scholarly journals FLT3 mutated acute myeloid leukemia: 2021 treatment algorithm

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Naval Daver ◽  
Sangeetha Venugopal ◽  
Farhad Ravandi
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Prognostic Significance ◽  
Treatment Algorithm ◽  
Molecular Testing ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Acute Myeloid

AbstractApproximately 30% of patients with newly diagnosed acute myeloid leukemia (AML) harbor mutations in the fms-like tyrosine kinase 3 (FLT3) gene. While the adverse prognostic impact of FLT3-ITDmut in AML has been clearly proven, the prognostic significance of FLT3-TKDmut remains speculative. Current guidelines recommend rapid molecular testing for FLT3mut at diagnosis and earlier incorporation of targeted agents to achieve deeper remissions and early consideration for allogeneic stem cell transplant (ASCT). Mounting evidence suggests that FLT3mut can emerge at any timepoint in the disease spectrum emphasizing the need for repetitive mutational testing not only at diagnosis but also at each relapse. The approval of multi-kinase FLT3 inhibitor (FLT3i) midostaurin with induction therapy for newly diagnosed FLT3mut AML, and a more specific, potent FLT3i, gilteritinib as monotherapy for relapsed/refractory (R/R) FLT3mut AML have improved outcomes in patients with FLT3mut AML. Nevertheless, the short duration of remission with single-agent FLT3i’s 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 FLT3i’s remain ongoing challenges that compel the development and rapid implementation of multi-agent combinatorial or sequential therapies for FLT3mut AML.

scholarly journals The prognostic impact of lymphocyte subsets in newly diagnosed acute myeloid leukemia

2018 ◽  
Vol 53 (3) ◽  
pp. 198 ◽  
Author(s):  
Yumi Park ◽  
Jinsook Lim ◽  
Seonyoung Kim ◽  
Ikchan Song ◽  
Kyechul Kwon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphocyte Subsets ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Acute Myeloid

scholarly journals Invasive Fungal Disease in Patients with Newly Diagnosed Acute Myeloid Leukemia

2021 ◽  
Vol 7 (9) ◽  
pp. 761
Author(s):  
Anastasia I. Wasylyshyn ◽  
Kathleen A. Linder ◽  
Carol A. Kauffman ◽  
Blair J. Richards ◽  
Stephen M. Maurer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Proportional Hazards ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Antifungal Prophylaxis ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Acute Myeloid

This single-center retrospective study of invasive fungal disease (IFD) enrolled 251 adult patients undergoing induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) from 2014–2019. Patients had primary AML (n = 148, 59%); antecedent myelodysplastic syndrome (n = 76, 30%), or secondary AML (n = 27, 11%). Seventy-five patients (30%) received an allogeneic hematopoietic cell transplant within the first year after induction chemotherapy. Proven/probable IFD occurred in 17 patients (7%). Twelve of the 17 (71%) were mold infections, including aspergillosis (n = 6), fusariosis (n = 3), and mucomycosis (n = 3). Eight breakthrough IFD (B-IFD), seven of which were due to molds, occurred in patients taking antifungal prophylaxis. Patients with proven/probable IFD had a significantly greater number of cumulative neutropenic days than those without an IFD, HR = 1.038 (95% CI 1.018–1.059), p = 0.0001. By cause-specific proportional hazards regression, the risk for IFD increased by 3.8% for each day of neutropenia per 100 days of follow up. Relapsed/refractory AML significantly increased the risk for IFD, HR = 7.562 (2.585–22.123), p = 0.0002, and Kaplan-Meier analysis showed significantly higher mortality at 1 year in patients who developed a proven/probable IFD, p = 0.02. IFD remains an important problem among patients with AML despite the use of antifungal prophylaxis, and development of IFD is associated with increased mortality in these patients.

scholarly journals Single-agent and combination biologics in acute myeloid leukemia

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 548-556 ◽  
Author(s):  
Guillaume Richard-Carpentier ◽  
Courtney D. DiNardo
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Gemtuzumab Ozogamicin ◽  
Targeted Agents ◽  
Newly Diagnosed ◽  
Rational Drug ◽  
Genomic Characterization ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by recurrent genetic, epigenetic, and metabolic abnormalities. As a result of our increasing knowledge of the underlying biology of AML leading to rational drug development, several new targeted agents have been recently added to our therapeutic arsenal. The BCL2 inhibitor venetoclax in combination with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs) is safe and effective in older patients with newly diagnosed AML ineligible for intensive chemotherapy. Glasdegib, a hedgehog pathway inhibitor, may be used in combination with LDAC for the same indication and improves survival compared with LDAC alone. In newly diagnosed, fit, older patients with therapy-related AML or AML with myelodysplasia-related changes, the liposome-encapsulated combination of daunorubicin and cytarabine (CPX-351) has shown superiority over the 7 + 3 regimen. The presence of an IDH1 or IDH2 mutation can be effectively targeted by ivosidenib or enasidenib, respectively. Gemtuzumab ozogamicin improves event-free survival in CD33+ patients with favorable or intermediate-risk cytogenetics. With new targeted agents available, comprehensive genomic characterization of AML at diagnosis and relapse is increasingly necessary to select optimal treatment. Herein, we review the new single-agent and combination biologics (omitting FLT3 inhibitors, which are discussed separately) and provide recommendations on how to best use and manage patients on these regimens in clinical practice.

