PhD Scientific Days 2022

Pathology and Oncology II. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Trametinib Therapy and Disease Monitoring by Mutation Specific Droplet Digital PCR in Relapsed Pediatric Acute Myeloid Leukemia: a Case Report

Előadó neve

Dr. Krizsán, Szilvia

Előadó munkahelye

1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

+36202334232

Előadó e-mail címe

krizsan.szilvia@med.semmelweis-univ.hu

Az előadás címe

Trametinib Therapy and Disease Monitoring by Mutation Specific Droplet Digital PCR in Relapsed Pediatric Acute Myeloid Leukemia: a Case Report

Szerző(k) neve és munkahelye

Szilvia Krizsán1, Péterffy Borbála1, Lajos Hegyi1, Dániel János Erdélyi2, Krisztián Kállay3, Gergely Kriván3, Gábor Kovács3, Donát Alpár1*, Csaba Bödör1*

1 HCEMM-SE Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; 2Second Department of Pediatrics, Semmelweis University, Budapest, Hungary; 3Pediatric Hematology and Stem Cell Transplantation Unit, Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Pathology and Oncology II. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

English

Preferred session

Pathology and Oncology

Összefoglaló szövege

Introduction: Pediatric acute myeloid leukemia has a relatively poor prognosis, as relapse remains the major cause of treatment failure in 30% of patients. Lack of sensitive molecular markers for the detection of measurable residual disease (MRD) is a major challenge. Here, we present the case of a relapsed pediatric AML patient with NRAS mutation, where droplet digital PCR (ddPCR) was used for MRD monitoring following HSCT and trametinib maintenance treatment.
Clinical history: A 1.5-year-old boy presented with fever, tonsillitis, jaundice and pronounced hepatosplenomegaly in August 2016. The peripheral blood count revealed severe anemia and thrombocytopenia. Flow cytometry detected 20% blasts, while histology examination of the bone marrow showed dysplastic features. The patient was treated according to the AML-BFM 98 protocol. The treatment resulted in complete remission with MRD positivity as determined by flow cytometry. In February 2017, he received allogeneic hematopoietic stem cell transplantation (HSCT) with Bu-Flu + ATG conditioning regimen.
18 months following the HSCT, the patient relapsed with 25% blasts detected in the bone marrow, while FISH analysis revealed clonal evolution as a subclonal chromosome 8 trisomy emerged. FLA-HAM salvage therapy was administered to the patient. At this time, targeted next-generation sequencing (NGS) of 54 genes was performed revealing an NRAS p.Q61R mutation. For disease monitoring purposes, a droplet digital PCR assay was designed specifically for this mutation. We were able to detect the mutation retrospectively both at diagnosis and at relapse with VAFs of 14% and 8%, respectively. In January 2019, the patient underwent a second HSCT. One-month post-HSCT, MEK inhibitor trametinib maintenance therapy was initiated with an aim of targeting the residual cells with NRAS mutation. The patient is currently monitored every 3 months using ddPCR, and he remained in complete clinical and molecular remission for more than two years following his second HSCT.
Conclusion: Treatment of pediatric AML remains an unsolved challenge, as risk of relapse is high and due to the lack of molecular markers early recognition of relapses is difficult. The presented case demonstrates how NGS can identify potent targets of novel therapies and how new sensitive technologies can be utilized in disease monitoring.

This work was funded by the EU’s Horizon 2020 research and innovation program under grant agreement No. 739593, by the Ministry of Innovation and technology of Hungary from the National Research, Development and InnovationFund, financed under the K21_137948, FK20_134253, TKP2021-EGA-24 and TKP2021-NVA-15 funding schemes, the EFOP-3.6.3-VEKOP-16-2017-00009 grant, and Elixir Hungary.

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine

Supervisor

Dr. Bödör Csaba, Dr. Alpár Donát

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4662

Start

11:20

End

11:25

Authors (legacy)

Szilvia Krizsán1, Péterffy Borbála1, Lajos Hegyi1, Dániel János Erdélyi2, Krisztián Kállay3, Gergely Kriván3, Gábor Kovács3, Donát Alpár1*, Csaba Bödör1*

1 HCEMM-SE Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; 2Second Department of Pediatrics, Semmelweis University, Budapest, Hungary; 3Pediatric Hematology and Stem Cell Transplantation Unit, Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary