Vol 13, No 1 (2022)
Case report
Published online: 2022-03-31

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Treatment of a patient with acute myeloid leukaemia with FLT3-ITD mutation

Katarzyna Jerzmanowska1, Agnieszka Pluta1
Hematology in Clinical Practice 2022;13(1):31-36.

Abstract

Acute myeloid leukaemia (AML) is an aggressive myeloid malignancy characterized by ineffective haematopoiesis. A hallmark of AML is unusual cytogenetic and molecular diversity, which determines treatment and has a major impact on patient response to treatment and survival. The mutations most detected in AML are those in the FMS-like tyrosine kinase 3 gene (FLT3). A case report is presented of a patient with AML with FLT3-ITD mutation who was treated with standard induction and consolidation chemotherapy in combination with midostaurin.

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References

  1. Döhner K, Schlenk RF, Habdank M, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005; 106(12): 3740–3746.
  2. Pluta A, Robak T, Brzozowski K, et al. Early induction intensification with cladribine, cytarabine, and mitoxantrone (CLAM) in AML patients treated with the DAC induction regimen: a prospective, non-randomized, phase II study of the Polish Adult Leukemia Group (PALG). Leuk Lymphoma. 2020; 61(3): 588–603.
  3. Cancer stat facts: leukemia — acute myeloid leukemia (AML). https://seer.cancer.gov/statfacts/html/amyl.html (March 23, 2021).
  4. Wierzbowska A. Postępy w leczeniu ostrej białaczki szpikowej u dorosłych. Acta Haematol Pol. 2008; 39(4): 639–650.
  5. Döhner H, Estey EH, Amadori S, et al. European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010; 115(3): 453–474.
  6. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017; 129(4): 424–447.
  7. Rosnet O, Matteï MG, Marchetto S, et al. Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene. Genomics. 1991; 9(2): 380–385.
  8. Rosnet O, Schiff C, Pébusque MJ, et al. Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells. Blood. 1993; 82(4): 1110–1119.
  9. Schlessinger J, Lemmon MA. Nuclear signaling by receptor tyrosine kinases: the first robin of spring. Cell. 2006; 127(1): 45–48.
  10. Kiyoi H, Naoe T. Biology, clinical relevance, and molecularly targeted therapy in acute leukemia with FLT3 mutation. Int J Hematol. 2006; 83(4): 301–308.
  11. Kihara R, Nagata Y, Kiyoi H, et al. Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia. 2014; 28(8): 1586–1595.
  12. Ley TJ, Miller C, Ding Li, et al. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013; 368(22): 2059–2074.
  13. Zmorzyński S, Koczkodaj D, Michalak M, et al. Badanie wewnątrztandemowej duplikacji genu FLT3 u chorych z ostrą białaczką szpikową. Acta Haematol Pol. 2012; 43(2): 229–233.
  14. Libura M, Giebel S, Piatkowska-Jakubas B, et al. Cladribine added to daunorubicin-cytarabine induction prolongs survival of FLT3-ITD+ normal karyotype AML patients. Blood. 2016; 127(3): 360–362.
  15. Wang ES. Beyond midostaurin: Which are the most promising FLT3 inhibitors in AML? Best Pract Res Clin Haematol. 2019; 32(4): 101103.
  16. Mead AJ, Linch DC, Hills RK, et al. 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. Blood. 2007; 110(4): 1262–1270.
  17. Whitman SP, Ruppert AS, Radmacher MD, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood. 2008; 111(3): 1552–1559.
  18. Fröhling S, Schlenk RF, Breitruck J, et al. AML Study Group Ulm. Acute myeloid leukemia. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 2002; 100(13): 4372–4380.
  19. Whitman SP, Archer KJ, Feng L, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res. 2001; 61(19): 7233–7239.
  20. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017; 377(5): 454–464.
  21. https://www.nccn.org/ (March 23, 2021).
  22. Holowiecki J, Grosicki S, Giebel S, et al. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012; 30(20): 2441–2448.
  23. Boissel N, Cayuela JM, Preudhomme C, et al. Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy. Leukemia. 2002; 16(9): 1699–1704.
  24. Fischer T, Stone RM, Deangelo DJ, et al. Phase IIB trial of oral midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010; 28(28): 4339–4345.
  25. Daunorubicin, cytarabine, and midostaurin in treating patients with newly diagnosed acute myeloid leukemia. https://clinicaltrials.gov/ct2/show/study/NCT00651261 (May 24, 2022).



Hematology in Clinical Practice