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Clonal monocytosis reflects a preneoplastic or neoplastic sustained increase in the absolute monocyte count in the absence of reactive causes. Causes of clonal monocytosis include clonal cytopenias with monocytosis and acute and chronic myeloid neoplasms. Chronic myelomonocytic leukemia is a prototypical myelodysplastic/myeloproliferative overlap neoplasm in adults, characterized by sustained peripheral blood monocytosis. Kidney abnormalities, including acute kidney injury and chronic kidney disease, are frequent in patients with chronic myelomonocytic leukemia and are predictors of worse outcomes. In addition, acute kidney injury/chronic kidney disease often limits eligibility for allogeneic stem cell transplantation or enrollment in clinical trials. In this review, we highlight clonal monocytosis-related etiologies that give rise to acute kidney injury and chronic kidney disease, with special emphasis on chronic myelomonocytic leukemia and lysozyme-induced nephropathy. Monocytes produce lysozyme, which, in excess, can accumulate in and damage the proximal renal tubular epithelium. Early identification of this etiology and a timely reduction in monocyte counts can salvage kidney function. Other etiologies of kidney injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, autoimmune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of kidney injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Approximately one-third of patients with myeloid disorders like myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) exhibit inflammatory and autoimmune disorders (IADs). These IADs often include atypical and incomplete forms of common autoimmune conditions, and exhibit resistance to conventional immunosuppressive therapies. There is growing interest in molecular relationships between IADs and MDS/CMML to find potential targeted therapies. Recently, patients with somatic mutations in the UBA1 gene were identified as having VEXAS syndrome. Herein, we present a concise case-series illustrating concurrent elderly-onset inflammatory manifestations and myeloid disorders (MDS, CMML, and idiopathic cytopenia of undetermined significance). These patients manifested inflammatory or autoimmune symptoms, including erythema nodosum, Raynaud's phenomenon, Sjogren syndrome, and refractory pruritus, having onset after 60-years of age. The inflammatory manifestations were largely refractory to traditional immunosuppressive regimens. Remarkably, treatment with a JAK-1 inhibitor, upadacitinib, in two cases yielded marked resolution of inflammatory symptoms, facilitating the gradual tapering of corticosteroids, improvement of hemoglobin levels, and reduction in serum C-reactive protein levels. Upon loss of response to upadacitinib, JAK-2 inhibitor ruxolitinib provided clinical benefit in one of the cases, facilitating further tapering of glucocorticoids. This arena warrants further exploration through prospective studies of larger cohorts to delineate optimal management strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We present a case of acute-onset orbital inflammation with rapidly progressive proptosis, episcleral venous stasis with raised intraocular pressure and loss of vision in a patient with a recent diagnosis of chronic myelomonocytic leukaemia (CMML). The patient's orbital inflammation and ocular hypertension showed no response to topical and systemic pressure-lowering agents and non-steroidal anti-inflammatory agents but resolved rapidly after the commencement of intravenous steroids. The patient was subsequently treated with the hypomethylating agent azacitidine with good systemic control of CMML with no further orbital inflammation. CMML is strongly associated with systemic inflammatory disease, possibly due to the upregulation of inflammatory pathways in the abnormal monocytes. CMML is a rare cause of orbital or ocular inflammation but should be considered in patients with persistent monocytosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A 67-year-old woman with past medical history of chronic myelomonocytic leukemia (CMML) presented with a chief complaint of headache, diplopia, and hearing impairment in the right ear. Examination revealed impaired ocular movement in the left eye and sensorineural hearing loss in the right ear. Cerebrospinal fluid analysis showed increased cell count and protein, and MRI showed contrast enhancement of hypertrophic dura mater. Since there were no other abnormalities which would have been a cause of hypertrophic pachymeningitis, it was considered as systemic autoimmune/inflammatory disorder (SAID) associated with CMML. Treatment with steroid, cyclophosphamide, and methotrexate led to improvement of the symptoms. SAIDs develop in up to 25% of patients with myelodysplastic syndromes (MDS) or CMML, which may be the only symptoms of MDS/CMML. As a phenotype of SAIDs, systemic vasculitis, connective tissue diseases, and neutrophilic diseases are frequently reported; however, isolated involvement of central nerve system is rarely reported. To our knowledge, this is the first report of hypertrophic pachymeningitis as SAID associated with CMML. To clarify the pathogenesis of neurologic involvement of SAIDs, accumulation of cases is necessary.

Competing Interests: Conflicts of interest Dr Piguet has received honoraria or fees for consulting and/or speaking for AbbVie, Almirall, Celgene, Janssen, Novartis, and Pfizer and has received departmental support for Cardiff University from AbbVie, Almirall, Alliance, Beiersdorf UK Ltd, Biotest, Celgene, Dermal, Eli Lilly, Galderma, Genus Pharma, Globe Micro, Janssen-Celag, La Roche-Posay, L'Oreal, LEO Pharma, Meda, MSD, Novartis, Pfizer, Sinclair Pharma, Spirit, Stiefel, Samumed, Thornton Ross, TyPham, and UCB and for University of Toronto from Sanofi. Dr Croitoru has received honoraria or fees for consulting and/or speaking for AbbVie, Amgen, Bausch Health, Boehringer-Ingelheim, Novartis, Pfizer, Sanofi-Regeneron, and UCB. Drs Huang, McMullan, and Maazi have no conflicts of interests to declare.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy, typically characterised by cutaneous lesions and bone marrow involvement. We present a unique case of a woman in her 70s, initially seen for a spontaneous swelling on her left external ear resembling a haematoma, which recurred after initial treatment, triggering further evaluation.Diagnostic challenges arose as the patient displayed positive markers for Myeloperoxidase (MPO) (p-ANCA), suggesting vasculitis. Dermatology considered various differential diagnoses, but imaging and tests ruled out significant pathology. Steroid treatment led to improvement, but coincided with a surge in white cell count (WCC), prompting an urgent haematological review.Subsequent investigations, including a punch biopsy of the external ear and a bone marrow biopsy revealed BPDCN concurrent with chronic myelomonocytic leukaemia. This case highlights the challenging diagnostic journey, emphasising the need for multidisciplinary collaboration and the potential for unique BPDCN presentations, expanding our understanding of this malignancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Traditionally, skin involvement in chronic myelomonocytic leukemia (CMML) has been considered to be either specific (leukemia cutis) or non-specific, with granulomatous dermatitis included in the latter group. More recently, the true nature of the myeloid cells present in the cutaneous infiltrates of this theoretically reactive dermatitis is being clarified with the use of new molecular techniques such as next-generation sequencing. The same mutations in bone marrow (BM) myeloid neoplastic cells and in the cells of cutaneous infiltrates have been found. We present the case of a 77-year-old man who presented with spread and treatment-resistant skin granulomatous lesions previous to the diagnosis of CMML. The same clonal mutations in SRSF2, IDH1, and RUNX1 were found in both skin and BM with resolution of the lesions after the initiation of azacytidine. In conclusion, we report an exceptional case in which specific granulomatous cutaneous lesions have preceded and allowed the earlier diagnosis of an underlying CMML and a review of all previous similar cases in the literature, including molecular alterations., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Splenic infarction is a rare cause of acute abdomen. The two main causes are thromboembolic diseases and infiltrative hematological disorders. The splenic abscess is the result of a hematogenous seeding, whose causes are trauma, splenic artery embolization, endocarditis, and immunocompromised states., Clinical Case: 48-year-old male patient with a history of chronic myelomonocytic leukemia on mercaptopurine-based treatment, who presented intermittent asthenia, adynamia, and abdominal distension for 2 months; a computed tomography of the abdomen with intravenous contrast was performed, reporting areas of infarction and an image suggestive of a splenic abscess in the upper pole, for which an open splenectomy was performed with adequate clinical evolution. A documentary review of the disease and of the therapeutic options was carried out, with an emphasis on surgical management., Conclusion: The main cause of morbidity and mortality in the case presented was splenic infarction, which is aggravated by the presence of hematological diseases; therefore, the identification of those patients at risk of complications will allow in a timely manner a diagnostic and therapeutic approach, and the detection of those who require urgent surgical management., (Licencia CC 4.0 (BY-NC-ND) © 2024 Revista Médica del Instituto Mexicano del Seguro Social.)

