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2.
Gan To Kagaku Ryoho ; 51(2): 119-124, 2024 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-38449394

RESUMO

The cumulative incidence of secondary cancers in childhood cancer survivors at 20 years after treatment is 2-5%, which is 3-20 times higher than in the general population. Risk factors include radiation therapy, alkylating agents, platinum drugs, and topoisomerase Ⅱ inhibitors. A retrospective cohort study of 15 pediatric oncology hospitals in Japan revealed that the time to development of a second cancer varies from 5 years or less for hematologic tumors, 10 years or less for bone/soft tissue tumors, approximately 10 years for brain tumors, and 15-20 years for thyroid and adult-type cancers. Some secondary cancers have a poor prognosis. Primary prevention of secondary cancers is the same as in the general population, and early detection and treatment are important. The key points of consensus on secondary cancers by the North American Children's Oncology Group guidelines and the International Guideline Harmonization Group were presented. In the future, it will be important to share information on the benefits and risks of cancer screening with childhood cancer survivors and their families.


Assuntos
Neoplasias Encefálicas , Neoplasias Hematológicas , Segunda Neoplasia Primária , Criança , Humanos , Detecção Precoce de Câncer , Estudos Retrospectivos
3.
Influenza Other Respir Viruses ; 18(3): e13264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468434

RESUMO

BACKGROUND: We aimed to describe a cohort of hematologic patients with COVID-19 treated with antivirals early. METHODS: Non-interventional chart review study. Comparison of baseline characteristics and outcomes in high-risk hematologic patients treated with remdesivir between December 2021 and April 2022 versus those treated with nirmatrelvir/ritonavir between May and August 2022. RESULTS: Eighty-three patients were analyzed. Forty-two received remdesivir, and 41 nirmatrelvir/ritonavir. Patients with remdesivir were younger, vaccinated with lower number of doses, and received prior corticosteroids less frequently and sotrovimab, hyperimmune plasma and corticosteroids more often. Viral shedding median (IQR) duration was 18 (13-23) and 11 (8-21) days in the remdesivir and nirmatrelvir/ritonavir groups, respectively (p = 0.004). Median (IQR) Ct values before treatment were similar in both groups. Within 5 days of treatment, median (IQR) Ct values were 26 (23-29) and 33 (30-37) in the remdesivir and nirmatrelvir/ritonavir groups, respectively (p < 0.0001). All patients were hospitalized for remdesivir administration and only four (9.8%) in the nirmatrelvir/ritonavir group. The overall outcomes in this cohort of COVID-19 patients with Omicron variant was good, as no patient needed oxygen or ICU admission. One patient in remdesivir group died from septic shock. No severe adverse event was recorded in both treatment groups. CONCLUSIONS: Patients with hematologic malignancies and non-severe COVID-19 who received nirmatrelvir/ritonavir experienced faster decrease in viral load and shorter viral shedding. Furthermore, besides the advantage of oral administration, nirmatrelvir/ritonavir administration reduced the need of hospital admission.


Assuntos
COVID-19 , Neoplasias Hematológicas , Lactamas , Leucina , Nitrilas , Prolina , Humanos , Ritonavir/uso terapêutico , SARS-CoV-2 , Corticosteroides , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19
4.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473775

RESUMO

This comprehensive review delves into the multifaceted roles of mesenchymal stem cells (MSCs) in leukemia, focusing on their interactions within the bone marrow microenvironment and their impact on leukemia pathogenesis, progression, and treatment resistance. MSCs, characterized by their ability to differentiate into various cell types and modulate the immune system, are integral to the BM niche, influencing hematopoietic stem cell maintenance and functionality. This review extensively explores the intricate relationship between MSCs and leukemic cells in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia. This review also addresses the potential clinical applications of MSCs in leukemia treatment. MSCs' role in hematopoietic stem cell transplantation, their antitumor effects, and strategies to disrupt chemo-resistance are discussed. Despite their therapeutic potential, the dual nature of MSCs in promoting and inhibiting tumor growth poses significant challenges. Further research is needed to understand MSCs' biological mechanisms in hematologic malignancies and develop targeted therapeutic strategies. This in-depth exploration of MSCs in leukemia provides crucial insights for advancing treatment modalities and improving patient outcomes in hematologic malignancies.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Humanos , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neoplasias Hematológicas/patologia , Biologia , Microambiente Tumoral
5.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38474011

