Background:

Therapy-related myeloid neoplasms develop after cytotoxic chemotherapy or radiation therapy. The available data on the outcome of pts with t-de novo AML without antecedent history of myelodysplastic syndrome (MDS) is limited.

Methods:

We reviewed the records of pts with newly diagnosed AML who presented to our tertiary care center from 1/2000 to 1/2014. t-de novo AML was defined as having at least 20% blasts in bone marrow with a history of any previous cytotoxic chemotherapy or radiation therapy, and without an antecedent history of MDS. Leukemia-free survival (LFS) was defined as time from achieving complete response (CR) to relapse or death. The overall survival (OS) and LFS in pts with t-de novo AML were compared to those of with de novo AML with normal karyotype (NK) and complex karyotype (CK).

Results:

Among 1677 pts with newly diagnosed AML, 383 had de novo NK-AML, 218 had de novo CK-AML, and 187 had t-de novo AML. The median follow-up was 9.3 months (range; 0.2-161.0). Pt characteristics and outcomes are described in Table 1. Among the 187 pts, 69 had a history of lymphoma; 63 pts breast cancer (Ca); 10 pts colon Ca; 10 pts sarcoma; 8 pts prostate; 7 pts bladder Ca; 6 pts uterine Ca; 5 pts lung Ca; 5 pts head and neck Ca; 30 pts other type of Ca. Among the pts with t-de novo AML, 15 pts (8%) had a favorable-risk karyotype by WHO, 53 pts (28%) intermediate-risk karyotype, and 119 pts (64%) poor-risk karyotype. The median LFS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% confidence interval [CI]; 5.1-8.7), 19 months (95% CI; 13.0-25.2), and 6 months (95% CI; 9.0-13.5) (p<.001), respectively. The median OS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% CI; 5.9-8.9), 21 months (95% CI; 16.2-25.5), and 12 months (95%CI; 10.6-13.5) (p<.001), respectively. The results of univariate (UVA) and multivariate analysis (MVA) associated with OS were summarize in Table 1. MVA identified age over 60, white blood cell count (WBC) over 10 x103/µL, thrombocytopenia below 30 x103/µL, non-favorable cytogenetic abnormalities, positive RAS mutation, and the absence of CR or CR with incomplete platelet recovery (CRp) as poor prognostic features related to OS.

Conclusion:

LFS and OS were shorter in patients with t-de novo AML than in those with NK-AML but did not differ significantly from patients with CK-AML.

Abstract 2273. Table 1.

Patient Characteristics and Outcomes

t-de novo AML
[n= 187]		 de novo AML
with NK [n= 383]		de novo AML with CK [n= 218]P
Age at diagnosis, median (years) 64 (21-89]  63 (17-90) 67 (18-87)  
Prior radiation therapy, No. (%) 101 (54)  0 0  
Prior chemotherapy, No. (%) 186 (99)  0 0  
White blood cell count at diagnosis, median (x103/µL) 3.2 (0.2-191)  4.3 (0.2-390.0) 2.9 (0.5-278.2)  
Hemoglobin at diagnosis, median (g/dL) 9.1 (4.5-12.9)  9.1 (4-14.6) 9.0 (2.5-14.2)  
Platelet count at diagnosis, median (x103/µL) 34 (4-454)  51 (3-469) 42 (2-319)  
LDH at diagnosis, median (IU/L) 1359 (210-22090)  1189 (200-42000) 1274 (231-20572)  
Peripheral blood blast percent at diagnosis, median (%) 8 (0-98)  9.5 (0-98) 10 (0-98)  
Bone marrow blast percent at diagnosis, median (%) 41 (0-96)  44 (0-96) 33 (0-97)  
Molecular genetic abnormalities at diagnosis, No. (%) 
FLT3-ITD  17 (9) 96 (25) 5 (2)  
FLT3-D835  6 (3) 23 (6) 1 (1)  
NPM1  7 (4) 104 (27) 4 (2)  
JAK2  3 (2) 6 (2) 8 (4)  
RAS  17 (9) 50 (13) 8 (4)  
RUNX1-RUNX1T1  4 (2) 0 0  
CBFb-MYH  6 (3) 0 0  
Response, No. (%)  <0.001 
Complete response  89 (48) 237 (62) 76 (35) 
Complete response without platelet recovery  15 (8) 1 (0) 15 (7) 
1-year LFS, (%)  33 60 27 <0.001 
2-year LFS, (%)  33 52 20 <0.001 
1-year OS, (%)  34 68 30 <0.001 
2-year OS, (%)  24 46 13 <0.001 
UVA and MVA of OS in t-de novo AML 
  UVA MVA Hazard ratio 95% CI 
Age at diagnosis 
Age =< 60 years  -    
Age >60 years  < .001 .001 2.238 1.417-3.534 
White blood cell count (WBC) (x103/µL) 
WBC =< 10.0  -    
WBC > 10.0  .002 .037 1.617 1.030-2.540 
Hemoglobin (Hgb) (g/dL) 
Hgb >= 8  -    
Hgb < 8  .749    
Platelet count (Plt) (x103/µL) 
Plt >= 30  -    
Plt < 30  .008 .004 1.852 1.224-2.803 
LDH (IU/L) 
LDH =<1000  -    
LDH > 1000  .640    
Peripheral blood blast percent (PB blast)(%) 
PB blast =< 10%  -    
PB blast >10%  .178    
Bone marrow blast percent (BM blast) (%) 
BM blast =<40%  -    
BM blast >40%  .393    
Cytogenetic abnormality 
Favorable  -    
Non-Favorable  .002 .019 5.836 1.342-25.370 
FLT3-ITD 
Negative  -    
Positive  .768    
RAS 
Negative  -    
Positive  .047 .003 2.576 1.367-4.856 
Response 
CR or CRp  -    
Non-CR or CRp  <.001 .009 .331 0.145-0.757 
CR  -    
Non-CR  <.001 0.903 .950 0.418-2.160 
      
