Abstract
Background:
FLT3 gene mutations, particularly internal tandem duplications (FLT3-ITD), are present in approximately 25%–30% of patients with acute myeloid leukemia (AML) and are important drivers of leukemogenesis; less frequently, FLT3 mutations occur as tyrosine kinase domain (TKD) variants. Non-canonical variants, such as juxtamembrane domain (JMD) in-frame insertions, are rare and their pathogenic mechanisms and therapeutic sensitivities are less defined.
Case description:
We report a 13-year-old female patient with refractory AML harboring a novel in-frame insertion in the FLT3 JMD NC_000013.11(NM_004119.3):c.1780_1781insGGGTCCCTCCGCCTACCC; p.(Phe594delinsTrpValProProProThrLeu) identified by next-generation sequencing (NGS). The disease was resistant to standard intensive chemotherapy but showed marked sensitivity to the FLT3 inhibitor sorafenib. Following relapse upon sorafenib discontinuation due to cardiac toxicity, the patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) while in active disease (M3 marrow). A sequential myeloablative conditioning regimen consisting of melphalan, fludarabine, and fractionated total body irradiation (TBI-8 Gray) was employed. Post-transplant, sorafenib maintenance was resumed for 2 years.
Outcomes:
The patient achieved sustained complete remission and remains disease-free 63 months post-HSCT, despite significant pre-transplant comorbidities including fungal pneumonia and a pulmonary artery pseudo-aneurysm.
Conclusion:
This case suggests that non-canonical FLT3 JMD insertions may be actionable molecular alterations and highlights the need for further investigation of FLT3 inhibitor efficacy and the therapeutic relevance of these rare mutations in AML.
Introduction
The FLT3 (FMS-like tyrosine kinase 3) gene encodes a class III receptor tyrosine kinase essential for hematopoietic stem cell proliferation and survival (). In acute myeloid leukemia (AML), FLT3 mutations occur in approximately 25%–30% of cases, with internal tandem duplications (ITDs) in exons 14 and 15 and point mutations in the tyrosine kinase domain (TKD) being the most prevalent (, ). These mutations disrupt the auto-inhibitory function of the juxtamembrane domain (JMD) or the activation loop, leading to constitutive, ligand-independent activation of downstream signaling pathways such as PI3K/AKT, RAS/MAPK, and STAT5 (, ). FLT3 mutations in AML confer markedly worse prognosis; the Japanese Childhood AML Cooperative Study (AML-99) reported a 3-year overall survival of 35.3% in FLT3-ITD-positive patients versus 84.3% in FLT3-wild-type patients (). These outcomes are substantially improved by the addition of targeted FLT3 inhibitors to treatment regimens (, ). While the prognostic impact of canonical FLT3-ITD and TKD mutations is well-established, non-canonical variants, including small in-frame insertions or deletions within the JMD, remain poorly characterized ().
We present a unique case of pediatric AML driven by a novel FLT3 JMD in-frame insertion NC_000013.11(NP_004110.2):p.(Phe594delinsTrpValProProProThrLeu). This case illustrates the possible pathogenicity of the variant, the clinical response to sorafenib, and the successful application of an intensified sequential conditioning regimen (Melphalan/Fludarabine/TBI-8) for allogeneic hematopoietic stem cell transplantation (HSCT) in the setting of active disease.
Case description
Patient presentation and diagnostic assessment
A 13-year-old female patient presented with a history of fatigue, petechiae, splenomegaly, and bilateral cervical lymphadenopathy. Laboratory investigations revealed leukocytosis, anemia, and thrombocytopenia, with 20% blasts on the peripheral smear. Bone marrow (BM) biopsy showed 100% cellularity with infiltration by immature myeloid cells. Flow cytometry confirmed a CD45+ population (82%) expressing CD34, CD38-dim, CD13, CD7, CD15, CD117, CD58, and CD11c, but negative for CD33, CD11b, CD64, CD4, MPO, and CD3. Cytogenetics revealed a normal karyotype, and FISH was negative for common AML translocations.
