flt3 itd mutation prognosisflt3 itd mutation prognosis

1,2 Real-time pCR, which has . Yilmaz, M. et al. FLT3 Mutation and AML: Symptoms, Testing, and More - Healthline CR+CRi rates between groups were compared with a chi-square test. PubMed Central All four patients with ITD insertions in TKD1 had mutations in DNTM3A, compared with 39 out of 96 patients (41%) with ITD insertions in the JMD domain (P=0.031). Therefore, there is a lack of consensus regarding the prognostic importance of the ITD IS and the subdomains that confer this adverse outcome. Dhner, H. et al. volume11, Articlenumber:104 (2021) Biophys. Clinical trial enrollment (if available) is always the first option, in both frontline and R/R FLT3mut AML. PubMed is a PhD candidate at Universidad Autnoma de Madrid (UAM). 19, 889903 (2018). However, in addition to QTcF prolongation, quizartinib is also more myelosuppressive than many other FLT3 inhibitors likely due to the inhibition of KIT. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. On the other hand, we obtained a value (0.52) that was close to significant in the analysis of the prognostic impact of the FLT3-ITD AR according to the 2017 ELN cutoff8. Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens. Background and aims: To explore the relationship between FLT3 (encoding Fms related tyrosine kinase 3) internal tandem duplication (ITD) mutations with the prognosis of acute promyelocytic leukemia. This value highlights the scarce prognostic value of the measure. Although the label indication for gilteritinib is as a single agent we have never used it as a single agent but always in combination with either HMA alone, venetoclax alone or as a triplet with HMA and venetoclax. Rosnet, O. et al. To test the prognostic significance of the ITD length and its clinical applicability, we used recurrent previously published cutoffs, which were analyzed in series ranging from 28 to 100 intensively treated patients. Blood 97, 24342439 (2001). Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. mutations (1-year survival < 1% vs 42% in their presence vs absence) which should be incorporated in patient counseling. Gale, R. E. et al. Cancer Cell 1, 433443 (2002). Oncol. Correspondence to Approximately 30% of patients with newly diagnosed acute myeloid leukemia (AML) harbor mutations in the fms-like tyrosine kinase 3 (FLT3) gene. Multivariate analysis showed that age < 65 years, FLT3-ITD and CEBPA bZIP in-frame mutation were independent prognostic factors. Article Strati, P. et al. FLT3-ITD and its current role in acute myeloid leukaemia contracts here. Nevertheless, there are numerous and contradictory manuscripts regarding the prognostic importance of the length and insertion site of the ITD fragment. An FLT3/ITD mutation was present in 27% of the patients and was associated with leukocytosis and a high percentage of bone marrow blast cells (P <.001 for both). 15, 17 In our cohort, the prevalence of FLT3-ITD mutation of de novo AML patients was 21.5%. Additionally, different subdomains of TKD1 (HR or beta1-sheet) have been highlighted as those conferring an adverse outcome10. Green indicates non-mutated genes, red indicates mutated genes and white indicates non-mutated genes. The first-generation FLT3is lack specificity for FLT3 and inhibit multiple downstream RTKs that may result in more off-target toxicities. Conclusion: The frequency of NPM1/FLT3 mutations in the study cohort showed less rate than in other studies with a distinct pattern. We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. Absence of FLT3-ITD mutation 0.07 . We also performed an ROC curve analysis for OS prediction excluding those 10 patients with more than 1 ITD insertion and obtained an AUC of 0.521. 381, 17281740 (2019). Prognostication refinement in NPM1mutated acute myeloid leukemia NPM1, FLT3-ITD, CEBPA, and c-kit mutations in 312 Chinese patients with de novo acute myeloid leukemia. N. Engl. Perl, A. E. et al. Synergistic effect of BCL2 and FLT3 co-inhibition in acute myeloid leukemia. Taken together, utilizing baseline FLT3-ITDmut AR to guide the post-remission therapy remains controversial. has received research funding from Astellas, and Novartis and has served as a member of advisory board in Astellas and Novartis. Clin. Article Identification of novel FLT3 Asp835 mutations in adult acute myeloid leukaemia. 