ABSTRACT
The emergence of chimeric antigen receptor T cell (CAR-T cell) therapy has revolutionized cancer treatment, particularly for hematologic malignancies. This commentary discusses developments in CAR-T cell therapy, focusing on the molecular mechanisms governing T cell fate and differentiation. Transcriptional and epigenetic factors play a pivotal role in determining the specificity, effectiveness, and durability of CAR-T cell therapy. Understanding these mechanisms is crucial to improve the efficacy and decrease the adverse events associated with CAR-T cell therapies, unlocking the full potential of these approaches. T cell differentiation in CAR-T cell product manufacturing plays an important role in clinical outcomes. A positive correlation exists between the clinical efficacy of CAR-T cell therapy and signatures of memory, whereas a negative correlation has been observed with signatures of effector function or exhaustion. The effectiveness of CAR-T cell products is likely influenced by T-cell frequency and by their ability to proliferate, which is closely linked to early T cell differentiation. The differentiation process involving distinct T memory cell subsets is initiated upon antigen elimination, indicating infection resolution. In chronic infections or cancer, T cells may undergo exhaustion, marked by continuous inhibitory receptor expression, decreased cytokine production, and diminished proliferative capacity. Other cell subsets, such as CD4+ T cells, innate-like T lymphocytes, NKT cells, and cord blood-derived hematopoietic stem cells, offer unique advantages in developing the next-generation CAR-T cell-based therapies. Future research should focus on optimizing T-cell-enhancing approaches and developing strategies to potentially cure patients with hematological diseases and solid tumors.
ABSTRACT
Histone deacetylase inhibitors (HDACi) can modulate the acetylation status of proteins, influencing the genomic instability exhibited by cancer cells. Poly (ADP ribose) polymerase (PARP) inhibitors (PARPi) have a direct effect on protein poly (ADP-ribosyl)ation, which is important for DNA repair. Decitabine is a nucleoside cytidine analogue, which when phosphorylated gets incorporated into the growing DNA strand, inhibiting methylation and inducing DNA damage by inactivating and trapping DNA methyltransferase on the DNA, thereby activating transcriptionally silenced DNA loci. We explored various combinations of HDACi and PARPi +/- decitabine (hypomethylating agent) in pancreatic cancer cell lines BxPC-3 and PL45 (wild-type BRCA1 and BRCA2) and Capan-1 (mutated BRCA2). The combination of HDACi (panobinostat or vorinostat) with PARPi (talazoparib or olaparib) resulted in synergistic cytotoxicity in all cell lines tested. The addition of decitabine further increased the synergistic cytotoxicity noted with HDACi and PARPi, triggering apoptosis (evidenced by increased cleavage of caspase 3 and PARP1). The 3-drug combination treatments (vorinostat, talazoparib, and decitabine; vorinostat, olaparib, and decitabine; panobinostat, talazoparib, and decitabine; panobinostat, olaparib, and decitabine) induced more DNA damage (increased phosphorylation of histone 2AX) than the individual drugs and impaired the DNA repair pathways (decreased levels of ATM, BRCA1, and ATRX proteins). The 3-drug combinations also altered the epigenetic regulation of gene expression (NuRD complex subunits, reduced levels). This is the first study to demonstrate synergistic interactions between the aforementioned agents in pancreatic cancer cell lines and provides preclinical data to design individualized therapeutic approaches with the potential to improve pancreatic cancer treatment outcomes.
Subject(s)
Azacitidine , Decitabine , Drug Synergism , Histone Deacetylase Inhibitors , Pancreatic Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Decitabine/pharmacology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Cell Line, Tumor , Histone Deacetylase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Azacitidine/pharmacology , Azacitidine/analogs & derivatives , Apoptosis/drug effects , Antineoplastic Combined Chemotherapy Protocols/pharmacologyABSTRACT
A patient in his 40s with splenic angiosarcoma metastatic to the liver underwent splenectomy, chemotherapy, and partial hepatectomy before being treated on a clinical trial with CTLA4 and PD1 inhibitors. He had received pneumococcal and meningococcal vaccines post-splenectomy. On week 10, he developed grade 3 immune-related colitis, successfully treated with the anti-tumor necrosis factor-alpha inhibitor infliximab and steroids. After 4 cycles of treatment, scans showed partial response. He resumed anti-PD1 therapy, and 6 hours after the second dose of anti-PD1 he presented to the emergency room with hematemesis, hematochezia, hypotension, fever, and oxygen desaturation. Laboratory tests demonstrated acute renal failure and septicemia (Streptococcus pneumoniae). He died 12 hours after the anti-PD1 infusion from overwhelming post-splenectomy infection (OPSI). Autopsy demonstrated non-viable liver tumors among other findings. In conclusion, patients undergoing immunotherapy and with prior history of asplenia should be monitored closely for OPSI as they may be at increased risk.