PCR-based screening for FLT3-ITD and NPM1 was negative. However, next-generation sequencing (NGS) (Centogene, Germany) utilizing a 35-gene myeloid panel identified a novel in-frame insertion in FLT3 exon 14: NC_000013.11(NM_004119.3):c.1780_1781insGGGTCCCTCCGCCTACCC; NC_000013.11(NP_004110.2):p.(Phe594delinsTrpValProProProThrLeu). The variant was not present in gnomAD, Online Mendelian Inheritance in Man (OMIM), Clinvar, UniProt, The Cancer Genome Atlas (TCGA), or the local Saudi genomic databases. In addition, to verify that the sequence is not derived from adjacent FLT3 regions, we examined the full sequence of FLT3 (NCBI Reference Sequence: NG_007066.1) and screened for the presence of the inserted sequence GGGTCCCTCCGCCTACCC. Based on this, we did not find this sequence to be present anywhere in the FTL3 genomic region. Other FLT3-ITD variants in the same region reported to date with HGVS-based nomenclature are shown for comparison (Table 1).
Table 1
| Position (FLT3: NM_004119.2) | FLT3-ITD mutation(nucleotide) | FLT3-ITD mutation (amino acid) | COSMIC mutation ID |
|---|---|---|---|
| 594 | c.1780_1781ins GGGTCCCTCCGCCTACCC | p.D593_F594insWVPPPTL | Current case |
| 594 | c.1780_1781insCAGAGAATATGAATATGATCT | p.D593_F594insSENMNMI | COSM10189273 |
| 594 | c.1780_1781insCCCCGAATGAGTACTTCTACGTTGATT | p.D593_F594insSPNEYFYVD | COSM10112855 |
| 594 | c.1780_1781insCCCCGGAAGATAATGAGTACTTCTACGTTGATT | p.D593_F594insSPEDNEYFYVD | COSM1317908 |
| 594 | c.1780_1781insGGAGAGAGAGAGATAATGATAATGAGTACTTCTACGTTGATT | p.D593_F594insWRERDNDNEYFYVD | COSM5879541 |
| 594 | c.1780_1781insGGGGGTACTTCTACGTTGATT | p.D593_F594insWGYFYVD | COSM19951 |
Current case and previously reported FLT3-ITD mutations in the same genomic location.
Therapeutic intervention and clinical course
The patient was treated according to the Children’s Oncology Group AAML0531 protocol. Induction with ADE (cytarabine, daunorubicin, and etoposide) failed to clear the blasts (97% residual). Subsequent salvage with FLAG (fludarabine, cytarabine, and G-CSF) also resulted in persistent disease (90% blasts). Given the NGS findings, the FLT3 inhibitor sorafenib was added to clofarabine and high-dose cytarabine. This targeted approach achieved complete morphological remission (2% blasts). Unfortunately, the patient developed severe complications, including fungal pneumonia with a life-threatening pulmonary artery branch pseudo-aneurysm and cardiac dysfunction. Sorafenib was discontinued due to cardiotoxicity, leading to an immediate relapse. Re-challenge with chemotherapy (clofarabine/high-dose cytarabine) without sorafenib failed to regain remission. Other FLT3 inhibitors could not be administered because of limited availability and lack of approval for pediatric use by national regulatory authorities.
Over several months, the patient received additional salvage cycles (including azacitidine/low-dose sorafenib, azacitidine/venetoclax, and TVTC: topotecan, vinorelbine, clofarabine, and thiotepa) (), with the aim of controlling disease activity while allowing for pulmonary fungal infection control and cardiac function recovery. BM blasts and peripheral blasts persisted (Figure 1).
Figure 1
Allogeneic HSCT and conditioning
Following radiologic stabilization of the invasive pulmonary fungal infection and improvement in cardiac function (shortening fraction 30%), the patient proceeded to a 10/10 HLA-matched sibling donor allogeneic HSCT despite persistent active leukemia. Pre-transplant BM evaluation demonstrated 35% blasts without additional cytogenetic or molecular abnormalities. At transplantation, the white blood cell count was 12 × 109/L, platelet count was 45 × 109/L, and 5% circulating blasts were present. A sequential myeloablative conditioning regimen consisting of melphalan (140 mg/m², day −11), fludarabine (30 mg/m²/day, days −6 to −3), and fractionated total body irradiation (2 Gy twice daily, days −2 to −1; total dose 8 Gy) was administered (). Peripheral blood stem cells were infused at a CD34+ cell dose of 8 × 106/kg. Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate (10 mg/m² on days +1, +3, and +6). Immunosuppression tapering was initiated on day +45 to facilitate a graft-versus-leukemia effect through controlled alloreactivity.
