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1.
Leukemia ; 38(5): 1131-1142, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38575672

RESUMO

Myelodysplastic neoplasms (MDS) are characterized by clonal evolution starting from the compartment of hematopoietic stem and progenitors cells (HSPCs), leading in some cases to leukemic transformation. We hypothesized that deciphering the diversity of the HSPCs compartment may allow for the early detection of an emergent sub-clone that drives disease progression. Deep analysis of HSPCs repartition by multiparametric flow cytometry revealed a strong disorder of the hematopoietic branching system in most patients at diagnosis with different phenotypic signatures closely related to specific MDS features. In two independent cohorts of 131 and 584 MDS, the HSPCs heterogeneity quantified through entropy calculation was decreased in 47% and 46% of cases, reflecting a more advanced state of the disease with deeper cytopenias, higher IPSS-R risk and accumulation of somatic mutations. We demonstrated that patients with lower-risk MDS and low CD34 + CD38+HSPCs entropy had an adverse outcome and that this parameter is as an independent predictive biomarker for progression free survival, leukemia free survival and overall survival. Analysis of HSPCs repartition at diagnosis represents therefore a very powerful tool to identify lower-risk MDS patients with a worse outcome and valuable for clinical decision-making, which could be fully integrated in the MDS diagnostic workflow.


Assuntos
Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Prognóstico , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/diagnóstico , Células-Tronco Hematopoéticas/patologia , Células-Tronco Hematopoéticas/metabolismo , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adulto , Mutação , Biomarcadores Tumorais , Taxa de Sobrevida
2.
Front Oncol ; 14: 1353896, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515568

RESUMO

Introduction: Immune checkpoint inhibitors (ICIs) are used in several advanced malignancies and may cause various immune-related adverse events (irAEs). Among them, hematological irAEs are less described. Acquired amegakaryocytic thrombocytopenia (AAT) is a rare immune hematologic disorder characterized by severe thrombocytopenia and complete absence of megakaryocytes in bone marrow. Case presentation: Herein, we present the case of a patient in their 40s with metastatic melanoma who developed an AAT after 12 cycles of nivolumab (anti-PD1). His platelet count decreased by ≤5 × 109/l without other cytopenia. Bone marrow biopsy showed normal cellularity with a complete absence of megakaryocyte and T-CD8+ lymphocyte infiltration. Given the failure of systemic steroids, eltrombopag was started, an oral thrombopoietin receptor agonist (TPO-RA), and his platelet count subsequently increased with complete response. Discussion: Four other cases are described on literature with the same features than non-ICI-related AAT. All cases occurred after anti-PD/PD-L1 treatment with a median onset of 5 weeks. The presentation of our case is quite different with delayed cytopenia. Both ciclosporin and TPO-RA seem to be efficient therapies. Conclusion: TPO-RA could be preferred in oncologic patients, but safety data are still missing to define clear guidelines for immune-related AAT management.

