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Abstract To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety. date disease reallife real life attacks vasoocclusive vaso occlusive events syndrome transfusion which part physicians physician s report safety

https://doi.org/10.1016/j.htct.2024.01.001

Production of dendritic cell vaccines using different methods with equivalent results: Implications for emerging centers results
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Duarte, Adriana da Silva Santos

; Zangirolami, Audrey Basso

; Santos, Irene

; Niemann, Fernanda Soares

; Honma, Helen Naemi

; Amaro, Emerson Clayton

; Perroud Jr., Maurício Wesley

; Pericole, Fernando Vieira

; Gilli, Simone Cristina Olenscki

; Benites, Bruno Deltreggia

; Saad, Sara Teresinha Olalla

Hematology, Transfusion and Cell Therapy

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Mar 2024, Volume 46 Nº 1 Páginas 30 - 35

Resumo: En | Texto: En | PDF: En

Introduction Dendritic cell (DC) vaccines have demonstrated good efficacy in preventing relapse and in increasing survival of patients affected by a variety of both solid and hematological tumors. Most protocols used to generate these cells involve the automated separation of peripheral blood monocytes from patients. This approach requires specialized equipment, which elevates the cost of this type of therapy, potentially limiting the widespread access to patients. Method: In this study, we compare the yield and quality of dendritic cells generated from monocytes and isolated by an automated method or by manual methods using gradient centrifugation. Results The results demonstrate the equivalence of the 3 methods in relation to the yield and final quality of the product, however with considerable differences between the costs of these procedures. In addition, this study also demonstrates the feasibility of the antigenic pulse with autologous tumor cell lysates, constituting a source of antigens, not only easily obtained and manipulated, but also specific to the patient's tumor. Conclusion These findings may have important implications for emerging centers interested in using this medical approach and potentially increase the access of a greater number of patients to this therapeutic option. DC (DC tumors equipment therapy Method centrifugation product procedures addition lysates antigens manipulated patient s option

https://doi.org/10.1016/j.htct.2022.11.006

Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients
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Colella, Marcos Paulo

; Morini, Beatriz Corey

; Niemann, Fernanda

; Lopes, Matheus Rodrigues

; Saad, Sara Olalla

; Favaro, Patricia

Hematology, Transfusion and Cell Therapy

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Set 2023, Volume 45 Nº 3 Páginas 324 - 329

Resumo: En | Texto: En | PDF: En

ABSTRACT Introduction: Chronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD. Objective and Method: Due to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD. Results: Our results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls. Conclusion: Moreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD. Introduction graftversushost graft versus host (cGvHD transplant survive ligandreceptor ligand receptor processes responses Recently GvHD Method alloHCT allo HCT longterm long term Results alloHCT, HCT, status controls Conclusion Moreover knowledge

https://doi.org/10.1016/j.htct.2022.05.005

Evaluation of different protocols for culturing mesenchymal stem cells derived from murine bone marrow
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Pissarra, Mariana Ferreira

; Torello, Cristiane Okuda

; Saad, Sara Teresinha Olalla

; Lazarini, Mariana

Hematology, Transfusion and Cell Therapy

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Out 2022, Volume 44 Nº 4 Páginas 560 - 566

Resumo: En | Texto: En | PDF: En

ABSTRACT Introduction: Culturing bone marrow mesenchymal stem cells (BM-MSCs) is a key point in different fields of research, including tissue engineering and regenerative medicine and studies of the bone marrow microenvironment. However, isolating and expanding murine BM-MSCs in vitro has challenged researchers due to the low purity and yield of obtained cells. In this study, we aimed to evaluate five different protocols to culture murine BM-MSCs in vitro. Methods: All protocols were based on the adhesion capacity of BM-MSCs to the tissue culture plastic surface and varied in the types of plate, culture media, serum, additional supplementation and initial cell density. Flow cytometry analysis was used to investigate lineage purity after expansion. Results: The expression of CD45 and CD11b was detected in the cultures generated according to all protocols, indicating low purity with the presence of hematopoietic cells and macrophages. The cellular growth rate and morphology varied between the cultures performed according to each protocol. Cells cultured according to protocol 5 (8 × 107cells/plate, Roswell Park Memorial Institute (RPMI) culture medium during first passage and then Iscove’s Modified Delbecco’s Medium (IMDM) culture medium, both supplemented with 9% fetal bovine serum, 9% horse serum, 12μM L-glutamine) presented the best performance, with a satisfactory growth rate and spindle-shape morphology. Conclusion: Our results point out that the purity and satisfactory growth rate of murine BM-MSC cultures are not easily achieved and additional approaches must be tested for a proper cell expansion.

https://doi.org/10.1016/j.htct.2021.02.005

Effectiveness of a home-based therapeutic exercise program on lower back pain and functionality in Sickle Cell Disease (SCD) patients
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Zanoni, Camila Tatiana

; Galvão, Fábio

; Maria, Renata Manzano

; Zulli, Roberto

; Ricciardi, Janaina Bosso

; Cliquet Junior, Alberto

; Saad, Sara Teresinha Olalla

Hematology, Transfusion and Cell Therapy

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Set 2021, Volume 43 Nº 3 Páginas 268 - 279

Resumo: En | Texto: En | PDF: En

ABSTRACT Objective: To investigate the effectiveness of a home-based therapeutic exercise program on lower back pain and functionality of SCD patients. Setting: A Hematology and Transfusion Medicine Center, University of Campinas (HEMOCENTRO-UNICAMP). Methods: This was a prospective study, with a three-month follow-up of SCD patients with lower back pain. The lumbar spine functionality was evaluated by questionnaires, trunk flexion and extension analyses by fiber-optic-electrogoniometry and measurements of muscle strength of trunk flexor and extensors. The Intervention Group (IG) comprised 18 volunteers, median age 44y (28–58) and the control group (CG) comprised 15 volunteers, median age 42y (19–58), who did not perform exercises. The protocol consisted of daily home-based exercises with two evaluations: at the beginning and end of a three-month program. In order to compare the groups at baseline, the Fishers´ exact test and Mann–Whitney test were used for categorical and numeric variables, respectively. The Wilcoxon test was used for related samples comparing numeric measures of each group over time with a 5% (p < 0.05) significance level. Results: After the intervention, patients demonstrated a significant improvement, according to the Visual-Analog-Scale (VAS; p = 0.01), Rolland Morris Disability questionnaire (RMDQ; p < 0.01) and trunk flexion and extension muscle strength (p < 0.01). No significant differences were found for the Start-Back-Screening-Tool-Brazil (SBST) and in measures of trunk flexion and extension range-of-motion (RoM). Conclusion: Results suggest that daily home-based exercises for a three-month period ameliorate pain and improve disability related to lower back pain and muscle strength.

https://doi.org/10.1016/j.htct.2020.05.004 30 downloads

Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria
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Cançado, Rodolfo D

; Araújo, Aderson da Silva

; Sandes, Alex Freire

; Arrais, Celso

; Lobo, Clarisse Lopes de Castro

; Figueiredo, Maria Stella

; Gualandro, Sandra Fátima Menosi

; Saad, Sara Teresinha Olalla

; Costa, Fernando Ferreira

Hematology, Transfusion and Cell Therapy

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Set 2021, Volume 43 Nº 3 Páginas 341 - 348

Resumo: En | Texto: En | PDF: En

Paroxysmal nocturnal hemoglobinuria is a chronic, multi-systemic, progressive and lifethreatening disease characterized by intravascular hemolysis, thrombotic events, serious infections and bone marrow failure. Paroxysmal nocturnal hemoglobinuria results from the expansion of a clone of hematopoietic cells that due to an inactivating mutation of the X-linked gene PIG-A are deficient in glycosylphosphatidylinositol-linked proteins. Early diagnosis, using flow cytometry performed on peripheral blood, the gold standard test to confirm the diagnosis of paroxysmal nocturnal hemoglobinuria, is essential for improved patient management and prognosis. The traditional therapy for paroxysmal nocturnal hemoglobinuria includes blood transfusion, anti-thrombosis prophylaxis or allogeneic bone marrow transplantation. The treatment that has recently become available is the complement blockade by the anti-C5 monoclonal antibody eculizumab. In this consensus, we are aiming to review the diagnosis and treatment of the paroxysmal nocturnal hemoglobinuria patients, as well as the early recognition of its systemic complications. These procedures express the opinions of experts and have been based on the best available evidence and international guidelines, with the purpose of increasing benefits and reducing harm to patients.

https://doi.org/10.1016/j.htct.2020.06.006 23 downloads

Echocardiografic abnormalities in patients with sickle cell/β-thalassemia do not depend on the β-thalassemia phenotype
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Benites, Bruno Deltreggia

; Cisneiros, Ianara Silva

; Bastos, Stephany Oliveira

; Lino, Ana Paula Beppler Lazaro

; Costa, Fernando Ferreira

; Gilli, Simone Cristina Olenscki

; Saad, Sara Teresinha Olalla

Hematology, Transfusion and Cell Therapy

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Jun 2019, Volume 41 Nº 2 Páginas 158 - 163

