Publications by authors named "Vanderson Rocha"

297 Publications

Philadelphia-positive B-lymphoblastic leukemia in a middle-income country - A real-world multicenter cohort.

Leuk Res 2021 Jul 13;110:106666. Epub 2021 Jul 13.

Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.

Outside of clinical trials, few studies have addressed the outcomes of Ph+ acute lymphoblastic leukemia (ALL) in adults, especially from developing world. In this study, we conducted a multicenter analysis on the outcomes of patients aged > 15 years with Ph+ ALL, aiming to get to know an overview of the Brazilian experience as well as to explore baseline factors associated with relapse and mortality in our setting. Over these 10 years, patients were treated with diverse protocols, all of them always combined with a frontline tyrosine-kinase inhibitor. A total of 123 Ph+ ALL patients was included. Imatinib was the first line TKI in 97 %. The complete response rate was 79 %. The early death rate was 15 %, being associated with increasing age at diagnosis (p = 0.06). The use of intensive versus attenuated induction regimen was not associated with higher induction mortality (p = 0.99). Overall, 29 % of patients aged ≤ 60 years underwent allogeneic transplantation, 87 % in first CR. 4-year overall survival (OS) and relapse-free survival were 25 % and 24 %, respectively. The incidence of relapse (death as a competitor) was 29 %, while the non-relapse mortality was 42 %. Only age was independently associated with OS, and lactate dehydrogenase level and central nervous disease at diagnosis were related to relapse in our cohort. This is the first historical cohort multicenter study on Ph+ ALL from Brazil. Reporting these outcomes is essential to encourage public policies to expand access to new drugs and transplantation in middle-income countries.
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http://dx.doi.org/10.1016/j.leukres.2021.106666DOI Listing
July 2021

Outcomes and Prognostic Factors in a Large Cohort of Hospitalized Cancer Patients With COVID-19.

JCO Glob Oncol 2021 06;7:1084-1092

Medical Oncology Division, Instituto do Cancer do Estado de São Paulo, Faculty of Medicine, Sao Paulo University, Sao Paulo, Brazil.

Purpose: Patients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19.

Methods: All consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes.

Results: Five hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST.

Conclusion: A high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.
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http://dx.doi.org/10.1200/GO.21.00087DOI Listing
June 2021

Dental Biofilm Microbiota Dysbiosis Is Associated With the Risk of Acute Graft--Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

Front Immunol 2021 18;12:692225. Epub 2021 Jun 18.

Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, Brazil.

Acute graft--host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High and high relative abundance at preconditioning were associated with a higher risk of aGVHD (67% 33%; HR = 2.89, P = 0.04 and 73% 37%; HR = 2.74, P = 0.04, respectively), while high relative abundance was associated with a lower risk of aGVHD (27% 73%; HR = 0.24, P < 0.01). bloom during allo-HSCT was observed in 17% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% 40%; HR = 4.07, P < 0.001) and severe aGVHD (60% 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT.
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http://dx.doi.org/10.3389/fimmu.2021.692225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250416PMC
June 2021

Steroid-refractory chronic graft-versus-host disease: treatment options and patient management.

Bone Marrow Transplant 2021 Jul 3. Epub 2021 Jul 3.

Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington, Seattle, Seattle, WA, USA.

Chronic graft-versus-host disease (cGVHD) is one of the major causes of late mortality after allogenic hematopoietic stem cell transplantation. Moderate-to-severe cGVHD is associated with poor health-related quality of life and substantial disease burden. While corticosteroids with or without calcineurin inhibitors comprise the first-line treatment option, the prognosis for patients with steroid-refractory cGVHD (SR-cGVHD) remains poor. The mechanisms underlying steroid resistance are unclear, and there are no standard second-line treatment guidelines for patients with SR-cGVHD. In this review, we provide an overview on current treatment options of cGVHD and use a series of theoretical case studies to elucidate the rationale of choices of second- and third-line treatment options for patients with SR-cGVHD based on individual patient profiles.
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http://dx.doi.org/10.1038/s41409-021-01389-5DOI Listing
July 2021

Post-acute sequelae of SARS-CoV-2 infection (PASC): a protocol for a multidisciplinary prospective observational evaluation of a cohort of patients surviving hospitalisation in Sao Paulo, Brazil.

BMJ Open 2021 06 30;11(6):e051706. Epub 2021 Jun 30.

Departamento de Cardio-Pneumologia, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil.

Introduction: COVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity.

Methods And Analyses: We will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1-2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6-9 months and 12-15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics.

Ethics And Dissemination: All components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples.

Trial Registration Number: RBR-8z7v5wc; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2021-051706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249176PMC
June 2021

Outcomes after Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide: A Systematic Review and Meta-Analysis Comparing Myeloablative with Reduced-Intensity Conditioning Regimens and Bone Marrow with Peripheral Blood Stem Cell Grafts.

Transplant Cell Ther 2021 Jun 16. Epub 2021 Jun 16.

Bone Marrow Transplantation Unit, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.

Haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplantation cyclophosphamide (PTCy) may be the sole available curative option for several hematologic malignancies. However, the best choice of conditioning regimen and graft source has not been established. This study was conducted to compare myeloablative conditioning (MAC) regimens with reduced-intensity conditioning (RIC) regimens and peripheral blood stem cell (PBSC) grafts with bone marrow (BM) grafts in the haplo-HCT setting with PTCy. We performed a systematic review and meta-analysis of studies comparing MAC with RIC and PBSC with BM in the haplo-HCT. The search was conducted in PubMed and TRIALS on February 2, 2021, without a date limit. We excluded studies with >30% non-PTCy graft-versus-host disease (GVHD) prophylaxis and >30% nonmalignant diseases. We screened 570 abstracts from PubMed and TRIALS and selected 20 for full-text review and 17 for inclusion in the qualitative and quantitative analyses. For PBSC versus BM grafts, we found no difference in overall survival (OS; hazard ratio [HR], 1.05; P = .61; nPBSC = 1983; nBM = 2124), progression-free survival (PFS; HR, 0.95; P = .52; nPBSC = 2663, nBM = 2769), graft-versus-host disease (GVHD)-free relapse-free survival (GRFS; HR, 1.16; P = .07; nPBSC = 1454; pBM = 1647), or nonrelapse mortality (HR, 1.14; P = .13; nPBSC = 1664; nBM = 1862). Relapse was lower with the use of PBSC grafts (HR, 0.84; P = .001; nPBSC = 2663; nBM = 2769). The rates of acute GVHD (aGVHD) and chronic GVHD (cGVHD) were higher with PBSC grafts (aGVHD grade II-IV: HR, 1.67; P < .001; nPBSC = 2663; nBM = 2802; aGVHD grade III-IV: HR, 1.82; P < .001; nPBSC = 1826; nBM = 2000; cGVHD: HR, 1.46; P = .002; nPBSC = 2686; nBM = 2815). Engraftment was higher with PBSC grafts (HR, 1.27; P < .001; nPBSC = 1461; nBM = 1717). Comparing MAC and RIC, the use of MAC was associated with less relapse (HR, 0.70; P < .001; nMAC = 1929; nRIC = 2662), higher nonrelapse mortality (HR, 1.24; P = .002; nMAC = 2016; nRIC = 2790), but better PFS (HR, 0.86; P = .002; nMAC = 1929; nRIC = 2662). There were no differences between the 2 conditioning regimens in OS (HR, .95; P = .32; nMAC = 2123; nRIC = 3155), GRFS (HR, 0.97; P = .67; nMAC = 1182; nRIC = 1330), grade II-IV aGVHD (HR, 1.01; P = .81; nMAC = 2099; nRIC = 3090), or cGVHD (HR, 1.05; P = .44; nMAC=1929; nRIC = 2662). This analysis shows that the use of BM grafts is associated with comparable outcomes as seen with PBSC grafts despite a lower incidence of GVHD and a higher relapse rate. The use of MAC regimens is associated with improved PFS. These results suggest that for fit patients, MAC remains the optimal conditioning regimen in terms of mortality, and that the use of PBSC grafts may further decrease relapse risk and hasten engraftment, provided that further strategies can be incorporated to decrease GVHD. Prospective comparisons are awaited.
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http://dx.doi.org/10.1016/j.jtct.2021.06.011DOI Listing
June 2021

Oral mucositis in paediatric cancer patients undergoing allogeneic hematopoietic stem cell transplantation preventively treated with professional dental care and photobiomodulation: Incidence and risk factors.

Int J Paediatr Dent 2021 Jun 11. Epub 2021 Jun 11.

Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil.

Background: Oral mucositis (OM) is an important side effect related to allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it has been associated with a significative reduction of quality of life. A negative impact of this toxicity in paediatric patients could result in increased use of parenteral feeding and opioids, longer periods of hospitalization, and a higher risk of systemic infection.

Aim: To investigate the clinical features and clinical outcomes associated with OM development and severity in hematological cancer paediatric patients undergoing allo-HSCT who underwent professional dental care (PDC) and photobiomodulation (PBM) as prophylactic treatment.

Design: Medical data and OM presentation were retrieved retrospectively from all patients younger than 18 years who were submitted to allo-HSCT between 2013 and 2016. The incidence of OM was assessed and graded by two oral medicine specialists following the WHO guidelines, and it was correlated with clinical parameters.

Results: Forty-nine consecutive paediatric patients were included. OM was diagnosed in 73.5% of patients, and in 36.1% of patients, OM was classified as severe. Acute lymphoblastic leukemia as a primary diagnosis and the use of a myeloablative regimen were associated with OM development. The primary diagnosis and use of total body irradiation (TBI) were associated with aggressive OM. Neither the incidence nor the severity of OM affected the overall survival, whereas only the use of a myeloablative regimen and a high body mass index (BMI) were determinants of lower OM-free survival rates.

Conclusions: A myeloablative conditioning and a high BMI were observed to be independent prognostic determinants of a lower OMFS rate. The cluster analysis allowed us to outline patient profiles with greater susceptibility to the development and severity of oral mucositis, which seems to be a useful tool to determine the risk of OM in paediatric patients.
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http://dx.doi.org/10.1111/ipd.12850DOI Listing
June 2021

Umbilical cord blood transplants facilitated by the French cord blood banks network. On behalf of the Agency of Biomedicine, Eurocord and the French society of bone marrow transplant and cell therapy (SFGM-TC).

Bone Marrow Transplant 2021 May 14. Epub 2021 May 14.

Eurocord, Hopital Saint-Louis, AP-HP, Institut de Recherche de Saint-Louis (IRSL) EA3518, Université de Paris, Paris, France.

The public French Cord Blood Banks Network was established in 1999 with the objective of standardizing the practices governing umbilical cord blood (UCB) banking in France. The Network adopted a strategy to optimize its inventory and improve the quality of its banked units based on a quality improvement process using outcome data regularly provided by Eurocord. This study aimed to describe the results, over 10 years, of UCBT facilitated by a national network that used the same criteria of UCB collection and banking and to assess how modifications of banking criteria and unit selection might influence transplant outcomes. Nine hundred and ninety-nine units (593 single-unit and 203 double-unit grafts) were released by the Network to transplant 796 patients with malignant (83%) and non-malignant (17%) diseases. Median cell dose exceeded 3.5 × 10 TNC/kg in 86%. There was a trend to select units more recently collected and with higher cell dose. Neutrophil engraftment was 88.2% (85.7-90.7) and 79.3% (72.6-86.5) respectively for malignant and non-malignant diseases with a trend to faster recovery with higher cell doses. The respective 3-year transplant-related mortality were 31.1% (27.5-35.1) and 34.3% (27.0-43.5). OS was 49% ± 4 in malignant and 62% ± 4 in non-malignant disorders. In multivariate analysis, cell dose was the only unit-related factor associated with outcomes. Our results reflect the benefit on clinical outcomes of the strategy adopted by the Network to bank units with higher cell counts.
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http://dx.doi.org/10.1038/s41409-021-01313-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120495PMC
May 2021

Outcomes of Unmanipulated Haploidentical Transplantation Using Post-Transplant Cyclophosphamide (PT-Cy) in Pediatric Patients With Acute Lymphoblastic Leukemia.

Transplant Cell Ther 2021 05 21;27(5):424.e1-424.e9. Epub 2021 Jan 21.

Pediatric Hematology, Oncology and Stem Cell Transplantation Department, University of Regensburg, Regensburg, Germany.

HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL. Median age was 9 years, and median follow-up was 2.7 years. Disease status was CR1 for 24%, CR2 for 45%, CR+3 for 12%, and active disease for 19%. All patients received PT-Cy day +3 and +4. Bone marrow (BM) was the stem cell source in 115 patients (64%). Cumulative incidence of 42-day engraftment was 88.9%. Cumulative incidence of day-100 acute graft-versus-host disease (GVHD) grade II-IV was 28%, and 2-year chronic GVHD was 21.9%. At 2 years, cumulative incidence of nonrelapse mortality (NRM) was 19.6%. Cumulative incidence was 41.9% for relapse and 25% for patients in CR1. Estimated 2-year leukemia free survival was 65%, 44%, and 18.8% for patients transplanted in CR1, CR2, CR3+ and 3% at 1 year for active disease. In multivariable analysis for patients in CR1 and CR2, disease status (CR2 [hazard ratio {HR} = 2.19; P = .04]), age at HCT older than 13 (HR = 2.07; P = .03) and use of peripheral blood stem cell (PBSC) (HR = 1.98; P = .04) were independent factors associated with decreased overall survival. Use of PBSC was also associated with higher NRM (HR = 3.13; P = .04). Haplo-HCT with PT-Cy is an option for children with ALL, namely those transplanted in CR1 and CR2. Age and disease status remain the most important factors for outcomes. BM cells as a graft source is associated with improved survival.
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http://dx.doi.org/10.1016/j.jtct.2021.01.016DOI Listing
May 2021

Prognostic assessment for chronic myelomonocytic leukemia in the context of the World Health Organization 2016 proposal: a multicenter study of 280 patients.

Ann Hematol 2021 Jun 1;100(6):1439-1449. Epub 2021 May 1.

Laboratorio de Genética Hematológica, Instituto de Medicina Experimental (IMEX-CONICET)/Academia Nacional de Medicina, Buenos Aires, Argentina.

Knowledge on chronic myelomonocytic leukemia (CMML) patients from Argentina and Brazil is limited. Our series of 280 patients depicted an older age at diagnosis (median 72 years old), 26% of aberrant karyotypes, and a prevalence of myelodysplastic (60%) and CMML-0 subtypes (56%). The median overall survival (OS) was 48.2 months for patients in CMML-0 (Ref.), 24.7 months for those in CMML-1 (HR = 2.0, p = 0.001), and 8.8 months for patients in CMML-2 (HR = 4.6, p < 0.001). In the CMML-0 category, median OS were different between myelodysplastic and myeloproliferative subtypes (63.7 vs 21.2 months, p < 0.001); however, no differences were observed within CMML-1 and CMML-2 subtypes (24.7 vs 23.7 months, p = 0.540, and 9.1 vs 8.2 months, p = 0.160). The prognostic impact of 24 variables and 7 prognostic systems was adjusted to the WHO 2016 after validating their usefulness. Multivariate analysis were performed, and the final model revealed Hb ≥ 8 -< 10g/dL (HR 1.7), Hb < 8g/dL (HR 2.8), poor karyotypes (HR 2.1), WHO 2016-CMML-1 (HR 2.1), and CMML-2 (HR 3.5) as independent adverse clinical parameters in our cohort with a borderline influence of platelets count < 50 × 10/L (HR 1.4). We could validate several scoring systems, the WHO 2016 proposal and its prognostic capability, along with accessible covariates, on predicting the outcome in our series of CMML patients from Latin America.
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http://dx.doi.org/10.1007/s00277-021-04539-3DOI Listing
June 2021

Carbapenem-resistant Serratia marcescens bloodstream infection in hematopoietic stem cell transplantation patients: Will it be the next challenge?

Transpl Infect Dis 2021 Apr 29:e13630. Epub 2021 Apr 29.

Medical Research Laboratory, Bacteriology-LIM-54, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Surveillance programs have been reporting decreasing rates of carbapenem-sensitivity in Serratia marcescens, leading to a concern regarding the few remaining therapeutic options to treat these multidrug-resistant (MDR) organisms. Here, we describe a case series of 11 stem cell hematopoietic transplantation patients infected (N = 6) or colonized (N = 5) by carbapenem-resistant S marcescens (CrSm) from 2010 to 2013. The comorbidities found were acute renal insufficiency (3/11), neutropenia (7/11), and mucositis (8/11), and the mortality rate was 64%. KPC was the most prevalent carbapenemase detected (8/11) and tigecycline and gentamicin were the antimicrobials used as treatment.
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http://dx.doi.org/10.1111/tid.13630DOI Listing
April 2021

Stem Cell Transplantation for Diamond-Blackfan Anemia. A Retrospective Study on Behalf of the Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplantation Group (EBMT).

Transplant Cell Ther 2021 03 25;27(3):274.e1-274.e5. Epub 2020 Dec 25.

Hospital Universitario La Paz, Madrid, Spain.

Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients.
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http://dx.doi.org/10.1016/j.jtct.2020.12.024DOI Listing
March 2021

Variant genotypes associated with reduced expression of RhCE antigens among Brazilian blood donors.

Transfusion 2021 06 9;61(6):1923-1931. Epub 2021 Mar 9.

Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, Brazil.

Background: The genetic diversity of the RHCE gene locus has been explored in diverse populations of different racial backgrounds. Data referring to the diversity of RHCE encoding weakened expression of C, c, E, and e in multiethnic populations is still incomplete.

Methods: Samples from Brazilian blood donors presenting reduced expression of C, c, E, or e on gel method were selected for the study. All exons and flanking introns of RHCE were genotyped though direct Sanger sequencing for the included donors.

Results: Sixty-six donors were included: 23 with weak C, 22 with weak c, 6 with weak E, 14 with weak e, and 1 with weak c and E. Among the samples with weak C, the following altered RH*C were encountered: RHCE*CeMA (n = 3), RHCE*Ce941C (n = 1), and RHCE*CeVA (n = 1). RHD*D-CE(4-7)-D was detected in six cases, RHCE*CE was presumably present in five cases, and seven cases were unexplained. Two altered alleles underlay the weak c phenotype: RHCE*ceJAL (n = 20) and RHCE*ce340T (n = 2), and two altered RHCE justified weak e: RHCE*ceMO (n = 6) and RHCE*ceJAL (n = 8). Three variant RHCE were associated with weak E: RHCE*cEJU (n = 4), RHCE*cE382C (n = 1), and RHCE*cEIV (n = 1). The RHCE*cE905A justified one case of weak c and E.

Conclusion: We describe the distribution of RHCE variants found in association with weak expression of C, c, E, and e in blood donors of multiethnic origin, which differs in comparison to that previously reported for people of African or Caucasian descent.
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http://dx.doi.org/10.1111/trf.16355DOI Listing
June 2021

Occult and active hepatitis B virus detection in donated blood in São Paulo, Brazil.

Transfusion 2021 05 9;61(5):1495-1504. Epub 2021 Mar 9.

Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, Brazil.

Background: The present study determined the HBV antigen, antibody, and DNA status in blood donations deemed to be HBV positive. Individuals with an occult HBV infection (OBI), defined as being positive for HBV DNA but negative for HBV surface antigen (HBsAg), as well as those with active infection (HBsAg-positive), were identified and characterized.

Study Design And Methods: From a total pool if 198,363 blood donations, we evaluated in a cross-sectional study, 1106 samples that were positive in screening tests for antibody to HBV core antigen (HBcAb), HBsAg, and/or HBV DNA by nucleic acid testing (NAT-HBV). The presence of genetic variants in the HBV pol/S gene in individuals with an active HBV infection was also determined.

Results: OBIs were detected in six of 976 samples (0.6%) that were positive only for HBcAb. The rate of HBV active infection was 0.024% (48/198,363) and there was a predominance of HBV sub-genotype A1 (62.2%, 28/45), followed by D3 (17.8%, 8/45). Mutations in the S gene were found in 57.8% (26/45) and immune escape mutations in 37.8% (17/45) of active HBV-infected donors. Among them, T123N, G145A, and D144G high-impact immune escape mutations were identified.

Conclusion: Highly sensitive molecular tests improve the capacity to detect OBIs. When NAT is performed in pooled samples, HBcAb test has value in the detection of donors with OBI and improves transfusion safety. Mutations in the S gene are frequent in HBsAg-positive blood, including those associated with diagnostic failure and vaccine escape mutations.
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http://dx.doi.org/10.1111/trf.16344DOI Listing
May 2021

Changes in blood donation and utilization secondary to Covid-19 outbreak.

Transfus Apher Sci 2021 06 17;60(3):103102. Epub 2021 Feb 17.

Fundação Pró-Sangue São Paulo Hemocenter, São Paulo, Brazil; Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.

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http://dx.doi.org/10.1016/j.transci.2021.103102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888989PMC
June 2021

New genetic prognostic biomarkers in primary central nervous system lymphoma (PCNSL).

Brain Behav 2021 04 16;11(4):e02061. Epub 2021 Feb 16.

Department of Hematology, Hemotherapy and Cell Therapy, Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil.

Background: PCNSL is a rare extranodal NHL with poor prognosis. Tumorigenesis has been associated with hyperactivation of BCR downstream and NFkB pathways. We studied the prognosis of the relative expression profile of target genes of NFkB pathway (MYC, BCL2), the essential transcriptional regulator in hematopoiesis LMO2, the checkpoint regulation pathway MGMT, the transcription factor POU2F1, the immune checkpoint gene PDCD1, and the proto-oncogene and transcriptional repressor gene BCL6 and its proteins in PCNSL.

Methods: This study is a retrospective cohort study; 35 immunocompetent PCNSL-DLBCL patients had their gene expression (RT-qPCR) normalized to internal control gene GUSB.

Results: Median patient age was 62 years, median OS was 42.6 months (95% CI: 26.6-58.6), PFS was 41 months (95% CI: 19.7-62.4), and DFS was 59.2 months (95% CI 31.9-86.6). A moderate correlation was found between the gene/protein expressions of MYC (kappa = 0.596, p = .022) and of BCL2 (kappa = 0.426, p = .042). Relative gene expression of MYC ≥ 0.201 (HR 6.117; p = .003) was associated with worse 5-year OS. Relative gene expression of MYC ≥ 0.201 (HR 3.96; p = .016) and MGMT ≥ 0.335 (HR 3.749; p = .056) was associated with worse PFS. Age > 60 years and IELSG score moderate/high were also associated with worse prognosis.

Conclusions: Overexpression of MYC and overexpression of MGMT were prognostic markers associated with unfavorable clinical outcomes in PCNSL.
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http://dx.doi.org/10.1002/brb3.2061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035458PMC
April 2021

MR 4log and low levels of NK cells are associated with higher molecular relapse after imatinib discontinuation: Results of a prospective trial.

Leuk Res 2021 02 21;101:106516. Epub 2021 Jan 21.

Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

Background: Treatment-free survival (TFS) in chronic myeloid leukemia (CML) is a new goal. This prospective study aims to evaluate imatinib discontinuation's feasibility and safety in patients with deep molecular response MR4 (BCR-ABL1 < 0.01 % IS).

Methods: Study was approved by the ethical committee and registered at Clinicaltrials.gov (NCT03239886). Incluision criteria were: age ≥ 18y, chronic phase, first-line imatinib for 36 months, MR4 for 12 months, no previous transplant or resistance. Imatinib was resumed when two samples confirmed the loss of MMR. The primary endpoint was molecular recurrence-free survival (MRFS) at 24 months. Lymphocyte subpopulations were counted in peripheral blood before discontinuation.

Results: 31 patients were included from Dec/2016 until Oct/2017. Median age was 54years, 58 % male, 58 % low Sokal, 65 % b3a2 transcripts, and 61 % were in MR4.5. Imatinib therapy's median time was 9.7y (3-14.9 y), median time of MR4 was 6.9y (1.6-10.3y). MRFS at 24 months was 55 % (95 % CI 39-75). Thirteen patients relapsed, 46 % after six months of discontinuation, and all patients recovered MMR. Median time to recover MMR was one month. MR4.5 was the only factor associated with MRFS. NK cells proportion at baseline was lower in patients with only MR4 who relapsed after discontinuation.

Conclusion: With a median duration of sustained MR4 above five years, as recommended by most TKI discontinuation guidelines, the TFS was similar to previous studies. Only MR4.5 was associated with lower risk of relapse. Further studies are needed to evaluate whether patients with only MR4 and low NK cell levels are suitable for discontinuation.
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http://dx.doi.org/10.1016/j.leukres.2021.106516DOI Listing
February 2021

Correlation between SARS-COV-2 antibody screening by immunoassay and neutralizing antibody testing.

Transfusion 2021 04 25;61(4):1181-1190. Epub 2021 Jan 25.

Instituto de Medicina Tropical, FMUSP, São Paulo, Brazil.

Background: The efficacy of convalescent plasma (CP), an alternative for the treatment of COVID-19, depends on high titers of neutralizing antibodies (nAbs), but assays for quantifying nAbs are not widely available. Our goal was to develop a strategy to predict high titers of nAbs based on the results of anti-SARS-CoV-2 immunoassays and the clinical characteristics of CP donors.

Study Design And Methods: A total of 214 CP donors were enrolled and tested for the presence of anti-SARS-CoV-2 antibodies (IgG) using two commercial immunoassays: EUROIMMUN (ELISA) and Abbott (Chemiluminescence). Quantification of nAbs was performed using the Cytopathic Effect-based Virus Neutralization test. Three criteria for identifying donors with nAbs ≥ 1:160 were tested: - C1: Curve ROC; - C2: Conditional decision tree considering only the IA results and - C3: Conditional decision tree including both the IA results and the clinical variables.

Results: The performance of the immunoassays was similar referring to both S/CO and predictive value for identifying nAbs titers ≥1:160. Regarding the studied criteria for identifying CP donors with high nAbs titers: (a) C1 showed 76.1% accuracy if S/CO = 4.65, (b) C2 presented 76.1% accuracy if S/CO ≥4.57 and (c) C3 had 71.6% accuracy if S/CO was ≥4.57 or if S/CO was between 2.68-4.57 and the last COVID-19-related symptoms were recent (within 19 days).

Conclusion: SARS-CoV-2 IgG immunoassays (S/CO) can be used to predict high anti-SARS-CoV-2 nAbs titers. This study has proposed different criteria for identifying donors with ≥1:160 nAbs titers, all with high efficacy.
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http://dx.doi.org/10.1111/trf.16268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013621PMC
April 2021

Detection and analysis of blood donors seropositive for syphilis.

Transfus Med 2021 Apr 21;31(2):121-128. Epub 2021 Jan 21.