4.
Lancet Haematol ; 11(1): e38-e50, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38065203

RESUMO

BACKGROUND: Sabatolimab is an immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes. METHODS: STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries. Adult patients (aged ≥18 years) with intermediate-risk, high-risk, and very high-risk myelodysplastic syndromes (according to Revised International Prognostic Scoring System criteria) who had not received previous treatment were included. Patients were randomly assigned (1:1) to intravenous sabatolimab (400 mg on day 8 and 22) or placebo plus a hypomethylating agent (intravenous decitabine 20 mg/m2 on day 1-5 or intravenous or subcutaneous azacitidine 75 mg/m2 on day 1-7 or day 1-5 and day 8 and 9) every 28 days until treatment discontinuation. The two primary endpoints were complete response rate and progression-free survival, assessed in the full analysis set, which included all randomly assigned patients. Complete response was analysed, as prespecified, 7 months after the last patient was randomly assigned. All other analyses presented, including progression-free survival, were done at the final data cutoff prespecified via a protocol amendment on Sept 2, 2021. Safety was assessed in in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03946670, and is ongoing. FINDINGS: Between July 29, 2019, and Aug 10, 2020, 127 patients were randomly assigned to sabatolimab plus a hypomethylating agent group (sabatolimab group; n=65) or placebo plus a hypomethylating agent (placebo group; n=62). The median age of participants was 73 years (IQR 69-77), of whom 86 (68%) of 127 patients were male and 77 (61%) were White. The primary endpoints were not met. Complete response (cutoff date of March 10, 2021) was achieved in 14 (22%; 95% CI 12·3-33·5) of 65 patients in the sabatolimab group vs 11 (18%; 9·2-29·5) of 62 patients in the placebo group (p=0·77). At the cutoff date of the final analysis (March 1, 2022), median follow-up for progression-free survival was 17·8 months (IQR 16·6-19·4) in the sabatolimab group and 19·2 months (17·7-22·3) in the placebo group, and the median progression-free survival was 11·1 months (95% CI 7·6-17·6) in the sabatolimab group vs 8·5 months (6·9-11·3) in the placebo group (hazard ratio 0·75 [95% CI 0·48-1·17]; p=0·1022). The most common adverse events of any grade were neutropenia (35 [56%] of 62 patients in the sabatolimab group vs 43 [68%] of 63 patients in the placebo group), thrombocytopenia (30 [48%] vs 32 [51%]), constipation (29 [47%] vs 24 [38%]), diarrhoea (27 [44%] vs 14 [22%]), anaemia (22 [35%] vs 34 [54%]), febrile neutropenia (22 [35%] vs 15 [24%]), and leukopenia (15 [24%] vs 20 [32%]). One patient developed a serious potential treatment-related immune-mediated adverse event in the sabatolimab group. There was one treatment-related death in the sabatolimab group due to pneumonitis. INTERPRETATION: The addition of sabatolimab to hypomethylating agents in this study did not result in a significant improvement in complete response rates or progression-free survival. Sabatolimab had a manageable safety in most patients with higher-risk myelodysplastic syndromes. A randomised phase 3 trial is ongoing to assess the potential benefit of sabatolimab plus azacitidine on overall survival in this setting. FUNDING: Novartis Pharmaceuticals.


Assuntos
Síndromes Mielodisplásicas , Trombocitopenia , Adulto , Humanos , Masculino , Adolescente , Idoso , Feminino , Azacitidina/efeitos adversos , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Trombocitopenia/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/etiologia , Método Duplo-Cego , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
5.
Clin Exp Med ; 23(3): 803-813, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35953763

RESUMO

BACKGROUND: Systemic inflammatory and autoimmune diseases (SIADs) occur in 10-20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow.


Assuntos
Monócitos , Síndromes Mielodisplásicas , Humanos , Síndromes Mielodisplásicas/genética , Inflamação , Células Dendríticas , Mutação
7.
Clin Exp Rheumatol ; 40(7): 1336-1342, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35579092

RESUMO

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.


Assuntos
Doenças Autoimunes , Leucemia Mielomonocítica Crônica , Síndromes Mielodisplásicas , Tromboembolia Venosa , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Estudos de Casos e Controles , Humanos , Leucemia Mielomonocítica Crônica/complicações , Leucemia Mielomonocítica Crônica/epidemiologia , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/epidemiologia , Estudos Retrospectivos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
8.
Br J Haematol ; 198(3): 535-544, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35438802

RESUMO

In order to improve the outcome observed with azacitidine (AZA) in higher-risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA-PLUS was a phase II trial that, in a "pick a winner" approach, randomly assigned patients with higher-risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA-LEN And AZA-IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy-related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our "pick a winner" randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/uso terapêutico , Humanos , Idarubicina/uso terapêutico , Lenalidomida/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Resultado do Tratamento , Ácido Valproico/uso terapêutico
9.
Platelets ; 33(8): 1153-1158, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-35348426

RESUMO

Impaired platelet production is a mechanism of immune thrombocytopenia (ITP). Morphological abnormalities of megakaryocytes (MKs) are sometimes observed in this disease. Two studies have suggested an association between MK abnormalities and response to corticosteroids in primary ITP, but none have investigated this association for thrombopoietin-receptor agonists (TPO-RAs). This was the aim of this study. The source of population was the French CARMEN registry with prospective follow-up of adult patients with incident ITP. We included patients with primary ITP, treated by TPO-RA and with a bone marrow smear before initiating TPO-RA. MK abnormalities were categorized by the presence of dysplasia and by the stage of maturation. Among 451 patients screened, 38 were included in the analysis. There was no difference in the median percentage of dysplastic MKs between responders to TPO-RA (4.0%, 95% confidence interval - CI: 2.3-6.4) and non-responders (4.5%, 95% CI: 0.7-7.1). There was a slightly higher proportion of granular MKs (4.5%, 95% CI: 3-6) and basophilic MKs (30.1%, 95% CI: 21.9-39.1) in non-responders compared to responders (granular: 2.0%, 95% CI: 0-4.1; basophilic: 21.3%, 95% CI: 11.4-40.7). In conclusion, MK abnormalities were not associated with response achievement in ITP patients treated with TPO-RA in this series of 38 patients.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adulto , Medula Óssea , Humanos , Megacariócitos/fisiologia , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores de Trombopoetina/agonistas , Trombocitopenia/tratamento farmacológico , Trombopoetina/farmacologia , Trombopoetina/uso terapêutico
10.
Eur J Gen Pract ; 28(1): 15-22, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35179084

RESUMO

BACKGROUND: The general practitioner (GP) is central to managing patients with cancer, whose numbers are increasing worldwide. The GP's involvement requires better coordination between involved partners, in particular oncologists and GPs. OBJECTIVES: To conduct a feasibility study of remote participation of GPs in multi-disciplinary consultation meetings (MCMs). We analysed participation, participants' satisfaction, and their impact on therapeutic decisions. METHODS: We conducted a feasibility study in the regional cancer centre of Toulouse, France. All patient cases discussed in the MCMs for myelodysplasia from 1 January to 31 March 2016 were included. Cases of patients aged over 18 years, with a diagnosis of myelodysplasia and registered with a GP were included if patients gave informed consent. One investigator collected the data provided by GPs during three telephone or video calls: before, during, and after the MCM, respectively. RESULTS: Of 86 patient cases discussed during three months of MCMs, 44 were eligible for GP participation; 27 GPs participated in discussions of 27 patient cases. The GP's participation in the MCM led to a change in management in five cases, with four times treatment intensifications and once de-intensification. Medical, social, family-related, and psychological domains were discussed with input from the GPs. Overall, all participants were satisfied with the MCMs. CONCLUSION: Remote participation of GPs in MCMs is feasible and may result in adapting oncological and haematological management for patients. This patient-centred approach requires a specific organisation that, when implemented, satisfies the needs of all participants.


Assuntos
Clínicos Gerais , Adulto , Estudos de Viabilidade , França , Clínicos Gerais/psicologia , Humanos , Oncologia , Pessoa de Meia-Idade , Encaminhamento e Consulta
12.
Br J Haematol ; 196(5): 1262-1270, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34738634

RESUMO

Data about the presentation and the management of primary immune thrombocytopenia (ITP) in very elderly patients (VEPs; aged ≥80 years) are lacking. The aim of the present study was to describe ITP in this subgroup. The data source was the prospective CARMEN-France registry. Patients included between 2013 and 2018 were selected. ITP presentation and management in VEPs was compared to elderly patients (EPs; aged 65-79 years). We assessed factors associated with bleeding at ITP onset in VEPs. Of 541 patients, 184 were included: 87 in the VEP group and 97 in the EP group. The mean age was 85·7 years in the VEP group. Comorbidities were more frequent in the VEP group (67·4% vs. 47·9%). The median platelet count at ITP onset was similar but severe bleeding tended to be more frequent in VEPs (10·3% vs. 4·1%, P = 0·1) as well as mortality. Exposure to ITP drugs, response to first-line treatment, need of second-line treatment, evolution towards persistency, occurrence of bleeding, infection and thrombosis did not differ between groups. In VEPs, factors associated to bleeding were female sex [odds ratio (OR) 4·75, 95% confidence interval (CI) 1·31-17·32] and platelet count of <20 × 109 /l (OR 10·05, 95% CI 4·83-67·39). Exposure to anticoagulants was strongly associated with severe bleeding (OR 7·61, 95% CI 1·77-32·83).


Assuntos
Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Gerenciamento Clínico , Feminino , França/epidemiologia , Hemorragia/epidemiologia , Humanos , Masculino , Contagem de Plaquetas , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/diagnóstico , Fatores de Risco
13.
Br J Haematol ; 194(2): 336-343, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34151423

RESUMO

Despite a moderate prevalence in low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), thrombocytopenia remains a risk of severe bleeding and therapeutic options are still limited. There are only a few studies with eltrombopag (ELT), a thrombopoietin receptor agonist, in those patients. In this retrospective multicentre study, ELT was used in 50 patients with MDS and 11 with CMML, with no excess of marrow blasts and platelet counts of <50 × 109 /l in a 'real-life' situation. Platelet response occurred in 47 (77%) patients. The median (range) duration of response was 8 (0-69) months. None of the eight still responders who discontinued ELT had relapsed, at a median (range) of 16 (6-23) months after ELT discontinuation. Although 36% of the patients were anti-coagulated or anti-aggregated only 10% of patients had Grade ≥3 bleeding events. Thrombotic events were observed in six (10%) patients, who all but one had a medical history of arterial or venous thrombosis. Progression to acute myeloid leukaemia occurred in four (7%) patients. In this first 'real-life' study, ELT was effective and generally well tolerated in patients with MDS/CMML without excess blasts.


Assuntos
Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Pirazóis/uso terapêutico , Receptores de Trombopoetina/agonistas , Trombocitopenia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Plaquetas/efeitos dos fármacos , Feminino , França/epidemiologia , Humanos , Leucemia Mielomonocítica Crônica/epidemiologia , Masculino , Síndromes Mielodisplásicas/epidemiologia , Estudos Retrospectivos , Trombocitopenia/epidemiologia
14.
Semin Arthritis Rheum ; 51(4): 845-852, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34175790

RESUMO

OBJECTIVE: Patients with inflammatory myopathies (IM) are known to have an increased risk of developing malignancies. Autoimmune and inflammatory diseases occur in up to 25% of patients with myelodysplastic syndrome (MDS). This study aimed to describe the rare association between IM and MDS. METHODS: We report here the main characteristics, treatment, and outcome of 21 patients (11 national cases and 10 additional cases from a literature review) with IM associated to MDS. RESULTS: Median age of patients at IM diagnosis was 66 years (range 26 - 78). Diagnosis of the two conditions were concomitant in most patients (n=14/21) whereas MDS diagnosis preceded IM diagnosis in 5 patients. Different types of IM were observed but dermatomyositis was the most frequent (59%). Compared to IM without MDS (IM/MDS-), patients with MDS (IM/MDS+) were older (median 66 vs 55, p=0.3), more frequently male (sex ratio M/F 1.125 vs 0.41, p=0.14) and positive for anti-TIF1γ (24% vs 4%, p=0.0039). Antisynthetase syndrome was never observed among IM/MDS+ patients (0% vs 28%, p=0.01). MDS WHO type was not univocal, but the prognostic score was of low risk in almost all cases. IM was usually steroid sensitive (82% of patients) but often steroid dependent (56% of patients). Overall survival of IM patients with MDS was worse compared to patients with IM without MDS (p=0.0002). CONCLUSION: IM associated with MDS are mainly represented by dermatomyositis and/or anti-TIF1γ autoantibodies. Antisynthetase syndrome has not been described in association with MDS. Despite low-risk MDS, overall survival of IM patients with MDS is worse than IM patients without MDS.


