RESUMO
The variant allele frequency (VAF) of driver mutations (JAK2, CALR) in myeloproliferative neoplasms is associated with features of advanced disease and complications. Ruxolitinib and interferon were reported to variably reduce the mutant VAF, but the long-term impact of molecular responses (MR) remains debated. We prospectively measured changes in JAK2 and CALR VAF in 77 patients with polycythemia vera and essential thrombocythemia, treated with ruxolitinib for a median of 8 years, and assessed correlation with complete clinical and hematological response (CCHR) and outcomes. At last observation time, JAK2 VAF reduced overall from a median of 68% (range, 20%-99%) to 3.5% (0%-98%). A profound and durable MR (DMR; defined as a VAF stably ≤2%), including complete MR in 8%, was achieved in 20% of the patients, a partial MR (PMR; VAF reduction >50% of the baseline level) in 25%, and 56% had no molecular response (NMR). A CCHR was reached by 69% overall, independently of any degree of MR achieved; conversely, a DMR correlated with longer duration of CCHR and, most importantly, with reduced rate of progression to myelofibrosis and with longer myelofibrosis-free, event-free and progression-free survival. Achievement of PMR also had some favorable impact on outcomes, compared to NMR. A baseline JAK2 VAF <50%, and a VAF reduction of ≥35% after 2 years of treatment, predicted for the achievement of DMR and reduced progression to myelofibrosis. Overall, these findings support the clinical value of achieving profound, durable MR and its consideration as surrogate endpoint in future clinical trials.
Assuntos
Janus Quinase 2 , Mutação , Policitemia Vera , Pirazóis , Trombocitemia Essencial , Humanos , Janus Quinase 2/genética , Policitemia Vera/genética , Policitemia Vera/tratamento farmacológico , Trombocitemia Essencial/genética , Trombocitemia Essencial/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Pirazóis/uso terapêutico , Idoso de 80 Anos ou mais , Pirimidinas/uso terapêutico , Nitrilas/uso terapêutico , Frequência do Gene , Alelos , Calreticulina/genética , Estudos Prospectivos , Resultado do TratamentoRESUMO
Contemporary risk models in primary myelofibrosis (PMF) include the mutation (MIPSS70) and mutation/karyotype enhanced (MIPSS70 plus/v2.0) international prognostic scoring systems. High molecular risk (HMR) mutations incorporated in one or both of these models include ASXL1, SRSF2, EZH2, IDH1/2, and U2AF1Q157; the current study examines additional prognostic contribution from more recently described HMR mutations, including CBL, NRAS, KRAS, RUNX1, and TP53. In a cohort of 363 informative cases (median age 58 years; 60% males), mutations included JAK2 61%, CALR 24%, MPL 6%, ASXL1 29%, SRSF2 10%, U2AF1Q157 5%, EZH2 10%, IDH1/2 4%, TP53 5%, CBL 5%, NRAS 7%, KRAS 4%, and RUNX1 4%. At a median follow-up of 4.6 years, 135 (37%) deaths and 42 (11.6%) leukemic transformations were recorded. Univariate analysis confirmed significant survival impact from the original MIPSS70/plus/v2.0 HMR mutations as well as CBL (HR 2.8; p < .001), NRAS (HR 2.4; p < .001), KRAS (HR 2.1; p = .01), and TP53 (HR 2.4; p = .004), but not RUNX1 mutations (HR 1.8; p = .08). Multivariate analysis (MVA) that included both the original and more recently described HMR mutations confirmed independent prognostic contribution from ASXL1 (HR 1.8; p = .007), SRSF2 (HR 4.3; p < .001), U2AF1Q157 (HR 2.9, p = .004), and EZH2 (HR 2.4; p < .001), but not from IDH1/2 (p = .3), TP53 (p = .2), CBL (p = .3), NRAS (p = .8) or KRAS (p = .2) mutations. The lack of additional prognostic value from CBL, NRAS, KRAS, RUNX1, and TP53 was further demonstrated in the setting of (i) MVA of mutations and karyotype, (ii) MVA of MIPSS70/plus/v2.0 composite scores and each one of the recently described HMR mutations, except TP53, and iii) modified MIPSS70/plus/plus v2.0 that included CBL, NRAS, KRAS, and TP53 as part of the HMR constituency, operationally referred to as "HMR+" category. Furthermore, "HMR+" enhancement of MIPSS70/plus/plus v2.0 did not result in improved model performance, as measured by C-statistics. We conclude that prognostic integrity of MIPSS70/plus/plus v2.0, as well as their genetic components, was sustained and their value not significantly upgraded by the inclusion of more recently described HMR mutations, including CBL, NRAS, KRAS, and RUNX1. Additional studies are needed to clarify the apparent additional prognostic value of TP53 mutation and its allelic state.
Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Mielofibrose Primária , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Prognóstico , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Mutação , Proteína Supressora de Tumor p53/genética , Proteínas de Membrana/genética , GTP Fosfo-Hidrolases/genéticaRESUMO
The recent invasion of Callinectes sapidus in the Lesina Lagoon has raised great concern about its potential impacts on the ecosystem and on local fisheries. The effects of the blue crab presence on the receiving ecosystem were evaluated from both a donor-side perspective, through the application of emergy analysis, and a user-side perspective, by means of interviews to the local fishermen. While emergy analysis showed that C. sapidus brings to an increase of both natural capital and ecosystem functions values, results from interviews highlighted that the major problem caused by the presence of the blue crab in the lagoon concerned the local economy. As the first quantitative assessment of the ecological and economic impact of C. sapidus in invaded habitats, the present investigation provided original and useful information for a comprehensive risk assessment of the species in European waters and in Mediterranean Sea.
Assuntos
Braquiúros , Animais , Ecossistema , Pesqueiros , Mar MediterrâneoRESUMO
Prognostic modeling in myelofibrosis (MF) has classically pursued the integration of informative clinical and hematological parameters to separate patients' categories with different outcomes. Modern stratification includes also genetic data from karyotype and mutations. However, some poorly standardized variables, as peripheral blood (PB) blast count by morphology, are still included. In this study, we used multiparameter flow cytometry (MFC) with the aim of improving performance of existing scores. We studied 363 MF patients with available MFC files for PB CD34+ cells count determination at diagnosis. We adapted Ogata score to MF context including 2 parameters: absolute CD34+ cells count (/µL) and granulocytes to lymphocytes SSC ratio. A score of 1 was attributed to above-threshold values of each parameter. Accordingly, patients were categorized as MFClow (score = 0, 62.0%), MFCint (score = 1, 29.5%), and MFChigh (score = 2, 8.5%). MFClow had significantly longer median OS (not reached) compared to MFCint (55 months) and MFChigh (19 months). We integrated MFC into established models as a substitute of morphological PB blasts count. Patients were reclassified according to MFC-enhanced scores, and concordance (C-) indexes were compared. As regards IPSS, C-indexes were 0.67 and 0.74 for standard and MFC-enhanced model, respectively (Z score - 3.82; p = 0.0001). MFC-enhanced MIPSS70+ model in PMF patients yielded a C-index of 0.78, outperforming its standard counterpart (C-index 0.73; Z score - 2.88, p = 0.004). Our data suggest that the incorporation of MFC-derived parameters, easily attainable from standard assay used for CD34+ cells determination, might help to refine the current prognostic stratification models in myelofibrosis.
Assuntos
Mielofibrose Primária , Antígenos CD34 , Citometria de Fluxo , Humanos , Mutação , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , PrognósticoRESUMO
Arterial (AT) and venous (VT) thrombotic events are the most common complications in patients with polycythemia vera (PV) and are the leading causes of morbidity and mortality. In this regard, the impact of JAK2V617F variant allele frequency (VAF) is still debated. The purpose of the current study was to analyze the impact of JAK2V617F VAF in the context of other established risk factors for thrombosis in a total of 865 2016 WHO-defined PV patients utilizing two independent cohorts: University of Florence (n = 576) as a training cohort and Policlinico Gemelli, Catholic University, Rome (n = 289) as a validation cohort. In the training cohort VT free-survival was significantly shorter in the presence of a JAK2V617F VAF > 50% (HR 4; p < 0.0001), whereas no difference was found for AT (HR 0.9; p = 0.8). Multivariable analysis identified JAK2V617F VAF > 50% (HR 3.8, p = 0.001) and previous VT (HR 2.2; p = 0.04) as independent risk factors for future VT whereas diabetes (HR 2.4; p = 0.02), hyperlipidemia (HR 2.3; p = 0.01) and previous AT (HR 2; p = 0.04) were independent risk factors for future AT. Similarly, JAK2V617F VAF > 50% (HR 2.4; p = 0.01) and previous VT (HR 2.8; p = 0.005) were confirmed as independent predictors of future VT in the validation cohort. Impact of JAK2V617F VAF > 50% on VT was particularly significant in conventional low-risk patients, both in Florence (HR 10.6, p = 0.005) and Rome cohort (HR 4; p = 0.02). In conclusion, we identified JAK2V617F VAF > 50% as an independent strong predictor of VT, supporting that AT and VT are different entities which might require distinct management.
Assuntos
Janus Quinase 2/genética , Policitemia Vera/genética , Trombose Venosa/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Policitemia Vera/complicações , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/etiologia , Adulto JovemRESUMO
The current retrospective study involving a total of 1607 patients was designed to identify clinical and molecular variables that were predictive of inferior myelofibrosis-free survival (MFS) in WHO-defined essential thrombocythemia (ET), utilizing three independent patient cohorts: University of Florence, Italy (n = 718); Mayo Clinic, USA (n = 479) and Policlinico Gemelli, Catholic University, Rome, Italy (n = 410). The Florence patient cohort was first examined to identify independent risk factors for MFS, which included age > 60 years (HR 2.5, 95% CI 1.3-4.9), male sex (2.1, 1.2-3.9), palpable splenomegaly (2.1, 1.2-3.9), CALR 1/1-like or MPL mutation (3.4, 1.9-6.1) and JAK2V617F variant allele frequency > 35% (4.2, 1.6-10.8). Subsequently, an operational molecular risk category was developed and validated in the other two cohorts from Mayo Clinic and Rome: "high molecular risk" category included patients with JAK2V617F VAF >35%, CALR type 1/1-like or MPL mutations; all other driver mutation profiles were assigned to "low molecular risk" category. The former, compared to the latter molecular risk category, displayed significantly higher risk of fibrotic transformation: Florence cohort with respective fibrotic transformation risk rates of 8% vs. 1.2% at 10 years and 33% vs. 8% at 20 years (p < 0.001; HR 6.1; 95% CI 3.2-11.7); Mayo Cohort, 16% vs. 7% at 10 years and 44% vs. 25% at 20 years (p < 0.001; HR 2.5; 95% CI 1.6-4.1); and Rome cohort 7.8% vs. 4.6% at 10 years and 31.2% vs. 7.1% at 20 years (p = 0.007, HR 2.7; 95% CI 1.3-5.8). The present study provides practically useful risk signals for fibrotic transformation in ET and facilitates identification of patients who require close monitoring and appropriate counseling.
Assuntos
Trombocitemia Essencial/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Fibrose , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Receptores de Trombopoetina/genética , Estudos Retrospectivos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Adulto JovemRESUMO
Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19/virologia , Ensaios de Uso Compassivo , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , COVID-19/diagnóstico , COVID-19/metabolismo , Terapia Combinada , Comorbidade , Feminino , Humanos , Inibidores de Janus Quinases/farmacologia , Masculino , Pessoa de Meia-Idade , Nitrilas , Estudos Prospectivos , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirimidinas , Índice de Gravidade de Doença , Resultado do Tratamento , Carga ViralRESUMO
Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2-dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).
Assuntos
Aspirina/administração & dosagem , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Adulto , Idoso , Aspirina/farmacocinética , Ciclo-Oxigenase 1/sangue , Inibidores de Ciclo-Oxigenase/farmacologia , Método Duplo-Cego , Epoprostenol/urina , Humanos , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/farmacocinética , Trombocitemia Essencial/sangue , Trombocitemia Essencial/urinaRESUMO
Splenomegaly is a key clinical manifestation of myelofibrosis, and splenectomy is currently indicated in patients with drug refractory, symptomatic splenomegaly or with the aim of improving refractory cytopenias. Transformation to acute myeloid leukemia occurs in up to 20% of patients with myelofibrosis, while cases of myeloid sarcoma have been reported very unfrequently. In this manuscript, we report the case of a 60-year-old man with a history of primary myelofibrosis who underwent splenectomy because of drug-refractory massive splenomegaly, systemic symptoms and anemia. At the opening of the peritoneal cavity, the spleen resulted massively enlarged and tenaciously entrapped by a pervasive neoplastic-like tissue. The extensive involvement of the abdomen fatally complicated the surgical procedure. At postmortem examination, the spleen showed a diffuse infiltration of immature cells that were also found in the peritoneum, bowel, liver, lungs and myocardium. After immunohistochemical, cytogenetic, flow cytometric and molecular characterization of neoplastic population, a diagnosis of disseminated myeloid sarcoma of the spleen was made. This case report highlights a very unusual case of myeloid sarcoma originating from the spleen in a patient with myelofibrosis who had no evidence of bone marrow or peripheral blood involvement by leukemic cells. Molecular characterization showed that leukemic cells originated from the founding clone of the chronic phase. The sarcoma could not be suspected based on clinical findings and was diagnosed only at the time of surgical procedure and autopsy. This case suggests that leukemic transformation of myelofibrosis can originate outside the bone marrow and, presumably rarely, present as a granulocytic sarcoma.
Assuntos
Mielofibrose Primária/patologia , Sarcoma Mieloide/patologia , Esplenomegalia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/tratamento farmacológico , Sarcoma Mieloide/etiologia , Esplenomegalia/etiologia , Esplenomegalia/cirurgiaRESUMO
Understanding which drivers cause diversity patterns is a key issue in conservation. Here we applied a spatially explicit model to predict marine benthic diversity patterns according to environmental factors in the NW Mediterranean Sea. While most conservation-oriented diversity studies consider species richness only and neglect equitability, we measured separately species richness, equitability, and 'overall' diversity (i.e., the Shannon-Wiener H' function) on a dataset of 890 benthic species × 209 samples. Diversity values were predicted by means of Random Forest regression, on the basis of 10 factors: depth, distance from the coast, distance from the shelf break, latitude, sea-floor slope, sediment grain size, sediment sorting, distance from harbours and marinas, distance from rivers, and sampling gear. Predictions by Random Forests were accurate, the main predictors being latitude, sediment grain size, depth and distance from the coast. Based on predicted values, diversity hotspots were identified as those localities where indices were in the 15% top segment of ranked values. Only a minority of the diversity hotspots was included within the boundaries of the protection institutes established in the region. Marine protected areas are often created in sites harbouring important coastal habitats, which risks neglecting the diversity hidden in the sedimentary seafloor. We suggest that marine protected areas should accommodate portions of sedimentary habitat within their boundaries to improve diversity conservation.
Assuntos
Biodiversidade , Ecossistema , Conservação dos Recursos Naturais , Mar MediterrâneoAssuntos
Neoplasias da Medula Óssea/genética , Transtornos Mieloproliferativos/genética , Subunidade p45 do Fator de Transcrição NF-E2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Medula Óssea/mortalidade , Feminino , Granulócitos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/mortalidade , Análise de Sobrevida , Adulto JovemRESUMO
This study investigates the bottlenose dolphin (Tursiops truncatus, Montagu 1821) habitat use in the Portofino marine protected area (NW Italy) and adjacent waters, a core area for the dolphins and a highly touristic area in the Mediterranean Sea. A permanent automated real-time passive acoustic monitoring system, able to detect and track dolphins continuously, was tested in the area within the activities of the Life+ Nature project ARION. The habits of bottlenose dolphins was investigated considering the resident rate inside the area, which quantifies the amount of time dolphins spent in these waters, by means of random forest regression. The dependency of dolphin resident rate was analyzed in relation to four explanatory variables: sea surface temperature, season, time of day, and proximity to the coast. Dolphins spent more time in the area during spring and when sea surface temperature ranged between 15-16°C. Summer resulted the season with lower dolphin residency with significant difference between working day and weekend, in the last the lowest residency was recorded. Main findings provide important information to properly manage the area in order to protect bottlenose dolphins.