Resumo: En | Texto: En | PDF: En

ABSTRACT Objectives and methods: We evaluated possible relationships between echocardiographic findings and clinical and laboratory parameters, in a cohort of Brazilian patients diagnosed with sickle cell/β-thalassemia, to better understand the cardiac involvement in this disease. Results: Left atrial (LA) and left ventricular (LV) dilation were found in 19.5 and 11% of patients, respectively; systolic left ventricular dysfunction was present in a single patient. There were no differences in masses and volumes of cardiac chambers comparing Sβ0 with Sβ+ patients, and no relationship between these parameters and specific complications of the disease. However, parameters of altered ventricular geometry were significantly correlated with serum creatinine, hepatic transaminases and bilirubin levels. Moreover, 3 patients presented stroke; they were significantly older [53 (41-56) × 37.5 (18-70), p = 0.048], had higher values of LV posterior wall diastolic thickness [10 (10-11) × 8 (6-14), p = 0.03], LV mass [226 (194-260) × 147 (69-537), p = 0.039] and LA/aortic ratio [1.545 (1.48-1.61) × 1.26 (0.9-1.48), p = 0.032]. Conclusions: Cardiac involvement in this disease does not appear to depend on the thalassemia phenotype. The presence of signs of myocardial remodeling in this group of patients was related to multi-organ impairment and rendered a higher propensity for stroke in older patients, suggesting the need for greater vigilance and control of associated factors.

https://doi.org/10.1016/j.htct.2018.09.003 334 downloads

Novel mutations associated with pyruvate kinase deficiency in Brazil
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Svidnicki, Maria Carolina Costa Melo

; Santos, Andrey

; Fernandez, Jhonathan Angel Araujo

; Yokoyama, Ana Paula Hitomi

; Magalhães, Isis Quezado

; Pinheiro, Vitoria Regia Pereira

; Brandalise, Silvia Regina

; Silveira, Paulo Augusto Achucarro

; Costa, Fernando Ferreira

; Saad, Sara Teresinha Olalla

Hematology, Transfusion and Cell Therapy

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Mar 2018, Volume 40 Nº 1 Páginas 5 - 11

Resumo: En | Texto: En | PDF: En

Abstract Background: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype–phenotype correlations. Method: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A). Results: Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found. Conclusion: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants.

https://doi.org/10.1016/j.bjhh.2017.08.007 2261 downloads

IRAK1 expression in bone marrow cells does not impact patient outcomes in myelodysplastic syndromes
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Campos, Paula de Melo

; Machado-Neto, João Agostinho

; Lorand-Metze, Irene

; Costa, Fernando Ferreira

; Saad, Sara Teresinha Olalla

; Traina, Fabiola

Hematology, Transfusion and Cell Therapy

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Mar 2018, Volume 40 Nº 1 Páginas 92 - 95

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1016/j.bjhh.2017.10.001 347 downloads

10.

Stathmin 1 expression in plasma cell neoplasms
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Machado-Neto, João Agostinho

; Pericole, Fernando Vieira

; Costa, Fernando Ferreira

; Traina, Fabiola

; Olalla Saad, Sara Teresinha

Revista Brasileira de Hematologia e Hemoterapia

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Jun 2017, Volume 39 Nº 2 Páginas 183 - 185

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1016/j.bjhh.2017.02.005 355 downloads

11.

Telomere length correlates with disease severity and inflammation in sickle cell disease
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Colella, Marina Pereira

; Santana, Barbara A.

; Conran, Nicola

; Tomazini, Vinicius

; Costa, Fernando F.

; Calado, Rodrigo T.

; Saad, Sara T. Olalla

Revista Brasileira de Hematologia e Hemoterapia

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Jun 2017, Volume 39 Nº 2 Páginas 140 - 145

Resumo: En | Texto: En | PDF: En

ABSTRACT Background: Telomeres, the ends of linear chromosomes, shorten during mitotic cell division and erosion may be aggravated by inflammation or proliferative and oxidative stress. As the bone marrow is under hyperproliferative pressure in sickle cell disease and several tissues are submitted to chronic inflammation, this study sought to determine the telomere length of patients with sickle cell disease. Methods: The mean telomere length was measured in peripheral blood leukocytes by quantitative polymerase chain reaction. The age-adjusted telomere to single copy gene ratio was compared between 91 adult sickle cell disease patients and 188 controls. Results: Sickle cell disease patients had significantly shorter telomeres than the controls (p-value < 0.0001). Moreover, among sickle cell disease genotypes, Hb SS patients had significantly shorter telomeres compared to Hb SC and Hb Sβ patients (p-value < 0.0001). Patients on hydroxyurea also had shorter telomeres in comparison to those off the drug (p-value = 0.02). A positive correlation was observed between telomere length and hemoglobin level (r = 0.3; p-value = 0.004), whereas negative correlations were detected between telomere length and lymphocyte count (r = -0.3; p-value = 0.005) and interleukin-8 serum levels (r = -0.4; p-value = 0.02). Conclusions: The findings of this study indicate that telomeres are short in sickle cell disease patients and that telomere erosion directly correlates with disease genotype, inflammation markers, and the use of hydroxyurea.

https://doi.org/10.1016/j.bjhh.2017.02.007 1112 downloads

12.