Subject(s)
Hemangiosarcoma , Liver Neoplasms , Splenectomy , Splenic Neoplasms , Humans , Splenectomy/adverse effects , Male , Hemangiosarcoma/therapy , Splenic Neoplasms/secondary , Splenic Neoplasms/therapy , Fatal Outcome , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/adverse effects , Immunotherapy/methods , Adult , Pneumococcal Infections/etiology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , CTLA-4 Antigen/antagonists & inhibitorsABSTRACT
Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) is a surrogate marker for symptom evaluation in Chronic Myeloproliferative Neoplasms. There is not enough data to show the relationship between MPN-SAF TSS, JAK2 mutation allele burden, and thrombosis. In this retrospective analysis, we aimed to determine the genetic burdens, clinical features, and relationship with MPN-SAF TSS in MPN patients. One hundred thirty JAK2V617F positive MPN were included in our study. We have calculated MPN-SAF TSS and compared it with clinical features. Patients with higher JAK2V617F mutation allele burden had higher MPN-SAF TSS (p-value 0,008). Patients with thrombosis had higher MPN-SAF TSS scores than patients without thrombosis (p-value 0.003). The mean MPN-SAF TSS was higher in primary myelofibrosis (PMF) patients compared to PV and ET patients. Thrombosis was associated with increased symptom severity in several domains, including fatigue, abdominal discomfort, inactivity, night sweats, pruritus, weight loss, and early satiety. Additionally, an increase in JAK2 allele burden was observed with higher symptom scores. The MPN-SAF TSS proved to be a reliable tool for assessing symptom burden in Turkish MPN patients. Furthermore, a significant association between thrombosis occurrence and symptom severity suggests that thrombotic events may contribute to symptom development. Notably, increasing JAK2 allele burden was correlated with more severe symptoms, highlighting its potential role in predicting disease burden. This study emphasizes the importance of symptom assessment in MPN patients and supports the incorporation of MPN-SAF TSS in routine clinical practice to enhance patient care and management.
ABSTRACT
Objective: In this study, we investigated the effects of calreticulin (CALR) and JAK2V617F mutational status on clinical course and disease outcomes in Turkish patients with essential thrombocythemia (ET). Materials and Methods: Seventeen centers from Türkiye participated in the study and CALR- and JAK2V617F-mutated ET patients were evaluated retrospectively. Results: A total of 302 patients were included, of whom 203 (67.2%) and 99 (32.8%) were JAK2V617F- and CALR-positive, respectively. CALR-mutated patients were significantly younger (51 years vs. 57.5 years, p=0.03), with higher median platelet counts (987x109/L vs. 709x109/L, p<0.001) and lower median hemoglobin levels (13.1 g/dL vs. 14.1 g/dL, p<0.001) compared to JAK2V617F-mutated patients. Thromboembolic events (TEEs) occurred in 54 patients (17.9%), 77.8% of which were arterial. Compared to CALR mutation, JAK2V617F was associated with a higher risk of thrombosis (8.1% vs. 22.7%, p=0.002). Rates of transformation to myelofibrosis (MF) and leukemia were 4% and 0.7%, respectively, and these rates were comparable between JAK2V617F- and CALR-mutated cases. The estimated overall survival (OS) and MF-free survival of the entire cohort were 265.1 months and 235.7 months, respectively. OS and MF-free survival durations were similar between JAK2V617F- and CALR-mutated patients. Thrombosis-free survival (TFS) was superior in CALR-mutated patients compared to JAK2V617F-positive patients (5-year TFS: 90% vs. 71%, respectively; p=0.001). Age at diagnosis was an independent factor affecting the incidence of TEEs. Conclusion: In our ET cohort, CALR mutations resulted in higher platelet counts and lower hemoglobin levels than JAK2V617F and were associated with younger age at diagnosis. JAK2V617F was strongly associated with thrombosis and worse TFS. Hydroxyurea was the most preferred cytoreductive agent for patients with high thrombosis risk.