Assuntos
Acústica , Golfinho Nariz-de-Garrafa , Ecossistema , Monitoramento Ambiental/métodos , Animais , Monitoramento Ambiental/instrumentação , Análise de Regressão , Estações do AnoAssuntos
Fidelidade a Diretrizes , Transtornos Mieloproliferativos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Itália , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/terapia , Inquéritos e QuestionáriosAssuntos
Policitemia , Substituição de Aminoácidos , Eritropoetina/sangue , Feminino , Ferritinas/sangue , Humanos , Janus Quinase 2/genética , Testes de Função Renal , Testes de Função Hepática , Masculino , Mutação de Sentido Incorreto , Médicos , Policitemia/sangue , Policitemia/diagnóstico , Policitemia/genéticaRESUMO
Refractoriness to ruxolitinib in patients with myelofibrosis (MF) was associated with clonal evolution; however, whether genetic instability is promoted by ruxolitinib remains unsettled. We evaluated the mutation landscape in 71 MF patients receiving ruxolitinib (n = 46) and hydroxyurea (n = 25) and correlated with response. A spleen volume response (SVR) was obtained in 57% and 12%, respectively. Highly heterogenous patterns of mutation acquisition/loss and/or changes of variant allele frequency (VAF) were observed in the 2 patient groups without remarkable differences. In patients receiving ruxolitinib, driver mutation type and high-molecular risk profile (HMR) at baseline did not impact on response rate, while HMR and sole ASXL1 mutations predicted for SVR loss at 3 years. In patients with SVR, a decrease of ≥ 20% of JAK2V617F VAF predicted for SVR duration. VAF increase of non-driver mutations and clonal progression at follow-up correlated with SVR loss and treatment discontinuation, and clonal progression also predicted for shorter survival. These data indicate that (i) ruxolitinib does not appreciably promote clonal evolution compared with hydroxyurea, (ii) VAF increase of pre-existing and/or (ii) acquisition of new mutations while on treatment correlated with higher rate of discontinuation and/or death, and (iv) reduction of JAK2V617F VAF associated with SVR duration.
Assuntos
Hidroxiureia/uso terapêutico , Mutação , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Pirazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrilas , Mielofibrose Primária/diagnóstico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas , Resultado do TratamentoRESUMO
The availability of marine habitats maps remains limited due to difficulty and cost of working at sea. Reduced light penetration in the water hampers the use of optical imagery, and acoustic methods require extensive sea-truth activities. Predictive spatial modelling may offer an alternative to produce benthic habitat maps based on complete acoustic coverage of the seafloor together with a comparatively low number of sea truths. This approach was applied to the coralligenous reefs of the Marine Protected Area of Tavolara - Punta Coda Cavallo (NE Sardinia, Italy). Fuzzy clustering, applied to a set of observations made by scuba diving and used as sea truth, allowed recognising five coralligenous habitats, all but one existing within EUNIS (European Nature Information System) types. Variable importance plots showed that the distribution of habitats was driven by distance from coast, depth, and lithotype, and allowed mapping their distribution over the MPA. Congruence between observed and predicted distributions and accuracy of the classification was high. Results allowed calculating the occurrence of the distinct coralligenous habitats in zones with different protection level. The five habitats are unequally protected since the protection regime was established when detailed marine habitat maps were not available. A SWOT (Strengths-Weaknesses-Opportunities-Threats) analysis was performed to identify critical points and potentialities of the method. The method developed proved to be reliable and the results obtained will be useful when modulating on-going and future management actions in the studied area and in other Mediterranean MPAs to develop conservation efforts at basin scale.