VANDERSON GERALDO ROCHA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection(2024) PLACA, Desiree Rodrigues; FONSECA, Dennyson Leandro M.; MARQUES, Alexandre H. C.; POUR, Shahab Zaki; USUDA, Julia Nakanishi; BAIOCCHI, Gabriela Crispim; PRADO, Caroline Aliane de Souza; SALGADO, Ranieri Coelho; FILGUEIRAS, Igor Salerno; FREIRE, Paula Paccielli; ROCHA, Vanderson; CAMARA, Niels Olsen Saraiva; CATAR, Rusan; MOLL, Guido; JURISICA, Igor; CALICH, Vera Lucia Garcia; GIIL, Lasse M.; RIVINO, Laura; OCHS, Hans D.; CABRAL-MIRANDA, Gustavo; SCHIMKE, Lena F.; CABRAL-MARQUES, OtavioIntroduction Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs).Methods and results We analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response.Conclusion This work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g., IFIT5, ISG15, and HERC5) for anti-dengue-specific therapies and effective vaccination development.
- Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation(2024) DIAZ, Ana Claudia Marques Barbosa; WITKIN, Steven Sol; ALMEIDA-NETO, Cesar de; MENDRONE-JUNIOR, Alfredo; ROCHA, Vanderson; COSTA, Silvia Figueiredo; RAMOS, Jessica Fernandes; MENDES-CORREA, Maria CassiaHepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.
- Multicenter Long-Term Follow-Up of Allogeneic Hematopoietic Cell Transplantation with Omidubicel: A Pooled Analysis of Five Prospective Clinical Trials(2023) LIN, Chenyu; SCHWARZBACH, Aurelie; SANZ, Jaime; MONTESINOS, Pau; STIFF, Patrick; PARIKHA, Suhag; BRUNSTEIN, Claudio; CUTLER, Corey; LINDEMANS, Caroline A.; HANNA, Rabi; KOH, Liang Piu; JAGASIA, Madan H.; VALCARCEL, David; MAZIARZ, Richard T.; KEATING, Amy K.; HWANG, William Y. K.; REZVANI, Andrew R.; KARRAS, Nicole A.; FERNANDES, Juliana F.; ROCHA, Vanderson; BADELL, Isabel; RAM, Ron; SCHILLER, Gary J.; VOLODIN, Leonid; WALTERS, Mark C.; HAMERSCHLAK, Nelson; CILLONI, Daniela; FRANKFURT, Olga; MCGUIRK, Joseph P.; KURTZBERG, Joanne; SANZ, Guillermo; SIMANTOV, Ronit; HORWITZ, Mitchell E.Omidubicel is an umbilical cord blood (UCB)-derived ex vivo-expanded cellular therapy product that has dem-onstrated faster engraftment and fewer infections compared with unmanipulated UCB in allogeneic hematopoietic cell transplantation. Although the early benefits of omidubicel have been established, long-term outcomes remain unknown. We report on a planned pooled analysis of 5 multicenter clinical trials including 105 patients with hematologic malignancies or sickle cell hemoglobinopathy who underwent omidubicel transplantation at 26 academic transplantation centers worldwide. With a median follow-up of 22 months (range, .3 to 122 months), the 3-year estimated overall survival and disease-free survival were 62.7% and 56.4%, respectively. With up to 10 years of follow-up, omidubicel showed durable trilineage hematopoiesis. Serial quantitative assessments of CD3(+), CD4(+), CD8(+), CD19(+), CD116(+)CD56(+), and CD123(+) immune subsets revealed median counts remaining within normal ranges through up to 8 years of follow-up. Secondary graft failure occurred in 5 patients (5%) in the first year, with no late cases reported. One case of donor-derived myeloid neoplasm was reported at 40 months post-transplantation. This was also observed in a control arm patient who received only unmanipulated UCB. Overall, omidubicel demonstrated stable trilineage hematopoiesis, immune competence, and graft durability in extended follow-up. (c) 2023 The American Society for Transplantation and Cellular Therapy.
- Applying mucosal barrier injury laboratory-confirmed bloodstream infection criteria in patients with solid tumors and hematologic malignancies: A retrospective cohort study looking for the real source of infection(2023) SILVA, Ana Carolina Puin da; VIEIRA, Michely Fernandes; FREIRE, Maristela Pinheiro; VAZ, Lumena; BONAZZI, Patricia Rodrigues; IBRAHIM, Karim Yaqub; DIZ, Maria Del Pilar Esteves; HOFF, Paulo Marcelo; PEREIRA, Juliana; ROCHA, Vanderson Geraldo; ABDALA, EdsonWe evaluated the interference of the mucosal barrier injury (MBI) laboratory-confirmed bloodstream infection (MBI-LCBI) criteria on the central-line-associated bloodstream infection (CLABSI) incidence density, and the proportion of catheter-related bloodstream infections (CRBSIs) among those classified as MBI. We detected 339 CLABSIs: 15.0% were classified as MBI-LCBIs, and among these, 19.6% were classified as CRBSIs.