Subject(s)
Primary Myelofibrosis , Thrombocythemia, Essential , Thrombosis , Humans , Calreticulin/genetics , Disease Progression , Hemoglobins , Mutation , Retrospective Studies , Thrombocythemia, Essential/drug therapy , Thrombocythemia, Essential/genetics , Thrombosis/etiology , Thrombosis/genetics , Turkey/epidemiologyABSTRACT
To overcome challenges associated with adoptive cell therapy (ACT), we developed a personalized autologous T-cell therapy program. Patients with advanced cancer with HLA-A *02:01 allele and tumor expression of PRAME, MAGEA1, MAGEA4, MAGEA8, NY-ESO-1, COL6A3 exon 6, MXRA5, and/or MMP1 underwent leukapheresis and T-cell product manufacturing. Patients received lymphodepletion, IMA101 infusion and interleukin 2 for 14 days. Of 214 screened patients, 14 were treated (6, IMA101; 8, IMA101 and atezolizumab). The most common adverse events were cytokine release syndrome (G1, n = 6; G2, n = 4) and cytopenia. At 6 weeks, 12 (85.7%) patients had stable disease. Three patients had prolonged disease stabilization for 12.9, 7.3, and 13.7 months, respectively. The median progression-free survival and overall survival were 3.4 months and 9.4 months, respectively. Target-specific T cells expanded to constitute up to 78.7% of CD8+ cells. In conclusion, IMA101 was feasible and well tolerated, leveraging the potential of multi-targeted ACT that warrants further investigation.
Subject(s)
Antigens, Neoplasm , Neoplasms , Humans , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Neoplasms/therapy , CD8-Positive T-Lymphocytes , Immunotherapy, Adoptive/adverse effectsABSTRACT
Objective: In recent years, new developments have been incorporated into daily practice in the management of immune thrombotic thrombocytopenic purpura (iTTP). In particular, clinical scoring systems could help clinicians with clinical decision-making and early recognition. However, older patients frequently present with more organ involvement and in unusual ways. The ways in which age could affect these clinical prediction scoring systems remain unclear. We evaluated the use of PLASMIC and French scores in patients over 60 years of age. Materials and Methods: We performed a retrospective cross-sectional analysis of patients over 60 years of age with a presumptive diagnosis of iTTP between 2014 and 2022 at 10 centers. We calculated PLASMIC and French scores and compared our data with a single-center analysis of younger patients presenting with thrombotic microangiopathy. Results: Our study included 30 patients over 60 years of age and a control group of 28 patients younger than 60 years. The diagnostic sensitivity and specificity of a French score of ≥1 were lower in older patients compared to the control group (78.9% vs. 100% and 18.2% vs. 57.1%, respectively). The diagnostic sensitivity and specificity of a PLASMIC score of ≥5 were 100% vs. 95% and 27.3% vs. 100% for the study group and control group, respectively. Our study showed a higher mortality rate in older patients compared to the control group (30% vs. 7.1%, p=0.043). Conclusion: For a limited number of patients (n=6), our results showed that rituximab can reduce mortality. Given that the reliability of clinical prediction scores for iTTP in older patients may be lower, more caution must be undertaken in interpreting their results.
Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Purpura, Thrombotic Thrombocytopenic , Thrombosis , Thrombotic Microangiopathies , Humans , Aged , Middle Aged , Purpura, Thrombotic Thrombocytopenic/diagnosis , Purpura, Thrombotic Thrombocytopenic/therapy , Retrospective Studies , Cross-Sectional Studies , Reproducibility of Results , Thrombotic Microangiopathies/diagnosis , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/therapy , ADAMTS13 ProteinABSTRACT
Over the past 15 years, rapid progress has been made in developmental therapeutics, especially regarding the use of matched targeted therapies against specific oncogenic molecular alterations across cancer types. Molecular tumour boards (MTBs) are panels of expert physicians, scientists, health-care providers and patient advocates who review and interpret molecular-profiling results for individual patients with cancer and match each patient to available therapies, which can include investigational drugs. Interpretation of the molecular alterations found in each patient is a complicated task that requires an understanding of their contextual functional effects and their correlations with sensitivity or resistance to specific treatments. The criteria for determining the actionability of molecular alterations and selecting matched treatments are constantly evolving. Therefore, MTBs have an increasingly necessary role in optimizing the allocation of biomarker-directed therapies and the implementation of precision oncology. Ultimately, increased MTB availability, accessibility and performance are likely to improve patient care. The challenges faced by MTBs are increasing, owing to the plethora of identifiable molecular alterations and immune markers in tumours of individual patients and their evolving clinical significance as more and more data on patient outcomes and results from clinical trials become available. Beyond next-generation sequencing, broader biomarker analyses can provide useful information. However, greater funding, resources and expertise are needed to ensure the sustainability of MTBs and expand their outreach to underserved populations. Harmonization between practice and policy will be required to optimally implement precision oncology. Herein, we discuss the evolving role of MTBs and current and future considerations for their use in precision oncology.
Subject(s)
Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/genetics , Precision Medicine/methods , Medical Oncology , Drugs, Investigational/therapeutic use , BiomarkersABSTRACT
T cell differentiation is a highly regulated, multi-step process necessary for the progressive establishment of effector functions, immunological memory, and long-term control of pathogens. In response to strong stimulation, as seen in severe or chronic infections or cancer, T cells acquire a state of hypo-responsiveness known as exhaustion, limiting their effector function. Recent advances in autologous chimeric antigen receptor (CAR)-T cell therapies have revolutionized the treatment of hematologic malignancies by taking advantage of the basic principles of T cell biology to engineer products that promote long-lasting T cell response. However, many patients' malignancies remain unresponsive to treatment or are prone to recur. Discoveries in T cell biology, including the identification of key regulators of differentiation and exhaustion, offer novel opportunities to have a durable impact on the fate of CAR-T cells after infusion. Such next-generation CAR-T cell therapies and their clinical implementation may result in the next leap forward in cancer treatment for selected patients. In this context, this review summarizes the foundational principles of T cell differentiation and exhaustion and describes how they can be utilized and targeted to further improve the design and efficacy of CAR-T cell therapies.
Subject(s)
Hematologic Neoplasms , Receptors, Chimeric Antigen , Humans , Cell Differentiation , Hematologic Neoplasms/therapy , Immunologic Memory , Immunotherapy, Adoptive , Cell- and Tissue-Based TherapyABSTRACT
OBJECTIVE: In immune thrombocytopenia (ITP), which is a common acquired bleeding disorder, cytotoxic T-cell-mediated cellular immune response against both circulating platelets and bone marrow megakaryocytes are the most important mechanisms in the pathogenesis. METHODS: In our study, we evaluated the features of 33 patients with ITP, over 80 years of age. RESULTS: The median age of the patients was 90, 15 patients were female (45.4%). The mean platelet count of the patients was 39×109/L and the mean mean platelet volume was 10,33fL. Twelve patients had a target thrombocyte count greater than 30×109/L, while 20 patients had a target platelet count of 75×109/L or greater with an absolute indication of antiaggregation. In the environmental spread, 18 dysplasia findings were observed. CONCLUSION: Morphologic observations suggesting dysplasia including micromegakaryocytes and a non-dysplastic but dysmegakaryopoietic finding, multiple segmented nuclei may be related to the degree of thrombocytopenia and response to treatment. Likewise, nondysplastic features including immature forms, emperipolesis, bare nucleus, hypolobulation, and hypersegmented nucleus were related to the degree of thrombocytopenia.
ABSTRACT
Advances in molecular technologies and targeted therapeutics have accelerated the implementation of precision oncology, resulting in improved clinical outcomes in selected patients. The use of next-generation sequencing and assessments of immune and other biomarkers helps optimize patient treatment selection. In this review, selected precision oncology trials including the IMPACT, SHIVA, IMPACT2, NCI-MPACT, TAPUR, DRUP, and NCI-MATCH studies are summarized, and their challenges and opportunities are discussed. Brief summaries of the new ComboMATCH, MyeloMATCH, and iMATCH studies, which follow the example of NCI-MATCH, are also included. Despite the progress made, precision oncology is inaccessible to many patients with cancer. Some patients' tumors may not respond to these treatments, owing to the complexity of carcinogenesis, the use of ineffective therapies, or unknown mechanisms of tumor resistance to treatment. The implementation of artificial intelligence, machine learning, and bioinformatic analyses of complex multi-omic data may improve the accuracy of tumor characterization, and if used strategically with caution, may accelerate the implementation of precision medicine. Clinical trials in precision oncology continue to evolve, improving outcomes and expediting the identification of curative strategies for patients with cancer. Despite the existing challenges, significant progress has been made in the past twenty years, demonstrating the benefit of precision oncology in many patients with advanced cancer.