Ten-eleven translocation 2 ( TET2 ) plays a pivotal role in epigenetic regulation, cell differentiation, and the inflammatory response. It also mediates the transcriptional regulation for inflammatory cytokines, particularly interleukin-6. While loss-of-function mutation in TET2 has been associated with hematological malignancies, it has been increasingly recognized to cause atherosclerotic disease. The increased atherogenicity is thought to be the result of increased production of pro-inflammatory interleukin-1β cytokines following activation of NLRP3 inflammasomes. We present a unique case of recurrent atherothrombosis in an elderly man who was diagnosed with chronic myelomonocytic leukemia in the setting of TET2 mutation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Systemic inflammatory or autoimmune diseases (SIAD) are observed in up to a quarter of patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), with a broad clinical spectrum including asymptomatic biological abnormalities, isolated inflammatory clinical manifestations (recurrent fever, arthralgia, neutrophilic dermatoses…) or identified systemic diseases (giant cell arteritis, recurrent polychondritis…). Recent advances in molecular biology have shed new light on the pathophysiological mechanisms that link inflammatory manifestations and myeloid hemopathies, particularly in VEXAS syndrome following the identification of somatic mutations in the UBA1 gene, or in neutrophilic dermatoses with the concept of myelodysplasia cutis. Although the presence of SIAD does not seem to affect overall survival or the risk of transformation into acute myeloid leukemia, their treatment remains a challenge given the frequent high level of corticosteroid dependence as well as the poor efficacy and tolerance (cytopenias, infections) of conventional immunosuppressive agents. Recent prospective data supports the interest of a therapeutic strategy using demethylating agents and notably azacitidine to target the pathological clone., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Azacitidine (Aza) combined with donor lymphocyte infusions (DLI) is an established treatment for relapse of myeloid malignancies after allogeneic transplantation. Based on its immunomodulatory and anti-leukemic properties we considered Lenalidomide (Lena) to act synergistically with Aza/DLI to improve outcome. We, therefore, prospectively investigated tolerability and efficacy of this combination as first salvage therapy for adults with post-transplant relapse of acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia. Patients were scheduled for eight cycles Aza (75 mg/m2 day 1-7), Lena (2.5 or 5 mg, days 1-21) and up to three DLI with increasing T-cell dosages (0.5×106-1.5×107 cells/kg). Primary endpoint was safety, while secondary endpoints included response, graft-versus-host disease (GvHD) and overall survival (OS). Fifty patients with molecular (52%) or hematological (48%) relapse of myelodysplastic syndromes (n=24), acute myeloid leukemia (n=23) or chronic myelomonocytic leukemia (n=3) received a median of seven (range, 1-8) cycles including 14 patients with 2.5 mg and 36 with 5 mg Lena daily dosage. Concomitantly, 34 patients (68%) received at least one DLI. Overall response rate was 56% and 25 patients (50%) achieved complete remission being durable in 80%. Median OS was 21 months and 1-year OS rate 65% with no impact of type of or time to relapse and Lena dosages. Treatment was well tolerated indicated by febrile neutropenia being the only grade ≥3 non-hematologic adverse event in >10% of patients and modest acute (grade 2-4 24%) and chronic (moderate/severe 28%) GvHD incidences. In summary, Lena can be safely added to Aza/DLI without excess of GvHD and toxicity. Its significant anti-leukemic activity suggests that this combination is a novel salvage option for post-transplant relapse (clinicaltrials gov. Identifier: NCT02472691).

Competing Interests: Conflicts of interest the authors declare they have no conflicts of interest.

