:30(36):4533-4540
  17. 17. Kaplan-Meier estimates of (A) 3-year overall survival, (B) 3-year event-free survival, (C) cumulative incidence of 3-year relapse, and (D) nonrelapse mortality (NRM) in 163 patients, according to the prior-to-transplantation treatment received. ©2012 by American Society of Clinical Oncology Damaj G et al. JCO 2012;30:4533-4540
  18. 18. Pretransplatation therapy with Azacytidine vs Induction chemotherapy and Postransplantation Outcome in Patients with MDS •Retrospective analysis: 68 patients who underwent allogeneic HSCT for MDS/AML transformed from MDS. •Patients who received Aza were older than IC-treated patients(medain 60 vs 47years). The risk of post-HSCT mortality , non-relapse mortality, and relapse were lower in the Aza-group compared to IC. After adjustment for cytogenetic risk, IPSS and donor, the rates for post-HSCT relapse for the 2 cohorts were similar. N 1-yr OS post-HSCT mortality Non-relapse mortality relapse ratio Aza 35 57% HR 0.68 HR 0.99 0.34 IC 33 36% Gerts AT et al : Biol Blood Marrow Transplant 2012; 18: 1211-1218
  19. 19. Overall survival after HSCT according to pretransplantation therapy: Aza vs IC P = 0.24 1-year OS: 57% vs 36% Gerts AT et al : Biol Blood Marrow Transplant 2012; 18: 1211-1218
  20. 20. Nonrelapse mortality following HSCT according to pretransplantation therapy: Aza vs IC NS, p = 0.98 Gerts AT et al : Biol Blood Marrow Transplant 2012; 18: 1211-1218
  21. 21. Relapse mortality following HSCT according to pretransplantation therapy: Aza vs IC P = 0.04 Gerts AT et al : Biol Blood Marrow Transplant 2012; 18: 1211-1218
  22. 22. Relapsed-free survival after HSCT according to pretransplantation therapy: Azacytidine vs IC P = 0.14 Gerts AT et al : Biol Blood Marrow Transplant 2012; 18: 1211-1218
  23. 23. Optimal time to consider proceeding to HSCT in MDS patients who are treated with Azacytidine - Benefit of Azacytidine therapy can be estimated according to the “Aza prognostic score” using ECOG, PB blasts, Rbc-transfusion dependent and IPSS karyotype.
  24. 24. Considerations of when to proceed to an allogeneic HCT in a transplantation-eligible patient with higher-risk MDS in the context of an anticipated prior treatment with AZA according to the AZA prognostic score. Platzbecker U Hematology 2013;2013:522-528
  25. 25. Survival analysis according to the salvage treatment regimens. ©2011 by American Society of Clinical Oncology Prébet T et al. JCO 2011;29:3322-3327 (*) Univariate analysis (log-rank test) showed significant differences between palliative care and intensive chemotherapy (CT; P = .04), investigational therapy (IT; P < .001), or allogeneic stem-cell transplantation (ASCT; P < .001). (†)There was also a significant difference between intensive CT and IT (P = .05) and intensive CT and ASCT (P = .008). The difference between IT and ASCT reached borderline significance (P = .09).
  26. 26. Outline • Terminology: RAEB-t , Oligoblastic AML • Type of induction therapy prior to HSCT • Does the disease burden at the time of HSCT matter? • Will pre-transplantation therapy lead to lower relapse rate and superior longer survival? • Pre-HSCT therapy with induction chemotherapy • Pre-HSCT therapy with DNA hypomethylating agents • Strategies in preperation for HSCT and Recommendations from the experts
  27. 27. Considerations for choosing the optimal treatment before allogeneic HCT in MDS Platzbecker U Hematology 2013;2013:522-528
  28. 28. How we treat higher-risk myelodysplastic syndromes? Mikkael Sekeres and Corey Cutler Blood 2014;123(60}; 829-836
  29. 29. Therapeutic algorithm for adult patients with primary MDS and Int-2 or high IPSS score European LeukemiaNet Blood 2013;122(17):2943-2964
  30. 30. Conclusion • With the acceptable toxicity and potential for cytoreduction, HMA including Azacytidine or Decitabine can be used as pretransplantation therapy. • Induction chemotherapy is considered in young MDS patients with favorable and intermediate-karyotype, good performance status and high percentage of blasts. • No pre-transplantation treatment is needed in MDS patients with • co-morbidities, low blasts percentages.

×