Follow-up and outcomes
Successful neutrophil and platelet engraftment occurred by the third week. Full donor chimerism (100%) was achieved and maintained at days +30, +60, and +100. Post-transplant complications included BK virus-associated hemorrhagic cystitis and EBV/adenovirus viremia, all of which were managed successfully.
Sorafenib maintenance was initiated at 100 mg daily and continued for 2 months. After confirmation of sustained cardiac stability, the dose was increased to 150 mg daily for 2 months and subsequently to 200 mg daily, which was continued until 2 years post-transplant. Sorafenib was then discontinued. At 63 months after allogeneic HSCT, the patient remains in complete remission with 100% donor chimerism.
Protein structure and impact
To assess and visualize the structural alteration to the FTL3 protein caused by our reported mutation, we performed several in silico protein structure predictions using SWISS-model (, ). The main model used our reported mutation (Phe594delinsTrpValProProProThrLeu) and the wild-type protein structure was used as the alignment template (protein structure P36888.1 for FTL3). Similarly, we performed the same modeling steps using other mutations reported in literature: (i) NC_000013.11(NP_004110.2):p.(F594delinsSL) (), a smaller insertion–deletion mutation with a different amino acid composition than our reported mutation; (ii) NC_000013.11(NP_004110.2):p.(Tyr597_Glu598insAspValAspPheArgGluTyr) (), an established ITD mutation; and (iii) NC_000013.11(NP_004110.2): p.(Phe594_Asp600delinsSerProProProHis), a deletion of phenylalanine and an insertion of several proline amino acids, similar to our reported mutation. Mutant structures were superimposed against the original wild-type FLT3 protein (P36888.1) based on the upstream and downstream amino acid sequences surrounding the mutation site (i.e., 580–590 and 596–606 of the wild-type protein). Results of the homology modeling and comparisons are presented in Figures 2, 3.
Figure 2
Figure 3
Discussion
This report characterizes a novel in-frame insertion in the FLT3 JMD NC_000013.11(NP_004110.2):p.(Phe594delinsTrpValProProProThrLeu) and highlights its role as a pathogenic driver in AML. According to ACMG criteria, the variant is classified as likely pathogenic based on its absence in population databases (PM2), protein length change in a non-repeat region (PM4), and the highly specific clinical phenotype of refractory AML with rapid response to FLT3 inhibition (PP4) ().
Possible pathogenicity of the FLT3 JMD insertion
The JMD of FLT3 normally maintains the kinase in an inactive state by blocking the ATP-binding pocket. Structural disruption of this region, typically via ITDs, promotes ligand-independent dimerization and constitutive activation (). The identified insertion involves codon Phe594, a residue within the JMD known to be critical for autoinhibition. Similar non-canonical JMD insertions have been shown in vitro to induce autonomous receptor signaling and cellular transformation (). In our patient, the strict therapeutic dependence on sorafenib—evidenced by remission only upon its addition and immediate relapse upon its withdrawal—provides clinical evidence supporting an activating effect of this novel mutation.
In silico prediction of the impact of FLT3 JMD insertion on JMD protein structure
Based on our homology modeling observations, it is evident that our reported mutation alters the JM-Z domain. In addition, the proline chain inserted is predicted to have a different structure than previously reported ITD mutation and even non-ITD mutation with a similar proline insertion. Given the clinical observations when using FLT3 inhibitors and considering that the publicly reported mutations have been confirmed to have moderate to high impact and are likely oncogenic, we can hypothesize that our reported mutation is likely to be affecting the JMD domain and possibly disrupting the JM-Z/N-lobe interaction, similar to other reported FLT3 mutations but with different structural conformation.
