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Agradecimentos: This study was funded by (1) Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (grant numbers 2018/14132-0 and 2021/03421-3); (2) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil—CAPES (finance code 001); and (3) Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (grant number 311841/2018-0) Abstract: Multiple myeloma (MM) accounts for 10-15% of all hematologic malignancies, as well as 20% of deaths related to hematologic malignant tumors, predominantly affecting bone and bone marrow. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (FDG-PET/CT) is an important method to assess the tumor burden of these patients. It is often challenging to classify the extent of disease involvement in the PET scans for many of these patients because both focal and diffuse bone lesions may coexist, with varying degrees of FDG uptake. Different metrics involving volumetric parameters and texture features have been proposed to objectively assess these images. Here, we review some metabolic parameters that can be extracted from FDG-PET/CT images of MM patients, including technical aspects and predicting MM outcome impact. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters known to be independent predictors of MM outcome. However, they have not been adopted in clinical practice due to the lack of measuring standards. CT-based segmentation allows automated, and therefore reproducible, calculation of bone metabolic metrics in patients with MM, such as maximum, mean and standard deviation of the standardized uptake values (SUV) for the entire skeleton. Intensity of bone involvement (IBI) is a new parameter that also takes advantage of this approach with promising results. Other indirect parameters obtained from FDG-PET/CT images, such as visceral adipose tissue glucose uptake and subcutaneous adipose tissue radiodensity, may also be useful to evaluate the prognosis of MM patients. Furthermore, the use and quantification of new radiotracers can address different metabolic aspects of MM and may have important prognostic implications FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto

Agradecimentos: The authors would like to thank the Nuclear and Energy Research Institute (IPEN-CNEN), Sao Paulo, Brazil for supplying the radiopharmaceuticals used in the present project [IPEN/UNICAMP agreement No. 01342000458/2017-15]. The authors are grateful for the financial support from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [grant numbers 2009/54065-0, 2018/00654-4]. This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) [Finance Code 001] Abstract: Purpose The parameter intensity of bone involvement (IBI) was recently proposed to quantitatively assess patients with multiple myeloma using F-18-fluorodeoxyglucose-PET combined with computed tomography (F-18-FDG PET/CT) images. Here, we aimed to calculate IBI variation (Delta IBI) between two consecutive PET/CT of the same patient and verified its relationship with a subjective visual analysis of the images and with clinical outcome. Methods Consecutive whole-body F-18-FDG PET/CT performed to assess the outcomes of 29 patients diagnosed with multiple myeloma were retrospectively evaluated. Delta IBI was calculated after bone segmentation, using liver standardized uptake value as a threshold to determine metabolically active volumes in the skeleton. For each pair of consecutive PET/CTs, two nuclear medicine physicians classified visually the most recent image as PET-remission, PET-progression or PET-stable when compared to the previous examination. Results The lowest Delta IBI was -1.27 and the highest was 0.29. PET-remission was related to Delta IBI 0 (median = 0.02; -0.07 to +0.29). Delta IBI around zero was found in images classified as PET-stable (median = 0.00; -0.08 to +0.06). Significant difference in Delta IBI was found between the three groups. Multivariate stepwise analysis showed that IBI value at diagnostic PET/CT, serum calcium and percentage of plasma cells in the bone marrow are independent prognostic factors. Conclusion Delta IBI provides quantitative data for variations of F-18-FDG uptake in the bone marrow during the follow-up of the patients. In addition, higher IBI values at diagnosis are associated with a higher risk of patient's death FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES Fechado