RESUMO

Homeobox genes encode developmental transcription factors regulating tissue-specific differentiation processes and drive cancerogenesis when deregulated. Dendritic cells (DCs) are myeloid immune cells occurring as two types, either conventional or plasmacytoid DCs. Recently, we showed that the expression of NKL-subclass homeobox gene VENTX is restricted to conventional DCs, regulating developmental genes. Here, we identified and investigated homeobox genes specifically expressed in plasmacytoid DCs (pDCs) and derived blastic plasmacytoid dendritic cell neoplasm (BPDCN). We analyzed gene expression data, performed RQ-PCR, protein analyses by Western blot and immuno-cytology, siRNA-mediated knockdown assays and subsequent RNA-sequencing and live-cell imaging. Screening of public gene expression data revealed restricted activity of the CUT-class homeobox gene CUX2 in pDCs. An extended analysis of this homeobox gene class in myelopoiesis showed that additional CUX2 activity was restricted to myeloid progenitors, while BPDCN patients aberrantly expressed ONECUT2, which remained silent in the complete myeloid compartment. ONECUT2 expressing BPDCN cell line CAL-1 served as a model to investigate its regulation and oncogenic activity. The ONECUT2 locus at 18q21 was duplicated and activated by IRF4, AUTS2 and TNF-signaling and repressed by BMP4-, TGFb- and IL13-signalling. Functional analyses of ONECUT2 revealed the inhibition of pDC differentiation and of CDKN1C and CASP1 expression, while SMAD3 and EPAS1 were activated. EPAS1 in turn enhanced survival under hypoxic conditions which thus may support dendritic tumor cells residing in hypoxic skin lesions. Collectively, we revealed physiological and aberrant activities of CUT-class homeobox genes in myelopoiesis including pDCs and in BPDCN, respectively. Our data may aid in the diagnosis of BPDCN patients and reveal novel therapeutic targets for this fatal malignancy.


Assuntos
Genes Homeobox , Neoplasias Hematológicas , Humanos , Diferenciação Celular , Linhagem Celular , Células Mieloides/metabolismo , Células Dendríticas/metabolismo , Neoplasias Hematológicas/patologia , Fatores de Transcrição/metabolismo , Proteínas de Homeodomínio/genética
6.
Front Immunol ; 15: 1348852, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464520

RESUMO

CD47 is a cell-surface ligand that is overexpressed in various malignancies and that binds to SIRPα on macrophages to promote tumor cell evasion of phagocytosis. Blocking the CD47-SIRPα axis can increase the phagocytosis of macrophages to exert antitumor effects. CD47-based immunotherapy is a current research focus. The combination of anti-CD47 antibodies with other drugs has shown encouraging response rates in patients with hematological tumors, but side effects also occur. Bispecific antibodies and SIRPα/Fc fusion proteins appear to balance the efficacy and safety of treatment. We review the latest clinical research advances and discuss the opportunities and challenges associated with CD47-based immunotherapy for hematological malignancies.


Assuntos
Neoplasias Hematológicas , Neoplasias , Humanos , Antígeno CD47/metabolismo , Fagocitose , Macrófagos , Neoplasias/terapia , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/metabolismo
7.
Saudi Med J ; 45(3): 295-306, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38438211

RESUMO

OBJECTIVES: To determine the prevalence of leukemia in the Aseer region of Saudi Arabia and the importance of hematological, biochemical and coagulation profiles for leukemic patients in the context of disease management. METHODS: This retrospective study comprised 210 patients between 2012 and 2022 who had been diagnosed with leukemia at different ages. The multiple unpaired t-test was used to compare leukemic patients with control samples, which consisted of healthy individuals, and p<0.05 was taken as significant. The data was compiled from Aseer Central Hospital in the Aseer region and collected through peripheral blood smear and bone marrow biopsy (2012-2017) or by flow cytometry (2018-2022), according to the hospital information system and registry data. RESULTS: Of the total 210 leukemic patients (61.4% males and 38.6% females), 104 cases (2012-2017) were diagnosed based on peripheral blood smear and bone marrow biopsy, and 106 cases (2018-2022) based on flow cytometry. Fifteen subtypes of leukemia were identified, with chronic myeloid leukemia being the most common (34.2%), followed by acute myeloid leukemia (17.6%), chronic lymphoblastic leukemia (11.9%), and B-cell acute lymphoid leukemia (9.5%). Other rare cases were also found. CONCLUSION: Of the 210 leukemia cases diagnosed in the Aseer region between 2012-2022, the most common subtype was chronic myeloid leukemia, followed by acute myeloid leukemia. In all leukemia subtypes, distinctive significant changes were observed in hematological parameters, biochemical parameters, and coagulation profiles.


Assuntos
Neoplasias Hematológicas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide Aguda , Feminino , Masculino , Humanos , Prevalência , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Neoplasias Hematológicas/epidemiologia
8.
Scand J Immunol ; 99(3): e13341, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38441169

RESUMO

Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies. Increased levels of EVs have been reported for several haematological malignancies, and we similarly report here elevated EV concentrations in plasma from paediatric BCP-ALL patients. Plasma EVs are very heterogeneous in terms of their cellular origin, thus identifying a cancer selective EV-marker is challenging. Here, we undertook a reductionistic approach to identify protein markers selectively associated to plasma EVs derived from BCP-ALL patients. The EV proteome of primary BCP-ALL cell-derived EVs were compared against EVs from healthy donor B cells and the BCP-ALL cell line REH, and further against EVs isolated from plasma of healthy paediatric donors and paediatric BCP-ALL patients. With this approach, we identified a signature of 6 proteins (CD317, CD38, IGF2BP1, PCNA, CSDE1, and GPR116) that were specifically identified in BCP-ALL derived EVs only and not in healthy control EVs, and that could be exploited as diagnostic biomarkers.


Assuntos
Vesículas Extracelulares , Neoplasias Hematológicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Criança , Linfócitos B , Biomarcadores , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Proteínas de Ligação a DNA , Proteínas de Ligação a RNA
9.
Cancer Discov ; 14(3): 396-405, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426560

RESUMO

SUMMARY: The recognition of host genetic factors underlying susceptibility to hematopoietic malignancies has increased greatly over the last decade. Historically, germline predisposition was thought to primarily affect the young. However, emerging data indicate that hematopoietic malignancies that develop in people of all ages across the human lifespan can derive from germline predisposing conditions and are not exclusively observed in younger individuals. The age at which hematopoietic malignancies manifest appears to correlate with distinct underlying biological pathways. Progression from having a deleterious germline variant to being diagnosed with overt malignancy involves complex, multistep gene-environment interactions with key external triggers, such as infection and inflammatory stimuli, driving clonal progression. Understanding the mechanisms by which predisposed clones transform under specific pressures may reveal strategies to better treat and even prevent hematopoietic malignancies from occurring.Recent unbiased genome-wide sequencing studies of children and adults with hematopoietic malignancies have revealed novel genes in which disease-causing variants are of germline origin. This paradigm shift is spearheaded by findings in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) as well as acute lymphoblastic leukemia, but it also encompasses other cancer types. Although not without challenges, the field of genetic cancer predisposition is advancing quickly, and a better understanding of the genetic basis of hematopoietic malignancies risk affects therapeutic decisions as well as genetic counseling and testing of at-risk family members.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Criança , Humanos , Síndromes Mielodisplásicas/genética , Interação Gene-Ambiente , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , Mutação em Linhagem Germinativa , Leucemia Mieloide Aguda/genética
10.
Cell Transplant ; 33: 9636897241231892, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433349

RESUMO

Immune cell therapy as a revolutionary treatment modality, significantly transformed cancer care. It is a specialized form of immunotherapy that utilizes living immune cells as therapeutic reagents for the treatment of cancer. Unlike traditional drugs, cell therapies are considered "living drugs," and these products are currently customized and require advanced manufacturing techniques. Although chimeric antigen receptor (CAR)-T cell therapies have received tremendous attention in the industry regarding the treatment of hematologic malignancies, their effectiveness in treating solid tumors is often restricted, leading to the emergence of alternative immune cell therapies. Tumor-infiltrating lymphocytes (TIL) cell therapy, cytokine-induced killer (CIK) cell therapy, dendritic cell (DC) vaccines, and DC/CIK cell therapy are designed to use the body's natural defense mechanisms to target and eliminate cancer cells, and usually have fewer side effects or risks. On the other hand, cell therapies, such as chimeric antigen receptor-T (CAR-T) cell, T cell receptor (TCR)-T, chimeric antigen receptor-natural killer (CAR-NK), or CAR-macrophages (CAR-M) typically utilize either autologous stem cells, allogeneic or xenogeneic cells, or genetically modified cells, which require higher levels of manipulation and are considered high risk. These high-risk cell therapies typically hold special characteristics in tumor targeting and signal transduction, triggering new anti-tumor immune responses. Recently, significant advances have been achieved in both basic and clinical researches on anti-tumor mechanisms, cell therapy product designs, and technological innovations. With swift technological integration and a high innovation landscape, key future development directions have emerged. To meet the demands of cell therapy technological advancements in treating cancer, we comprehensively and systematically investigate the technological innovation and clinical progress of immune cell therapies in this study. Based on the therapeutic mechanisms and methodological features of immune cell therapies, we analyzed the main technical advantages and clinical transformation risks associated with these therapies. We also analyzed and forecasted the application prospects, providing references for relevant enterprises with the necessary information to make informed decisions regarding their R&D direction selection.


Assuntos
Neoplasias Hematológicas , Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Neoplasias/terapia , Imunoterapia , Terapia Baseada em Transplante de Células e Tecidos
11.
JAMA Netw Open ; 7(3): e241112, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436954

RESUMO

Importance: In recent years, there has been a focus on reducing the socioeconomic gap in survival for hematological malignant neoplasms. Understanding recent developments is important to develop further intervention to improve care. Objective: To investigate the temporal trend in associations of socioeconomic status (SES) with survival among 3 aggressive hematological malignant neoplasms: multiple myeloma (MM), acute myeloid leukemia (AML), and diffuse large B-cell lymphoma (DLBCL). Design, Setting, and Participants: This nationwide, population-based cohort study used retrospectively collected data from 3 clinical registries of patients diagnosed in Denmark between January 1, 2005, and December 31, 2020, with follow-up until December 31, 2021. Analyses were stratified by diagnosis year (2005-2009, 2010-2014, and 2015-2020). Participants were patients aged 25 to 65 years with hematological malignant neoplasms. Patients with missing data on education were excluded. Data were analyzed from October 14, 2022, to January 2, 2024. Exposure: Education was used as a proxy for SES and defined low- and high-SES groups based on the completion of tertiary education. Main Outcomes and Measures: The main outcome was overall survival (OS), analyzed using Kaplan-Meier (log rank) method and Cox proportional hazards regression adjusted for age, sex, performance status, comorbidities, and disease-specific prognostic indices. Two-year OS through time and survival difference were estimated using flexible parametric survival models. Results: A total of 5677 patients (median [IQR] age, 58 [51-62] years; 3177 [57.0%] male) were assessed, including 1826 patients with MM, 1236 patients with AML, and 2509 patients with DLBCL. The 2-year OS increased over time for patients with MM (78.8% [95% CI, 75.4%-82.3%] to 91.4% [95% CI, 89.3%-93.5%]), AML (42.2% [95% CI, 37.8%-47.1%] to 52.7% [95% CI, 48.0%-57.9%]), and DLBCL (80.1% [95% CI, 77.4%-82.8%] to 88.1% [95% CI, 86.0%-90.3%]). For MM and DLBCL, no association of SES with survival was observed after adjustment (MM: hazard ratio [HR], 0.99 [95% CI, 0.85-1.15]; DLBCL: HR, 1.08 [95% CI, 0.91-1.29]). For AML, a negative association was observed between low SES and survival (HR, 1.49 [95% CI, 1.25-1.76]), but the association was attenuated in recent years. The difference in hazard for patients with low SES and AML was observed in the first 2 years after diagnosis. Conclusions and Relevance: These findings suggest that survival has improved among patients with these hematological malignant neoplasms. While patients with MM and DLBCL had increased survival in all groups, disparities were observed in AML outcomes, primarily in the first years after diagnosis. These results suggest that differences originate in factors specific to AML.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Linfoma Difuso de Grandes Células B , Mieloma Múltiplo , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos de Coortes , Estudos Retrospectivos , Classe Social
12.
BMC Infect Dis ; 24(1): 278, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438974

RESUMO

BACKGROUND: Procalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of procalcitonin (PCT) and to compare it with C-reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated. RESULTS: Seven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI [45-74%]) and 78% (95% CI [69-86%]). The diagnostic odds ratio was estimated at 5.47 (95% CI [2.86-10.46]). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI [26-83%]) and 75% (95% CI [68-82%]), and those for CRP were 67% (95% CI [35-88%]) and 73% (95% CI [69-77%]). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61-0.91 vs. 0.74, CI = 0.61-0.95, p = 0.93). CONCLUSION: While elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.