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INTRODUCTION: Thromboembolic events in myeloproliferative neoplasms (MPNs) are one of the most important causes of mortality and morbidity, in which vitamin K antagonists (VKAs) have been used mostly. Recently, direct oral anticoagulants (DOACs) are used in venous thromboembolism (VTE) and cancer-associated thrombosis (CAT). With the adoption of data from CAT and VTE, the usage of DOACs in MPNs is increasing. AREAS COVERED: In this paper, we performed a systematic review to the current literature regarding the usage of DOACs in MPNs. Eleven studies involving 944 patients were included. The reasons for initiating DOACs were secondary prophylaxis for thrombosis (arterial or venous) and atrial fibrillation (AF) in 562 and 382 patients, respectively. A total of 84 (8.9%) recurrent thrombotic (arterial or venous) events recorded. Forty-six (8.1%) events occurred in the thrombosis group (arterial or venous) and 38 (9.9%) events occurred in patients with AF. EXPERT OPINION: Ease of management and patient comfort should be regarded as benefits of DOACs compared to VKAs. However, it would be appropriate to bring an individualized approach until we obtain high-quality data with prospectively designed studies involving more patients and longer follow-up time concerning the use of DOACs in patients with MPNs.
Subject(s)
Atrial Fibrillation , Myeloproliferative Disorders , Neoplasms , Thrombosis , Venous Thromboembolism , Humans , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Anticoagulants/therapeutic use , Myeloproliferative Disorders/complications , Myeloproliferative Disorders/drug therapy , Thrombosis/complications , Atrial Fibrillation/chemically induced , Neoplasms/complications , Administration, Oral , Vitamin KABSTRACT
Viral infections emerge in the pathogenesis of subacute thyroiditis. Aside from this, subacute thyroiditis following vaccines utilizing inactivated viruses has been shown on rare occasions. Due to the COVID-19 pandemic, several vaccines have been developed all over the world; mass and unprecedented vaccination has thus been initiated. However, it is known that cases such as subacute thyroiditis have been reported, albeit rarely, after administration of COVID-19 vaccines. In this case report, we present a 59-year-old patient with multiple myeloma developing subacute thyroiditis following BNT162b2 vaccine. Patient had swelling in the neck, and his symptoms were controlled with non-steroidal anti-inflammatory drugs. Subacute thyroiditis following administration of the COVID-19 vaccine is rare; however, it is likely an under-reported condition that is difficult to detect. Clinicians should stay informed and have increased awareness of post-COVID-19 vaccine subacute thyroiditis.
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Acute promyelocytic leukemia (APL) differs from other forms of acute myeloid leukemia (AML), including coagulopathy, hemorrhage, disseminated intravascular coagulation (DIC), and treatment success with all-trans retinoic acid (ATRA). Despite ATRA, early deaths (ED) are still common in APL. Here, we evaluated factors associated with ED and applicability of scoring systems used to diagnose DIC. Ninety-one APL patients (55 females, 36 males, and median age 40 years) were included. ED was defined as deaths attributable to any cause between day of diagnosis and following 30th day. DIC was assessed based on DIC scoring system released by the International Society of Thrombosis and Hemostasis (ISTH) and Chinese Diagnostic Scoring System (CDSS). Patients' median follow-up time was 49.2 months, and ED developed in 14 (15.4% of) cases. Patients succumbing to ED had higher levels of the Eastern Cooperative Oncology Group Performance Status (ECOG PS), lactate dehydrogenase (LDH), and ISTH DIC, and lower fibrinogen levels (p <0.05). In multivariate Cox regression analysis, age >55 and ECOG PS ≥2 rates were revealed to be associated with ED. Based on ISTH and CDSS scores, DIC was reported in 47.3 and 58.2% of the patients, respectively. Despite advances in APL, ED is still a major obstacle. Besides the prompt recognition and correction of coagulopathy, those at high ED risk are recommended to be detected rapidly. Implementation of local treatment plans and creating awareness should be achieved in hematological centers. Common utilization of ATRA and arsenic trioxide (ATO) may be beneficial to overcome ED and coagulopathy in APL patients.