Differential profile of CDKN1A and TP53 expressions in bone marrow mesenchymal stromal cells from myeloid neoplasms
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Lopes, Matheus Rodrigues

; Machado-Neto, João Agostinho

; Traina, Fabiola

; Campos, Paula de Melo

; Saad, Sara Teresinha Olalla

; Favaro, Patricia

Revista Brasileira de Hematologia e Hemoterapia

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Dez 2016, Volume 38 Nº 4 Páginas 368 - 370

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1016/j.bjhh.2016.07.002 598 downloads

13.

Guidelines on neonatal screening and painful vaso-occlusive crisis in sickle cell disease: Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular: Project guidelines: Associação Médica Brasileira - 2016
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Braga, Josefina Aparecida Pellegrini

; Veríssimo, Mônica Pinheiro de Almeida

; Saad, Sara Teresinha Olalla

; Cançado, Rodolfo Delfini

; Loggetto, Sandra Regina

Revista Brasileira de Hematologia e Hemoterapia

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Jun 2016, Volume 38 Nº 2 Páginas 147 - 157

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1016/j.bjhh.2016.04.001 2165 downloads

14.

Somatic mutations of calreticulin in a Brazilian cohort of patients with myeloproliferative neoplasms
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Machado-Neto, João Agostinho

; Campos, Paula de Melo

; Albuquerque, Dulcinéia Martins de

; Costa, Fernando Ferreira

; Lorand-Metze, Irene

; Saad, Sara Terezinha Olalla

; Traina, Fabiola

Revista Brasileira de Hematologia e Hemoterapia

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Jun 2015, Volume 37 Nº 3 Páginas 211 - 214

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1016/j.bjhh.2015.03.012 1142 downloads

15.

Pilot randomized controlled trial to evaluate the effect of aquatic and land physical therapy on musculoskeletal dysfunction of sickle cell disease patients
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Zanoni, Camila Tatiana

; Galvão, Fábio

; Cliquet Junior, Alberto

; Saad, Sara Teresinha Olalla

Revista Brasileira de Hematologia e Hemoterapia

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Abr 2015, Volume 37 Nº 2 Páginas 82 - 89

Resumo: En | Texto: En | PDF: En

Objective: To compare the effect of aquatic and land-based physiotherapy in reducing musculoskeletal hip and lower back pain and increasing overall physical capabilities of sickle cell disease patients. Methods: Informed written consent was obtained from all volunteers who were submitted to evaluations using different functional scales: Lequesne's Algofunctional Questionnaire and Oswestry Disability Index, trunk and hip range of motion, goniometry, trunk and hip muscle strength assessment using load cell, and surface electromyography of the iliocostalis, long dorsal (longissimus), gluteus maximus, gluteus medius and tensor fasciae latae muscles. Ten patients were randomized into two groups: aquatic physiotherapy with a mean age of 42 years (range: 25-67) and conventional physiotherapy with a mean age of 49 years (range: 43-59). Both groups were submitted to a twelve-week program of two sessions weekly. Results: After the intervention, signiﬁcant improvements were observed regarding the Lequesne index (p-value = 0.0217), Oswestry Disability Index (p-value = 0.0112), range of motion of trunk extension (p-value = 0.0320), trunk ﬂexion muscle strength (p-value = 0.0459), hip extension and abduction muscle strength (p-value = 0.0062 and p-value = 0.0257, respec- tively). Range of motion of trunk and hip ﬂexion, extension, adduction and abduction, trunk extensor muscle strength and all surface electromyography variables showed no signiﬁcant statistical difference. Conclusion: Physical therapy is efﬁcient to treat musculoskeletal dysfunctions in sickle cell disease patients, irrespective of the technique; however, aquatic therapy showed a trend toward improvement in muscle strength. Further studies with a larger patient sample and longer periods of therapy are necessary to conﬁrm these results.

https://doi.org/10.1016/j.bjhh.2014.11.010 2537 downloads

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