5).The study protocol was conducted following the guidelines of the Declaration of Helsinki and approved by the Ethics Committee for Clinical Research of the Hospital UniversitarioFundacin Jimnez Daz (PIC169-18_FJD). Cite this article. Increase in bilirubin and transaminase can be seen with giltertiinib but are usually self-resolving and transient. Schneider F, Hoster E, Schneider S, Dufour A, Benthaus T, Kakadia PM, et al. For post-ASCT maintenance, our agent of choice has been gilteritinib 80120mg day either as a single agent or combined with low-dose azacitidine. PubMed Due to this, the development of tyrosine kinase inhibitors (TKI) blocking FLT3-ITD became a rational therapeutic concept. This work was supported in part by the MD Anderson Cancer Centre Support Grant (CCSG) CA016672, the MD Anderson Cancer Center Leukemia SPORE CA100632, the Charif. While the seven patients treated with the doublet had a CRc rate of 57% (n=4/7) and a median OS of 5.7 months, the fifteen R/R FLT3mut AML patients treated with the triplet had a CRc rate of 81% (n=11) with a projected 1-year OS of 60%. FLT3-ITD allelic ratio and HLF expression predict FLT3 inhibitor efficacy in adult AML, Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia, Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results, Distinct clinico-biological features in AML patients with low allelic ratio FLT3-ITD: role of allogeneic stem cell transplantation in first remission, Poor outcome of pediatric patients with acute myeloid leukemia harboring high FLT3/ITD allelic ratios, Mutational spectrum and prognostic stratification of intermediate-risk acute myeloid leukemia, Genomic landscape of patients with FLT3-mutated acute myeloid leukemia (AML) treated within the CALGB 10603/RATIFY trial, Impact of FLT3-ITD allele ratio and ITD length on therapeutic outcome in cytogenetically normal AML patients without NPM1 mutation, Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia, https://doi.org/10.3324/haematol.2020.263806, http://creativecommons.org/licenses/by/4.0/. J. Med. We tried to validate the thresholds of ITD length previously published (i.e., 39bp and 70bp) in intensivelytreated AML patients (n=161). Naval Daver, M. D. et al. Among 729 AML patients with FLT3-ITD mutations included in the PETHEMA AML epidemiologic registry between 2003 and 2019, FLT3-ITD length was available in 362: 188 males and 174 females; median age of 60.8years (range 17.191.4years). Yilmaz et al. Naval Daver, Richard F. Schlenk, Mark J. Levis, Alexander E. Perl, Naoko Hosono, Jessica K. Altman, Pierre-Yves Dumas, Emmanuel Raffoux, Christian Rcher, Richard A. Larson, Sumithra J. Mandrekar, Richard M. Stone, Iman Abou Dalle, Ahmad Ghorab, Gautam Borthakur, Ahmad I. Antar, Zaher K. Otrock, Ali Bazarbachi, Roni Shouval, Myriam Labopin, Arnon Nagler, Blood Cancer Journal Among 362 patients, NGS was performed in 118 patients using a panel of 39 genes. 6,, - 9 In normal bone marrow, FLT3 expression is DNA quantification was performed with a Nanodrop (Thermo Fisher Scientific, Waltham,MA) or Qubitfluorometer (Thermo Fisher Scientific, Waltham, MA). Thank you for visiting nature.com. Staurosporine, a potent inhibitor of phospholipid Ca++ dependent protein kinase. In another randomized phase III study comparing post-ASCT sorafenib maintenance (n=100) to non-maintenance (n=102), sorafenib demonstrated an improved 1-year OS (82.1% vs 68%, P=0.012) and a decreased 1-year cumulative incidence of relapse (7% vs 24.5%, P=0.001) in FLT3-ITDmut AML patients undergoing ASCT in CR143. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3internal tandem duplication status. Kottaridis, P. D. et al. However, whether these findings are specific to Ven + HMA therapy remains to be . J. Hematol. Naval Daver. Measurable residual disease, FLT3ITD mutation, and disease status have However, previous studies have shown that FLT3/ITD mutation was not an independent adverse prognostic factor in DEK/CAN-positive AML patients. In our cohort, FLT3-ITD was located in the JMD domain (JMD-B, JMD-S, JMD-Z and HR) in 98 patients and in the TKD1 domain (B1, NBL and B2) in four patients. N. Engl. A Conventional approach. We stop the venetoclax and the FLT3i after Day 14 in patients who achieve marrow remission (<5% blasts) and/or marrow aplasia/hypoplasia/insufficiency (<5% cellularity). The LACEWING phase III randomized trial evaluated gilteritinib with azacitidine vs azacitidine monotherapy (NCT02752035) in patients with newly diagnosed FLT3mut AML not eligible for intensive induction chemotherapy. Lancet Oncol. This study shows that the size of FLT3-ITD mutations has no prognostic impact in terms of survival, relapse or CR rate among newly diagnosed AML patients treated with first-line intensive regimens. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Among those with NPM1 wild-type, all FLT3-ITDmut patients had an increased risk of relapse and inferior OS, regardless of the AR17. Information regarding the ITD insertion site and mutational status of another 38 genes recurrently mutated in myeloid neoplasms was available in 106 and 118 patients, respectively. The median age of this group was 55.1years (range 17.185.3years); 76 males and 85 females. 94, 984991 (2019). Which FLT3 Inhibitor for Treatment of AML? The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. MRD detection in AML leverages cutoff points garnered from various detection methods include flow cytometry or real-time quantitative polymerase chain reaction (pCR). Although the presence of FLT3-ITD, as well as levels of the FLT3-ITD allelic ratio, have been described as prognostic factors in acute myeloid leukemia (AML), little is known about how the FLT3-ITD allelic ratio impacts patients&rsquo; outcomes when receiving an allogeneic hematopoietic stem cell transplantation (HSCT). Progress in Disease Detection Sets the Stage for MRD's Role in AML https://doi.org/10.1038/s41598-021-00050-x, DOI: https://doi.org/10.1038/s41598-021-00050-x. 1). (5) No data regarding minimal residual disease (MRD) were available in our cohort, and MRD data could be interesting to analyze in future studies. As Dr. Erba explained, patients with FLT3 -ITD-positive AML represent a particularly poor prognostic group. A total of 164 patients diagnosed with AML-NPM1 included in 2 consecutive CETLAM protocols and with DNMT3A and FLT3 status available were studied. 17 D2 D8, H-S Kim S Lee JH Kim 2018 Real-world evidence versus randomized controlled trial: Clinical research based on electronic medical records J Korean Med Sci 33 e213, RF Schlenk 2014 Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation Blood 124 3441 3449, I Abou Dalle 2020 Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia Blood Cancer J. The survival rates in patients 60 years of age were also similar across NPM1 mut /FLT3 wt, NPM1 mut /FLT3-ITD low, and NPM1 mut . Therefore, the value obtained is not significant, although it shows a slight trend toward being significant. Google Scholar. Full article: Advances in the drug therapies of acute myeloid leukemia To mitigate prolonged myelosuppression with the triplet and avoid over-treatment, we perform an early bone marrow assessment on Cycle 1 Day 14 (Fig. In older patients not eligible for intensive therapy, patients with primary refractory disease or early relapse with a persistent FLT3 mutation we would suggest gilteritinib based therapy. Nevertheless, the short duration of remission with single-agent FLT3is in R/R FLT3mut AML in the absence of ASCT, limited options in patients refractory to gilteritinib therapy, and diverse primary and secondary mechanisms of resistance to different FLT3is remain ongoing challenges that compel the development and rapid implementation of multi-agent combinatorial or sequential therapies for FLT3mut AML. Intriguingly, this was the first large study to show that the FLT3i may also benefit FLT3 wild-type patients, perhaps through multi-kinase blockade or prevention of emergent FLT3 clones at relapse28. (PDF) Prevalence and Effect Evaluation of