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      Acute myeloid leukemia synchronous with multiple myeloma successfully treated by azacytidine/lenalidomide and daratumumab without a decrease in myeloid clone size

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          Abstract

          Synchronous diagnosis of acute myeloid leukemia (AML) and symptomatic multiple myeloma (MM) is a rare situation that poses serious therapeutic difficulties. We report the case of a 68-year-old male which evolved simultaneously to symptomatic MM and AML. Both diseases first responded to treatment for 40 months after 7+3 induction and maintenance therapy of azacytidine + lenalidomide. MM relapsed first and was treated with azacytidine + daratumumab, which led an additional 15 months of progression-free survival. Little myeloid clonal size reduction over time was seen. This case shows that AML and MM can be effectively treated simultaneously using appropriate combinations.

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          Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents

          Jane Merlevede, Nathalie Droin, Tingting Qin … (2016)
          The cytidine analogues azacytidine and 5-aza-2'-deoxycytidine (decitabine) are commonly used to treat myelodysplastic syndromes, with or without a myeloproliferative component. It remains unclear whether the response to these hypomethylating agents results from a cytotoxic or an epigenetic effect. In this study, we address this question in chronic myelomonocytic leukaemia. We describe a comprehensive analysis of the mutational landscape of these tumours, combining whole-exome and whole-genome sequencing. We identify an average of 14±5 somatic mutations in coding sequences of sorted monocyte DNA and the signatures of three mutational processes. Serial sequencing demonstrates that the response to hypomethylating agents is associated with changes in DNA methylation and gene expression, without any decrease in the mutation allele burden, nor prevention of new genetic alteration occurence. Our findings indicate that cytosine analogues restore a balanced haematopoiesis without decreasing the size of the mutated clone, arguing for a predominantly epigenetic effect.
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            Daratumumab in multiple myeloma

            Ajay K. Nooka, Jonathan Kaufman, Craig C. Hofmeister … (2019)
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              Myeloid neoplasms secondary to plasma cell myeloma: an intrinsic predisposition or therapy-related phenomenon? A clinicopathologic study of 41 cases and correlation of cytogenetic features with treatment regimens.

              F. Wang, Catherine Yen-Yen Liu, Selim M. Arcasoy … (2012)
              We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%), acute myeloid leukemia (AML) in 4 (9.8%), and myeloproliferative neoplasm (MPN) or MDS/MPN in 3 (7.3%) cases. The latency from treatment to diagnosis of MN ranged from 9 to 384 months, with a median of 60 months. Of 37 cases with cytogenetic studies, complex abnormalities were detected in 22 (59.5%), -5(q)/-7(q) in 4 (10.8%), other abnormalities in 8 (21.6%), and normal karyotype in 3 (8.1%) cases. Complex abnormalities and -5(q)/-7(q) correlated directly with multiple chemotherapeutic regimens, particularly with combined melphalan/cyclophosphamide. Moreover, the features of cytogenetic abnormalities in our series were significantly different from those with concomitant PCM/MN who had significantly lower complex abnormalities. The latency, skewed proportion of MDS, and bias toward complex cytogenetic abnormalities/unbalanced aberrations of chromosomes 5/7 suggested an alkylating mutagenic effect on pathogenesis of secondary MN. Kaplan-Meier survival analysis demonstrated a median survival of 19 months, which was better than that for therapy-related (t)-MDS/AML. In contrast to t-MDS, the survival in our patients appeared to depend on subtypes of MDS as seen in de novo diseases.
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                Author and article information

                Contributors
                Bruno Quesnel
                Journal
                Journal ID (nlm-ta): Leuk Res Rep
                Journal ID (iso-abbrev): Leuk Res Rep
                Title: Leukemia Research Reports
                Publisher: Elsevier
                ISSN (Electronic): 2213-0489
                Publication date PMC-release: 23 April 2020
                Publication date Collection: 2020
                Publication date (Electronic): 23 April 2020
                Volume: 13
                Electronic Location Identifier: 100202
                Affiliations
                [a ]CHU Lille, Service des Maladies du Sang, F-59000 Lille, FRANCE
                [b ]CNRS, Inserm, UMR9020 – UMR-S 1277 - Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, FRANCE
                [c ]CHU Lille, Laboratory of Hematology, F-59000 Lille, FRANCE
                [d ]Univ. Lille, F-59000 Lille, FRANCE
                Author notes
                [* ]Corresponding author: Bruno QUESNEL, Service des Maladies du Sang, Centre Hospitalier et Universitaire de Lille, Rue Polonovski, F-59037, Lille, France. bruno.quesnel@ 123456chru-lille.fr
                Article
                Publisher ID: S2213-0489(20)30008-X Publisher ID: 100202
                DOI: 10.1016/j.lrr.2020.100202
                PMC ID: 7191213
                SO-VID: 06840f8c-ef0b-4326-86ed-a02ece44d5e6
                Copyright © © 2020 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 20 December 2019
                Date revision received : 15 April 2020
                Date accepted : 19 April 2020
                Categories
                Subject: Article

                Keywords: myeloma,aml,cmml,azacytidine,lenalidomide,daratumumab,clonality
                Data availability:
                Keywords: myeloma, aml, cmml, azacytidine, lenalidomide, daratumumab, clonality

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