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2.
Best Pract Res Clin Haematol ; 37(2): 101556, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39098798

RESUMO

Hematopoietic cell transplantation (HCT) was developed more than 65 years ago to treat malignant blood disorders and irreversible bone marrow failures, with the aim of replacing a diseased hematopoietic system with a healthy one (allogeneic HCT). Decades later, the procedure was adapted to apply maximal chemotherapy or radiotherapy, which would result in bone marrow failure, but could be remedied by an infusion of a patient's own cryopreserved bone marrow (autologous HCT). Both treatments are high-risk and complex, especially during the initial phases. However, concerted efforts, vision, and collaboration between physicians and centers worldwide have resulted in HCT becoming a standard of care for many hematological disorders with progressive improvements in outcomes. Registries and the collaboration of societies worldwide have enabled the delivery of this curative therapy to many patients with fatal hematological diseases. More than 1.5 million HCT were performed between 1957 and 2019, and activity is continuously increasing worldwide.


Assuntos
Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Humanos , Doenças Hematológicas/terapia
3.
Clin Lab ; 70(8)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39193950

RESUMO

BACKGROUND: The study aimed to investigate the difference in clinical efficacy between apheresis platelets and buffy coat-derived platelet concentrates infusion in patients with hematological diseases. METHODS: A total of 218 patients with hematological diseases were enrolled in Xi'an Central Hospital, from January 2023 to October 2023, and randomly divided into two groups: 109 patients were treated with apheresis platelet transfusion (AP group) and 109 patients with buffy coat derived platelet concentrates (BC-PC group). Platelet counts were measured before and 24 hours after transfusion, and the corrected platelet ascending number (CCI) and platelet recovery rate (PPR) were calculated. The clinical efficacy and blood transfusion reaction were observed. RESULTS: After 24 hours of platelet transfusion, there was no significant difference in the platelet count between the AP and BC-PC groups (p > 0.05). However, CCI and PPR significantly differed between the two groups (p < 0.05). Moreover, the incidence of transfusion reaction in the AP group was significantly lower than in the BC-PC group. CONCLUSIONS: The clinical efficacy of buffy coat-derived platelet concentrates is lower than that of apheresis platelets, but it can also improve the patient's condition and quality of life. Therefore, clinicians could rationally use BC-PC, according to the actual situation of the patients.


Assuntos
Buffy Coat , Plaquetas , Transfusão de Plaquetas , Plaquetoferese , Humanos , Plaquetoferese/métodos , Feminino , Masculino , Transfusão de Plaquetas/métodos , Pessoa de Meia-Idade , Adulto , Contagem de Plaquetas , Resultado do Tratamento , Idoso , Doenças Hematológicas/terapia , Doenças Hematológicas/sangue , Adulto Jovem
4.
Exp Hematol ; 136: 104583, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39059457

RESUMO

Embryonic and fetal hematopoietic stem and progenitor cells differ in some key properties from cells that are part of the adult hematopoietic system. These include higher proliferation and self-renewal capacity, different globin gene usage, and differing lineage biases. Although these evolved to cover specific requirements of embryonic development, they can have serious consequences for the pathogenesis of hematologic malignancies that initiate prebirth in fetal blood cells and may result in a particularly aggressive disease that does not respond well to treatments that have been designed for adult leukemias. This indicates that these infant/pediatric leukemias should be considered developmental diseases, where a thorough understanding of their unique biology is essential for designing more effective therapies. In this review, we will highlight some of these unique fetal properties and detail the underlying molecular drivers of these phenotypes. We specifically focus on those that are pertinent to disease pathogenesis and that may therefore reveal disease vulnerabilities. We have also included an extensive description of the origins, phenotypes, and key molecular drivers of the main infant and pediatric leukemias that have a known prenatal origin. Importantly, successes in recent years in generating faithful models of these malignancies in which cellular origins, key drivers, and potential vulnerabilities can be investigated have resulted in uncovering potential, new therapeutic avenues.


Assuntos
Células-Tronco Hematopoéticas , Humanos , Criança , Células-Tronco Hematopoéticas/patologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Doenças Hematológicas/patologia , Doenças Hematológicas/terapia , Doenças Hematológicas/genética , Doenças Hematológicas/etiologia , Animais , Lactente , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia , Leucemia/patologia , Leucemia/genética , Leucemia/etiologia , Leucemia/terapia
5.
Am Fam Physician ; 110(1): 58-64, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39028783

RESUMO

Hematologic emergencies are bleeding or clotting disorders that are hereditary or acquired and must be treated emergently to avoid significant morbidity or mortality. Patients experiencing a hematologic emergency may present with spontaneous bleeding, jaundice, petechiae, or purpura. Initial diagnostic testing should include a complete blood count. Patients who have bleeding associated with a hereditary disorder should receive clotting factor replacement before diagnostic testing. Acute chest syndrome is an uncommon but serious complication of sickle cell disease. Hemolysis caused by autoimmune disorders or iatrogenic errors from blood product transfusions has a distinct clinical presentation and requires immediate action. Severe thrombocytopenia presenting as immune or thrombotic thrombocytopenic purpura should be differentiated and treated appropriately. Disseminated intravascular coagulation and trauma coagulopathy are sometimes confused with each other, but both can cause serious injury and require unique treatments. Primary care physicians should promptly recognize patients who require emergent referral to a hematologic specialist.


Assuntos
Emergências , Humanos , Doenças Hematológicas/terapia , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/complicações , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/terapia , Transtornos da Coagulação Sanguínea/etiologia , Diagnóstico Diferencial
6.
Zhonghua Yi Shi Za Zhi ; 54(3): 145-149, 2024 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-38987005

RESUMO

Xuezheng Quanji(«¼) written by Sun Guangyu, a doctor in the Ming Dynasty, is the first known book on blood disorders in China. The book mainly deals with bleeding. The book begins with a collection of the Neijing and the treatises of the sages, focusing on systematically summarizing the theories and experiences of the past dynasties in the treatment of bleeding, interspersed with Sun's own opinions.The main part discusses four types of bleeding, summarizing Sun's profound experience in clinical practice, and many of his personal creative opinions.In terms of causes,Sun believed that there are three causes of bleeding and more due to heat. In terms of treatment,he opposed the abuse of bitter cold and attached great importance to nourishing yin and strengthening kidney and proposed four treatment methods of dispelling stasis, nourishing Yin and suppressing Yang, regulating Qi and blood, and tonifying deficiency. He advocated that bleeding should not be treated quickly, and emphasized that the disease should be judged according to the bleeding location and bleeding color to use herbs flexibly.Special attention should be paid to daily life care during and after illness as well.


Assuntos
Medicina Tradicional Chinesa , Humanos , Medicina Tradicional Chinesa/história , China , Doenças Hematológicas/história , Doenças Hematológicas/terapia , Livros/história , História Antiga , História Medieval
7.
J Manag Care Spec Pharm ; 30(7-a Suppl): S1-S12, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953485

RESUMO

In this market insights program, AMCP brought together a panel of experts representing various stakeholders: national and regional health plans, integrated health care systems, employer benefits groups, clinical experts, the Centers for Disease Control and Prevention, and patient advocacy organizations. The objectives were to gain insights into the current and evolving treatments in hemophilia, sickle cell disease, and ß-thalassemia; measure the effects of recently approved therapies on clinicians, payers, and patients; recognize emerging trends within the stop-loss market; address potential issues and obstacles related to monitoring and reporting outcomes; and identify concerns associated with both existing and emerging contracting and reimbursement models. This article aims to summarize expert perspectives on health care system challenges and strategies concerning the management of inherited blood disorders and to advance managed care professionals' understanding of their role in supporting care for these patients. The experts emphasized that when shaping coverage policies, a patient-centered approach is crucial, focusing on preserving organ function to maintain eligibility for future gene therapies among individuals with inherited blood disorders. These strategies, including benefit design modifications, specialized provider networks, and centralized mechanisms like registries, are vital for evaluating effectiveness, facilitating decision-making, and managing costs and risks associated with new and emerging treatment options for inherited blood disorders.


Assuntos
Programas de Assistência Gerenciada , Humanos , Anemia Falciforme/terapia , Anemia Falciforme/economia , Terapia Genética/economia , Doenças Hematológicas/terapia , Hemofilia A/terapia , Hemofilia A/tratamento farmacológico , Hemofilia A/economia , Programas de Assistência Gerenciada/economia
8.
Zhonghua Xue Ye Xue Za Zhi ; 45(4): 413-416, 2024 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-38951075

RESUMO

This article reviews the development history of chimeric antigen receptor macrophage (CAR-M) therapy, discusses its application in malignant hematologic diseases, introduces related clinical trials, analyzes the advantages and challenges faced by CAR-M therapy in clinical application, and looks forward to its future use in the treatment of malignant hematologic diseases.


Assuntos
Neoplasias Hematológicas , Macrófagos , Humanos , Neoplasias Hematológicas/terapia , Macrófagos/imunologia , Receptores de Antígenos Quiméricos/imunologia , Imunoterapia Adotiva/métodos , Doenças Hematológicas/terapia
9.
Int J Mol Sci ; 25(12)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38928087

RESUMO

Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent hematopoietic stem cell transplantation (HSCT) in the absence of an HLA-matched donor. Haploidentical HSCT (haplo-HSCT) can be an effective treatment for non-malignant pediatric disorders, such as primary immunodeficiencies or hemoglobinopathies, by enabling a much quicker selection of the appropriate donor for virtually all patients, low incidence of graft-versus-host disease (GVHD), and transplant-related mortality (TRM). Moreover, the outcomes of haplo-HSCT among children with hematological malignancies have improved radically. The most demanding tasks for clinicians are minimizing T-cell-mediated alloreactivity as well as early GVHD prevention. As a result, several T-cell depletion approaches, such as ex vivo T-cell depletion (TCD), and T-cell replete approaches, such as a combination of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide (PTCy), cyclosporine/tacrolimus, mycophenolate mofetil, or methotrexate, have been taken up. As more research is needed to establish the most beneficial form of therapy, haplo-HSCT is currently considered an alternative donor strategy for pediatric and adult patients with complications like viral and bacterial infections, invasive fungal disease, and GVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante Haploidêntico/métodos , Doenças Hematológicas/terapia , Condicionamento Pré-Transplante/métodos
10.
Br J Haematol ; 205(1): 229-235, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810989

RESUMO

This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT. Patients with Fanconi anaemia exhibit significantly reduced spermatogonial numbers. Patients with immunodeficiency or aplastic anaemia generally present within the normal range, while results in patients with myelodysplastic syndrome or myeloproliferative neoplasm vary. The study emphasizes the importance of assessing spermatogonial numbers in patients with severe haematological diseases for informed fertility preservation decisions.


Assuntos
Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Espermatogônias , Humanos , Masculino , Criança , Espermatogônias/patologia , Pré-Escolar , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Preservação da Fertilidade/métodos , Testículo/patologia , Testículo/efeitos da radiação , Espermatogênese/efeitos da radiação , Lactente , Síndromes Mielodisplásicas/terapia
11.
Ann Hematol ; 103(8): 3193-3198, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38734996

RESUMO

Tixagevimab and cilgavimab (EVA, Evusheld®), monoclonal antibody combination treatments, consisted of two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). EVA showed prophylactic and therapeutic effects against coronavirus disease 2019. The Japanese Society of Hematology recommended EVA for such patients with active treatment, but each institution decided on comprehensive administration. We develop a systematic procedure for comprehensive EVA injection prophylactically in patients with hematological malignancies without any over/under-indication. We listed all patients with the required indications from November 2022 to March 2023. We included 178 cases, 84 females and 94 males, with a median age of 70 (range: 19-90) years. Underlying diseases are myeloid neoplasms in 36 (20%), lymphoid neoplasms in 75 (73%), and others. Indications were intensively hematological malignancy treatment, rituximab treatment within 12 months, burton kinase inhibitor treatment, after chimeric antigen receptor T cell immunotherapy, and after stem cell transplantation in 74 (41%), 73 (41%), 3 (2%), 5 (3%), and 23 (13%) cases, respectively. Of the 178 cases, 22 (12.4%) refused EVA injection. Further, 42 and 136 cases were administered outpatient and inpatient, respectively. Over 95% of the listed cases received EVA injection within 3 months. No severe toxicities were observed among them (N = 156), and 8 (5.2%) cases had breakthrough SARS-CoV-2 infection, which was significantly lower (P = 0.02) than those without EVA (4 [18.2%] of 22 cases). Both groups showed no moderate or severe infection cases. This single-center experience showed that comprehensive EVA injection management effectively generated safer completion with preferable clinical impact.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Adulto , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Adulto Jovem , Neoplasias Hematológicas/terapia , Tratamento Farmacológico da COVID-19 , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/uso terapêutico , Doenças Hematológicas/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico
12.
Pediatr Transplant ; 28(4): e14780, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38766999

RESUMO

BACKGROUND: The aims of this study are to report our experience with treosulfan-based conditioning regimens for patients with non-malignant hematologic conditions, correlating clinical outcomes at different time points post-transplant with treosulfan exposure (AUC). METHODS: This study was a single-center observational study investigating overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) end-points post-transplant. The consequences of treosulfan AUC with respect to toxicity, correction of underlying disease, and long-term chimerism were also explored using pharmacokinetic analysis. RESULTS: Forty-six patients received 49 transplants with treosulfan and fludarabine-based conditioning between 2005 and 2023. Twenty-four patients also received thiotepa. Donor chimerism was assessed on either whole blood or sorted cell lines at different time points post-transplant. Thirty-nine patients received treosulfan pharmacokinetic assessment to evaluate cumulative AUC, with five infants receiving real-time assessment to facilitate daily dose adjustment. OS, DFS, and EFS were 87%, 81%, and 69%, respectively. Median follow-up was 32.1 months (range 0.82-160 months) following transplant. Lower EFS was associated with patient age (<1 year; p = .057) and lower cumulative treosulfan dose (<42 g/m2; p = .003). Stable donor chimerism in B-cell, NK-cell, and granulocyte lineages at 1-year post-transplant were more prevalent in patients receiving thiotepa conditioning. Two infants required daily dose adjustment to treosulfan to avoid high AUC. CONCLUSIONS: Excellent clinical outcomes and stable chimerism were observed in this patient series. The addition of thiotepa conferred no significant toxicity and trended toward sustained ongoing donor engraftment. Correlating treosulfan AUC with long-term patient outcomes is required.


Assuntos
Bussulfano , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Humanos , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Bussulfano/farmacocinética , Bussulfano/administração & dosagem , Condicionamento Pré-Transplante/métodos , Masculino , Transplante de Células-Tronco Hematopoéticas/métodos , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Resultado do Tratamento , Estudos Retrospectivos , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagem , Tiotepa/uso terapêutico , Tiotepa/administração & dosagem , Tiotepa/farmacocinética , Intervalo Livre de Doença , Seguimentos , Doenças Hematológicas/terapia , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Alquilantes/farmacocinética , Antineoplásicos Alquilantes/administração & dosagem
14.
Lancet Haematol ; 11(6): e459-e470, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734026

RESUMO

Genetically engineered chimeric antigen receptor (CAR) T cells have become an effective treatment option for several advanced B-cell malignancies. Haematological side-effects, classified in 2023 as immune effector cell-associated haematotoxicity (ICAHT), are very common and can predispose for clinically relevant infections. As haematopoietic reconstitution after CAR T-cell therapy differs from chemotherapy-associated myelosuppression, a novel classification system for early and late ICAHT has been introduced. Furthermore, a risk stratification score named CAR-HEMATOTOX has been developed to identify candidates at high risk of ICAHT, thereby enabling risk-based interventional strategies. Therapeutically, growth factor support with granulocyte colony-stimulating factor (G-CSF) is the mainstay of treatment, with haematopoietic stem cell (HSC) boosts available for patients who are refractory to G-CSF (if available). Although the underlying pathophysiology remains poorly understood, translational studies from the past 3 years suggest that CAR T-cell-induced inflammation and baseline haematopoietic function are key contributors to prolonged cytopenia. In this Review, we provide an overview of the spectrum of haematological toxicities after CAR T-cell therapy and offer perspectives on future translational and clinical developments.