Divisão de Pesquisa & Medicina Transfusional, Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, Brazil.

Background: The increasing incidence of syphilis worldwide has called attention to the risk of transmission by transfusion.

Aims: To determine the prevalence of active syphilis in blood donors and characterise the serological profile of syphilis-positive donors.

Methods: Samples positive for Treponema pallidum using the chemiluminescent microparticle immunoassay (CMIA) during blood donor screening from 2017 to 2018 were tested by the Venereal Disease Research Laboratory (VDRL) non-treponemal test and for anti-T. pallidum IgM by ELISA (Immunoassay Enzyme test for detection of IgM antibodies). The INNO-LIA Syphilis test (Line Immuno Assay solid test for confirmation antibodies to Treponema pallidum) was performed as a confirmatory test on samples that were positive on ELISA-IgM but negative on VDRL. ELISA-IgM (+) samples were also tested for T. pallidum DNA in sera by real-time polymerase chain reaction (PCR).

Results: Of 248 542 samples screened, 1679 (0.67%) were positive for syphilis by CMIA. Further analysis was performed on 1144 (68.1%) of these samples. Of those tested, 16% were ELISA IgM(+)/VDRL(+), 16.5% were ELISA IgM(-)/VDRL(+), 4.1% were ELISA IgM(+)/VDRL(-), and 63.4% were ELISA IgM (-)/VDRL(-). The INNO-LIA Syphilis test results were 33 (3%) positive, 2 (0.2%) undetermined and 12 (1%) negative. Of the 230 EIA-IgM(+) samples (20.1%), 5 (2.2%) were PCR positive. The prevalence of active syphilis in 2017 and 2018 was 0.1% and 0.07%, respectively, and overall prevalence of serologic markers for syphilis was highest among male, unmarried, 25-34-year-olds with a high school education and who were first-time donors.

Conclusion: There is a risk of transfusion-transmitted syphilis in blood banks that exclusively use the VDRL test for donor screening, as is currently the situation in some Brazilian blood centres, as well as in other blood centres around the world.
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http://dx.doi.org/10.1111/tme.12761DOI Listing
April 2021

Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome.

Sci Rep 2021 Jan 18;11(1):1675. Epub 2021 Jan 18.

Department of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.

Deregulated cellular energetics is formally incorporated as an emerging hallmark of cancer, however little is known about its processes in myelodysplastic syndromes (MDS). Using transcriptomic data of CD34+ cells from 159 MDS patients and 17 healthy donors, we selected 37 genes involved in cellular energetics and interrogated about its clinical and prognostic functions. Based on the low expression of ACLY, ANPEP, and PANK1, as well as high expression of PKM and SLC25A5, we constructed our Molecular-Based Score (MBS), that efficiently discriminated patients at three risks groups: favourable risk (n = 28; 3-year overall survival (OS): 100%); intermediate (n = 60; 76% [62-93%]) and adverse (n = 71; 35% [17-61%]). Adverse MBS risk was independently associated with inferior OS (HR = 10.1 [95% CI 1.26-81]; P = 0.029) in multivariable analysis using age, gender and the revised international prognostic score system as confounders. Transcriptional signature revealed that Favourable- and intermediate-risk patients presented enriched molecular programs related to mature myeloid progenitors, cell cycle progression, and oxidative phosphorylation, indicating that this cells differs in their origin, metabolic state, and cell cycle regulation, in comparison to the adverse-risk. Our study provides the first evidence that cellular energetics is transcriptionally deregulated in MDS CD34+ cells and establishes a new useful prognostic score based on the expression of five genes.
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http://dx.doi.org/10.1038/s41598-020-80918-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814118PMC
January 2021

Optimizing selection of double cord blood units for transplantation of adult patients with malignant diseases.

Blood Adv 2020 12;4(24):6327-6335

Eurocord, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut de Recherche Saint Louis (IRSL) EA3518, Université de Paris, Paris, France.

Double-unit unrelated cord blood transplantation (DUCBT) is an option in patients for whom a single unit is not sufficient to provide an adequate number of cells. As current guidelines on UCB unit selection are mainly based on single-unit UCB data, we performed a retrospective analysis of 1375 adult recipients of DUCBT for hematologic malignancies to determine optimal criteria for graft selection. Cryopreserved total nucleated cells (TNCs; ≤3.5 vs >3.5 × 107/kg: hazard ratio [HR], 1.53; 30% vs 45%; P = .01), number of HLA mismatches (≥2 vs 0-1: HR, 1.28; 42% vs 48%; P = .01), and ABO compatibility (minor/major ABO incompatibility vs compatibility: HR, 1.28; P = .04) were independent risk factors for OS. Cryopreserved CD34+ cell dose ≥0.7 × 105/kg in the winning UCB was associated with improved OS (HR, 1.34; P = .03). Low TNC (≤3.5 × 107/kg) and CD34+ (≤1.4 × 105/kg) cell doses were related to decreased neutrophil recovery (HR, 0.65 [P = .01] and HR, 0.81 [P = .01], respectively). DUCBT recipients with ≥2 HLA mismatches had a higher incidence of grade II-IV and III-IV acute graft-versus-host disease (HR, 1.26 [P = .03] and 1.59 [P = .02], respectively). Low TNC dose (HR, 1.57; P = .02) and receiving UCB with ≥2 HLA mismatches (HR, 1.35; P = .03) were associated with increased transplant-related mortality. Our data support selecting adequately HLA-matched UCB units with a double-unit cryopreserved TNC dose >3.5 × 107/kg and CD34+ cell dose of ≥0.7 × 105/kg per unit in DUCBT candidates.
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http://dx.doi.org/10.1182/bloodadvances.2020002258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756987PMC
December 2020

Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic.