Assuntos
Síndromes Mielodisplásicas , Miosite , Adulto , Idoso , Autoanticorpos , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Síndromes Mielodisplásicas/complicações , Miosite/complicações
15.
Kidney Int Rep ; 6(3): 737-745, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33732988

RESUMO

INTRODUCTION: The identification of specific molecular signatures and the development of new targeted drugs have changed the paradigm of onco-nephrology, now allowing a multiscale approach of kidney involvement related to hematologic malignancies relying on combined hematologic and molecular assessments. In this study, we aimed to refine the spectrum of kidney disorders associated with chronic myelomonocytic leukemia (CMML) or BCR-ABL-negative myeloproliferative neoplasms (MPNs), 2 very rare conditions scarcely described. METHODS: Case series. Patients with myeloid neoplasms who were referred to Toulouse University Hospital Nephrology Unit and were diagnosed with acute kidney injury (AKI), chronic kidney disease (CKD), or urine abnormalities were retrospectively included. RESULTS: Eighteen patients (males n=13, CMML n=8, essential thrombocytosis [ET] n=7, polycythemia vera [PV] n=1, and myelofibrosis n=2) developed kidney disease 7.7±2 years after the diagnosis of the malignancy. Twelve patients had AKI at presentation. Eight patients had glomerular presentation (high-range proteinuria 33%, microscopic hematuria 56%). Kidney biopsy (n=14) showed various patterns, including pauci-immune glomerulosclerosis (n=5), extramedullary hematopoiesis (n=6), or tubular atrophy and interstitial fibrosis with polymorphic inflammation (n=8). Immunostaining of CD61 confirmed the infiltration of megakaryocytes within glomeruli or interstitium in 5 of 8 patients. Other pictures of glomerulopathy were identified in 3 patients (IgA nephropathy n=2, AA amyloidosis n=1). Massive kidney infiltration by CMML was identified in 1 patient. After a mean follow-up of 24±6 months, malignancy was considered as stable in 11 patients (61%), but 22% of patients had progressed to end-stage renal failure. The remaining had persistently reduced kidney function. No correlation between the malignancy and the renal presentation and outcomes could be identified. CONCLUSIONS: Kidney complications of CMML/MPN are heterogenous, and kidney biopsy may help to identify new molecular targets to prevent the development of kidney fibrosis.

16.
Haematologica ; 106(5): 1414-1422, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33626866

RESUMO

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.


Assuntos
Leucemia Mieloide Aguda , Leucemia Mielomonocítica Crônica , Síndromes Mielodisplásicas , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Leucemia Mielomonocítica Crônica/complicações , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/terapia , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/terapia
17.
J Clin Oncol ; 39(14): 1575-1583, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33600210