Assuntos
Imunoterapia Adotiva , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Linfócitos T/imunologia , Doenças Hematológicas/terapia , Doenças Hematológicas/etiologia
15.
Arch Gynecol Obstet ; 309(6): 2863-2880, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38575798

RESUMO

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.


Assuntos
Criopreservação , Preservação da Fertilidade , Ovário , Humanos , Feminino , Preservação da Fertilidade/métodos , Estudos Retrospectivos , Adulto , Adulto Jovem , Adolescente , Doenças Hematológicas/terapia , Hormônio Antimülleriano/sangue , Hormônio Foliculoestimulante/sangue , Síndromes Mielodisplásicas/terapia
16.
Stem Cell Rev Rep ; 20(6): 1387-1405, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38644403

RESUMO

Base editors, developed from the CRISPR/Cas system, consist of components such as deaminase and Cas variants. Since their emergence in 2016, the precision, efficiency, and safety of base editors have been gradually optimized. The feasibility of using base editors in gene therapy has been demonstrated in several disease models. Compared with the CRISPR/Cas system, base editors have shown great potential in hematopoietic stem cells (HSCs) and HSC-based gene therapy, because they do not generate double-stranded breaks (DSBs) while achieving the precise realization of single-base substitutions. This precise editing mechanism allows for the permanent correction of genetic defects directly at their source within HSCs, thus promising a lasting therapeutic effect. Recent advances in base editors are expected to significantly increase the number of clinical trials for HSC-based gene therapies. In this review, we summarize the development and recent progress of DNA base editors, discuss their applications in HSC gene therapy, and highlight the prospects and challenges of future clinical stem cell therapies.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Terapia Genética , Doenças Hematológicas , Células-Tronco Hematopoéticas , Humanos , Terapia Genética/métodos , Edição de Genes/métodos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Doenças Hematológicas/terapia , Doenças Hematológicas/genética , Sistemas CRISPR-Cas/genética , Animais , Transplante de Células-Tronco Hematopoéticas
17.
J Clin Immunol ; 44(5): 105, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676773

RESUMO

Kabuki Syndrome (KS) is a multisystemic genetic disorder. A portion of patients has immunological manifestations characterized by increased susceptibility to infections and autoimmunity. Aiming to describe the clinical and laboratory immunological aspects of KS, we conducted a retrospective multicenter observational study on patients with KS treated in centers affiliated to the Italian Primary Immunodeficiency Network.Thirty-nine patients were enrolled, with a median age at evaluation of 10 years (range: 3 m-21y). All individuals had organ malformations of variable severity. Congenital heart defect (CHD) was present in 19/39 patients (49%) and required surgical correction in 9/39 (23%), with associated thymectomy in 7/39 (18%). Autoimmune cytopenia occurred in 6/39 patients (15%) and was significantly correlated with thymectomy (p < 0.002), but not CHD. Individuals with cytopenia treated with mycophenolate as long-term immunomodulatory treatment (n = 4) showed complete response. Increased susceptibility to infections was observed in 22/32 patients (69%). IgG, IgA, and IgM were low in 13/29 (45%), 13/30 (43%) and 4/29 (14%) patients, respectively. Immunoglobulin substitution was required in three patients. Lymphocyte subsets were normal in all patients except for reduced naïve T-cells in 3/15 patients (20%) and reduced memory switched B-cells in 3/17 patients (18%). Elevated CD3 + TCRαß + CD4-CD8-T-cells were present in 5/17 individuals (23%) and were correlated with hematological and overall autoimmunity (p < 0.05).In conclusion, immunological manifestations of KS in our cohort include susceptibility to infections, antibody deficiency, and autoimmunity. Autoimmune cytopenia is correlated with thymectomy and elevated CD3 + TCRαß + CD4-CD8-T-cells, and benefits from treatment with mycophenolate.