Agradecimentos: We thank the Nuclear and Energy Research Institute (IPEN-CNEN) São Paulo, Brazil, for kindly supplying radiopharmaceuticals used in the present project (IPEN/UNICAMP agreement No. 01342000458/2017-15). We are grateful for financial support from FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo), grant numbers 2009/54065-0 and 2018/00654-4. This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. CDR has a research grant from CNPq (National Council of Research) proc 311841/2018-0. ILM has a research grant from CNPq (National Council of Research) proc 305110/2018-7. This study was funded by (1) Energy Research Institute – IPEN, São Paulo, Brazil, (IPEN/UNICAMP agreement No. 01342000458/2017-15); (2) Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (grant numbers 2009/54065-0, 2018/14132-0 and 2018/00654-4); (3) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil – CAPES (finance code 001); and (4) Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (grant number 311841/2018-0) Abstract: Purpose F-18-fluorodeoxiglucose (F-18-FDG)-PET/CT has been widely used to evaluate multiple myeloma.Tc-99m-sestamibi (MIBI) scintigraphy has also been proposed for assessing multiple myeloma, but its use with state-of-the-art single-photon emission computed tomography/computed tomography (SPECT/CT) technology has not been fully evaluated.This study aimed to compare these two imaging modalities in multiple myeloma staging. Materials and methods Sixty-two patients with recently diagnosed multiple myeloma were submitted to whole-body(18)F-FDG-PET/CT and whole-body MIBI scans plus SPECT/CT of the chest and abdomen/pelvis. Number of focal lesions, contiguous soft tissue involvement (CSTI), extramedullary lesions (EMLs) and diffuse bone marrow (BM) involvement were recorded. Results PET/CT was positive in 59 patients (95%) and MIBI SPECT/CT in 58 (93%) (P = 0.69). MIBI detected more diffuse bone marrow involvement than PET/CT (respectively 78 vs. 58% of the patients), while PET/CT demonstrated more focal lesions than MIBI SPECT/CT (81 vs. 54% of the patients) (P = 0.002). PET/CT detected EMLs in four subjects and MIBI in one subject. CSTI was found in 28 (45%) and 23 (37%) patients on PET/CT and MIBI images, respectively (P = 0.36). Three patients with lytic lesions and no FDG uptake were MIBI positive, and two subjects with lytic lesions without MIBI uptake were FDG positive. Conclusion MIBI SPECT/CT performs similarly to(18)F-FDG-PET/CT in identifying sites of active disease in multiple myeloma staging. MIBI is more efficient than FDG for detecting the diffuse involvement of bone marrow but less efficient for detecting focal lesions. Some patients presented a 'mismatch' pattern of FDG/MIBI uptake FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto

Agradecimentos: The Nuclear and Energy Research Institute (IPEN-CNEN), Sao Paulo, Brazil, kindly supplied the radiopharmaceuticals used in the present project (IPEN/UNICAMP agreement 01342000458/2017-15). Financial support was provided by FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, grants 2009/54065-0 and 2018/00654-4). Celso Ramos has a research grant from CNPq (National Council of Research, proc 311841/2018-0). Irene Metze has a research grant from CNPq (National Council of Research, proc 305110/2018-7). No other potential conflict of interest relevant to this article was reported Abstract: Quantification of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) can be time-consuming. We evaluated the performance of an automatic multifocal segmentation (MFS) method of quantification in patients with different stages of Hodgkin lymphoma, using the multiple VOI (MV) method as reference. Methods: This prospective bicentric study included 50 patients with Hodgkin lymphoma who underwent staging F-18-FGD PET/CT. The examinations were centrally reviewed and processed with commercial MFS software to obtain MTV and TLG using 2 fixed relative thresholds (40% and 20% of SUV max ) for each lesion. All PET/CT scans were processed using the MV and MFS methods. Interclass correlation coefficients and Bland-Altman plots were used for statistical analysis. Repeated calculations of MW and TLG values by 2 observers with different degrees of PET/CT imaging experience were used to ascertain interobserver agreement on the MFS method. Results: The means and SDs obtained for the MW with MV and MFS were, respectively, 736 +/- 856 mL and 660 +/- 699 mL for the 20% threshold and 313 +/- 359 mL and 372 +/- 434 mL for the 40% threshold. The time spent calculating the MW was much shorter with the MFS method than with the MV method (median time, 11.6 min [range, 1-30 min] and 64.4 min [range, 1-240 min], respectively), especially in patients with advanced disease. Time spent was similar in patients with localized disease. There were no statistical differences between the MFS values obtained by the 2 different observers. Conclusion: MTV and TLG calculations using MFS are reproducible, generate similar results to those obtained with MV, and are much less timing-consuming. Main differences between the 2 methods were related to difficulties in avoiding overlay of VOIs in the MV technique. MV and MFS perform equally well in patients with a small number of lesions FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Fechado

Agradecimentos: The authors thank the 265 participants who kindly respond to the survey. Without their cooperation this survey could not have been accomplished. Additionally, the authors thank to the Grupo Latinoamericano de Mielodisplasia (GLAM), Grupo Rioplatense de Citometria de Flujo (GRCF), Brazilian Group of Flow Cytometry (GBCFLUX), Sociedad Peruana de Hematologia (SPH), International Clinical Cytometry Society (ICCS), European Society for Clinical Cell Analysis (ESCCA), International Society for Advancement of Cytometry (ISAC), Purdue University Cytometry mailing list, Dutch Cytometry Society and Iberian Cytometry Society (SIC) for their support and contribution to survey distribution Abstract: Flow cytometry (FC) is a valuable tool for the diagnosis of myelodysplastic syndromes (MDS). We present results of a survey carried out to evaluate FC current practice for MDS diagnosis in Latin America (LA), focusing on markers used and characteristics of the clinical diagnostic report. Compliance to IMDSflow recommendations was also evaluated. These practices were then compared with those used in other countries. An online survey was sent through the Grupo Latino-Americano de Mielodisplasia to LA cytometrists and other international scientific societies. 91 responses from 15?LA countries were received. The median of the number of markers used was 20 ± 4.5, but only 8.1% of participants adopted the complete panel proposed by the International/European LeukemiaNet Working Group (IMDSflow). We received 140 eligible answers from regions other than LA (66 Europe, 59 USA-Canada, 8 Oceania, 6 Asia and 1 Africa). LA utilized more markers for MDS diagnosis than USA/Canada (p = 0.006), but similar to Europe. The use of MDS scoring systems differed among regions: 10.3% in LA, 0% USA/Canada and 25.7% Europe reported the "Ogata score". Finally, 52.0% of all participants included a general interpretation statement in the final report about the consistency of the FC results with MDS diagnosis, with no statistical differences between regions.This survey shows a low compliance with the IMDSflow recommendations and a scarce use of the scoring systems proposed in the literature. However, the number of surface markers used is high. We will work to develop a FC consensus for MDS diagnosis adapted to the clinical practice requirements in LA Fechado

Agradecimentos: We thank the Nuclear and Energy Research Institute (IPEN-CNEN), São Paulo, Brazil, for kindly supplying the radiopharmaceuticals used in the present project (IPEN/UNICAMP agreement No. 01342000458/2017-15). We are grateful for financial support from FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo), Grant Numbers 2009/54065-0 and 2018/00654-4. The study was also partially financed by Cooperação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) finance code 001. ILM has a research grant from CNPq (National Council of Research) proc 305110/2018-7. CDR has a research grant from CNPq (National Council of Research) proc 311841/2018-0 Many efforts have been made to standardize the interpretation of F-18-FDG PET/CT in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of F-18-FDG PET/CT considering the extent and intensity of bone F-18-FDG uptake: Intensity of Bone Involvement (IBI). Whole body F-18-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with F-18-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement - PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00-1.35). Visual analysis categorized PET exams into three groups (negative/mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p < 0.0001). There was an inverse correlation between the patients' hemoglobin values and IBI (r = -0.248;p = 0.02). IBI score is an objective measure of bone and bone marrow involvement in MM, allowing the categorization of patients in different degrees of aggressiveness of the bone disease. The next step is to validate IBI in a larger group of patients, before and after treatment and in a multicentre setting. FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES Aberto

SIVA1, SIVA2, MDM2, TP53 and BCL2 expression in bone marrow cells from myelodysplastic syndromes (MDS) stratified by Revised International Prognostic Scoring System (IPSS-R). SIVA1 (A), SIVA2 (B), MDM2 (C) and TP53 (D) mRNA expression in total bone marrow cells from MDS patients stratified by IPSS-R into very low/low risk group and intermediate/high/very high risk group. Horizontal lines indicate medians. The numbers of subjects studied and p values are indicated; Mann–Whitney test. (PDF 32 kb)

SIVA1, SIVA2, MDM2 and TP53 expression in bone marrow cells from myelodysplastic syndromes (MDS) stratified by World Healthy Organization (WHO) 2008 classification. SIVA1 (A), SIVA2 (B), MDM2 (C) and TP53 (D) mRNA expression in total bone marrow cells from MDS patients stratified by WHO classification into refractory anemia (RA)/refractory anemia with ringed sideroblasts (RARS)/refractory cytopenia with multilineage dysplasia (RCMD) group and refractory anemia with excess blast-1 (RAEB-1)/refractory anemia with excess blast-2 (RAEB-2) group. Horizontal lines indicate medians. The numbers of subjects studied are indicated. (PDF 31 kb)

TP53 and MDM2 expressions and their correlation with SIVA1 and SIVA2 levels in bone marrow cells from healthy donors. Correlation analysis between SIVA1 or SIVA2 with MDM2 or TP53 expression in total bone marrow cells from healthy donors. The p and r values are indicated; Spearman correlation test. (PDF 25 kb)

Acompanhado de errata Abstract: Chronic lymphocytic leukemia is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+ and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood, lymph nodes, and spleen. The diagnosis is established by immunophenotyping circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai and Binet) established by physical examination and blood counts, as well as by several biological and genetic markers. In this update, we present the recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the diagnosis and treatment of chronic lymphocytic leukemia. The following recommendations are based on an extensive literature review with the aim of contributing to more uniform patient care in Brazil and possibly in other countries with a similar social-economic profile Aberto

Acompanhado de errata Abstract: Chronic lymphocytic leukemia is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+ and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood, lymph nodes, and spleen. The diagnosis is established by immunophenotyping circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai and Binet) established by physical examination and blood counts, as well as by several biological and genetic markers. In this update, we present the recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the diagnosis and treatment of chronic lymphocytic leukemia. The following recommendations are based on an extensive literature review with the aim of contributing to more uniform patient care in Brazil and possibly in other countries with a similar social-economic profile Aberto