Subject(s)
Disseminated Intravascular Coagulation , Leukemia, Promyelocytic, Acute , Thrombosis , Adult , Disseminated Intravascular Coagulation/therapy , Female , Humans , Male , Retrospective Studies , Risk Factors , Thrombosis/chemically induced , Tretinoin/therapeutic useABSTRACT
Objective: Eltrombopag remains a prominent option in the treatment of steroid-dependent or steroid-refractory immune thrombocytopenia (ITP) patients. Unfortunately, not all patients respond to eltrombopag. Antinuclear antibody (ANA) positivity can be seen at rates of up to 30% in ITP patients. Despite being widely used, more markers to predict the response to eltrombopag are still needed. In the present study, we aimed to show the association between ANA positivity and eltrombopag response in ITP patients. Materials and Methods: Patients who were diagnosed with ITP in the Trakya University Faculty of Medicine's Department of Hematology and who underwent eltrombopag treatment due to their resistance to steroids and other treatments were included in our study. ANA measurement was performed by indirect fluorescent antibody method and titers of 1:160 and above were considered positive. ANA measurements were made before starting eltrombopag. Results: Forty-five patients were included in our study, 33 being women and 12 men. The mean age of the patients was 45.73 years. There were 14 patients with ANA positivity and 31 patients were found to be ANA-negative. Response rates were higher in ANA-negative patients compared to ANA-positive patients in the 1st and 6th months of eltrombopag treatment (p<0.05). Conclusion: ANA positivity in ITP may indicate unresponsiveness to eltrombopag treatment, a finding that should be further supported by prospective studies involving more patients.
Subject(s)
Antibodies, Antinuclear , Benzoates , Hydrazines , Purpura, Thrombocytopenic, Idiopathic , Pyrazoles , Antibodies, Antinuclear/blood , Benzoates/therapeutic use , Female , Humans , Hydrazines/therapeutic use , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/immunology , Pyrazoles/therapeutic use , Treatment OutcomeSubject(s)
Activin Receptors, Type II , Liver Cirrhosis , Telangiectasia, Hereditary Hemorrhagic , Activin Receptors, Type II/genetics , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/genetics , Mutation , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasia, Hereditary Hemorrhagic/geneticsABSTRACT
Sarcopenia is defined as a progressive and generalized muscle disorder associated with certain physiological and pathological conditions. We aimed to evaluate the prevalence of sarcopenia in patients with HL using 18-fluoro deoxyglucose (FDG) PET/CT, which would provide a data of muscle mass with the CT compartment and also data of muscle metabolism with the 18-FDG compartment of the imaging modality. Fifty-nine patients diagnosed with HL were included in the study. PET/CT images before and after treatment were evaluated with regard to lumbar muscle mass and metabolism. Mean lumbar muscle evaluation with CT before treatment was 92, 40 HU, and after treatment was 89, 41 HU. Mean metabolic tumor volume (MTV) evaluated with FDG PET before treatment was 4, 13 mm3 while after treatment was 4, 10 mm3. The lumbar muscle mass in terms of HU which was evaluated with CT was observed to be decreased after treatment. Likewise, the metabolic evaluation was observed to be also decreased after treatment. Despite the decline in muscle mass after treatment in the whole group, this decline was particularly observed in the better initial performance group. In patients with BMI > 32, there was a significant decline in muscle mass. Abdominal nodal involvement was related with poorer muscle mass and quality. In HL care, particular attention should be given to patients who are younger and with better physical condition in terms of preserving the muscle reserves and preventing sarcopenia.
