Background

In 2001, the World Health Organization modified the French-American-British (FAB) classification for myelodysplastic syndrome (MDS) by folding the refractory anemia with excess blasts in transformation (RAEB-t) category into acute myeloid leukemia (AML). Whether this group of patients (pts) should be treated with AML versus MDS therapy remains controversial. A subset analysis of the AZA-001 trial showed that azacitidine prolongs overall survival (OS) in elderly pts with low blasts AML (bone marrow blasts [BM] 20-30%).

Aim

To compare the clinical outcome and OS of patients with MDS or AML with BM blasts between 10-30%, treated with hypomethylating agents (HMA) vs intensive chemotherapy (IC).

Patients and Methods

We conducted a retrospective analysis of newly diagnosed pts with MDS (or AML by WHO) and BM blasts between 10-30% treated with either HMA (alone or in combination with investigational therapies) or IC on clinical trials. Eligibility was based on pt characteristics and specific protocol inclusion criteria. A univariate Cox proportional hazards regression model was used to evaluate the overall effects of treatments and outcome (remission duration (RD), and OS). Then a regression model with the interactions between treatments and baseline covariates were used for subgroup analysis. The final model was obtained by a stepwise selection using 0.05 as a cut off of significant values.

Results

330 patients were included in the final analysis, with 93 (28%) HMA-treated pts and 237 (72%) pts treated with IC. Clinical characteristics at diagnosis are summarized in Table1. The overall response rate (ORR= CR+CR p) was 42% for the pts who treated with HMA and 60% for pts treated with IC (P = 0.01). The median RD was similar between the two groups (14.7 mos (m) vs. 14.7 mos, respectively, P = 0.74). Early induction mortality was also similar among the two groups (4-week mortality was 5% vs. 7%, respectively, and the 8-week mortality was 10% vs. 13 %, respectively). With median follow up of 37 mos (range, 1-94 mos), the median OS was 18.8 mos for pts who treated with HMA vs. 14.6 mos for pts treated with IC (P = 0.32). Moreover, the BM blasts percentage did not impact the overall outcome. In multivariate analysis, treatment with IC was associated with worse OS compared to HMA (HR 2.09, 95% CI 2.07-3.17, P = 0.003) but not for RD (HR 0.43, 95% CI 0.89-2.68, P = 0.13).

Table 1

Patients’ characteristics and responses

CharacteristicsAll patients No.%HMA No.%IC No.%P- value
Number 330  93 28 237 72  
Age, years        
Median 64  66  62  <0.001 
Range 13-90  13-90  17-84   
Age, years       0.03 
< 65 187 57 44 47 143 60  
> 65 143 43 49 53 94 40  
Sex        
Male 194 59 59 63 135 57 0.28 
Female 136 41 34 37 102 43  
History of prior Cx and /or Rx       0.26 
Yes 75 23 25 27 50 21  
No 255 77 68 73 187 79  
IPSS        
High 181 60 41 48 140 65 0.02 
Intermediate-2 107 36 38 45 69 32  
Intermediate-1 12 4 6 7 6 3  
Not applicable 30 NA 8 NA 22 NR  
Cytogenetic analysis        
Diploid/-Y 133 42 34 39 99 43 0.82 
5-/7- 111 35 32 37 79 34  
Other 86 23 27 24 59 23  
Complex cytogenetics        
Yes 112 34 33 35 79 33 0.76 
No 73 22 20 22 53 22  
Bone marrow blasts %        
10- 20 167 51 64 69 103 43 <0.0001 
21-30 163 49 29 31 134 57  
Median WBC x109/L Range 2.7
(0.4 123.4) 		 2.5
(0.4-25.6) 		 2.9
(0.9-123.4) 		 0.01 
Median hemoglobin g/dl Range 9.4 (4.2-13.5)  9.7
(6.8-13.5) 		 9.1
(4.2-13.5) 		 0.02 
Median platelets x103/mL Range 57 (3-746)  62
(11-588) 		 55
(3-746) 		 0.23 
Median bone marrow blasts %
Range 		19 (10-30)  15
(10-30) 		 20
(10-30) 		 <0.0001 
CharacteristicsAll patients No.%HMA No.%IC No.%P- value
Number 330  93 28 237 72  
Age, years        
Median 64  66  62  <0.001 
Range 13-90  13-90  17-84   
Age, years       0.03 
< 65 187 57 44 47 143 60  
> 65 143 43 49 53 94 40  
Sex        
Male 194 59 59 63 135 57 0.28 
Female 136 41 34 37 102 43  
History of prior Cx and /or Rx       0.26 
Yes 75 23 25 27 50 21  
No 255 77 68 73 187 79  
IPSS        
High 181 60 41 48 140 65 0.02 
Intermediate-2 107 36 38 45 69 32  
Intermediate-1 12 4 6 7 6 3  
Not applicable 30 NA 8 NA 22 NR  
Cytogenetic analysis        
Diploid/-Y 133 42 34 39 99 43 0.82 
5-/7- 111 35 32 37 79 34  
Other 86 23 27 24 59 23  
Complex cytogenetics        
Yes 112 34 33 35 79 33 0.76 
No 73 22 20 22 53 22  
Bone marrow blasts %        
10- 20 167 51 64 69 103 43 <0.0001 
21-30 163 49 29 31 134 57  
Median WBC x109/L Range 2.7
(0.4 123.4) 		 2.5
(0.4-25.6) 		 2.9
(0.9-123.4) 		 0.01 
Median hemoglobin g/dl Range 9.4 (4.2-13.5)  9.7
(6.8-13.5) 		 9.1
(4.2-13.5) 		 0.02 
Median platelets x103/mL Range 57 (3-746)  62
(11-588) 		 55
(3-746) 		 0.23 
Median bone marrow blasts %
Range 		19 (10-30)  15
(10-30) 		 20
(10-30) 		 <0.0001 
View Large
Conclusion

Although patients with MDS or AML with BM blasts between 10-30% initially achieve a higher ORR when treated with IC compared to HMA-based therapy, the OS was better for pts treated with HMA after accounting for all other covariates. Interestingly, BM blast percentages within this cohort did not impact overall outcome suggesting that pts with BM blasts 20-30% may achieve better outcome with MDS therapy.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
blast cells, bone marrow, chemotherapy regimen, myelodysplastic syndrome, brachial plexus neuritis, refractory anemia with excess blasts, azacitidine, cytogenetic analysis, disease remission, experimental treatment

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
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