Assuntos
Neoplasias Hematológicas , Neoplasias , Adulto , Humanos , Pró-Calcitonina , Neoplasias/complicações , Neoplasias Hematológicas/complicações , Proteína C-Reativa , Razão de Chances
13.
Medicine (Baltimore) ; 103(10): e37159, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457569

RESUMO

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic skin disease. The diagnosis of PG is mainly based on clinical manifestations. Therefore, the clinical features of PG are important for confirming the diagnosis of this disease. Herein, the clinical data of 2 young males with PG complicated with hematological malignancies were reported, and the literature were reviewed. CASE PRESENTATION: The first case was a 22-year-old male who was admitted due to a systemic rash, headache, and fever. Physical examination showed black scabs on the skins of the extremities, trunk, scalp, and face. Biopsy of the skin lesion showed epidermal edema, spongy formation, neutrophil infiltration, acute and chronic inflammatory cell infiltration in the dermis, showing purulent inflammation with epidermal erosion. The bone marrow biopsy showed obviously active proliferation of nucleated cells, granulocytes at various stages, abnormal morphological neutrophils, and occasionally observed young red blood cells. The diagnosis of PG and chronic myelomonocytic leukemia (CMML-0) was made. The second case was a 28-year-old male who presented a swollen, painful right calf following injury and then developed ulcers on skin and soft tissues. Bone marrow biopsy showed obviously active nucleated cell proliferation, suggesting a myeloid tumor. He was also diagnosed with PG and hematological malignancies. They both received hormone and antiinfection therapy. After treatment, their body temperature, infection, and skin lesions were improved. However, both of them were readmitted and had a poor prognosis. CONCLUSIONS: PG may be associated with hematological malignancies. For patients with typical skin lesions and obvious abnormal blood routines, it is necessary to investigate the possibility of PG with hematological malignancies.


Assuntos
Neoplasias Hematológicas , Pioderma Gangrenoso , Dermatopatias , Masculino , Humanos , Adulto Jovem , Adulto , Pioderma Gangrenoso/complicações , Pioderma Gangrenoso/diagnóstico , Pele/patologia , Dermatopatias/complicações , Biópsia/efeitos adversos , Neoplasias Hematológicas/complicações
14.
Nat Commun ; 15(1): 2054, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448430

RESUMO

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.


Assuntos
Anticorpos Biespecíficos , Neoplasias Hematológicas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Antígeno CD47 , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Citotoxicidade Celular Dependente de Anticorpos
15.
BMC Infect Dis ; 24(1): 296, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448809

RESUMO

Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.


Assuntos
Candidíase , Neoplasias Hematológicas , Leucemia Mieloide Aguda , Neutropenia , Feminino , Humanos , Adolescente , Candidíase/diagnóstico , Candidíase/tratamento farmacológico
16.
Sci Rep ; 14(1): 6400, 2024 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493200

RESUMO

Leukaemia of various subtypes are driven by distinct chromosomal rearrangement or genetic abnormalities. The leukaemogenic fusion transcripts or genetic mutations serve as molecular markers for minimal residual disease (MRD) monitoring. The current study evaluated the applicability of several droplet digital PCR assays for the detection of these targets at RNA and DNA levels (atypical BCR::ABL1 e19a2, e23a2ins52, e13a2ins74, rare types of CBFB::MYH11 (G and I), PCM1::JAK2, KMT2A::ELL2, PICALM::MLLT10 fusion transcripts and CEBPA frame-shift and insertion/duplication mutations) with high sensitivity. The analytical performances were assessed by the limit of blanks, limit of detection, limit of quantification and linear regression. Our data demonstrated serial MRD monitoring for patients at molecular level could become "digitalized", which was deemed important to guide clinicians in treatment decision for better patient care.


Assuntos
Neoplasias Hematológicas , Leucemia , Humanos , Neoplasia Residual/genética , Neoplasia Residual/diagnóstico , Reação em Cadeia da Polimerase , Leucemia/diagnóstico , Aberrações Cromossômicas , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Fatores de Elongação da Transcrição/genética
17.
Handb Clin Neurol ; 200: 419-429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494294

RESUMO

Paraneoplastic neurologic syndromes are rarely associated with hematologic malignancies. In their rarity, lymphomas are the diseases with more frequent paraneoplastic neurologic syndrome. High-risk antibodies are absent in most lymphoma-associated paraneoplastic neurologic syndromes, with the exception of antibodies to Tr/DNER in paraneoplastic cerebellar degeneration, mGluR5 in limbic encephalitis, and mGluR1 in some cerebellar ataxias. Peripheral nervous system paraneoplastic neurologic syndromes are rare and heterogeneous, with a prevalence of demyelinating polyradiculoneuropathy in non-Hodgkin lymphoma. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) is a rare, paraneoplastic syndrome due to an underlying plasma cell disorder. The diagnosis is based on defined criteria, and vascular endothelial growth factor (VEGF), not an antibody, is considered a reliable diagnostic marker that also mirrors therapy response. As with the paraneoplastic neurologic syndromes in solid tumors, therapies rely on cancer treatment associated with immunomodulatory treatment with better response in PNS with antibodies to surface antigens. The best outcome is generally present in Ophelia syndrome/limbic encephalitis with anti-mGluR5 antibodies, with frequent complete recovery. Besides patients with isolated osteosclerotic lesions (where radiotherapy is indicated), hematopoietic stem-cell transplantation is the therapy of choice in patients with POEMS syndrome. In the paraneoplastic neurologic syndromes secondary to immune checkpoint inhibitors, discontinuation of the drug together with immunomodulatory treatment is recommended.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Encefalite Límbica , Linfoma , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Fator A de Crescimento do Endotélio Vascular , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia
18.
Best Pract Res Clin Haematol ; 37(1): 101539, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38490767

RESUMO

Improvements made during the last decades in the management of patients with hematologic neoplasia have resulted in increase of overall survival. These advancements have become possible through progress in our understanding of genetic basis of different hematologic malignancies and their role in the current risk-adapted treatment protocols. In this review, we provide an overview of current cytogenetic and molecular genetic methods, commonly used in the genetic characterization of hematologic malignancies, describe the current developments in the cytogenetic and molecular diagnostics, and give an outlook into their future development. Furthermore, we give a brief overview of the most important public databases and guidelines for sequence variant interpretation.


Assuntos
Neoplasias Hematológicas , Humanos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Análise Citogenética , Biologia Molecular
19.
J Infect Dev Ctries ; 18(2): 235-242, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38484344

RESUMO

INTRODUCTION: Patients with severe neutropenia who develop septic shock (SS) have high mortality. This study aimed to evaluate the risk factors and mortality of SS in patients with HM and febrile neutropenia. METHODOLOGY: We included all patients with hematological malignancies (HM) who presented fever and severe neutropenia, admitted to an oncological tertiary care center in Mexico City for one year. RESULTS: Two hundred ninety-two episodes of fever and severe neutropenia were documented; 68 patients (23.2%) developed SS. Documented clinical infection was different between SS and non-SS patients (94.1% vs. 63.4%, p < 0.001); pneumonia was the most frequent infection (36.8% vs. 23.2%, p = 0.02). Also, in SS vs. non-SS, there were more positive cultures (69.1% vs. 38.4%, p < 0.001), higher frequency of Gram-negative bacteria (89.3% vs. 63.9%, p < 0.001), particularly Escherichia coli (68% vs. 44.2%) and Klebsiella spp. (23.4% vs. 15.1%). There were no differences when multidrug-resistant (MDR) microorganisms were compared. In the multivariate analysis, associated risk factors for SS were: prolonged neutropenia, a documented site of infection, and having received highly myelosuppressive chemotherapy. Risk factors for mortality at 30 days were: older patients, prolonged neutropenia, and SS. CONCLUSIONS: Severe and prolonged neutropenia was associated with SS development and mortality at 30 days. ICU management should be offered to all critically ill patients with HM if long-term survival of the underlying malignancy is expected.


Assuntos
Neutropenia Febril , Neoplasias Hematológicas , Neoplasias , Choque Séptico , Humanos , Choque Séptico/epidemiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias/complicações , Fatores de Risco , Escherichia coli , Neutropenia Febril/microbiologia , Estudos Retrospectivos
20.
Am J Hematol ; 99(4): 679-696, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38440808

RESUMO

DISEASE OVERVIEW: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogenous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. DIAGNOSIS: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11c, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral bone marrow infiltration and the presence of BRAFV600E somatic mutation. RISK STRATIFICATION: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4-34 positive HCL cases are associated with a poor prognosis, as well as HCL with TP53 mutations and HCL-V. TREATMENT: Patients should be treated only if HCL is symptomatic. Chemotherapy with risk-adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining cladribine (CDA) and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/refractory disease is based on the use of BRAF inhibitors (BRAFi) plus R, MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22, Bruton tyrosine kinase inhibitors (BTKi), and Bcl-2 inhibitors (Bcl-2i). However, the optimal sequence of the different treatments remains to be determined.


Assuntos
Neoplasias Hematológicas , Leucemia de Células Pilosas , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/terapia , Proteínas Proto-Oncogênicas B-raf , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia , Imunoterapia , Linfócitos B
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