FLT3 and NPM1 Mutations in Levis turned to FLT3-ITD mutations in acute myeloid leukemia (AML) to highlight the challenges with targeted therapy. Yamamoto, Y. et al. or reset password. Blood 136, 1617 (2020). Leukemia 26, 23532359 (2012). Regrettably, patients with information on the IS of ITD available had received different treatments: intensive chemotherapy, n=37; non-intensive therapy, n=14; clinical trials, n=6; and best supportive care, n=2. Statistical analyses were performed with SPSS 19.0 (IBM, Armonk, NY). However, a subsequent UKMRC study of 1600 patients with cytogenetic intermediate-risk AML showed that relapse risk did not differ based on the FLT3-ITDmut AR, and that the cumulative incidence of relapse in patients with NPM1mut was increased with a concurrent FLT3-ITDmut irrespective of the AR19. In the QuANTUM-R and ADMIRAL trials, only 4% and 12% of patients had received prior FLT3i therapy with induction, making it difficult to draw conclusions regarding the outcomes of contemporary patients, most of whom will have received a FLT3i (commonly midostaurin) with induction36,40. Conceptualization, T.C., J.M.A., E.B. Nevertheless, in three patients, similar VAFs (<5% difference) were detected, which might indicate that these mutations occurred at the same timepoint as the FLT3 mutation.No significant differences were found between the ITD length and the mutational status of any of the remaining genes (Fig. FLT3 testing was historically viewed as being purely prognostic; however, with the advent of FLT3 inhibitors, it will likely be seen as both prognostic and predictive. CAS In the absence of clinical trial options: among patients eligible for intensive chemotherapy who had a prior remission >1012 months, we would prefer a regimen incorporating intensive therapy (FLAG-Ida, CLAG-M, CLIA, MEC) in combination with a FLT3 inhibitor with an intent to achieve a rapid and hopefully deep remission and transition patients to ASCT followed by post-ASCT maintenance. Type I FLT3is are active against both the FLT3-ITD or TKD, type II inhibitors are only active against FLT3-ITD, not TKD. The presence of FLT3-ITD mutation correlates with a high leukemic burden with increased risk of relapse and is recognized to be a driver mutation in patients with AML ( 5 ). FLT3 mutations occur in more than 30% of patients with acute myeloid leukemia (AML) and are associated with short relapse-free and overall survival, including internal tandem duplication (ITD) and point mutations within the tyrosine kinase domain (TKD) [1, 2].To date, multiple FLT3 kinase inhibitors have been developed and some are approved for clinical use including sorafenib, Quizartinib . Mutations of FLT3 are found in approximately 30% of newly diagnosed AML patients and appear either as ITDs ( 25%) or point mutations in the tyrosine kinase domain (TKD) (710%)4. (D) OS according to the FLT3-ITD length and 2010 ELN genetic risk. The area under the ROC curve (AUC) for OS prediction was 0.504. Cortes, J. E. et al. A randomized, placebo-controlled phase III study of 3+7 with quizartinib (QuANTUM-First; NCT02668653) in patients with newly diagnosed FLT3-ITDmut AML eligible for induction therapy recently completed accrual. J. Haematol. Daver, N., Venugopal, S. & Ravandi, F. FLT3 mutated acute myeloid leukemia: 2021 treatment algorithm. Am. Leukemia 10, 19111918 (1996). At a median follow-up of 42 months, sorafenib demonstrated a 2-year estimated RFS of 85% and OS of 90.5% compared with 53.3% (P=0.002), and 66.2% with placebo, respectively (P=0.007). Metzelder, S. et al. Additionally, the area under the ROC curve, which serves as an indicator of the diagnostic capacity of the ITD length as a whole, was 0.504. The addition of sorafenib significantly improved the event-free survival (EFS; 21 months vs 9 months; P=0.013) and RFS (56% vs 38%), but not OS28, although a recent update suggested an emerging trend toward improved OS29. The FLT3-ITD AR was available in 140 intensively treated patients. Of note, we tested 3 different ITD length thresholds, and to be considered significant, the P value should be<0.025. The addition of sorafenib to standard AML treatment results in a substantial reduction in relapse risk and improved survival. ABSTRACT. CAS In patients with newly diagnosed AML, FLT3-ITDmut is a poor prognostic factor in terms of relapse-free (RFS) and overall survival (OS)7,8,9,10. B MD Anderson Cancer Center Approach. The clinical significance of FLT3 ITD mutation on the prognosis of J. Natl Compr. FLT3 -ITD and FLT3 point mutations show a gain-of-function phenotype with distinct signalling properties in vitro. This result is similar to the RATIFY study, in which 44% of patients lost FLT3 ITD under treatment with midostaurin 36. Blood 124, 34413449 (2014). 10, 588876- (2020). 11, 104 (2021). In our experienced cases FLT3-ITD mutation in MDS showed shorter duration to AML transformation and very poor prognosis. No significant difference was found between acute myeloid leukemia patients with these Hypomethylating agent and venetoclax with FLT3 inhibitor triplet therapy in older/unfit patients with FLT3 mutated AML, Mechanisms of resistance to cancer therapy, Cancel Activating FLT3 Mutants Show Distinct Gain-of-Function - PLOS 135, 397402 (1986). More recently, the emergence of BCR-ABL1-positive clone was shown as a resistance mechanism to multiple FLT3is72. Swaminathan et al. Prognostic relevance of FLT3-TKD mutations in AML: the combination Hematol. CNS Relapse in Acute Promyeloctyic Leukemia - academia.edu Activating FLT3 Mutants Show Distinct Gain-of-Function Phenotypes In Approximately one third of AML patients harbor constitutive activating internal tandem duplication in FLT3 (FLT3-ITD), which is associated with very poor prognosis. Pratz, K. W. et al. We currently recommend post-transplant maintenance with a FLT3i for at least 2 years (potentially indefinitely as there is limited data on the incidence of possible late relapses) in all FLT3mut AML. The current European Leukemia Net (ELN) guidelines categorize FLT3 -ITDmut AML as favorable (NPM1mut with FLT3 wild-type Or NPM1mut with FLT3-ITD AR<0.5), intermediate (NPM1mut with FLT3-ITD AR>0.5 Or NPM1WT with FLT3-ITD AR<0.5), or adverse (NPM1WT with FLT3-ITD AR>0.5)18. Upregulation of Bcl-2 confers resistance to FLT3 inhibition in FLT3-ITD AML with secondary acquired mutations. Perl, A. E. et al. PubMed Central Prognostic analyses were performed using the 70bp cutoff in 161 AML patients with FLT3-ITD mutations treated with IC (<70bp; n=119,70bp; n=42). QuANTUM-R, a phase 3 randomized controlled trial, evaluated quizartinib monotherapy vs investigator choice salvage chemotherapy in R/R FLT3-ITDmut AML. evaluated the impact of AR in 323 patients with newly diagnosed FLT3-ITDmut AML. SORAML, a randomized placebo-controlled trial evaluated the efficacy and tolerability of 3+7 induction-consolidation with or without sorafenib in patients 60 years with newly diagnosed AML, irrespective of a FLT3mut (only 34% had FLT3mut). Quizartinib is also being evaluated in combination with CPX-351 (NCT04209725) and with CLIA (NCT04047641) in treatment naive and R/R FLT3mut AML. "For patients with AML, the 5-year survival rate is only about 29%," said Dr. Erba. You are using a browser version with limited support for CSS. Am. We identified 1572 adult (age 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or . We found a statistically significant correlation among SF3B1, WT1 and EZH2 mutations and ITD length. Oncol. None of the studies has carried out an internal ITD length cutoff validation by dividing the patients into a training cohort and a validation cohort, which, given the arbitrary selection of the cutoffs used, would be necessary. Molecular Diagnostics | FLT3 (ITD and TKD) Mutation Detection Burchert, A. et al. Oncogene 21, 25552563 (2002). Go to: Introduction Prognostic significance of FLT3-ITD length in AML patients - Nature Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. No statistically significant differences were found (P=0.4) (Fig. Mutations of SF3B1, EZH2 and WT1 seem to be a more ancestral event than FLT3 mutations, as expected, given the VAF of the genes. Flow diagram showing all AML patients with FLT3-ITD mutations in the study period between 2003 and 