Abstract 3096

Relapsed or refractory AML is difficult to treat even with allogeneic BMT. In an attempt to reduce leukemia burden and limit toxicities from multiple re-induction attempts, we initiated a treatment strategy to offer allogeneic BMT prior to count recovery, within 3 to 4 weeks after re-induction. Among 156 consecutive AML patients referred to our BMT program between 01/2003 and 03/2008, 84 (54%) patients did not receive an allogeneic BMT due to: death (n=25, 30%), patient refusal (n=13, 16%), disease progression (n=13, 16%), autologous BMT (n=11, 13%) and other (n= 22, 26%). Seventy-two (46%) patients received an allogeneic BMT: 21 (29%) patients were prospectively identified with very high risk features (primary induction failure (PIF) or refractory relapse (RR)) and received re-induction with the intent-to-induce hypoplasia and transplant prior to count recovery. The remaining 51 patients received re-induction with the goal of inducing complete remission (CR) prior to BMT (the intent-to-induce remission group). Patient and BMT-related characteristics, as well as BMT outcomes are summarized in Table 1. Patients were prospectively accrued to myeloablative or reduced intensity BMT protocols depending on their age, KPS, co-morbidities, disease risk and the degree of HLA match. The intent-to-induce hypoplasia group had a lower 2-year PFS and OS (reflecting their very high risk disease characteristics). In subgroup analysis in patients with PIF or RR, there was no difference in 2-year PFS (15% vs. 22%, p=0.39) or 2-year OS (20% vs. 33%, p=0.32) between the intent-to-induce hypoplasia and the intent-to-induce remission groups. The overall and day 100 TRM was similar in both groups of patients with PIF or RR. Using this prospective strategy of identifying patients with very high risk disease with the intent to transplant them during hypoplasia after re-induction therapy, 46% of all the referred AML patients were able to undergo allogeneic BMT. This is higher than other published series where < 30% of patients proceeded to transplant where the goal of re-induction was to induce and achieve CR prior to transplant. Our data show that it is safe to transplant advanced AML patients early (within 3 to 4 weeks) after re-induction with acceptable mortality in patients with very high risk AML who otherwise might not be transplant candidates.

Table.

Patient Characteristics and Outcomes

FactorIntent-to-induce remission (N=51)Intent-to-induce hypoplasia (N=21)P
 N(%) N(%)  
Patient and Disease Characteristics 
Age at BMT    
18-40 16 (31) 4 (19) NS 
41-60 28 (55) 13 (62)  
61+ 7 (14) 4 (19)  
KPS at BMT    
≥90 23 (45) 1 (5) <0.01 
≤80 28 (55) 20 (95)  
WBC at diagnosis    
≥30 x 109/L 12 (24) 9 (43) NS 
<30 x 109/L 39 (76) 12 (57)  
Cytogenetics at diagnosis    
Favorable 2 (4) 1 (5) NS 
Intermediate 25 (49) 14 (67)  
Adverse 24 (47) 6 (29)  
De novo vs. Secondary AML    
De novo 39 (76) 17 (81) NS 
Secondary 12 (24) 4 (19)  
Disease status at BMT    
First CR 38 (75) 0 (0) <0.01 
Second or greater CR 4 (8) 1 (5)  
PIF/RR 9 (18) 20 (95)  
BMT-Related Characteristics 
Donor source    
Related 24 (47) 8 (38) NS 
Unrelated 27 (53) 13 (62)  
Stem cell type    
BM±PB 10 (20) 1 (5) NS 
PB 41 (80) 20 (95)  
HLA 10/10 match    
Matched 46 (90) 16 (76) NS 
Mismatched 5 (10) 5 (24)  
Gender match    
Matched 30 (59) 13 (62) NS 
Mismatched 21 (41) 8 (38)  
Myeloablative conditioning    
CT±V 15 (29) 0 (0) <0.01 
BuCy 5 (10) 1 (5)  
Reduced intensity conditioning    
FluMel 27 (53) 15 (71) <0.01 
FluCy 4 (8) 5 (24)  
Prior BMT    
Prior auto BMT 2 (4) 3 (14) NS 
No prior auto BMT 49 (96) 18 (86)  
BMT-Related Outcomes 
2-yr PFS 53% 18% <0.001 
2-yr OS 56% 23% <0.001 
Day 100 TRM 10% 33% 0.03 
FactorIntent-to-induce remission (N=51)Intent-to-induce hypoplasia (N=21)P
 N(%) N(%)  
Patient and Disease Characteristics 
Age at BMT    
18-40 16 (31) 4 (19) NS 
41-60 28 (55) 13 (62)  
61+ 7 (14) 4 (19)  
KPS at BMT    
≥90 23 (45) 1 (5) <0.01 
≤80 28 (55) 20 (95)  
WBC at diagnosis    
≥30 x 109/L 12 (24) 9 (43) NS 
<30 x 109/L 39 (76) 12 (57)  
Cytogenetics at diagnosis    
Favorable 2 (4) 1 (5) NS 
Intermediate 25 (49) 14 (67)  
Adverse 24 (47) 6 (29)  
De novo vs. Secondary AML    
De novo 39 (76) 17 (81) NS 
Secondary 12 (24) 4 (19)  
Disease status at BMT    
First CR 38 (75) 0 (0) <0.01 
Second or greater CR 4 (8) 1 (5)  
PIF/RR 9 (18) 20 (95)  
BMT-Related Characteristics 
Donor source    
Related 24 (47) 8 (38) NS 
Unrelated 27 (53) 13 (62)  
Stem cell type    
BM±PB 10 (20) 1 (5) NS 
PB 41 (80) 20 (95)  
HLA 10/10 match    
Matched 46 (90) 16 (76) NS 
Mismatched 5 (10) 5 (24)  
Gender match    
Matched 30 (59) 13 (62) NS 
Mismatched 21 (41) 8 (38)  
Myeloablative conditioning    
CT±V 15 (29) 0 (0) <0.01 
BuCy 5 (10) 1 (5)  
Reduced intensity conditioning    
FluMel 27 (53) 15 (71) <0.01 
FluCy 4 (8) 5 (24)  
Prior BMT    
Prior auto BMT 2 (4) 3 (14) NS 
No prior auto BMT 49 (96) 18 (86)  
BMT-Related Outcomes 
2-yr PFS 53% 18% <0.001 
2-yr OS 56% 23% <0.001 
Day 100 TRM 10% 33% 0.03 

NS: not significant, P>0.1

Disclosures:

Hahn:Novartis: stock.

Author notes

*

Asterisk with author names denotes non-ASH members.

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