t-de novo AML
[n= 187]		 de novo AML
with NK [n= 383]		de novo AML with CK [n= 218]P
Age at diagnosis, median (years) 64 (21-89]  63 (17-90) 67 (18-87)  
Prior radiation therapy, No. (%) 101 (54)  0 0  
Prior chemotherapy, No. (%) 186 (99)  0 0  
White blood cell count at diagnosis, median (x103/µL) 3.2 (0.2-191)  4.3 (0.2-390.0) 2.9 (0.5-278.2)  
Hemoglobin at diagnosis, median (g/dL) 9.1 (4.5-12.9)  9.1 (4-14.6) 9.0 (2.5-14.2)  
Platelet count at diagnosis, median (x103/µL) 34 (4-454)  51 (3-469) 42 (2-319)  
LDH at diagnosis, median (IU/L) 1359 (210-22090)  1189 (200-42000) 1274 (231-20572)  
Peripheral blood blast percent at diagnosis, median (%) 8 (0-98)  9.5 (0-98) 10 (0-98)  
Bone marrow blast percent at diagnosis, median (%) 41 (0-96)  44 (0-96) 33 (0-97)  
Molecular genetic abnormalities at diagnosis, No. (%) 
FLT3-ITD  17 (9) 96 (25) 5 (2)  
FLT3-D835  6 (3) 23 (6) 1 (1)  
NPM1  7 (4) 104 (27) 4 (2)  
JAK2  3 (2) 6 (2) 8 (4)  
RAS  17 (9) 50 (13) 8 (4)  
RUNX1-RUNX1T1  4 (2) 0 0  
CBFb-MYH  6 (3) 0 0  
Response, No. (%)  <0.001 
Complete response  89 (48) 237 (62) 76 (35) 
Complete response without platelet recovery  15 (8) 1 (0) 15 (7) 
1-year LFS, (%)  33 60 27 <0.001 
2-year LFS, (%)  33 52 20 <0.001 
1-year OS, (%)  34 68 30 <0.001 
2-year OS, (%)  24 46 13 <0.001 
UVA and MVA of OS in t-de novo AML 
  UVA MVA Hazard ratio 95% CI 
Age at diagnosis 
Age =< 60 years  -    
Age >60 years  < .001 .001 2.238 1.417-3.534 
White blood cell count (WBC) (x103/µL) 
WBC =< 10.0  -    
WBC > 10.0  .002 .037 1.617 1.030-2.540 
Hemoglobin (Hgb) (g/dL) 
Hgb >= 8  -    
Hgb < 8  .749    
Platelet count (Plt) (x103/µL) 
Plt >= 30  -    
Plt < 30  .008 .004 1.852 1.224-2.803 
LDH (IU/L) 
LDH =<1000  -    
LDH > 1000  .640    
Peripheral blood blast percent (PB blast)(%) 
PB blast =< 10%  -    
PB blast >10%  .178    
Bone marrow blast percent (BM blast) (%) 
BM blast =<40%  -    
BM blast >40%  .393    
Cytogenetic abnormality 
Favorable  -    
Non-Favorable  .002 .019 5.836 1.342-25.370 
FLT3-ITD 
Negative  -    
Positive  .768    
RAS 
Negative  -    
Positive  .047 .003 2.576 1.367-4.856 
Response 
CR or CRp  -    
Non-CR or CRp  <.001 .009 .331 0.145-0.757 
CR  -    
Non-CR  <.001 0.903 .950 0.418-2.160 
      
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Figure 1.
Figure 1. LFS and OS
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LFS and OS

Disclosures

Kantarjian:ARIAD, Pfizer, Amgen: Research Funding.

Topics:
brachial plexus neuritis, leukemia, myelocytic, acute, hemoglobin, karyotype determination procedure, complete remission, c-reactive protein, cyclic amp receptor protein, epley maneuver, ms-like tyrosine kinase 3, radiation therapy

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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