Science 2021 01 8;371(6526):288-292. Epub 2020 Dec 8.

Department of Zoology, University of Oxford, Oxford, UK.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in Manaus, the capital of Amazonas state in northern Brazil. The attack rate there is an estimate of the final size of the largely unmitigated epidemic that occurred in Manaus. We use a convenience sample of blood donors to show that by June 2020, 1 month after the epidemic peak in Manaus, 44% of the population had detectable immunoglobulin G (IgG) antibodies. Correcting for cases without a detectable antibody response and for antibody waning, we estimate a 66% attack rate in June, rising to 76% in October. This is higher than in São Paulo, in southeastern Brazil, where the estimated attack rate in October was 29%. These results confirm that when poorly controlled, COVID-19 can infect a large proportion of the population, causing high mortality.
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http://dx.doi.org/10.1126/science.abe9728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857406PMC
January 2021

How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians.

Front Immunol 2020 6;11:584950. Epub 2020 Nov 6.

Laboratory of Evolutionary Genetics, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.

A match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with "ethnicity" or "race") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as "Black" and "Mixed" on average have lower chances of finding matches than those who self-identify as "White" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.
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http://dx.doi.org/10.3389/fimmu.2020.584950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677137PMC
June 2021

Use of the HLA-B leader to optimize cord-blood transplantation.

Haematologica 2020 10 29;Online ahead of print. Epub 2020 Oct 29.

Eurocord, Hôpital Saint Louis APHP, Institut de Recherche de Saint-Louis (IRSL) EA3518, Université de Paris, Paris, France; Monacord, International Observatory on Sickle Cell Disease, Centre Scientifique de Monaco.

Cord-blood transplantation (CBT) can cure life-threatening blood disorders. The HLA-B leader affects the success of unrelated donor transplantation but its role in CBT is unknown. We tested the hypothesis that the HLA-B leader influences CBT outcomes in unrelated single-unit cord-blood transplants performed by Eurocord/European Blood and Marrow Transplant (EBMT) centers between 1990 and 2018 with data reported to Eurocord. Among 4822 transplants, 2178 had one HLA-B mismatch of which 1013 were HLA-A and HLA-DRB1-matched. The leader (M or T) was determined for each HLA-B allele in patients and units to define the genotype. Among single HLA-B-mismatched transplants, the patient/unit mismatched alleles were defined as leader-matched if they encoded the same leader, or leader-mismatched if they encoded different leaders; the leader encoded by the matched (shared) allele was determined. The risks of GVHD, relapse, non-relapse mortality and overall mortality were estimated for various leaderdefined groups using multivariable regression models. Among the 1013 HLA-A, -DRB1- matched transplants with one HLA-B mismatch, increasing numbers of cord-blood unit M-leader alleles was associated with increased risk of relapse (hazard ratio [HR] for each increase in one M-leader allele 1.30, 95% confidence interval [CI] 1.05 to 1.60, P 0.02). Furthermore, leader mismatching together with an M-leader of the shared HLA-B allele lowered non-relapse mortality (HR 0.44, 95% CI 0.23 to 0.81; P 0.009) relative to leader-matching and a shared T-leader allele. The HLA-B leader may inform relapse and non-relapse mortality risk after CBT. Future patients might benefit from the appropriate selection of units that consider the leader.
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http://dx.doi.org/10.3324/haematol.2020.264424DOI Listing
October 2020

Gemtuzumab ozogamicin is efficacious in attaining complete remission in relapsed/refractory acute leukemia prior to hematopoietic cell transplant: A case series.

Hematol Transfus Cell Ther 2020 Sep 13. Epub 2020 Sep 13.

Sírio-Libanês Hospital, São Paulo, SP, Brazil; Instituto do Câncer do Estado de São Paulo da Universidade de São Paulo (ICESP USP), São Paulo, SP, Brazil; Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil; Churchill Hospital, Oxford University Hospitals, United Kingdom; Laboratório Investigação Médica em Patogênese e Terapia dirigida em Onco-Imuno-Hematologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (LIM/31 HCFMUSP), São Paulo, SP, Brazil.

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http://dx.doi.org/10.1016/j.htct.2020.07.008DOI Listing
September 2020

Polymorphisms in Inflammatory Genes Modulate Clinical Complications in Patients With Sickle Cell Disease.

Front Immunol 2020 4;11:2041. Epub 2020 Sep 4.

INSERM U955, CHU Henri Mondor, Créteil, France.

