Dataset Information

Erdheim-Chester Disease and Acute Myeloid Leukemia with Mutated NPM1 in a Patient with Clonal Hematopoiesis: A Case Report.

ABSTRACT:

Background

Erdheim-Chester Disease (ECD) is a clonal non-Langerhans histiocytosis, classified as a macrophage-dendritic cell neoplasm in the 2016 WHO classification. The exact cell of origin of ECD is unknown, although some limited evidence suggests that it arises from myeloid progenitors.

Case presentation

A 43-year-old patient, diagnosed with BRAF ^V600E mutated ECD, developed NPM1⁺/FLT3⁺ acute myeloid leukemia (AML) with wild-type BRAF, 15 months after the initial ECD diagnosis. The patient received intensive chemotherapy plus midostaurin, followed by midostaurin maintenance. Six months into maintenance, the patient remains in complete remission with low-level measurable residual disease, whereas ECD shows a sustained partial metabolic response. Molecular karyotype at several distinct timepoints, namely ECD diagnosis, AML diagnosis, and following treatment of AML, highlighted a molecular signature, indicative of a persistent, underlying clonal hematopoiesis.

Conclusion

This case report suggests that ECD and AML might represent an expansion of two distinct clones in a background of clonal hematopoiesis, indicating their shared origin. Moreover, molecular karyotype might serve as a strong, inexpensive tool for revealing clonal hematopoiesis in cases of negative targeted next-generation sequencing. Finally, the moderate response of ECD to midostaurin suggests that kinase inhibition might have a potential role in ECD treatment.

SUBMITTER: Papageorgiou SG

PROVIDER: S-EPMC7678692 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Erdheim-Chester Disease and Acute Myeloid Leukemia with Mutated <i>NPM1</i> in a Patient with Clonal Hematopoiesis: A Case Report.

Papageorgiou Sotirios G SG Divane Aspasia A Roumelioti Maria M Kottaridi Christine C Bouchla Anthi A Georgakopoulos Alexandros A Ieremiadou Fotini F Daraki Aggeliki A Bazani Efthymia E Thomopoulos Thomas P TP Chatziioannou Sofia S Mavrogenis Andreas A Panayiotidis Panayiotis P Panayiotides Ioannis G IG Pappa Vasiliki V Foukas Periklis G PG

OncoTargets and therapy 20201116

<h4>Background</h4>Erdheim-Chester Disease (ECD) is a clonal non-Langerhans histiocytosis, classified as a macrophage-dendritic cell neoplasm in the 2016 WHO classification. The exact cell of origin of ECD is unknown, although some limited evidence suggests that it arises from myeloid progenitors.<h4>Case presentation</h4>A 43-year-old patient, diagnosed with <i>BRAF</i> <sup>V600E</sup> mutated ECD, developed <i>NPM1<sup>+</sup>/FLT3<sup>+</sup></i> acute myeloid leukemia (AML) with wild-type < ...[more]

PMID: 33235460

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Project description:IntroductionErdheim-Chester disease (ECD) is a rare disease that belongs to the group of Dendritic and histiocytic neoplasms. Only 2000 cases have been reported worldwide. It can present with a wide range of symptoms, making a differential diagnosis especially difficult. The primary and most important diagnostic tool is a biopsy of the affected organ/tissue. Nowadays the analysis of different mutations affecting the BRAF and MAPK pathways makes it possible to use targeted treatments, such as vemurafenib, dabrafenib, or cobimetinib.ObjectiveOur aim is to present the results of three male patients treated in our hematology department.ResultsOur BRAF mutation-positive patient presented with retroperitoneal tissue proliferation and diabetes insipidus. The initial therapy of choice was dabrafenib. After 3 months of treatment, 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) scans showed regression, and after 2 years of treatment, no disease activity was detected. In our second patient, a recurrent febrile state (not explained by other reasons) and diabetes insipidus suggested the diagnosis. A femoral bone biopsy confirmed BRAF-negative ECD. The first-line therapy was interferon-alpha. After 3 months of treatment, no response was observed on 18FDG-PET/CT, and treatment with cobimetinib was started. The control 18FDG-PET/CT imaging was negative. Our third patient was evaluated for dyspnea, and a CT scan showed fibrosis with hilar lymphadenomegaly. A lung biopsy confirmed BRAF-negative ECD. We started treatment with interferon-alpha, but unfortunately, no improvement was observed. Second-line treatment with cobimetinib resulted in a partial metabolic response (PMR) according to control 18FDG-PET/CT.ConclusionsOur results demonstrate that an appropriately chosen treatment can lead to a good therapeutic response, but dose reduction may be necessary due to side effects. With advanced targeted therapeutic treatment options, survival and quality of life are significantly improved.