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1.
J Investig Med High Impact Case Rep ; 12: 23247096231224366, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38214069

RESUMEN

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-1ß 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.


Asunto(s)
Dioxigenasas , Embolia , Leucemia Mielomonocítica Crónica , Tromboembolia , Trombosis , Masculino , Humanos , Anciano , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/patología , Epigénesis Genética , Mutación , Citocinas/genética , Proteínas de Unión al ADN/genética , Dioxigenasas/genética
2.
Int J Mol Sci ; 24(22)2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-38003211

RESUMEN

Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. Moreover, it is associated with SRSF2 mutations and, rarely, with CSF3R variants. We present the case of an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia, and myeloid precursors in the peripheral blood cells, the patient was subjected to a bone marrow examination. The diagnosis was consistent with CMML type 2. The Hemocoagulative test showed an increase in fibrinolysis markers. Next-generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML. The patient started Azacitidine treatment and achieved normal hemostatic process values. In conclusion, we identified a heterozygous germline mutation that, together with TET2 and SRSF2 variants, was responsible for the hemorrhagic manifestation.


Asunto(s)
Anemia , Leucemia Mielomonocítica Crónica , Humanos , Anciano de 80 o más Años , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/genética , Mutación de Línea Germinal , Predisposición Genética a la Enfermedad , Mutación , Células Germinativas , Receptores del Factor Estimulante de Colonias/genética
4.
Bull Cancer ; 110(11): 1147-1155, 2023 Nov.
Artículo en Francés | MEDLINE | ID: mdl-37414632

RESUMEN

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.


Asunto(s)
Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Enfermedades de la Piel , Humanos , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/genética , Azacitidina/uso terapéutico
6.
Haematologica ; 108(11): 3001-3010, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37259567

RESUMEN

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).


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Adulto , Humanos , Azacitidina/uso terapéutico , Lenalidomida , Leucemia Mielomonocítica Crónica/terapia , Leucemia Mielomonocítica Crónica/complicaciones , Transfusión de Linfocitos/efectos adversos , Síndromes Mielodisplásicos/patología , Trasplante Homólogo/efectos adversos , Enfermedad Crónica , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Linfocitos T/patología , Recurrencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos
9.
Leuk Res ; 127: 107043, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36801588

RESUMEN

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.


Asunto(s)
Leucemia Mieloide Aguda , Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Trombocitopenia , Masculino , Adulto , Humanos , Anciano , Femenino , Azacitidina/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Incidencia , Estudios Retrospectivos , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/epidemiología , Leucemia Mielomonocítica Crónica/complicaciones , Trombocitopenia/tratamiento farmacológico , Causalidad , Resultado del Tratamiento
11.
Int J Surg Pathol ; 31(4): 415-418, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35656760

RESUMEN

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.


Asunto(s)
Leucemia Mielomonocítica Crónica , Linfoma Folicular , Humanos , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/diagnóstico , Leucemia Mielomonocítica Crónica/patología , Linfoma Folicular/complicaciones , Linfoma Folicular/diagnóstico , Ganglios Linfáticos/patología
12.
Wien Med Wochenschr ; 173(1-2): 9-14, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36205826

RESUMEN

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.


Asunto(s)
Leucemia Mielomonocítica Crónica , Humanos , Leucemia Mielomonocítica Crónica/complicaciones , Estudios Retrospectivos , Pronóstico , Coagulación Sanguínea
15.
Clin Exp Rheumatol ; 40(7): 1336-1342, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35579092

RESUMEN

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.


Asunto(s)
Enfermedades Autoinmunes , Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Tromboembolia Venosa , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiología , Estudios de Casos y Controles , Humanos , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/epidemiología , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/epidemiología , Estudios Retrospectivos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología
16.
Am J Dermatopathol ; 44(9): 691-695, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35476037

RESUMEN

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.


Asunto(s)
Sarcoma de Células Dendríticas Interdigitantes , Leucemia Mielomonocítica Crónica , Neoplasias Cutáneas , Anciano , Sarcoma de Células Dendríticas Interdigitantes/patología , Células Dendríticas/patología , Humanos , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/patología , Masculino , Neoplasias Cutáneas/patología
18.
Leukemia ; 36(5): 1343-1350, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35279700

RESUMEN

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.


Asunto(s)
Neoplasias Hematológicas , Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Trastornos Mieloproliferativos , Neoplasias Cutáneas , Anciano , Médula Ósea , Hematopoyesis Clonal/genética , Células Dendríticas , Neoplasias Hematológicas/diagnóstico , Humanos , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/genética , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/genética , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética
19.
J Hematol Oncol ; 15(1): 12, 2022 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-35093134

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Neoplasias Primarias Secundarias/terapia , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia Mieloide Aguda/inducido químicamente , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/tratamiento farmacológico , Neoplasias Primarias Secundarias/inducido químicamente , Estudios Retrospectivos , Adulto Joven
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