- Paper Assessing the impact of prophylactic anidulafungin during remission induction of acute myeloid leukemia - A propensity-score matching analysis(2023) SILVA, Wellington Fernandes da; MENDES, Fernanda Rodrigues; MELO, Raphael da Costa Bandeira de; VELLOSO, Elvira Deolinda Rodrigues Pereira; ROCHA, Vanderson; REGO, Eduardo MagalhaesIntroduction: Invasive fungal infection (IFI) accounts for substantial morbidity during the treatment of acute myeloid leukemia (AML) in adults. Antifungal prophylaxis (AP) is needed during intensive chemotherapy, and posaconazole is not widely available. In this study, we aimed to examine the impact of prophylactic anidulafungin during intensive AML remission induction. Methods: This is a retrospective cohort encompassing newly diagnosed AML adult patients. All subjects received intensive chemotherapy and were divided into three groups: patients who did not receive any AP and patients who received fluconazole (150-400 mg/day) or anidulafungin (100 mg/day). Results: During AML induction, 82 patients did not receive AP, 108 and 14 patients received anidulafungin and fluconazole, respectively. IFI incidence was 27%, classified as possible, probable, and proven in 65, 2 and 33%, respectively. Multivariable analysis showed that lower neutrophil counts are associated with IFI (OR = 2.8), whereas age, genetic classification, and lymphocyte counts were not. To examine the impact of anidulafungin in comparison with 'no AP', a propensity score matching analysis was performed. Use of anidulafungin was not related to less IFI during induction, while neutrophil counts remained significant. Patients under prophylactic anidulafungin received less amphotericin B (p < 0.001) but not voriconazole (p = 0.49). Discussion: To our knowledge, this is the first study addressing the role of anidulafungin during AML induction. Here, the incidence of mold infections did not decrease with AP, suggesting that in a setting with a high incidence of IFI, broad spectrum AP might be more suitable.
- A model for preservation of thymocyte-depleted thymus(2023) DIAS, A. S.; DAMACENO-RODRIGUES, N. R.; GIMENEZ, T. M.; OLIVEIRA, P. M.; ZERBINI, M. C.; CARNEIRO-SAMPAIO, M.; FILHO, V. Odone; JATENE, M. B.; VASCONCELOS, D. M.; ROCHA, V.; NOVAK, E. M.DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196 & DEG;C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3 x 106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.
- Use of letermovir in umbilical cord blood transplantation based on risk scores(2023) FRANCO, Monica M. Rivera; RAFII, Hanadi; VOLT, Fernanda; KENZEY, Chantal; CAPPELLI, Barbara; SCIGLIUOLO, Graziana Maria; ROCHA, Vanderson; RAUS, Nicole; DALLE, Jean-Hugues; CHEVALLIER, Patrice; ROBIN, Marie; RUBIO, Marie Therese; RUGGERI, Annalisa; GLUCKMAN, Eliane
article 0 Citação(ões) na Scopus GVHD treatment with extracorporeal photopheresis in Brazil: a national survey(2022) FATOBENE, Giancarlo; CORDEIRO, Ana; MARIANO, Livia; SILVA, Marcia; BOUZAS, Luis; HAMERSCHLAK, Nelson; MACEDO, Maria Cristina; PETTA, Alessandra; FUNKE, Vaneuza; NOVIS, Yana; FLOWERS, Mary E.; ROCHA, Vanderson- Systemic amyloidosis journey from diagnosis to outcomes: a twelve-year real-world experience of a single center in a middle-income country(2022) SZOR, Roberta Shcolnik; FERNANDES, Fabio; LINO, Angelina Maria Martins; MENDONCA, Leonardo Oliveira; SEGURO, Fernanda Salles; FEITOSA, Valkercyo Araujo; CASTELLI, Jussara Bianchi; JORGE, Lecticia Barbosa; ALVES, Lucas Bassolli de Oliveira; NEVES, Precil Diego Miranda de Menezes; SOUZA, Evandro de Oliveira; CAVALCANTE, Livia Barreira; MALHEIROS, Denise; KALIL, Jorge; MARTINEZ, Gracia Aparecida; ROCHA, VandersonBackground: Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients' medical records were retrospectively reviewed. Results: One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, & GE; 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had & GE; 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I-II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG & GE; 2 were identified as independent risk factors for reduced survival. Conclusions: Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries.
- Umbilical Cord Mesenchymal Stromal Cells for Steroid-Refractory Acute Graft-versus-Host Disease(2023) DONADEL, Camila Derminio; PIRES, Bruno Garcia; ANDRE, Nathalia Cristine; COSTA, Thalita Cristina Mello; ORELLANA, Maristela Delgado; CARUSO, Samia Rigotto; SEBER, Adriana; GINANI, Valeria Cortez; GOMES, Alessandra Araujo; NOVIS, Yana; BARROS, George Mauricio Navarro; VILELLA, Neysimelia Costa; MARTINHO, Glaucia Helena; VIEIRA, Ana Karine; KONDO, Andrea Tiemi; HAMERSCHLAK, Nelson; FILHO, Jayr Schmidt; XAVIER, Erick Menezes; FERNANDES, Juliana Folloni; ROCHA, Vanderson; COVAS, Dimas Tadeu; CALADO, Rodrigo Tocantins; GUERINO-CUNHA, Renato Luiz; SANTIS, Gil Cunha DeBackground: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). Methods: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. Results: The median (range) age was 12.5 (0.3-65) years and the mean +/- SD dose (x10(6)/kg) was 4.73 +/- 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). Conclusions: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable.