oligoblastic AML
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Transcript of oligoblastic AML
Should patient with refractory anemia with excess blasts or those with oligoblastic AML
receive induction therapy prior to allogeneic transplantation?
Should patient with refractory anemia with excess blasts or those with oligoblastic AML
receive induction therapy prior to allogeneic transplantation?
My answer is“Yes”
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
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
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%
IPSS-Revised: Prognostic Variables
Greenberg et al Blood 2012
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
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
The only curative treatment modality for high risk MDS is allogeneic hematopoietic cell
transplantation(HSCT)
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
Type of treatment prior to transplantation
• AML induction-type chemotherapy • Hypomethylating agent(HMA) therapy
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
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
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.
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
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: 458-68Damaj G, et al: J Clin Oncol 2012; 30:4533-40
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
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.
Damaj G et al. JCO 2012;30:4533-4540©2012 by American Society of Clinical Oncology
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).
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%
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.
Gerts AT et al : Biol Blood Marrow Transplant 2012; 18: 1211-1218
Overall survival after HSCT according to pretransplantation therapy: Aza vs IC
P = 0.24
Gerts AT et al : Biol Blood Marrow Transplant 2012; 18: 1211-1218
1-year OS: 57% vs 36%
Nonrelapse mortality following HSCT according to pretransplantation therapy: Aza vs IC
Gerts AT et al : Biol Blood Marrow Transplant 2012; 18: 1211-1218
NS, p = 0.98
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
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
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.
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
Survival analysis according to the salvage treatment regimens.
Prébet T et al. JCO 2011;29:3322-3327©2011 by American Society of Clinical Oncology
(*) 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).
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
Considerations for choosing the optimal treatment before allogeneic HCT in MDS
Platzbecker U Hematology 2013;2013:522-528
How we treat higher-risk myelodysplastic syndromes?
Mikkael Sekeres and Corey Cutler Blood 2014;123(60}; 829-836
Therapeutic algorithm for adult patients with primary MDS and Int-2 or high IPSS score
European LeukemiaNet Blood 2013;122(17):2943-2964
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.