HSCT outcomes in AML with active disease: evolving evidence
Allogeneic HSCT for childhood AML is associated with significantly inferior outcomes when performed in the presence of active disease, with reported overall survival ranging from 18% to 44% compared with 56%–71% for patients transplanted in complete remission (–). Doherty et al. demonstrated a 2.4-fold higher relapse incidence among children transplanted with active disease [sub-distribution hazard ratio (HR) 2.42, p = 0.016], while an EBMT registry study reported a cumulative relapse incidence of 45.1% in patients with active t (, ) AML compared with 18.2% in those transplanted in first complete remission (). Similarly, disease not in remission before HSCT was the only independent predictor of inferior overall survival in a multicenter cohort (HR 2.27, p < 0.05) (). In a United Kingdom cohort of children with refractory AML, a pre-transplant BM blast burden ≤30% was associated with significantly better 5-year leukemia-free survival than >30% blasts (52% vs. 27%) ().
Although prospective pediatric data are lacking, the adult ASAP trial demonstrated that immediate allogeneic HSCT without prior remission–induction chemotherapy achieved survival comparable to conventional salvage therapy while reducing treatment-related toxicity and shortening the time to transplantation (). Long-term follow-up further identified ELN genetic risk, age, and comorbidity burden—not remission status at transplantation—as the primary determinants of survival (). Although these findings cannot be directly extrapolated to pediatric AML, they support the concept that failure to achieve morphological remission should not automatically preclude HSCT in carefully selected patients with refractory disease.
Our patient underwent HSCT for refractory AML with 35% BM blasts and multiple significant pre-transplant comorbidities, including cardiomyopathy and a pulmonary artery aneurysm, placing her at an exceptionally high risk of post-transplant relapse and mortality. Nevertheless, allogeneic HSCT followed by post-transplant sorafenib maintenance resulted in sustained leukemia-free survival exceeding 5 years.
Conditioning regimen for allogenic HSCT
Melphalan (140 mg/m²) combined with fludarabine and total body irradiation (8 Gy) provided potent cytoreduction in this case. High-dose melphalan is an effective myeloablative agent for refractory AML, and its combination with TBI has been associated with enhanced blast clearance and reduced relapse in relapsed/refractory disease (, ). Despite significant pre-transplant comorbidities, the patient tolerated the regimen, achieved durable engraftment, and remained leukemia-free for more than 5 years after HSCT.
The role of post-transplant TKI maintenance
Relapse remains the primary cause of failure after HSCT for FLT3-mutated AML. Recent evidence supports the use of FLT3 inhibitors like sorafenib as maintenance therapy post-HSCT to reduce relapse rates and improve overall survival (, 27). Our patient’s sustained remission (63 months) following 2 years of sorafenib maintenance reinforces the utility of this strategy, particularly for variants that exhibit high TKI sensitivity.
Strengths and limitations
A key strength of this report is the integration of longitudinal clinical follow-up exceeding 5 years, comprehensive molecular characterization, in silico structural modeling, and clinical response data related to a novel FLT3 JMD insertion. The concordance between homology-based structural predictions, the observed sensitivity to FLT3 inhibition, and the durable post-transplant remission provides convergent evidence supporting the putative pathogenicity and therapeutic relevance of this variant. A limitation is the absence of direct in vitro functional studies, such as phospho-FLT3 signaling assays or cellular transformation experiments, to definitively characterize the molecular consequences of the mutation, although the computational and clinical findings suggest an activating effect.
Patient perspective
At the time of writing, the patient has achieved sustained remission and has returned to normal daily activities, including attending college. Both the patient and her family express deep gratitude for this unexpected and highly favorable outcome in what was an exceptionally challenging clinical course. Prior to this, the family had largely lost hope, particularly after the disease proved refractory to many lines of therapy and following multiple consultations with international experts, all of whom indicated an extremely poor prognosis with a near-zero likelihood of cure. Currently, the patient is thriving, with a good quality of life, and the family is able to enjoy her recovery and reintegration into normal life.
Statements
Data availability statement
The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.
