FLT3 mutation + DNMT3A mutation

Although the patient was eligible to standard high-dose chemotherapy in the ordinary inpatient setting, in order to fulfill the patient’s wish to nurse the new born an out-patients treatment, consisting of hypomethylating agents with Azacytidine plus antiBcl2 (Venetoclax), was started. The follow-up was free for any adverse events and a complete haematological response was obtained after the fourth cycle; the bone marrow aspirate confirmed complete leukemia remission and the patient is now candidate to allogenic bone transplantation. Our case highlights the complexities of AML management in pregnancy; accordingly to recently published data, late onset of antileukemic therapy may be considered in special population.

We comprehensively evaluated the clinical and genetic characteristics, and expression profiles of AML patients with common mutations, and found that AML patients with triple mutations might be a distinct AML subtype, which should be redefined.

The advent of targeted next-generation sequencing and improved prognostic scoring systems for PMF inform decisions regarding allo-HSCT. The emergence of treatments targeting mutant enzymes (e.g., IDH1/2 inhibitors) or epigenetic pathways (BET and LSD1 inhibitors) along with new insights into the mechanisms of leukemogenesis will hopefully lead the way to superior management strategies and outcomes of MPN-BP patients.

"MLL-rearrangements and NPM1-mutations were found in approximately a quarter of the 91 AML patient (mostly relapsed or refractory) bone marrow samples analyzed. These alterations appeared to be mutually exclusive. FLT3 alterations were seen in a third of the MLL-AML cases and half of the NPM1-AML cases, seemingly more frequent than that previously reported."

The evaluation of F1H for its use in HM-SCREEN-Japan 01 facilitates the analysis of leukemia-associated genes that can be used as therapeutic targets, which have rarely been identified in AML thus far.

Elderly AML patients have specific molecular characteristics, and the incidence of methylation-related gene mutations is very high, showing a certain significance for clinical diagnosis and treatment.

No abstract available

According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next-generation sequencing screening.

A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients being treated with lomustine in combination with idarubicin and cytarabine and 167 without lomustine, identified 1088 mutations with an average of 3.3 mutations per patient. The benefit of lomustine in nonadverse chromosomal aberrations was restricted to patients with RUNX1, ASXL1, TP53, and FLT3-ITD/NPM1 mutations in contrast to the intermediate and favorable ELN2017 patients. This post-hoc analysis identified a subgroup of fit elderly AML patients with intermediate cytogenetics and molecular markers who may benefit from lomustine addition to intensive chemotherapy.

We analyzed 379 AML pts who received a HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning...A high CD34+/CD38- burden & high GPR56 expression at diagnosis only impacted outcome in de novo AML pts. Different LSC populations may be relevant for disease biology in s/tAML.

We analyzed 379 AML pts who received a HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning...A high CD34+/CD38- burden & high GPR56 expression at diagnosis only impacted outcome in de novo AML pts. Different LSC populations may be relevant for disease biology in s/tAML.

We analyzed 379 AML pts who received a HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning...A high CD34+/CD38- burden & high GPR56 expression at diagnosis only impacted outcome in de novo AML pts. Different LSC populations may be relevant for disease biology in s/tAML.

In conclusion, we showed that SETD2 deficiency was associated with poor outcomes in patients with MDS. Moreover, SETD2 deficiency may upregulate DVL3 expression and modulate genomic stability that caused AML transformation.

A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.

The VAF of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 mutations is associated with worse prognosis in patients with newly diagnosed AML.

FLT3-ITD positive patients who proceeded to alloHSCT had a survival probability similar to FLT3-ITD negative patients and the transplant outcome was no different when comparing high and low-AR-FLT3-ITD subgroups in terms of both OS and DFS. In conclusion, a comprehensive molecular profile for NK-AML allows for the identification of genetic lesions associated to different clinical outcomes and the selection of the most appropriate and effective treatment strategies, including stem cell transplantation and targeted therapies.

This study comprehensively analyzed the prognostic implications of gene mutations in elderly AML patients under decitabine-based treatment modality. Identification of genetic biomarkers to predict the subgroup of elderly AML patients who can benefit from decitabine-based regimens might have an immediate clinical utility to optimize the treatment of elderly AML patients.

DNMT3A, FLT3-ITD, and NPM1A are frequent mutations in Egyptian AML. FLT3-ITD mutations are frequent in older patients. DNMT3A and FLT3-ITD mutations were associated with an unfavorable prognosis, but the NPM1A mutation has tendency to indicate a good prognosis.