Assuntos
Anormalidades Múltiplas , Face/anormalidades , Doenças Hematológicas , Doenças Vestibulares , Humanos , Feminino , Estudos Retrospectivos , Masculino , Criança , Doenças Hematológicas/imunologia , Doenças Hematológicas/terapia , Adolescente , Itália , Doenças Vestibulares/imunologia , Pré-Escolar , Adulto Jovem , Anormalidades Múltiplas/imunologia , Lactente , Autoimunidade , Adulto
18.
Brain Nerve ; 76(3): 221-229, 2024 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-38514103

RESUMO

Many hematologic diseases can be complicated by neurological symptoms during the disease course. Hematologic diseases can contribute to strokes and neuropathies; thus, neurologists should be aware of them. Recent reports have increased of neurological side effects associated with new anticancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor-T cell therapy. The relationship between hematologic diseases and neurological complications is expected to become more prevalent.


Assuntos
Doenças Hematológicas , Doenças do Sistema Nervoso , Acidente Vascular Cerebral , Humanos , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/terapia
19.
Blood Adv ; 8(9): 2290-2299, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38447116

RESUMO

ABSTRACT: Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE) and the incidence of treatment-emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded expert adjudication. The incidence of TEAMV-PD in all patients (1068 PRPC and 1223 CPC) was less for PRPC (1.7 %) than CPC (3.1%) with a treatment difference of -1.5% (95% confidence interval [CI], -2.7 to -0.2). In patients requiring ≥2 PCs, the incidence of TEAMV-PD was reduced for PRPC recipients compared with CPC recipients (treatment difference, -2.4%; 95% CI, -4.2 to -0.6). CSPAE increased with increasing PC exposure but were not significantly different between the cohorts. For patients receiving ≥2 platelet transfusions, TEARDS occurred in 1.3% PRPC and 2.6% CPC recipients (P = .086). Bayesian analysis demonstrated PRPC may be superior in reducing TEAMV-PD and TEARDS for platelet transfusion recipients compared with CPC recipients, with 99.2% and 88.8% probability, respectively. In this study, PRPC compared with CPC demonstrated high probability of reduced severe pulmonary injury requiring assisted mechanical ventilation in patients with hematology disorders dependent on platelet transfusion. This trial was registered at www.ClinicalTrials.gov as #NCT02549222.


Assuntos
Transfusão de Plaquetas , Humanos , Transfusão de Plaquetas/efeitos adversos , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Lesão Pulmonar Aguda/etiologia , Plaquetas , Estudos Prospectivos , Adulto , Trombocitopenia/etiologia , Doenças Hematológicas/terapia
20.
Prog Mol Biol Transl Sci ; 203: 273-286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38360003

RESUMO

Blood disorders are defined as diseases related to the structure, function, and formation of blood cells. These diseases lead to increased years of life loss, reduced quality of life, and increased financial burden for social security systems around the world. Common blood disorder treatments such as using chemical drugs, organ transplants, or stem cell therapy have not yet approached the best goals, and treatment costs are also very high. RNA with a research history dating back several decades has emerged as a potential method to treat hematological diseases. A number of clinical trials have been conducted to pave the way for the use of RNA molecules to cure blood disorders. This novel approach takes advantage of regulatory mechanisms and the versatility of RNA-based oligonucleotides to target genes and cellular pathways involved in the pathogenesis of specific diseases. Despite positive results, currently, there is no RNA drug to treat blood-related diseases approved or marketed. Before the clinical adoption of RNA-based therapies, challenges such as safe delivery of RNA molecules to the target site and off-target effects of injected RNA in the body need to be addressed. In brief, RNA-based therapies open novel avenues for the treatment of hematological diseases, and clinical trials for approval and practical use of RNA-targeted are crucial.


Assuntos
Doenças Hematológicas , RNA , Humanos , RNA/uso terapêutico , Qualidade de Vida , Sistemas de Liberação de Medicamentos/métodos , Doenças Hematológicas/genética , Doenças Hematológicas/terapia
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