Day-21 bone marrow findings incorrectly designate residual leukaemia in FLT3-mutated acute myeloid leukaemia treated with intensive induction plus midostaurin: a morphology-focused study

Pathology. 2024 Jun;56(4):548-555. doi: 10.1016/j.pathol.2024.01.004. Epub 2024 Mar 13.

Abstract

Early induction response assessment with day-21 bone marrow (D21-BM) is commonly performed in patients with FLT3-mutated acute myeloid leukaemia (AML), where detection of residual leukaemia (RL; blasts ≥5%) typically results in the administration of a second induction course. However, whether D21-BM results predict for RL at the end of first induction has not been systematically assessed. This study evaluates the predictive role of D21-BM morphology in detecting RL following first induction. Between August 2018 and March 2022, all patients with FLT3-AML receiving 7+3 plus midostaurin, with D21-BM performed, were identified. Correlation between D21-BM morphology vs D21-BM ancillary flow/molecular results, as well as vs D28-BM end of first induction response, were retrospectively reviewed. Subsequently, D21-BMs were subjected to anonymised morphological re-assessments by independent haematopathologists (total in triplicate per patient). Of nine patients included in this study, three (33%) were designated to have RL at D21-BM, all of whom entered complete remission at D28-BM. Furthermore, only low-level measurable residual disease was detected in all three cases by flow or molecular methods at D21-BM, hence none proceeded to a second induction. Independent re-evaluations of these cases failed to correctly reassign D21-BM responses, yielding a final false positive rate of 33%. In summary, based on morphology alone, D21-BM assessment following 7+3 intensive induction plus midostaurin for FLT3-AML incorrectly designates RL in some patients; thus correlating with associated flow and molecular results is essential before concluding RL following first induction. Where remission status is unclear, repeat D28-BMs should be performed.

Keywords: 7+3 induction; Day-21 bone marrow; FLT3; acute myeloid leukaemia; false positive; haematopathology; midostaurin; morphology.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow* / pathology
  • Female
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / pathology
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm, Residual*
  • Remission Induction
  • Retrospective Studies
  • Staurosporine* / analogs & derivatives
  • Staurosporine* / therapeutic use
  • fms-Like Tyrosine Kinase 3* / genetics

Substances

  • Staurosporine
  • midostaurin
  • fms-Like Tyrosine Kinase 3
  • FLT3 protein, human