Identificação dos padrões espectrais da alteração hidrotermal da Mina Uruguai, Caçapava do Sul (RS), utilizando espectros de reflectância experimental

A series of spectral analysis was made with samples of Eopaleozoic sedimentary rocks affected by hydrothermal alteration associated with occurrences of copper in Uruguai Mine (Minas do Camaquã, Rio Grande do Sul State, Brazil). The database included spectral range visible, near infrared and shortwave (350-2500 nm) obtained from measurements of portable spectroradiometer ASD FieldSpec-3 High-Resolution. The mineralogical interpretation with spectral signatures was conducted with a support by The Spectral Geologist (TSG™ Pro) software, which allows a mineral phases discrimination present by comparing the absorption features in the mineral analysis with similar features of a spectral reference library spectrum. Spectral analysis from studied area samples allowed identified these main minerals: kaolinite, illite, chlorite, hematite and goethite. The mineral assemblages identified wereconsistent with hydrothermal alteration under conditions of low sulphur epithermal described in previous studies in this region. The results supported a potential use of reflectance spectroscopy in mineral exploration programs, especially in the early stages, even in areas with little favorable physiographic conditions.Uma série de análises espectrais foi efetuada em amostras de rochas sedimentares eopaleozoicas afetadas por alteração hidrotermal associada às ocorrências de cobre na Mina Uruguai (Minas do Camaquã, RS). A base de dados contemplou espectros na faixa do visível e infravermelho próximo (350 a 2500 nm) obtidos através de leituras em um espectrorradiômetro portátil ASD FieldSpec-3 High-Resolution. A interpretação mineralógica das assinaturas espectrais foi efetuada com o apoio do software The Spectral Geologist (TSGTM Pro) que permitiu a discriminação das fases minerais presentes por comparação das feições de absorção no espectro analisado com feições similares de minerais de uma biblioteca espectral de referência. A partir da análise espectral das amostras da área de estudo, puderam ser identificados os seguintes minerais principais: caulinita, ilita, clorita, hematita e goetita. As assembleias minerais identificadas se mostraram consistentes com alteração hidrotermal sob condições epitermais de baixo enxofre descrita em estudos anteriores na região. Os resultados obtidos reforçaram o potencial de utilização da espectroscopia de reflectância em programas de exploração mineral, especialmente nas fases iniciais, mesmo em áreas com condições fisiográficas pouco favoráveis

The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population

Background: Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19. Methods: We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions. Results: The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2\ua0serology were more frequently male (p\ua0=\ua00.027) and active workers (p\ua0=\ua00.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms. Conclusions: Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population

BCR::ABL1 levels at first month after TKI discontinuation predict subsequent maintenance of treatment-free remission: A study from the “GRUPPO TRIVENETO LMC”

We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087

Treatment-Free Remission in Chronic Myeloid Leukemia Patients Treated With Low-Dose TKIs: A Feasible Option Also in the Real-Life. A Campus CML Study

Treatment-free remission (TFR) has become a primary therapeutic goal in CML and is also considered feasible by international guidelines. TKIs dose reduction is often used in real-life practice to reduce adverse events, although its impact on TFR is still a matter of debate. This study aimed to explore the attitude of Italian hematologists towards prescribing TKIs at reduced doses and its impact on TFR. In September 2020, a questionnaire was sent to 54 hematology centers in Italy participating to the Campus CML network. For each patient, data on the main disease characteristics were collected. Most of the hematologists involved (64.4%) believed that low-dose TKIs should not influence TFR. Indeed, this approach was offered to 194 patients. At the time of TFR, all but 3 patients had already achieved a DMR, with a median duration of 61.0 months. After a median follow-up of 29.2 months, 138 (71.1%) patients were still in TFR. Interestingly, TFR outcome was not impaired by any of the variables examined, including sex, risk scores, BCR-ABL1 transcript types, previous interferon, type and number of TKIs used before treatment cessation, degree of DMR or median duration of TKIs therapy. On the contrary, TFR was significantly better after dose reduction due to AEs; furthermore, patients with a longer DMR duration showed a trend towards prolonged TFR. This survey indicates that low-dose TKI treatment is an important reality. While one third of Italian hematologists still had some uncertainties on TFR feasibility after using reduced doses of TKIs outside of clinical trials, TFR has often been considered a safe option even in patients treated with low-dose TKIs in the real-life setting. It should be noted that only 28.9% of our cases had a molecular recurrence, less than reported during standard dose treatment. Consequently, TFR is not impaired using low-dose TKIs

Molecular response and quality of life in chronic myeloid leukemia patients treated with intermittent TKIs: First interim analysis of OPTkIMA study

31noBackground: Intermittent treatment with TKIs is an option for the great majority (70%–80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. Methods: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0) and to improve Health Related Quality of Life (HRQoL). Results: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0/MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients’ HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). Conclusions: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0/MR4.0 in 81% of the patients during the first 12–24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.openopenMalagola M.; Iurlo A.; Abruzzese E.; Bonifacio M.; Stagno F.; Binotto G.; D'Adda M.; Lunghi M.; Crugnola M.; Ferrari M.L.; Lunghi F.; Castagnetti F.; Rosti G.; Lemoli R.M.; Sancetta R.; Coppi M.R.; Corsetti M.T.; Rege Cambrin G.; Romano A.; Tiribelli M.; Russo Rossi A.; Russo S.; Aprile L.; Gandolfi L.; Farina M.; Bernardi S.; Polverelli N.; Roccaro A.M.; De Vivo A.; Baccarani M.; Russo D.Malagola, M.; Iurlo, A.; Abruzzese, E.; Bonifacio, M.; Stagno, F.; Binotto, G.; D'Adda, M.; Lunghi, M.; Crugnola, M.; Ferrari, M. L.; Lunghi, F.; Castagnetti, F.; Rosti, G.; Lemoli, R. M.; Sancetta, R.; Coppi, M. R.; Corsetti, M. T.; Rege Cambrin, G.; Romano, A.; Tiribelli, M.; Russo Rossi, A.; Russo, S.; Aprile, L.; Gandolfi, L.; Farina, M.; Bernardi, S.; Polverelli, N.; Roccaro, A. M.; De Vivo, A.; Baccarani, M.; Russo, D

Unraveling the complexity of tyrosine kinase inhibitor-resistant populations by ultra-deep sequencing of the BCR-ABL kinase domain

In chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, tyrosine kinase inhibitor (TKI) therapy may select for drug-resistant BCR-ABL mutants. We used an ultra-deep sequencing (UDS) approach to resolve qualitatively and quantitatively the complexity of mutated populations surviving TKIs and to investigate their clonal structure and evolution over time in relation to therapeutic intervention. To this purpose, we performed a longitudinal analysis of 106 samples from 33 patients who had received sequential treatment with multiple TKIs and had experienced sequential relapses accompanied by selection of 1 or more TKI-resistant mutations. We found that conventional Sanger sequencing had misclassified or underestimated BCR-ABL mutation status in 55% of the samples, where mutations with 1% to 15% abundance were detected. A complex clonal texture was uncovered by clonal analysis of samples harboring multiple mutations and up to 13 different mutated populations were identified. The landscape of these mutated populations was found to be highly dynamic. The high degree of complexity uncovered by UDS indicates that conventional Sanger sequencing might be an inadequate tool to assess BCR-ABL kinase domain mutation status, which currently represents an important component of the therapeutic decision algorithms. Further evaluation of the clinical usefulness of UDS-based approaches is warranted