We illustrate a rare case of coexisting extramedullary manifestation of CMML and new onset follicular lymphoma within the same core-needle biopsy of a lymph node. We discuss the differences between extramedullary hematopoiesis and extramedullary manifestation of myeloid neoplasms. We also highlight the importance of generous tissue sampling and thorough examination of nodal tissue in the setting of an established myeloid neoplasm to avoid missing rare but possible nodal involvement.

Objective: Hypomethylating agents may have adverse effects such as cytopenias, cytopenia associated infections and fatality due to infections despite their favorable effects in the treatment of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The infection prophylaxis approach is based on expert opinions and real-life experiences. Hence, we aimed to reveal the frequence of infections, predisposing factors of infection and to analyse infection attributable mortality in patients with high-risk MDS, CMML and AML who received hypomethylating agents in our center where routine infection prophylaxis is not applied., Material-Method: 43 adult patients with AML or high-risk MDS or CMML who received HMA ≥ 2 consecutive cycles from January 2014 to December 2020 were enrolled in the study., Results: 43 patients and 173 treatment cycles were analyzed. The median age was 72 years and 61.3 % of patients were males. The distribution of the patients' diagnoses was; AML in 15 patients (34.9 %), high risk MDS in 20 patients (46.5 %), AML with myelodysplasia-related changes in 5 patients (11.6 %) and CMML in 3 patients (7 %). 38 infection events (21.9 %) occurred in 173 treatment cycles. 86.9 % (33 cycles) and 2.6 % (1 cycle) of infected cycles were bacterial and viral infections, respectively and 10.5 % (4 cycles) were bacterial and fungal concurrently. The most common origin of the infection was respiratory system. Hemoglobin count was lower and CRP level was higher at the beginning of the infected cycles significantly (p values were 0.002 and 0.012, respectively). Requirement of red blood cell and platelet transfusions were found to be significantly increased in the infected cycles (p values were 0.000 and 0.001, respectively). While > 4 cycles of treatment and increased platelet count were found to be protective against infection, > 6 points of Charlson Comorbidity Index (CCI) were found to increase the risk of infection. The median survival was 7.8 months in non-infected cycles while 6.83 months in infected cycles. This difference was not statistically significant (p value was 0.077)., Discussion: The prevention and management of infections and infection-related deaths in patients treated with HMAs is crucial. Therefore, patients with a lower platelet count or a CCI score of > 6 may be candidates for infection prophylaxis when exposed to HMAs., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In a retrospective study, we analyzed the prevalence of subnormal prothrombin time (PT) values in 104 patients with chronic myelomonocytic leukemia (CMML), their potential prognostic impact, and potential correlations with clinicolaboratory features. Reduced PT values (< 70%) were found in 45/104 (43%) patients. The median survival of patients with reduced PT values was significantly shorter than in patients with normal PT (19 vs. 49 months, p = 0.006). Patients with reduced PT had higher leukocyte counts, a higher proportion of circulating blast cells, and lower platelet counts. In patients for whom clinical information was available, there was no difference in the incidence of bleeding complications between patients with or without reduced PT. Our results show a high prevalence of plasmatic coagulation abnormalities in patients with CMML, which were associated with laboratory features of advanced disease. Moreover, subnormal PT values were identified as a new prognostic marker. Reduced PT values do not seem to have a clinical impact regarding bleeding complications., (© 2022. The Author(s).)

