Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended for core-binding factor mutated (CBF) AML patients achieving second complete remission (CR2). However, approximately 20% of patients may relapse after transplant and donor preference remains unclear. We compared in this EBMT global multicenter registry-based analysis the allo-HCT outcomes using either haploidentical (Haplo), matched siblings donors (MSD), or 10/10 matched unrelated donors (MUD). Data from 865 de novo adult CBF AML patients in CR2 receiving allo-HCT in 227 EBMT centers from 2010 to 2022 were analyzed, in which 329 MSD, 374 MUD, and 162 Haplo-HCTs were included. For the entire cohort, 503 (58%) patients were inv(16)/CBFB-MYH11 and 362 patients (42%) were t(8;21)/RUNX1-RUNX1T1 AML. On multivariate analysis, Haplo-HCT was associated with a lower Relapse Incidence (RI) compared to either MSD (hazard ratio [HR] = 0.56, 95% CI 0.32-0.97; p < .05) or MUD (HR = 0.57, 95% CI: 0.33-0.99, p < .05). No significant difference was observed among the 3 types of donors on LFS, OS and GRFS. CBF-AML with t(8;21) was associated with both higher RI (HR = 1.79, 95% CI 1.3-2.47; p < .01) and higher NRM (HR = 1.58, 95% CI 1.1-2.27; p < .01) than CBF-AML with inv(16), which led to worse LFS, OS and GRFS. To conclude, for CBF-AML patients in CR2, Haplo-HCTs were associated with a lower RI compared to MSD and MUD allo-HCTs. There was no difference on LFS, OS or GRFS. CBF AML patients with inv(16) had a better progonosis than those with t(8;21) after allo-HCT in CR2.

• MeSH
• akutní myeloidní leukemie * terapie   genetika   MeSH
• alografty MeSH
• dospělí MeSH
• haploidentická transplantace metody   MeSH
• incidence MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nepříbuzný dárce * MeSH
• recidiva * MeSH
• registrace MeSH
• senioři MeSH
• sourozenci * MeSH
• transkripční faktor PEBP2 genetika   MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

The aim of this study was to evaluate the prognostic impact of FLT3-ITD in core-binding factor acute myeloid leukemia (CBFAML) in an international, multicenter survey of 97 patients of whom 52% had t(8;21)(q22;q22) and 48% had inv(16)(p13q22)/t(16;16)(p13;q22). The median age of the patients was 53 years (range, 19-81). Complete remission after anthracycline-based induction (n=86) and non-intensive therapy (n=11) was achieved in 97% and 36% of the patients, respectively. The median follow-up was 4.43 years (95% confidence interval [95% CI]: 3.35-7.39 years). The median survival after intensive and non-intensive treatment was not reached and 0.96 years, respectively. Among intensively treated patients, inv(16) with trisomy 22 (n=11) was associated with a favorable 4-year relapse-free survival rate of 80% (95% CI: 59-100%) as compared to 38% (95% CI: 27-54%; P=0.02) in all other patients with CBFAML/ FLT3-ITD (n=75). Overall, 24 patients underwent allogeneic hematopoietic cell transplantation (HCT), 12 in first complete remission and 12 after relapse. Allogeneic HCT in first complete remission was not beneficial (P=0.60); however, allogeneic HCT seemed to improve median survival in relapsed patients compared to that of patients treated with chemotherapy (not reached vs. 0.6 years, respectively; P=0.002). Excluding patients with inv(16) with trisomy 22, our data indicate that compathe outcome of CBF-AML patients with FLT3-ITD may be inferior to that of patients without FLT3-ITD (based on previously published data), suggesting that prognostically CBF-AML patients with FLT3-ITD should not be classified as favorable-risk. FLT3-inhibitors may improve the outcome of these patients.

• MeSH
• akutní myeloidní leukemie * diagnóza   genetika   terapie   MeSH
• dospělí MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkripční faktor PEBP2 genetika   MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• tyrosinkinasa 3 podobná fms genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Mutational analysis of C-KIT, fms-like tyrosine kinase 3 (FLT3), and JAK2 genes was performed in 60 patients with core binding factor acute myeloid leukemia (CBF-AML). Patients reaching molecular remission had lower incidence of relapse and better overall survival (OS) than those not achieving molecular remission (p = 0.008 and 0.044, respectively). The overall incidence of C-KIT mutations was 33.3%, FLT3/internal tandem duplication (ITD) 6.6%, FLT3(D835) 10.0% and JAK2(V617F) mutations 3.3%. C-KIT mutations did not predict for clinical/molecular relapse (p = 0.33). OS of patients with C-KIT mutations was identical to patients without them when all patients with CBF-AML were analyzed together (p = 0.58). When AML1/ETO-positive patients were evaluated separately, OS in C-KIT-mutated patients was slightly inferior to unmutated ones (p = 0.14). Patients with CBF-AML with a mutated C-KIT gene were also more prone to extramedullary disease (p = 0.08). Of six patients harboring various FLT3(D835) mutations, four (66.7%) relapsed, whereas among 43 cases without these mutations, 16 relapses (37%) were observed (p = 0.08). Our results on minimal residual disease, C-KIT, and FLT3/ITDs are in line with previous studies. Surprisingly, a possible role for FLT3(D835) mutations was noted in addition. These results need validation in even larger patient cohorts than ours. For routine clinical practice, it may be meaningful to screen for C-KIT mutations in AML1/ETO-positive patients, as well as for FLT3(D835) mutations in CBF-AML.

• MeSH
• akutní myeloidní leukemie diagnóza   genetika   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• Janus kinasa 2 genetika   fyziologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monitorování fyziologických funkcí MeSH
• mutace fyziologie   MeSH
• následné studie MeSH
• předškolní dítě MeSH
• prognóza MeSH
• protoonkogenní proteiny c-kit genetika   fyziologie   MeSH
• reziduální nádor MeSH
• senioři MeSH
• transkripční faktor PEBP2 genetika   MeSH
• tyrosinkinasa 3 podobná fms genetika   fyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH