Impact of FLT3 Receptor (CD135) Detection by Flow Cytometry on Clinical Outcome of Adult Acute Myeloid Leukemia Patients

Kandeel, Eman Z.; Sayed, G.; El-Sharkawy, Nahla; Eldin, Dalia Negm; Nassar, Hanan R.; Ibrahiem, Dalia M.; Amin, Randa; Hanafi, Marwa; Khalil, Mohamed; Kamel, Azza M.

doi:10.1016/j.clml.2018.05.014

Cited by 10 publications

(3 citation statements)

References 25 publications

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“…Yet, in low‐AR or FLT3 wt AML cases, surviving signals may be activated by receptors and pathways not inhibited by midostaurin. It is well known that in some patients presenting with FLT3 wt , leukemic cells overexpress FLT3, which is predictive of a poor outcome 19,20 . Incorporation of midostaurin in the treatment regimen of such patients has a clinical rationale.…”

Section: Discussionmentioning

confidence: 99%

Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3‐ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission

Ofran

Leiba

Frisch

et al. 2020

European J of Haematology

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Objectives Midostaurin, a multikinase and FLT3 inhibitor, is the first non‐chemotherapy agent approved and widely adopted for the treatment of FLT3‐ITD acute myeloid leukemia (AML). Yet, its role in improving survival of patients referred to allogeneic stem cell transplantation (allo‐SCT) in first complete remission (CR1) needs to be defined. Methods This multicenter study retrospectively evaluated the outcome of 119 FLT3‐ITD AML patients [59 (49.6%) males and 60 females] intensively treated between 2015 and 2019 at five Israeli centers. In our cohort, allo‐SCT in CR1 was widely implemented (47%) and patient stratification was based on the current allelic ratio (AR) cutoff of 0.5. Results Ninety‐eight patients (82.3%) achieved CR1/CR with incomplete count recovery (CRi). Death during induction was reported in 7 (5.9%) patients. In multivariate analysis, midostaurin use and allo‐SCT in CR1 were the most significant factors affecting overall survival (OS). Midostaurin incorporation in chemotherapy regimens significantly improved CR + CRi rates (P = .002), reduced relapse rates (P = .02), and was remarkably advantageous for high‐AR patients (2‐year OS 82%). In low‐AR patients, the midostaurin effect was much less prominent. Conclusions Our results demonstrate benefits of midostaurin incorporation in intensive chemotherapy regimens, particularly for high‐AR AML patients to whom it should be offered along with allo‐SCT in CR1.

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Section: Discussionmentioning

confidence: 99%

Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3‐ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission

Ofran

Leiba

Frisch

et al. 2020

European J of Haematology

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“…[9][10][11] Even in cases in which no FLT3 coding mutation is detectable, the receptor can be overexpressed on the cell surface of leukemic blasts and contributes to the survival and proliferation of the leukemic clone. [12][13][14][15][16][17] Furthermore, chemotherapy-induced aplasia stimulates the BM stroma to produce FL, fueling the recovery, selection, and expansion of any AML clone that is positioned to take advantage of it.…”

Section: Introductionmentioning

confidence: 99%

“…The pervasiveness of aberrant FLT3 signaling across the spectrum of AML subtypes defies straightforward classification. FLT3 mutations are most common in AML with normal cytogenetics, but may also occur in the setting of other disease-defining genetic lesions such as inv( 16), t(8;21) and t (15,17). They frequently co-occur with other driver mutations such as DNMT3A, NPM1, and IDH1/2.…”

Section: Introductionmentioning

confidence: 99%

Potential targeting of FLT3 acute myeloid leukemia

Ambinder

Levis

2020

haematol

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Aberrant FLT3 receptor signaling is common in acute myeloid leukemia (AML) and has important implications for the biology and clinical management of the disease. Patients with FLT3-mutated AML frequently present with critical illness, are more likely to relapse after treatment, and have worse clinical outcomes than their FLT3 wild type counterparts. The clinical management of FLT3-mutated AML has been transformed by the development of FLT3 inhibitors, which are now in use in the frontline and relapsed/refractory settings. However, many questions regarding the optimal approach to the treatment of these patients remain. In this paper, we will review the rationale for targeting the FLT3 receptor in AML, the impact of FLT3 mutation on patient prognosis, the current standard of care approaches to FLT3-mutated AML management, and the diverse array of FLT3 inhibitors in use and under investigation. We will also explore new opportunities and strategies for targeting the FLT3 receptor. These include targeting the receptor in patients with non-canonical FLT3 mutations or wild type FLT3, pairing FLT3 inhibitors with other novel therapies, using minimal residual disease (MRD) testing to guide the targeting of FLT3, and novel immunotherapeutic approaches.

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γδ T Cells Number, CD200, and Flt3 Expression Is Associated with Higher Progression Free Survival in Patients with Chronic Myeloid Leukemia

Molina-Aguilar

Montiel‐Cervantes

Anguiano-Peñaloza

et al. 2020

Archives of Medical Research

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Impact of FLT3 Receptor (CD135) Detection by Flow Cytometry on Clinical Outcome of Adult Acute Myeloid Leukemia Patients

Cited by 10 publications

References 25 publications

Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3‐ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission

Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3‐ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission

Potential targeting of FLT3 acute myeloid leukemia

γδ T Cells Number, CD200, and Flt3 Expression Is Associated with Higher Progression Free Survival in Patients with Chronic Myeloid Leukemia

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