Abstract: Indeterminate dendritic cell tumor (IDCT) is an exceedingly rare neoplasm that can be associated with hematopoietic malignancies. We report a case of multifocal cutaneous blastic indeterminate dendritic cell tumor (BIDCT) in a 75-year-old man with chronic myelomonocytic leukemia showing blastic histiocytoid morphology, positivity for CD1a and S100, and no expression of langerin. We present a literature review on the 11 reported cases of IDCTs/BIDCTs associated with chronic myelomonocytic leukemia (CMML), including this case. The clinicopathological characteristics have been summarized. The IDCT and CMML cells are clonally related in 4 tested cases. Patients with IDCT/BIDCT associated with CMML seem to have worse clinical outcomes compared with patients with IDCT not associated with CMML., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE., Methods: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders., Results: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83)., Conclusions: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are reported in up to 20% patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), where a shared clonal origin is shown in individual case studies. In this study, we performed targeted next generating sequencing on multiple bone marrow (BM), skin or sorted cells from 51 BPDCN patients (68.7 years,14.4-84.7), and detected mutations in BM hematopoietic cells in 65% (30/46) and BPDCN in 100% (27/27), both components showing similar high frequencies of TET2 (60% versus 58%) and ASXL1 (33% versus 40%). Of 24 patients with paired mutation data, 13(54%) had shared mutations, with TET2(77%), ASXL1(37%) and ZRSR2(22%) the most commonly shared, and NRAS the most gained mutation in BPDCN(9/24, 38%). Karyotypic abnormalities were detected in 19/29(66%) BPDCN but only in 1/49 BM hematopoietic cells, providing additional evidence of clonal evolution. BM clonal hematopoiesis (CH) was associated with an older age (p < 0.001), being confounding factors in multivariate analysis; whereas <10% BM BPDCN infiltrate and stem cell transplant were associated with favorable outcomes. This study is the first to report a high prevalence of BM CH in BPDCN patients beyond an associated diagnosis of MDS/CMML, and demonstrates a frequent clonal relationship in elderly, findings contributing to the understanding of BPDCN clonal origin., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Case: We present a 70-year-old woman with history of chronic myelomonocytic leukemia with a right thigh hematoma after a corticosteroid hip injection. Aspiration of the hematoma was attempted, but she developed a significant transfusion requirement with paresthesias in a lateral femoral cutaneous nerve distribution, prompting transfer. Imaging demonstrated no active extravasation, and she was managed conservatively. At 8-month follow-up, she had a persistent consolidated hematoma on the right side, and she subsequently died of complications of her cancer., Conclusion: This case demonstrates an unusual complication from a common nonoperative modality, as well as important coagulopathies that must be considered in patients with leukemia., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B819)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Treated secondary acute myeloid leukemia (ts-AML)-i.e., AML arising from a previously treated antecedent hematologic disorder-is associated with very poor outcomes. The optimal frontline treatment regimen for these patients is uncertain., Methods: We retrospectively analyzed 562 patients who developed AML from preceding myelodysplastic syndrome or chronic myelomonocytic leukemia for which they had received a hypomethylating agent (HMA). Patients with ts-AML were stratified by frontline AML treatment with intensive chemotherapy (IC, n = 271), low-intensity therapy (LIT) without venetoclax (n = 237), or HMA plus venetoclax (n = 54)., Results: Compared with IC or LIT without venetoclax, HMA plus venetoclax resulted in higher CR/CRi rates (39% and 25%, respectively; P = 0.02) and superior OS (1-year OS 34% and 17%, respectively; P = 0.05). The benefit of HMA plus venetoclax was restricted to patients with non-adverse risk karyotype, where HMA plus venetoclax resulted in a median OS of 13.7 months and 1-year OS rate of 54%; in contrast, for patients with adverse risk karyotype, OS was similarly dismal regardless of treatment approach (median OS 3-5 months). A propensity score analysis accounting for relevant clinical variables confirmed the significant OS benefit of HMA plus venetoclax, as compared with other frontline treatment approaches. In a landmark analysis, patients with ts-AML who underwent subsequent hematopoietic stem cell transplantation (HSCT) had superior 3-year OS compared to non-transplanted patients (33% vs. 8%, respectively; P = 0.003)., Conclusions: The outcomes of ts-AML are poor but may be improved with use of an HMA plus venetoclax-based regimen, followed by HSCT, particularly in those with a non-adverse risk karyotype., (© 2022. The Author(s).)

Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes, and substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cells (LSC) in CMML reside in a CD34 + /CD38 - fraction of the malignant clone. Whereas CD34 + /CD38 - cells engrafted NSGS mice with overt CMML, no CMML was produced by CD34 + /CD38 + progenitors or the bulk of CD34 - monocytes. CMML LSC invariably expressed CD33, CD117, CD123 and CD133. In a subset of patients, CMML LSC also displayed CD52, IL-1RAP and/or CLL-1. CMML LSC did not express CD25 or CD26. However, in sAML following CMML, the LSC also expressed CD25 and high levels of CD114, CD123 and IL-1RAP. No correlations between LSC phenotypes, CMML-variant, mutation-profiles, or clinical course were identified. Pre-incubation of CMML LSC with gemtuzumab-ozogamicin or venetoclax resulted in decreased growth and impaired engraftment in NSGS mice. Together, CMML LSC are CD34 + /CD38 - cells that express a distinct profile of surface markers and target-antigens. During progression to sAML, LSC acquire or upregulate certain cytokine receptors, including CD25, CD114 and CD123. Characterization of CMML LSC should facilitate their enrichment and the development of LSC-eradicating therapies., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with cutaneous manifestations. Next-generation sequencing (NGS) is a tool capable of identifying clonal myeloid cells in the skin infiltrate and thus better characterize the link between hematological diseases and skin lesions., Objective: To assess whether skin lesions of MDS/CMML are clonally related to blood or bone marrow cells using NGS., Methods: Comparisons of blood or bone marrow and skin samples NGS findings from patients presenting with MDS/CMML and skin lesions in three French hospitals., Results: Among the 14 patients recruited, 12 patients (86%) had mutations in the skin lesions biopsied, 12 patients (86%) had a globally similar mutational profile between blood/bone marrow and skin, and 10 patients (71%) had mutations with a high variant allele frequency (>10%) found in the myeloid skin infiltrate. Mutations in TET2 and DNMT3A , both in four patients, were the most frequent. Two patients harbored a UBA1 mutation on hematopoietic samples., Limitations: Limited number of patients and retrospective collection of the data. Blood and skin sampling were not performed at the exact same time point for two patients., Conclusion: Skin lesions in the setting of MDS/CMML are characterized by a clonal myeloid infiltrate in most cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Martin de Frémont, Hirsch, Gimenez de Mestral, Moguelet, Ditchi, Emile, Senet, Georgin-Lavialle, Hanslik, Maurier, Adedjouma, Abisror, Mahevas, Malard, Adès, Fenaux, Fain, Chasset and Mekinian.)

Introduction: Myelodysplasia (MDS) can occur as systemic manifestations such as connective tissue diseases or vasculitis. Rheumatological manifestations are also described in such context. Herein, we report the observation of a patient with chronic myelomonocytic leukemia (CMML) who developed systemic manifestations: polymyalgia rheumatica and pericarditis., Case Report: A 78-year-old patient was referred for the exploration of two months history of inflammatory shoulder pain associated with biological inflammatory syndrome. He presented with asthenia, anorexia and loss of 5kg in one month. He had a three years follow-up for a CMML without any specific treatment. All of the explorations carried out showed a typical polymyalgia rheumatica. A pericardial effusion requiring emergency drainage was synchronously diagnosed. All the symptoms occurred during a worsening of his hematological disease. The rheumatological manifestation was favorable after a short corticosteroid therapy and pericarditis did not recur after 2 years of follow-up., Conclusion: It should be necessary to screen patients for MDS in a context of systemic manifestation, especially in elderly patients with an abnormal blood count (cytopenia, macrocytosis and monocytosis)., (Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20 % of cases. Among them, immune thrombocytopenia (ITP) has been reported but large studies assessing this association are missing. Whether such patients have a particular phenotype and require particular management is unclear. This study analyzes the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison (i) to patients with primary ITP without MDS/CMML and (ii) to patients with MDS/CMML without ITP. Forty-one MDS/CMML-associated ITP patients were included, with chronic ITP in 26 (63%) patients, low-risk myelodysplasia in 30 (73%) patients and CMML in 24 (59%) patients. An associated autoimmune disease was noted in 10 (24%) patients. In comparison to primary ITP patients, MDS/CMML-associated ITP patients had a higher occurrence of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulin (IVIg) (56%). Response achievement with IVIg was more frequent in primary ITP than in MDS/CMML-associated ITP patients. Response rates to second-line therapies were not statistically different between primary ITP and MDS/CMMLassociated ITP patients. Ten percent (n=4) of patients with MDS/CMML-associated ITP had multirefractory ITP versus none in primary ITP controls. After a median follow-up of 60 months, there was no difference in overall survival between MDS/CMML-associated ITP and primary ITP patients. Leukemia-free-survival was significantly better in MDS/CMMLassociated ITP patients than in MDS/CMML without ITP MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multirefractory profile than primary ITP, similar response profile to primary ITP therapy except for IVIg, and less progression toward acute myeloid leukemia than MDS/CMML without ITP.

