Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc
Journal website https://www.thejh.org

Short Communication

Volume 13, Number 3, June 2024, pages 86-93

Frameshift Mutations in Leukemia-Associated Genes Correlate With Superior Outcomes in Patients Undergoing Allogeneic Stem Cell Transplant for De Novo Acute Myeloid Leukemia

Figures

Figure 1.
Figure 1. Overall survival based on non-NPM1 frameshift (FS) vs. non-FS status (all patients).
Figure 2.
Figure 2. Relapse-free survival based on non-NPM1 frameshift (FS) vs. non-FS status (all patients).
Figure 3.
Figure 3. Relapse-free survival based on non-NPM1 frameshift (FS) vs. non-FS status (de novo only).
Figure 4.
Figure 4. Overall survival based on non-NPM1 frameshift (FS) vs. non-FS status (de novo only).
Figure 5.
Figure 5. Post-transplant overall survival of RUNX1 mutated patients. FS: frameshift.

Tables

Table 1. Demographics and Disease Characteristics
 
VariablesNo frameshift≥ 1 non-NPM1 frameshiftP value
*P < 0.05. NCCN: National Comprehensive Cancer Network; IQR: interquartile range; MUD: matched unrelated donor; MSD: matched sibling donor; IV: intravenous; GvHD: graft-vs-host disease; AML: acute myeloid leukemia; Ara-C: cytarabine; HiDAC: high-dose cytarabine.
Age (median)62 (IQR: 49 - 69)65 (IQR: 55 - 72)0.57
Disease risk category (NCCN)0.011*
Favorable; n (%)11 (11)9 (16)2 (5)
Intermediate29 (31)22 (38)7 (18)
Adverse55 (58)26 (45)29 (76)
Transplant type0.17
MUD27 (63)15 (48)12(75)
MSD8 (19)7 (23)1 (11)
Cord8 (19)5 (16)3 (19)
Haploidentical44 (13)0 (0)
Missing482622
Conditioning regimen0.61
High-dose mitoxantrone and Ara-C16 (66)9 (56)7 (88)
IV arsenic1 (4)1 (6)0 (0)
Cyclophosphamide and etoposide1 (4)1 (6)0 (0)
Clofarabine1 (4)1 (6)0 (0)
HiDAC5 (21)4 (25)1 (12)
Missing714129
Morphologic residual disease at transplant8/27 (30)6/18 (33)2/9 (22)0.55
Missing684028
GvHD33/66 (50)18/38 (47)15/28 (54)0.62
De novo AML78 (82)50 (86)28 (76)0.25
Secondary AML17 (18)8 (14)9 (24)0.25

 

Table 2. Mutated Genes at Diagnosis With Respective Numbers of Frameshift and Non-Frameshift Variants
 
GeneFrameshiftsNon-frameshift variants
NPM1260
RUNX1136
TET277
BCOR64
ASXL143
WT141
STAG247
ETV622
ZRSR222
CEBPA26
TP5329
PHF616
EZH213
FLT328
NRAS19
DNMT3A19
IDH214
IDH112
PTPN1111
SRSF210
CBL4
U2AF14
SETBP14
JAK23
SF3B13
JAK32
KIT2

 

Table 3. Outcome Summary: FS vs. No-FS (Univariate Analysis)
 
HR (log rank) FS vs. no-FS (CI)P value (log rank) FS vs. no-FS
FS: frameshift; HR: hazard ratio; CI: confidence interval.
Overall survival all patients0.56 (0.34 - 0.95)0.043
Relapse-free survival all patients0.55 (0.23 - 1.30)0.2
Overall survival de novo only0.55 (0.30 - 1.02)0.058
Relapse-free survival de novo only0.24 (0.082 - 0.68)0.038

 

Table 4. Outcome and Multivariate Analysis of Relevant Factors
 
Overall survivalRelapse
Hazard ratioP valueHazard ratioP value
*P < 0.05. AML: acute myeloid leukemia; GvHD: graft-vs-host disease.
All cases
  FS vs. no FS0.49 (0.26 - 0.87)0.018*0.42 (0.16 - 1.11)0.08
  Age1.01 (0.99 - 1.03)0.421 (0.97 - 1.03)0.94
  Disease risk group (NCCN) vs. intermediate
    Favorable0.98 (0.38 - 2.45)0.9800.96
    Adverse1.19 (0.64 - 2.22)0.580.82 (0.29 - 2.3)0.9
  Secondary AML2.3 (1.18 - 4.46)0.014*4.12 (0.51 - 12.3)0.006*
  GvHD positive1.43 (0.84 - 2.43)0.190.81 (0.32 - 2.07)0.66
De novo only
  FS vs. no FS0.45 (0.22 - 0.92)0.028*0.16 (0.03 - 0.79)0.024*
  Age1.01 (0.99 - 1.03)0.431 (0.96 - 1.03)0.985
  Disease risk group vs. intermediate
    Favorable1.01 (0.38 - 2.68)0.9900.95
    Adverse1.09 (0.55 - 2.18)0.781.54 (0.51 - 4.7)0.45
  GvHD positive1.68 (0.91 - 3.1)0.11.28 (0.4 - 4.09)0.67