scholarly journals Diagnostic and molecular testing patterns in patients with newly diagnosed acute myeloid leukemia in the Connect ® MDS/AML Disease Registry

eJHaem ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 58-68
Author(s):  
Daniel A. Pollyea ◽  
Tracy I. George ◽  
Mehrdad Abedi ◽  
Rafael Bejar ◽  
Christopher R. Cogle ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Testing ◽  
Newly Diagnosed ◽  
Disease Registry ◽  
Testing Patterns ◽  
Acute Myeloid

Cellular Vascular Endothelial Growth Factor Is a Predictor of Outcome in Patients With Acute Myeloid Leukemia

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3717-3721 ◽  
Author(s):  
Alvaro Aguayo ◽  
Elihu Estey ◽  
Hagop Kantarjian ◽  
Taghi Mansouri ◽  
Cristi Gidel ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Acute Myeloid Leukemia ◽  
Growth Factor ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Vascular Endothelial ◽  
Newly Diagnosed ◽  
Endothelial Growth Factor ◽  
Vegf Level ◽  
Acute Myeloid

Abstract Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells. It has been associated with angiogenesis, growth, dissemination, metastasis, and poor outcome in solid tumors. To assess cellular VEGF levels and their prognostic significance in newly diagnosed acute myeloid leukemia (AML), we used a radioimmunoassay (RIA) to quantify VEGF levels in stored samples obtained before treatment from 99 patients with newly diagnosed AML treated at the MD Anderson Cancer Center from 1996 to 1998. Outcome in the 99 patients was representative of that observed in all patients seen at this institution with this diagnosis during these years, but the 99 patients had higher white blood cell (WBC) and blast counts than the other patients. Results of the RIA were confirmed by Western blot. There was a relationship between increasing VEGF levels and shorter survival (P = .01), as well as shorter disease-free survival, both from start of treatment and from complete response (CR) date. In contrast, there was no relationship between VEGF level and WBC or blast count, or between VEGF level and such established prognostic factors as age, cytogenetics, performance status, or presence of an antecedent hematologic disorder, and multivariate analysis indicated that VEGF was still prognostic for the above outcomes after accounting for these factors, as well as treatment. Our results suggest that at least in AML patients with higher WBC and blast counts, cellular VEGF level is an independent predictor of outcome.

Adverse Prognostic Significance of KIT Mutations in Adult Acute Myeloid Leukemia With inv(16) and t(8;21): A Cancer and Leukemia Group B Study

2006 ◽  
Vol 24 (24) ◽  
pp. 3904-3911 ◽  
Author(s):  
Peter Paschka ◽  
Guido Marcucci ◽  
Amy S. Ruppert ◽  
Krzysztof Mrózek ◽  
Hankui Chen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Direct Sequencing ◽  
Prognostic Significance ◽  
Prognostic Impact ◽  
Core Binding Factor ◽  
Relapse Risk ◽  
Binding Factor ◽  
Acute Myeloid

Purpose To analyze the prognostic impact of mutated KIT (mutKIT) in core-binding factor acute myeloid leukemia (AML) with inv(16)(p13q22) and t(8;21)(q22;q22). Patients and Methods Sixty-one adults with inv(16) and 49 adults with t(8;21), assigned to postremission therapy with repetitive cycles of higher dose cytarabine were analyzed for mutKIT in exon 17 (mutKIT17) and 8 (mutKIT8) by denaturing high-performance liquid chromatography and direct sequencing at diagnosis. The median follow-up was 5.3 years. Results Among patients with inv(16), 29.5% had mutKIT (16% with mutKIT17 and 13% with sole mutKIT8). Among patients with t(8;21), 22% had mutKIT (18% with mutKIT17 and 4% with sole mutKIT8). Complete remission rates of patients with mutKIT and wild-type KIT (wtKIT) were similar in both cytogenetic groups. In inv(16), the cumulative incidence of relapse (CIR) was higher for patients with mutKIT (P = .05; 5-year CIR, 56% v 29%) and those with mutKIT17 (P = .002; 5-year CIR, 80% v 29%) compared with wtKIT patients. Once data were adjusted for sex, mutKIT predicted worse overall survival (OS). In t(8;21), mutKIT predicted higher CIR (P = .017; 5-year CIR, 70% v 36%), but did not influence OS. Conclusion We report for the first time that mutKIT, and particularly mutKIT17, confer higher relapse risk, and both mutKIT17 and mutKIT8 appear to adversely affect OS in AML with inv(16). We also confirm the adverse impact of mutKIT on relapse risk in t(8;21) AML. We suggest that patients with core-binding factor AML should be screened for mutKIT at diagnosis for both prognostic and therapeutic purposes, given that activated KIT potentially can be targeted with novel tyrosine kinase inhibitors.

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