Introduction: Lysozyme-induced nephropathy is a rare and unknown complication of chronic myelomonocytic leukemia with overproduction of lysozyme by tumoral cells leading to proximal tubular cells injuries. The present case reports a lysozyme nephropathy secondary to chronic myelomonocytic leukemia., Observation: We reported a case of a 82-years-old woman who presented an acute renal failure in a context of diarrhea and vomiting. Her background was characterized by untreated chronic myelomonocytic leukemia and high blood pressure. Despite rehydration, renal function deteriorated. Renal biopsy revealed a tubulo-interstitial lysozyme-induced nephropathy with a vacuolization of the tubular epithelium by eosinophilic droplets stained by anti-lysozyme antibody, without tumoral infiltration of the renal parenchyma., Conclusion: Lysozyme-induced nephropathy is a rare disease which can be suspected biologically and needs histologic confirmation. Other causes of renal failure secondary to chronic myelomonocytic leukemia have to be eliminated first in these patients. The treatment is symptomatic and is associated with treatments of the underlying hematologic pathology., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Rationale: Extramedullary invasion of chronic myelomonocytic leukemia (CMML) usually occurs in the liver, spleen, and lymph nodes, while the pleural infiltration of CMML is rare. The presence of pleural effusion is usually associated with uncontrolled leukocytosis and increased monocytes., Patient Concerns: Here we reported a rare case of CMML-0 with pleural effusion as the first manifestation in a 44-year-old woman. The pleural effusion was caused by blasts infiltration confirmed by the flow cytometer and the pleural biopsy., Diagnoses: CMML with pleural invasion., Interventions: The patient was treated with azacitidine 75 mg/m d for 2 cycles, followed by daily oral intake of hydroxyurea (500 mg/d)., Outcomes: Pleural effusion was resolved and chest pain was relieved., Lessons: The current case indicated that leukemic infiltration into pleura could occur despite mild leukocytes, while demethylation may be an effective therapy.

Objectives: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare autoimmune disorder characterized by auto-antibodies to Willebrand factor (vWF) cleaving enzyme (ADAMTS13), resulting in unusually large vWF multimers that lead to platelet aggregation, microthrombi formation and microangiopathic hemolytic anemia. Hemolysis in aTTP is mechanical; thus, direct antiglobulin test (Coombs test) is usually negative. Multiple autoimmune conditions and various auto-antibodies have been described in the context of chronic myelomonocytic leukemia (CMML). In this paper, we describe the first case of CMML with auto-antibodies to ADAMTS13, presenting initially as plasmapheresis-refractory Coombs-positive aTTP. Results: Although our patient was not treated for CMML, a complete remission of aTTP was eventually achieved with rituximab. Conclusion; We propose that aTTP should be in the differential diagnosis of CMML patients with thrombocytopenia and anemia (Coombs positive or not) who develop signs of thrombotic microangiopathy. Further studies are much needed to decipher the immune-mediated processes in CMML.