Table 2.

Definitions of transfusion-dependence and anemia response criteria in MDSs


Clinical trial
TDATRANon-TDAResponse criteria for TDAResponse criteria for non-TDA
Epoetin alfa
Phase 3 study in low-risk MDS
Fenaux et al24  
1-4 units in 8 wk before baseline visit Not applicable Hb ≤10 g/dL without transfusions in the prior 8 wk TI per IWG-2006
No transfusions for ≥8 consecutive weeks + increase in Hb by ≥1.5 g/dL
Baseline Hb value taken before the last transfusion preceding enrollment 
IWG-2006
≥1.5 g/dL increase in Hb for ≥8 wk
Modified IWG-2006
Increase in Hb ≥1.5 g/dL lasting <8 wk was considered a response if epoetin alfa was discontinued and when restarting at lower dose, Hb increased by ≥1.5 g/dL 
Darbepoetin alpha
Phase 3 study in low-risk MDS
Platzbecker et al25  
1-4 units in each of 2 consecutive 8-wk periods before randomization Not applicable Not applicable TI per IWG-2006
No transfusions over ≥8 consecutive weeks + increase in Hb by ≥1.5 g/dL 
Not applicable 
MEDALIST
Phase 3 study
Luspatercept vs placebo in MDS with ring sideroblasts
Fenaux et al26  
≥2 units in 8 wk during the 16 wk before randomization Not applicable Not applicable TI rate at week 24
No transfusions over ≥8 consecutive weeks 
Not applicable 
COMMANDS
Phase 3 study
Luspatercept vs epoetin alfa in low-risk MDS
Platzbecker et al27  
2-6 units in 8 wk for ≥8 wk before randomization Not applicable Not applicable TI rate at week 24
No transfusions over ≥12 consecutive weeks + concurrent mean
Hb increase ≥1.5 g/dL 
Not applicable 

Clinical trial
TDATRANon-TDAResponse criteria for TDAResponse criteria for non-TDA
Epoetin alfa
Phase 3 study in low-risk MDS
Fenaux et al24  
1-4 units in 8 wk before baseline visit Not applicable Hb ≤10 g/dL without transfusions in the prior 8 wk TI per IWG-2006
No transfusions for ≥8 consecutive weeks + increase in Hb by ≥1.5 g/dL
Baseline Hb value taken before the last transfusion preceding enrollment 
IWG-2006
≥1.5 g/dL increase in Hb for ≥8 wk
Modified IWG-2006
Increase in Hb ≥1.5 g/dL lasting <8 wk was considered a response if epoetin alfa was discontinued and when restarting at lower dose, Hb increased by ≥1.5 g/dL 
Darbepoetin alpha
Phase 3 study in low-risk MDS
Platzbecker et al25  
1-4 units in each of 2 consecutive 8-wk periods before randomization Not applicable Not applicable TI per IWG-2006
No transfusions over ≥8 consecutive weeks + increase in Hb by ≥1.5 g/dL 
Not applicable 
MEDALIST
Phase 3 study
Luspatercept vs placebo in MDS with ring sideroblasts
Fenaux et al26  
≥2 units in 8 wk during the 16 wk before randomization Not applicable Not applicable TI rate at week 24
No transfusions over ≥8 consecutive weeks 
Not applicable 
COMMANDS
Phase 3 study
Luspatercept vs epoetin alfa in low-risk MDS
Platzbecker et al27  
2-6 units in 8 wk for ≥8 wk before randomization Not applicable Not applicable TI rate at week 24
No transfusions over ≥12 consecutive weeks + concurrent mean
Hb increase ≥1.5 g/dL 
Not applicable 
Established anemia response criteriaDefinitionsErythroid response
IWG-2006
Cheson et al28 
 
Screening period, 8 wk for evaluation of transfusion burden and baseline Hb
Pretreatment Hb <11 g/dL
TDA (≥4 units in 8 wk for Hb <9 g/dL)
TI (<4 units in 8 wk for Hb <9 g/dL) 
≥1.5 g/dL increase in Hb for ≥8 wk
Reduction of ≥4 units transfusions/8 wk compared with the pretreatment transfusion in the prior 8 wk 
Revised IWG-2018
Platzbecker et al29  
Screening period, 16 wk for evaluation of transfusion burden and baseline Hb
Baseline Hb:
Mean of all available Hb values during 16-wk screening period.
Values before transfusion should be used for TD patients and should be ≥7 d apart
Pretreatment Hb <10 g/dl
NTD (0 units in 16 wk)
LTB (3-7 units in 16 wk in at least 2 transfusion episodes, maximum 3 in 8 wk)
HTB (≥8 units in 16 wk, ≥4 in 8 wk) 
NTD
Hb ≥1.5 g/dL for ≥8 wk over 16-24 wk compared with the lowest mean of 2 Hb values within 16 wk before treatment
LTB
TI, defined by the absence of transfusions for ≥8 wk over 16-24 wk
HTB
Major response: TI, defined by the absence of transfusions for ≥8 wk over 16-24 wk
Minor response: Transfusion reduction by ≥50% over a minimum of 16 wk
Same transfusion policy should be applied compared with 16 wk before treatment 
Established anemia response criteriaDefinitionsErythroid response
IWG-2006
Cheson et al28 
 
Screening period, 8 wk for evaluation of transfusion burden and baseline Hb
Pretreatment Hb <11 g/dL
TDA (≥4 units in 8 wk for Hb <9 g/dL)
TI (<4 units in 8 wk for Hb <9 g/dL) 
≥1.5 g/dL increase in Hb for ≥8 wk
Reduction of ≥4 units transfusions/8 wk compared with the pretreatment transfusion in the prior 8 wk 
Revised IWG-2018
Platzbecker et al29  
Screening period, 16 wk for evaluation of transfusion burden and baseline Hb
Baseline Hb:
Mean of all available Hb values during 16-wk screening period.
Values before transfusion should be used for TD patients and should be ≥7 d apart
Pretreatment Hb <10 g/dl
NTD (0 units in 16 wk)
LTB (3-7 units in 16 wk in at least 2 transfusion episodes, maximum 3 in 8 wk)
HTB (≥8 units in 16 wk, ≥4 in 8 wk) 
NTD
Hb ≥1.5 g/dL for ≥8 wk over 16-24 wk compared with the lowest mean of 2 Hb values within 16 wk before treatment
LTB
TI, defined by the absence of transfusions for ≥8 wk over 16-24 wk
HTB
Major response: TI, defined by the absence of transfusions for ≥8 wk over 16-24 wk
Minor response: Transfusion reduction by ≥50% over a minimum of 16 wk
Same transfusion policy should be applied compared with 16 wk before treatment 

HTB, high transfusion burden; LTB, low transfusion burden; NTD, non–transfusion dependent; TI, transfusion independent.

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