Ethics statement
The studies involving humans were approved by Research Counsil of King Fahad Medical City, Riyadh, Saudi Arabia. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin. Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.
Author contributions
WB: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. MA-R: Writing – review & editing. FM: Writing – review & editing. AA: Writing – review & editing. TF: Methodology, Writing – review & editing. MA: Writing – review & editing. AP: Investigation, Methodology, Software, Writing – review & editing.
Funding
The author(s) declared that financial support was not received for this work and/or its publication.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
1
RosnetOMatteïMGMarchettoSBirnbaumD. Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene. Genomics. (1991) 9:380–5. doi: 10.1016/0888-7543(91)90270-o
2
GriffithJBlackJFaermanCSwensonLWynnMLuFet al. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell. (2004) 13:169–78. doi: 10.1016/s1097-2765(03)00505-7
3
ArberDAOraziAHasserjianRThieleJBorowitzMJLe BeauMMet al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. (2016) 127:2391–405. doi: 10.1182/blood-2016-03-643544
4
BystromRLevisMJ. An update on FLT3 in acute myeloid leukemia: Pathophysiology and therapeutic landscape. Curr Oncol Rep. (2023) 25:369–78. doi: 10.1007/s11912-023-01389-2
5
DöhnerHEsteyEGrimwadeDAmadoriSAppelbaumFRBüchnerTet al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. (2017) 129:424–47. doi: 10.1182/blood-2016-08-733196
6
ShimadaATakiTTabuchiKTaketaniTHanadaRTawaAet al. Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia: A study of the Japanese childhood AML Cooperative Study Group. Pediatr Blood Cancer. (2008) 50:264–9. doi: 10.1002/pbc.21318
7
OñateGPratcoronaMGarridoAArtigas-BaleriABatallerATormoMet al. Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort. Blood Cancer J. (2023) 13:69. doi: 10.1038/s41408-023-00839-1
8
MatsukawaTOnozawaMKondoTKanayaMHidakaDOtaSet al. FLT3 inhibitors and hematopoietic cell transplantation prolong survival in patients with FLT3-ITD-positive AML. Ann Hematol. (2024) 103:5333–40. doi: 10.1007/s00277-024-06125-9
9
LuthraRPatelKPReddyNGHaghshenasVRoutbortMJHarmonMAet al. Next-generation sequencing-based multigene mutational screening for acute myeloid leukemia using MiSeq: applicability for diagnostics and disease monitoring. Haematologica. (2014) 99:465–73. doi: 10.3324/haematol.2013.093765
10
RamaswamyKSteinherzPGAgrawalAKForlenzaCJMauguenARoshalMet al. Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML. Blood Adv. (2022) 6:2688–94. doi: 10.1182/bloodadvances.2021005753
11
SteckelNKGrothCMikeschJTrenschelROttingerHKordelasLet al. High‐dose melphalan‐based sequential conditioning chemotherapy followed by allogeneic haematopoietic stem cell transplantation in adult patients with relapsed or refractory acute myeloid leukaemia. Br J Haematol. (2018) 180:840–53. doi: 10.1111/bjh.15137
12
BienertSWaterhouseAde BeerTAPTaurielloGStuderGBordoliLet al. The SWISS-MODEL Repository-new features and functionality. Nucleic Acids Res. (2017) 45:D313–9. doi: 10.1093/nar/gkw1132
13
WaterhouseABertoniMBienertSStuderGTaurielloGGumiennyRet al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. (2018) 46:W296–303. doi: 10.1093/nar/gky427
14
ReindlCBagrintsevaKVempatiSSchnittgerSEllwartJWWenigKet al. Point mutations in the juxtamembrane domain of FLT3 define a new class of activating mutations in AML. Blood. (2006) 107:3700–7. doi: 10.1182/blood-2005-06-2596
15
Abu-DuhierFMGoodeveACWilsonGAGariMAPeakeIRReesDCet al. FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br J Haematol. (2000) 111:190–5. doi: 10.1046/j.1365-2141.2000.02317.x
16
RichardsSAzizNBaleSBickDDasSGastier-FosterJet al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. (2015) 17:405–24. doi: 10.1038/gim.2015.30
17
ZhangWKonoplevaMShiYXMcQueenTHarrisDLingXet al. Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst. (2008) 100:184–98. doi: 10.1093/jnci/djm328
18
ThiedeCSteudelCMohrBSchaichMSchäkelUPlatzbeckerUet al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. (2002) 99:4326–35. doi: 10.1182/blood.v99.12.4326
19
DohertyERedellMSasaGYassineKJohnTCraddockJet al. Outcomes after allogeneic hematopoietic stem cell transplantation for pediatric acute myeloid leukemia in the contemporary era. Biol Blood Marrow Transplant. (2020) 26:Supplement S100. doi: 10.1016/j.bbmt.2019.12.602
20
BhatSJainSYadevSNirmalGKalraGDaruvalaSet al. Hematopoietic stem cell transplant for acute myeloid leukaemia in children and adolescents: multicentric experience from India. Blood. (2024) 144:7434. doi: 10.1182/blood-2024-207098
21
AndreozziFGalimardJEMaertensJAljurfMCleshamKSanzJet al. Outcomes of 544 Patients with t(6;9)/DEK::NUP214 acute myeloid leukemia undergoing allogeneic stem cell transplantation: an EBMT study on behalf of the acute leukemia working party (ALWP) and the pediatric diseases working party (PDWP). Bone Marrow Transplant. (2026) 61:838–46. doi: 10.1038/s41409-026-02857-6
22
O’HarePLucchiniGCumminsMVeysPPotterMLawsonSet al. Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience. Bone Marrow Transplant. (2017) 52:825–31. doi: 10.1038/bmt.2017.3
23
StelljesMMiddekeJMBugGWagner-DrouetEMMüllerLPSchmidCet al. Remission induction versus immediate allogeneic haematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukaemia (ASAP): a randomised, open-label, phase 3, non-inferiority trial. Lancet Haematol. (2024) 11:e324–35. doi: 10.1016/S2352-3026(24)00065-6
24
StelljesMMiddekeJMBugGWagner-DrouetEMMüllerLPSchmidCet al. Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial. Blood. (2025) 146:2293–305. doi: 10.1182/blood.2025028730
25
RonnackerJUrbahnMAReichertsCKollochLBerningPCallSet al. Blast clearance after high dose-melphalan conditioning for allogeneic stem cell transplantation in relapsed and refractory acute myeloid leukemia. Blood. (2023) 142:4911. doi: 10.1182/blood-2023-180723
26
AntarAKharfan-DabajaMAMahfouzRBazarbachiA. Sorafenib maintenance appears safe and improves clinical outcomes in FLT3-ITD acute myeloid leukemia after allogeneic hematopoietic cell transplantation. Clin Lymphoma Myeloma Leuk. (2015) 15:298–302. doi: 10.1016/j.clml.2014.12.005
27
XuanLWangYHuangFFanZXuYSunJet al. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Lancet Oncol. (2020) 21:1201–12. doi: 10.1016/S1470-2045(20)30455-1
Summary
Keywords
acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, FLT3, melphalan, next-generation sequencing, sorafenib, total body irradiation
Citation
Peer-Zada AA, Al-Rimawi M, Malaeb F, Faquih T, Alhamdoosh M, Alsultan A and Ballourah W (2026) Novel juxtamembrane FLT3 in-frame insertion in a child with refractory AML: a case report of durable remission following allogeneic HSCT and FLT3 inhibitor therapy. Front. Oncol. 16:1852452. doi: 10.3389/fonc.2026.1852452
Received
10 April 2026
Revised
08 August 2026
Accepted
17 August 2026
Published
25 September 2026
Volume
16 - 2026
Edited by
Francesco Paolo Tambaro, AORN Santobono-Pausilipon, Italy
Reviewed by
Naghmeh Niktoreh, University of Duisburg-Essen, Germany
Mateusz Pospiech, University of Southern California, United States
Updates
Copyright
© 2026 Peer-Zada, Al-Rimawi, Malaeb, Faquih, Alhamdoosh, Alsultan and Ballourah.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Walid Ballourah, wld999@hotmail.com
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.