2019 on the basis of genetic data and treatment administered. AR is defined as the ratio of ITD-mutated alleles to wild-type allele (FLT3ITD/FLT3 wild-type)13. Log in with Facebook Log in with Google. Andrew, H. et al. Rllig, C. et al. Taking into account the great number of comparisons performed, we cannot assume a real relationship between these mutations. FLT3 -ITD is a negative prognostic factor that remains prognostically relevant even after intensive chemotherapy and/or stem cell transplant. Lancet Oncol. Get the most important science stories of the day, free in your inbox. Unfortunately, in our study, information on the site of insertion was not available in the whole cohort, and few patients harbored a TKD1 insertion.We did not carry out a statistical analysis of the insertion site given the heterogeneity in the treatment of patients analyzed and the small number of patients with an ITD inserted in the TKD1 domain. Genetic biomarkers of sensitivity and resistance to venetoclax monotherapy in patients with relapsed acute myeloid leukemia. FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. J. Hematol. Oncol. Rollig, C. et al. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Hematol. Article 373 1136 1152, N Daver RF Schlenk NH Russell MJ Levis 2019 Targeting FLT3 mutations in AML: Review of current knowledge and evidence Leukemia 33 299 312, Article (4) Only five patients in our cohort received treatment with midostaurin (2 in induction and 3 in consolidation treatment); therefore, we were not able to draw conclusions regarding the prognostic impact of the length of the ITD as described in previous studies29,30. You are using a browser version with limited support for CSS. Google Scholar. Although activity was seen, the response rates were overall modest with this combination and the combination of HMA with midostaurin is not one that we routinely use or recommend for frontline FLT3-mutated AML47. We retrospectively reviewed 3555 acute myeloid leukemia patients, who have been assessed for FLT3 mutation at our institution . Two cases with an NPM1 mut missense each occurred concomitant with type-A mutation. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Eur. FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. The non-intensive chemotherapy group received FLUGA (fludarabine+Ara-C), n=22; azacytidine, n=15; and decitabine, n=5, and one patient was treated with IDA-FLAG-Lite. If material is not included in the articles Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Front. SORMAIN, a placebo-controlled randomized phase II trial evaluated post-transplant sorafenib maintenance in patients with FLT3-ITDmut AML with RFS post-ASCT as the primary endpoint. J. Hematol. Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy. J. Med. Alotaibi, A. S. et al. The randomized phase III ADMIRAL trial evaluated gilteritinib vs investigator choice salvage chemotherapy in patients with R/R FLT3mut AML. PubMed Juan M. Alonso-Dominguez. Article While the adverse prognostic impact of FLT3-ITDmut in AML has been clearly proven, the prognostic significance of FLT3-TKDmut remains speculative. FLT3 is a receptor tyrosine kinase that is involved in regulating proliferation of hematopoietic progenitor cells. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Fig. (C) OS according to the FLT3-ITD length and allelic ratio. Prognostic impact of low allelic ratio FLT3- ITD and NPM1 mutation in Whitman, S. P. et al. Any variant allele frequency data were reported rarely. * Genes with a P value<0.05 in the MannWhitney test correlating mutational status with ITD length. (D) OS according to the FLT3-ITD length and 2010 ELN genetic risk. A Conventional approach. Blood 130, 723 (2017). Cancer Netw. In patients with FLT3mut AML who relapsed after first ASCT, sorafenib was found to be tolerable with long-lasting remissions in 7 of 29 patients treated, suggesting a potential synergy with post-ASCT alloimmune effects41. CR or CRi was achieved in 70% of the patients in both groups (P=0.9). Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment.
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