Sickle cell disease (SCD), the most common monogenic disease worldwide, is marked by a phenotypic variability that is, to date, only partially understood. Because inflammation plays a major role in SCD pathophysiology, we hypothesized that single nucleotide polymorphisms (SNP) in genes encoding functionally important inflammatory proteins might modulate the occurrence of SCD complications. We assessed the association between 20 SNPs in genes encoding Toll-like receptors (TLR), NK cell receptors (NKG), histocompatibility leukocyte antigens (HLA), major histocompatibility complex class I polypeptide-related sequence A (MICA) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and the occurrence of six SCD clinical complications (stroke, acute chest syndrome (ACS), leg ulcers, cholelithiasis, osteonecrosis, or retinopathy). This study was performed in a cohort of 500 patients. We found that the 4696480 3804099 , and HLA-G, 9380142 genotypes were more frequent in patients who had fewer complications. Also, in logistic regression, the HLA-G 9380142 allele increased the risk of cholelithiasis ( vs. , OR 1.57, 95%CI 1.16-2.15; vs. , OR 2.47, 95%CI 1.34-4.64; = 0.02). For SNPs located in the loci, in logistic regression, the A allele in three SNPs was associated with a lower frequency of retinopathy, namely, 2246809 ( vs. : OR 0.22, 95%CI 0.09-0.50; vs. : OR 0.47, 95%CI 0.31-0.71; = 0.004, for patients of same origin), 2617160 ( vs. : OR 0.67, 95%CI 0.48-0.92; vs. : OR 0.45, 95%CI 0.23-0.84; = 0.04), and 2617169 ( vs. : OR 0.33, 95%CI 0.13-0.82; vs. : OR 0.58, 95%CI 0.36-0.91, = 0.049, in patients of same SCD genotype). These results, by uncovering susceptibility to, or protection against SCD complications, might contribute to a better understanding of the inflammatory pathways involved in SCD manifestations and to pave the way for the discovery of biomarkers that predict disease severity, which would improve SCD management.
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http://dx.doi.org/10.3389/fimmu.2020.02041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510050PMC
April 2021

A multicenter comparative acute myeloid leukemia study: can we explain the differences in the outcomes in resource-constrained settings?

Leuk Lymphoma 2021 01 30;62(1):147-157. Epub 2020 Sep 30.

Service of Hematology, Transfusion and Cell Therapy and Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31) HCFMUSP, University of Sao Paulo Medical School, Sao Paulo, Brazil.

Outcomes in acute myeloid leukemia (AML) are dependent on patient- and disease-characteristics, treatment, and socioeconomic factors. AML outcomes between resource-constrained and developed countries have not been compared directly. We analyzed two cohorts: from São Paulo state, Brazil (USP,  = 312) and Oxford, United Kingdom (OUH,  = 158). USP cohort had inferior 5-year overall survival compared with OUH (29% vs. 49%, adjusted-=.027). USP patients have higher early-mortality (23% vs. 6% <.001) primarily due to multi-resistant Gram-negative bacterial and fungal infections. USP had higher 5-year cumulative incidence of relapse (60% vs. 50%, =.0022), were less likely to undergo hematopoietic stem cell transplant (HSCT) (28% vs. 75%, <.001) and waited longer for HSCT (median, 23.8 vs. 7.2 months, <.001). Three-year survival in relapsed patients was worse in USP than OUH (10% vs. 39%, <.001). Our study indicates that efforts to improve AML outcomes in Brazil should focus on infection prevention and control, and access to HSCT.
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http://dx.doi.org/10.1080/10428194.2020.1827252DOI Listing
January 2021

Acquired hemophagocytic lymphohistiocytosis as initial manifestation of multiple myeloma: A case report and literature review.

Medicine (Baltimore) 2020 Sep;99(39):e22299

Department of Hematology, Hemotherapy and Cell Therapy, Medicine School, Sao Paulo University (FMUSP).

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a condition characterized by a hyperinflammatory state and persistent macrophage activation, resulting in reactive phagocytosis of the hematopoietic elements. In children, it is usually a hereditary disorder, while in adults it is usually acquired secondary to viral infections, collagenoses, or tumors. Although accounting for 10% of hematologic malignancies, HLH is rarely associated with multiple myeloma (MM) and other plasmacytic dyscrasias.

Patient Concerns: A 64-year-old Brazilian man seeked medical care with a 3-month history of intermittent fever, weight loss, night sweats, and progressive anemic symptoms.

Diagnosis: Total blood count showed severe bicytopenia (normocytic-normochromic anemia and thrombocytopenia), biochemical exams showed elevation of creatinine, as well as monoclonal peak in serum protein electrophoresis, high IgA dosage, and serum immunofixation with IgA kappa paraprotein. Bone marrow biopsy showed 30% of monoclonal and phenotypically anomalous plasmocytes, confirming the diagnosis of MM. Diagnosis of HLH was established by the presence of clinical and laboratory criteria: fever, splenomegaly, cytopenias, hypofibrinogenemia, hyperferritinemia, elevation of triglycerides, and several figures of erythrophagocytosis in bone marrow aspirate.

Interventions: The patient experienced pulse therapy with methylprednisolone for hemophagocytic lymphohistiocytosis, followed by initial therapy for multiple myeloma with cyclophosphamide and dexamethasone.

Outcomes: Once the diagnosis of MM and secondary hemophagocytic syndrome was established, the patient had a rapid clinical deterioration despite the established therapeutic measures, evolving with cardiovascular failure, acute liver failure, acute disseminated intravascular coagulation, worsening renal dysfunction requiring dialysis support, respiratory dysfunction, and lowering of consciousness, characterizing rapid multiple organ dysfunction, ultimately leading to the death of the patient.

Innovation: Here, we aimed to describe the sixth reported case of HLH associated with MM, according to cases cataloged in the PubMed database, and the first case evaluated by 18-fluordeoxyglucose positron emission tomography (18-FDG-PETCT).

Conclusion: Our case report seeks to provide support for a better clinical and laboratory characterization of this rare paraneoplastic entity associated with MM, and aims to call the attention of hematologists and intensivists to this condition that falls within the scope of the differential diagnosis of rapid onset multiple organ failure in patients with plasmacytic neoplasms.
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http://dx.doi.org/10.1097/MD.0000000000022299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523830PMC
September 2020
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