The conditioning regimen was FLU/BU AUC 5300 (18 patients), FLU/BU AUC 3500 (1 patient), or fludarabine/melphalan 140 mg/m2 (19 patients)...Three patients with a-GVHD grade II responded to prednisone at 1MG/KG prednisone , 1 to prednisone and ruxolitinib that had been discontinued before transplant and 3 did not require steroids... The combination of tacrolimus-sirolimus-panobinostat seems to be an effective strategy to reduce aGVHD in unrelated-donor or related-donor transplant with a 18% incidence of aGVHD compared with 43% reported with tacrolimus-sirolimus in our previous study. Correlative studies compared to control patients will be presented at the meeting. Clinical Trial Registry: NCT02588339 https://clinicaltrials.gov/ct2/show/NCT02588339?term=panobinostat+and+GVHD&draw=1&rank=1

The conditioning regimen was FLU/BU AUC 5300 (18 patients), FLU/BU AUC 3500 (1 patient), or fludarabine/melphalan 140 mg/m2 (19 patients)...Three patients with a-GVHD grade II responded to prednisone at 1MG/KG prednisone , 1 to prednisone and ruxolitinib that had been discontinued before transplant and 3 did not require steroids... The combination of tacrolimus-sirolimus-panobinostat seems to be an effective strategy to reduce aGVHD in unrelated-donor or related-donor transplant with a 18% incidence of aGVHD compared with 43% reported with tacrolimus-sirolimus in our previous study. Correlative studies compared to control patients will be presented at the meeting. Clinical Trial Registry: NCT02588339 https://clinicaltrials.gov/ct2/show/NCT02588339?term=panobinostat+and+GVHD&draw=1&rank=1

The conditioning regimen was FLU/BU AUC 5300 (18 patients), FLU/BU AUC 3500 (1 patient), or fludarabine/melphalan 140 mg/m2 (19 patients)...Three patients with a-GVHD grade II responded to prednisone at 1MG/KG prednisone , 1 to prednisone and ruxolitinib that had been discontinued before transplant and 3 did not require steroids... The combination of tacrolimus-sirolimus-panobinostat seems to be an effective strategy to reduce aGVHD in unrelated-donor or related-donor transplant with a 18% incidence of aGVHD compared with 43% reported with tacrolimus-sirolimus in our previous study. Correlative studies compared to control patients will be presented at the meeting. Clinical Trial Registry: NCT02588339 https://clinicaltrials.gov/ct2/show/NCT02588339?term=panobinostat+and+GVHD&draw=1&rank=1

These mutations included: single nucleotide variants, DNMT3A, CEBPA, NRAS, CEBPA, TET2, PTPN11, NPM1, IDH2, TP53, SMC3, RUNX1, JAK2, and FLT3; structural variants, CBFB/MYH11, KMT2A/MLLT3, and KMT2A/AFDN... Our ctDNA monitoring could identify patients who were more likely to relapse. Additional enrollment and further follow-up are needed to confirm this promising result. Clinical Trial Registry: KSGCT1702 is registered at Japanese Trial Registry # UMIN000033003

These mutations included: single nucleotide variants, DNMT3A, CEBPA, NRAS, CEBPA, TET2, PTPN11, NPM1, IDH2, TP53, SMC3, RUNX1, JAK2, and FLT3; structural variants, CBFB/MYH11, KMT2A/MLLT3, and KMT2A/AFDN... Our ctDNA monitoring could identify patients who were more likely to relapse. Additional enrollment and further follow-up are needed to confirm this promising result. Clinical Trial Registry: KSGCT1702 is registered at Japanese Trial Registry # UMIN000033003

These mutations included: single nucleotide variants, DNMT3A, CEBPA, NRAS, CEBPA, TET2, PTPN11, NPM1, IDH2, TP53, SMC3, RUNX1, JAK2, and FLT3; structural variants, CBFB/MYH11, KMT2A/MLLT3, and KMT2A/AFDN... Our ctDNA monitoring could identify patients who were more likely to relapse. Additional enrollment and further follow-up are needed to confirm this promising result. Clinical Trial Registry: KSGCT1702 is registered at Japanese Trial Registry # UMIN000033003

The conditioning regimen was FLU/BU AUC 5300 (18 patients), FLU/BU AUC 3500 (1 patient), or fludarabine/melphalan 140 mg/m2 (19 patients)...Three patients with a-GVHD grade II responded to prednisone at 1MG/KG prednisone , 1 to prednisone and ruxolitinib that had been discontinued before transplant and 3 did not require steroids... The combination of tacrolimus-sirolimus-panobinostat seems to be an effective strategy to reduce aGVHD in unrelated-donor or related-donor transplant with a 18% incidence of aGVHD compared with 43% reported with tacrolimus-sirolimus in our previous study. Correlative studies compared to control patients will be presented at the meeting. Clinical Trial Registry: NCT02588339 https://clinicaltrials.gov/ct2/show/NCT02588339?term=panobinostat+and+GVHD&draw=1&rank=1

These mutations included: single nucleotide variants, DNMT3A, CEBPA, NRAS, CEBPA, TET2, PTPN11, NPM1, IDH2, TP53, SMC3, RUNX1, JAK2, and FLT3; structural variants, CBFB/MYH11, KMT2A/MLLT3, and KMT2A/AFDN... Our ctDNA monitoring could identify patients who were more likely to relapse. Additional enrollment and further follow-up are needed to confirm this promising result. Clinical Trial Registry: KSGCT1702 is registered at Japanese Trial Registry # UMIN000033003