IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen

Libura, Marta; Białopiotrowicz, Emilia; Giebel, Sebastian; Wierzbowska, Agnieszka; Roboz, Gail J.; Piątkowska−Jakubas, Beata; Pawelczyk, Marta; Górniak, Patryk; Borg, Katarzyna; Wojtas, Magdalena; Florek, Izabella; Matiakowska, Karolina; Jaźwiec, Bożena; Solarska, Iwona; Noyszewska‐Kania, Monika; Piechna, Karolina; Zawada, Magdalena; Czekalska, Sylwia; Salamanćzuk, Z.; Karabin, Karolina; Wasilewska, Katarzyna; Paluszewska, Monika; Urbanowska, Elżbieta; Gajkowska-Kulik, Justyna; Semeńczuk, Grażyna; Rybka, Justyna; Wróbel, Tomasz; Ejduk, Anna; Kata, Dariusz; Grosicki, Sebastian; Robak, Tadeusz; Pluta, Agnieszka; Kominek, Agata; Piwocka, Katarzyna; Pyziak, Karolina; Sroka-Porada, Agnieszka; Wróbel, Anna; Przybyłowicz, Agnieszka; Wojtaszewska, Marzena; Lewandowski, Krzysztof; Gil, Lidia; Piekarska, Agnieszka; Knopińska, Wanda; Bołkuń, Łukasz; Warzocha, Krzysztof; Kuliczkowski, Kazimierz; Sacha, Tomasz; Basak, Grzegorz W.; Jędrzejczak, Wiesław Wiktor; Hołowiecki, Jerzy; Juszczyński, Przemysław; Haus, Olga

doi:10.1038/s41598-021-88120-y

Cited by 7 publications

(2 citation statements)

References 54 publications

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“…Cladribine has also been reported to have hypomethylating activity ( 45 ), which was proven in previous studies by Libura et al. ( 46 ). Patients diagnosed with AML and coexisting IDH1/2 mutations leading to DNA hypermethylation and epigenetic dysregulation had more successful outcomes when cladribine was applied in the induction protocol.…”

Section: Discussionsupporting

confidence: 55%

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

Karasek,

Armatys,

Skarupski

et al. 2024

Front. Oncol.

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IntroductionMixed-phenotype acute leukemia (MPAL) is a rare disease with poor prognosis. So far, no standard approach has been established as the “know-how” of MPAL is based only on retrospective analyses performed on small groups of patients.Materials and methodsIn this study, a retrospective analysis of the outcomes of adult MPAL patients included in the PALG registry between 2005 and 2024 who received the CLAG-M hybrid protocol as induction or salvage therapy was performed.ResultsSixteen of 98 MPAL patients received CLAG-M: eight as first-line and eight as salvage therapy. In the first line, two patients achieved partial response (PR), and six achieved complete remission (CR), of whom four successfully underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). Two patients who did not undergo alloHSCT promptly relapsed. Within the whole group, the overall response rate (ORR) was 75% (n = 12/16). With the median follow-up of 13 months, six out of eight patients remain in CR, however, two of them died due to acute graft versus host disease. Out of eight patients who received CLAG-M in the second line, four patients (50%) obtained CR. AlloHSCT was conducted in seven cases, six of which were in CR. Only two patients remained in CR at the time of the last follow-up. Tolerance to treatment was good. The median times for severe neutropenia and thrombocytopenia were 22 days (range, 16–24) and 17 days (range, 12–24), respectively. Overall, grade 3-4 infections were observed in 12 cases, and all infections presented successful outcomes.ConclusionsCLAG-M is an effective first-line salvage regimen for MPAL with an acceptable safety profile. Early achievement of CR with prompt alloHSCT allows for satisfactory disease control.

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Section: Discussionsupporting

confidence: 55%

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

Karasek,

Armatys,

Skarupski

et al. 2024

Front. Oncol.

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“…Recent correlative studies between molecular biomarkers and clinical outcomes primarily focus on single-genes or broad, heterogeneous risk groups 13,[31][32][33] . This has challenged integration of findings into generalizable clinical algorithms to guide patient management.…”

Section: Discussionmentioning

confidence: 99%

Unified classification and risk-stratification in Acute Myeloid Leukemia

et al. 2022

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Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each class represents diverse biological AML subgroups, and is associated with distinct clinical presentation, likelihood of response to induction chemotherapy, risk of relapse and death over time. Secondary AML-2, emerges as the second largest class (24%), associates with high-risk disease, poor prognosis irrespective of flow Minimal Residual Disease (MRD) negativity, and derives significant benefit from transplantation. Guided by class membership we derive a 3-tier risk-stratification score that re-stratifies 26% of patients as compared to standard of care. This results in a unified framework for disease classification and risk-stratification in AML that relies on information from cytogenetics and 32 genes. Last, we develop an open-access patient-tailored clinical decision support tool.

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Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients

Shi,

Chen,

Jin

et al. 2024

Ann Hematol

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IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen

Cited by 7 publications

References 54 publications

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

Unified classification and risk-stratification in Acute Myeloid Leukemia

Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients

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