Subject(s)
Fluorodeoxyglucose F18/therapeutic use , Hodgkin Disease/complications , Hodgkin Disease/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Sarcopenia/etiology , Adult , Age Factors , Aged , Female , Hodgkin Disease/pathology , Hodgkin Disease/therapy , Humans , Male , Middle Aged , Sarcopenia/pathology , Young AdultABSTRACT
Objective: Several clinical scoring systems have been developed for the differential diagnosis of thrombotic microangiopathies (TMAs), all to predict and identify patients with ADAMTS13 deficiency and to start treatment as soon as possible. The first scoring system in this regard was the Bentley score, and the French score and PLASMIC score were developed afterwards. Materials and Methods: We aimed to evaluate the laboratory parameters and clinical features of patients who underwent plasma exchange with a prediagnosis of TTP at our clinic between 2007 and 2019 and whose ADAMTS13 enzyme levels were measured and to compare the findings with the scoring systems. Results: Data of 35 patients were evaluated. Twelve patients were evaluated as high risk according to all three scoring systems. A statistically significant relation was observed between all three scoring systems and ADAMTS13 levels. Conclusion: A moderate correlation was found between all three scoring systems and ADAMTS13 levels. We observed similar potential strength of all three scoring systems to predict TTP among other TMAs and we conclude that they are applicable in daily practice.
Subject(s)
Anemia, Hemolytic/blood , Anemia, Hemolytic/diagnosis , Thrombotic Microangiopathies/blood , Thrombotic Microangiopathies/diagnosis , ADAMTS13 Protein/deficiency , Adult , Aged , Aged, 80 and over , Anemia, Hemolytic/etiology , Clinical Decision-Making , Diagnosis, Differential , Disease Management , Disease Susceptibility , Female , Humans , Male , Middle Aged , Severity of Illness Index , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/therapy , Young AdultABSTRACT
INTRODUCTION: Multiple myeloma (MM) is a potentially incurable haematological malignancy with devastating manifestations including lytic bone lesions leading to fractures and renal insufficiency. As a disease of patients with a mean age of 66 years, both the disease and the continuous efforts of treatments lead to frailty and devastation. From this stand point, we aimed to evaluate the development of muscle loss in MM patients and also with a new method of sarcopenia evaluation, F-18 FDG PET/CT. While used for bone disease routinely, this method brings a fresh perspective of metabolic quantitation of alteration of muscles which may be regarded as muscle quality. MATERIALS AND METHODS: Data and images of 105 patients with MM both before and after treatment were evaluated in a retrospective manner. RESULTS: Both female and male patients were observed to be effected after MM treatment in terms of lumbar and femoral muscle evaluations with CT. Metabolic evaluations confirmed a loss of quality in muscles in terms of metabolic volume and total lesion glycolysis. CONCLUSION: Sarcopenia should be evaluated in every patient and regarded as a treatment target. FDG PET/CT is an easy and handy tool to assess muscle mass and quality as well as MM disease status.
Subject(s)
Multiple Myeloma , Sarcopenia , Female , Fluorodeoxyglucose F18 , Humans , Infant, Newborn , Male , Multiple Myeloma/complications , Multiple Myeloma/diagnostic imaging , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Retrospective Studies , Sarcopenia/diagnostic imaging , Sarcopenia/etiology , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: Invasive fungal infections (IFI) are important and trending causes of mortality in patients with acute leukemia, especially during the remission induction. METHODS: In this study, 225 patients who were diagnosed with acute myeloid leukemia (AML) and undergoing intensive treatment for remission induction were enrolled in a retrospective manner. RESULTS: Within the whole group, which consisted of 225 patients, 90 patients received prophylactic antifungal treatment (PAT) (40%), while 135 patients did not (60%) receive. The mean cost of hospitalization was 9.151,6 (2.872,6-20.483,3) US dollars. Gender distribution and mean ages of groups were similar. One hundred fourteen patients not on PAT (84.4%) and five patients on PAT (5.5%) received intravenous antifungal treatment. Thirty-two of the patients who were not on PAT (23.7%) and 11 of the patients on PAT died during remission induction (12.22%). The mean day of the hospitalization was 22.61 days for the patients on PAT and 33.89 days for the patients who were not on PAT. In patients on PAT, the mean number of transfused platelet units was six (0-9), while 12.51 (4-43) units for patients who were not on PAT. CONCLUSION: In our study, the oral suspension form of posaconazole was observed to be cost-effective to prevent IFI with a significant decrease in mortality during remission induction treatment.