RESUMO

PURPOSE: TP53-mutated (TP53m) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have very poor outcome irrespective of the treatment received, including 40% responses (20% complete remission [CR]) with azacitidine (AZA) alone, short response duration, and a median overall survival (OS) of approximately 6 months. Eprenetapopt (APR-246), a novel first-in-class drug, leads to p53 protein reconformation and reactivates its proapoptotic and cell-cycle arrest functions. PATIENTS AND METHODS: This phase II study assessed the safety and efficacy of eprenetapopt in combination with AZA in untreated high or very high International Prognostic Scoring System-R TP53m MDS and AML patients. RESULTS: Fifty-two TP53m patients (34 MDS, 18 AML [including seven with more than 30% blasts]) were enrolled. In MDS, we observed an overall response rate (ORR) of 62%, including 47% CR, with a median duration of response at 10.4 months. In AML, the ORR was 33% including 17% CR (27% and 0% CR in AML with less than and more than 30% marrow blasts, respectively). Seventy-three percent of responders achieved TP53 next-generation sequencing negativity (ie, variant allele frequency < 5%). The main treatment-related adverse events were febrile neutropenia (36%) and neurologic adverse events (40%), the latter correlating with a lower glomerular filtration rate at treatment onset (P < .01) and higher age (P = .05), and resolving with temporary drug interruption without recurrence after adequate eprenetapopt dose reduction. With a median follow-up of 9.7 months, median OS was 12.1 months in MDS, and 13.9 and 3.0 months in AML with less than and more than 30% marrow blasts, respectively. CONCLUSION: In this very high-risk population of TP53m MDS and AML patients, eprenetapopt combined with AZA was safe and showed potentially higher ORR and CR rate, and longer OS than reported with AZA alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Mutação , Síndromes Mielodisplásicas/tratamento farmacológico , Quinuclidinas/administração & dosagem , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Azacitidina/efeitos adversos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Quinuclidinas/efeitos adversos
18.
J Cancer Educ ; 36(1): 65-71, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31410821

RESUMO

In response to the complexity of medical care in oncology, 2 years ago, we designed a new teaching method (SPOC, Small Private Online Course) to improve cancer treatment and its management by emphasizing the community-hospital interface. The educational objective of this study was to evaluate after 1 year if the interest for this teaching remained constant over the long term to meet both educational and financial requirements. We designed a questionnaire including 18 questions grouped in 3 main parts describing the profile of the participants, his/her own experience, and the current utilization of the SPOC. Of 1574 participants of the 2 first sessions, 182 (11.5%) completed the questionnaire after 1 year. The majority of respondents were between the ages of 31 and 60 and belonged to a paramedical group (47.81%). After 1 year, 84.6% participants were satisfied or very satisfied with the content of the SPOC, 83.6% would recommended it, and 67% would be interested in using an updated SPOC again. Only 4.9% kept some contacts with other participants and 4.9% with teachers. 31.3% considered that the SPOC had a medium impact on their professional activity, 33.5% a lot, and 2.7% completely whereas 24.7% considered that it had little impact. The evaluation at 1 year showed that this digital learning method had a global positive impact on the professional practice of the participants. This study highlighted the empowerment of participants after this kind of teaching, but the network between participants was not enhanced.


Assuntos
Oncologia , Ensino , Adulto , Retroalimentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Eur J Haematol ; 106(5): 616-626, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33340150

RESUMO

OBJECTIVE: Hematological treatment decisions in older adults with hematological malignancies are complex. Our objective is to study the impact of a comprehensive geriatric assessment on hematological treatment decision in older patients and the factors associated with change in treatment plan. METHODS: We conducted a cross-sectional analysis of patients aged 65 years and above with hematological malignancies, hospitalized between 2008 and 2019 at the University Cancer Institute of Toulouse. They were assessed by a geriatrician/nurse team using a comprehensive geriatric assessment (CGA). A penalized logistic regression model with elastic net regularization was used to identify factors associated with change in hematological treatment plan. RESULTS: A total of 424 patients were included. Main hematological malignancies were lymphoma (36.1 %), acute myeloid leukemia (26.9 %) and myelodysplastic syndrome (19.8%). Change in hematological treatment plan was suggested after CGA for 92 patients (21.7%). Factors associated with change in treatment plan were functional impairment according to ADL and IADL scale, mobility impairment, the presence of comorbidity defined by the Charlson score >1 and increasing age. CONCLUSION: A CGA has a significant impact on hematological treatment decision in older patients. Functional and mobility impairment, comorbidities and age are predictive factors of change in treatment plan.


Assuntos
Tomada de Decisão Clínica , Avaliação Geriátrica , Avaliação do Impacto na Saúde , Neoplasias Hematológicas/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Gerenciamento Clínico , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Prognóstico
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