| Autor: |
Badar T; Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL. badar.talha@mayo.edu., Nanaa A; John H. Stroger, Jr. Hospital of Cook County, IL., Atallah E; Division of Hematology and Medical Oncology, Medical College of Wisconsin, Milwaukee, WI., Shallis RM; Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT., Craver EC; Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL., Li Z; Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL., Goldberg AD; Division of Hematologic Malignancies, Department of Medicine Memorial Sloan Kettering Cancer Center, NY., Saliba AN; Division of Hematology, Mayo Clinic, Rochester, MN., Patel A; Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL., Bewersdorf JP; Division of Hematologic Malignancies, Department of Medicine Memorial Sloan Kettering Cancer Center, NY., Duvall A; Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL., Burkart M; Robert H. Lurie Comprehensive Cancer Center, Northwestern Hospital, Chicago, Illinois., Bradshaw D; Division of Hematology and Oncology, Georgia Cancer Center, GA., Abaza Y; Robert H. Lurie Comprehensive Cancer Center, Northwestern Hospital, Chicago, Illinois., Stahl M; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Palmisiano N; Division of Hematology and Oncology, Jefferson University Hospital, Philadelphia, PA., Murthy GSG; Division of Hematology and Medical Oncology, Medical College of Wisconsin, Milwaukee, WI., Zeidan AM; Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT., Kota V; Division of Hematology and Oncology, Georgia Cancer Center, GA., Patnaik MM; Division of Hematologic Malignancies, Department of Medicine Memorial Sloan Kettering Cancer Center, NY., Litzow MR; Division of Hematologic Malignancies, Department of Medicine Memorial Sloan Kettering Cancer Center, NY. |
| Abstrakt: |
While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation (TP53MT) compared to a single-hit (SH) mutation in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an in-depth analysis utilizing data from ten US academic institutions to study differences in molecular characteristics and outcomes of SH (N=139) versus MH (N=243) TP53MT AML. Complex cytogenetics were more common in MH than in SH TP53MT AML (P<0.001); whereas ASXL1 (P<0.001), RAS (P<0.001), splicing factor (P=0.003), IDH1/2 (P=0.001), FLT3 ITD (P<0.001) and NPM1 (P=0.005) mutations clustered significantly with SH TP53MT AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between patients with SH or MH disease (event-free survival: 3.0 vs. 2.20 months, respectively, P=0.22; overall survival: 8.50 vs. 7.53 months, respectively, P=0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation as a time-dependent covariate were associated with superior event-free survival (hazard ratio [HR]=0.44, 95% confidence interval [95% CI]: 0.19-1.01, P=0.05 and HR=0.34, 95% CI: 0.18-0.62, P<0.001) and overall survival (HR=0.24, 95% CI: 0.08-0.71, P=0.01 and HR=0.28, 95% CI: 0.16-0.47, P<0.001). Complex cytogenetics (HR=1.56, 95% CI: 1.01-2.40, P=0.04) retained an unfavorable significance for overall survival. Our analysis suggests that MH TP53MT is less relevant in independently predicting outcomes in patients with AML than in those with MDS. |
