Improved survival of AML patients by addition of cladribine to standard induction chemotherapy

Doma, Saša Anžej; Škerget, Matevž; Pajič, Tadej; Sever, Matjaž

doi:10.1007/s00277-020-03923-9

Cited by 8 publications

(3 citation statements)

References 18 publications

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“…Patients who relapsed had a median time of relapse of 12 months after the previous occurrence of the disease. The majority of r/r patients had previously received daunorubicin-cytarabine-based chemotherapy: 75 patients DA3+7, 27 patients DA3+7+cladribine [17,18], and 2 patients received hypomethylating agents before FLAG(-Ida).…”

Section: Resultsmentioning

confidence: 99%

FLAG/FLAG-Ida Regimen in Secondary and Relapsed/Refractory Acute Myeloid Leukemia—Even in the Era of New Treatment Modalities Still a Significant Player

Anžej Doma,

Sever,

Jakoš

et al. 2024

JCM

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(1) Background: Relapsed/refractory (r/r) and secondary acute myeloid leukemia are highlighted by chemoresistance and poor outcomes. The aim of the study was to assess the efficacy and toxicity of fludarabine, cytarabine, and granulocyte-colony stimulation factor (FLAG) with or without idarubicin (-Ida) and to discuss novel therapies in this setting. (2) Methods: Clinical and cytogenetic data on 130 consecutive patients with r/r and secondary AML treated at our center were retrospectively analyzed. (3) Results: There were 48, 56, and 26 patients with relapsed, refractory, and secondary AML, respectively. The median age was 60 years. The overall response was achieved in 70% of patients. The median overall survival (OS) time for the whole group was 9.4 months. In total, 47% of patients proceeded to allogeneic hematopoietic stem cell transplantation (aHSCT) and these patients had significantly prolonged OS compared to the others (63 months vs. 4.2 months; p < 0.001). Among the variables, including age, FLT3 mutation status, European LeukemiaNet (ELN) 2022 classification risk, FLAG vs. FLAG-Ida, and aHSCT, a multivariate analysis revealed that only aHSCT significantly influenced overall survival. (4) Conclusions: FLAG(-Ida) chemotherapy remains an effective salvage chemotherapy for patients with r/r and secondary AML with a plan of proceeding to aHSCT.

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Section: Resultsmentioning

confidence: 99%

FLAG/FLAG-Ida Regimen in Secondary and Relapsed/Refractory Acute Myeloid Leukemia—Even in the Era of New Treatment Modalities Still a Significant Player

Anžej Doma,

Sever,

Jakoš

et al. 2024

JCM

Self Cite

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“…Through the analysis of treatment response and survival, the study found that the response rate in the DAC group was significantly higher than that in the DA3+7 group, and the overall survival in the DAC group was also exceptionally prolonged. This suggested that the addition of cladribine to standard induction chemotherapy regimens could improve response rates and overall survival in patients with AML [7].…”

Section: Induction Of Chemotherapymentioning

confidence: 99%

Clinical Treatment Value of Acute Myeloid Leukemia in Different Genotypes

Ji,

Niu

2024

J Clin Med Res

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Acute myeloid leukemia (AML), a disease formed by mutations in pluripotent stem cells or mildly differentiated precursor cells, is a clonal malignant disease of the hematopoietic system. In recent years, with the application of immunology, cytogenetics, and molecular biology, a deeper understanding of the biological properties of AML tumor cells has laid the foundation for accurate classification, diagnosis, prognosis, and selection of the optimal treatment for AML. This article reviewed the relevant literature on the difference in clinical diagnosis and treatment value of AML in different genotypes in recent years.

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“…AML has emerged as the leading cause of leukemia-related deaths in the US 2 . While outcomes of pediatric AML have improved significantly 3 , AML remains a major clinical concern particularly among older patients 4 and those with relapsed disease 5 – 8 Despite introduction of new therapies, the 5-year survival remains below 30%. It appears that the efficacy of currently available treatments and their combinations may have reached a plateau 9 – 11 .…”

Section: Introductionmentioning

confidence: 99%

In silico predicted compound targeting the IQGAP1-GRD domain selectively inhibits growth of human acute myeloid leukemia

Sahasrabudhe,

Liesveld,

Minhajuddin

et al. 2024

Sci Rep

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Acute myeloid leukemia (AML) is fatal in the majority of adults. Identification of new therapeutic targets and their pharmacologic modulators are needed to improve outcomes. Previous studies had shown that immunization of rabbits with normal peripheral WBCs that had been incubated with fluorodinitrobenzene elicited high titer antibodies that bound to a spectrum of human leukemias. We report that proteomic analyses of immunoaffinity-purified lysates of primary AML cells showed enrichment of scaffolding protein IQGAP1. Immunohistochemistry and gene-expression analyses confirmed IQGAP1 mRNA overexpression in various cytogenetic subtypes of primary human AML compared to normal hematopoietic cells. shRNA knockdown of IQGAP1 blocked proliferation and clonogenicity of human leukemia cell-lines. To develop small molecules targeting IQGAP1 we performed in-silico screening of 212,966 compounds, selected 4 hits targeting the IQGAP1-GRD domain, and conducted SAR of the ‘fittest hit’ to identify UR778Br, a prototypical agent targeting IQGAP1. UR778Br inhibited proliferation, induced apoptosis, resulted in G2/M arrest, and inhibited colony formation by leukemia cell-lines and primary-AML while sparing normal marrow cells. UR778Br exhibited favorable ADME/T profiles and drug-likeness to treat AML. In summary, AML shows response to IQGAP1 inhibition, and UR778Br, identified through in-silico studies, selectively targeted AML cells while sparing normal marrow.

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Improved survival of AML patients by addition of cladribine to standard induction chemotherapy

Cited by 8 publications

References 18 publications

FLAG/FLAG-Ida Regimen in Secondary and Relapsed/Refractory Acute Myeloid Leukemia—Even in the Era of New Treatment Modalities Still a Significant Player

FLAG/FLAG-Ida Regimen in Secondary and Relapsed/Refractory Acute Myeloid Leukemia—Even in the Era of New Treatment Modalities Still a Significant Player

Clinical Treatment Value of Acute Myeloid Leukemia in Different Genotypes

In silico predicted compound targeting the IQGAP1-GRD domain selectively inhibits growth of human acute myeloid leukemia

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