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Cureus Apr 2024Introduction Multiple myeloma (MM) is a hematological disorder characterized by aberrant multiplication of malignant plasma cells in the bone marrow. The current...
Real-World Outcomes in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated With Bortezomib/Cyclophosphamide/Dexamethasone and Bortezomib/Lenalidomide/Dexamethasone as Upfront Treatment.
Introduction Multiple myeloma (MM) is a hematological disorder characterized by aberrant multiplication of malignant plasma cells in the bone marrow. The current mainstay of treatment for patients with newly diagnosed MM (NDMM) is a triplet regimen with a proteasome inhibitor, immunomodulatory imide, and dexamethasone. The two most common of these triplet regimens are VLD (bortezomib/lenalidomide/dexamethasone) and VCD (bortezomib/cyclophosphamide/dexamethasone). This study aims to compare the outcomes between these two therapies in transplant-ineligible patients with NDMM. Methods We conducted a retrospective study at the Aga Khan University Hospital in Karachi, Pakistan. All NDMM transplant-ineligible patients either receiving VLD or VCD therapy between January 2015 and December 2022 were included in our study. Hematological parameters before and after treatment were obtained from hospital records. Response to treatment was classified according to the International Myeloma Working Group (IMWG) response criteria as either complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), or progressive disease (PD). The response to treatment as well as overall survival (OS) and progression-free survival (PFS) was compared between VCD and VLD therapy. A p-value of 0.05 or less was taken to be statistically significant. Results Twenty (23.8%) patients in the VCD group and 20 (23.0%) in the VLD group underwent complete remission. Seven (8.3%) patients experienced disease progression in the VCD group, while the figure stood at three (3.4%) in the VLD group. There was no statistically significant difference in the overall response rate between the VCD (58; 69.0%) and VLD (70; 80.5%) groups (p=0.086), a difference that was not statistically significant on the Chi-square test. OS was comparable between VCD (69.1 months, 95%CI: 61.3-77.0) and VLD (76.9 months, 95%CI: 69.0-85.0) therapies. Conclusions The study did not identify any statistically significant distinction in the treatment outcomes between the VCD and VLD regimens among NDMM patients ineligible for transplantation. Nevertheless, the study highlights the positive outcomes observed with both treatments in this specific patient cohort. This implies that either regimen could be deemed suitable as a treatment option for patients in low- and middle-income countries. Since both regimens demonstrate comparable effectiveness, assessing the cost-effectiveness of these regimens is crucial. Future research should also explore the economic aspects of the two treatment options.
PubMed: 38800157
DOI: 10.7759/cureus.58999 -
Reumatologia 2024The treatment of Behçet's disease has improved significantly with the introduction of biologic therapies. However, there is still a need for more information about...
INTRODUCTION
The treatment of Behçet's disease has improved significantly with the introduction of biologic therapies. However, there is still a need for more information about their use. This study aimed to evaluate the indications, response, and side effects of biologic agents in patients with refractory or severe Behçet's disease in the south of Iran, their follow-up and reasons for changing the biologics.
MATERIAL AND METHODS
A retrospective analysis was conducted on 44 patients aged 16-65 years who were prescribed biologic agents for at least 6 months. The clinical history, partial and complete remission at 6 and 12 months, occurrence of side effects, and need for switching to a second or third biologic agent were recorded.
RESULTS
The most common indications for starting biologic agents were ophthalmic (68.2%), parenchymal brain involvement (15.9%), and arthritis (11.4%). Improvement was observed in various manifestations of Behçet's disease, with complete remission in 86, 51.6, 92.8, 66.7, 42.9, 33.3, and 80.0% of oral aphthous lesions, ophthalmic activity, genital aphthous lesions, skin activity, arthritis, brain parenchymal lesions, and vascular activity, respectively, 6 months after starting biologic agents. These rates were unchanged or increased at the 12-month follow-up. In 25.0% of patients, a switch to a second biologic agent was necessary due to severe disease, side effects, or refractory disease. Side effects occurred in 16.3% and 33.3% of patients on the first and second biologic agents, respectively. The majority of side effects were not serious.
CONCLUSIONS
We found a promising improvement at 6-month and 12-month follow-ups with various biologic agents in treating Behçet's disease with an acceptable safety profile.
PubMed: 38799775
DOI: 10.5114/reum/183467 -
Frontiers in Immunology 2024There was little evidence of autologous stem cell transplantation (ASCT) as consolidation therapy after remission of induction for patients with Peripheral T-cell...
Consolidation therapy with autologous stem cell transplantation after remission of induction chemotherapy prolongs the survival of patients with peripheral T-cell lymphoma.
BACKGROUND
There was little evidence of autologous stem cell transplantation (ASCT) as consolidation therapy after remission of induction for patients with Peripheral T-cell lymphoma (PTCL). In this study, we conducted a comparative analysis of real-world survival outcomes between consolidation therapy and observation in patients with PTCL.
METHODS
A total of 92 patients with peripheral T-cell lymphoma (PTCL) who were admitted to the Department of Hematology, Huadong Hospital Affiliated with Fudan University from January 2013 to April 2019 were divided into two groups based on whether they were treated with high-dose therapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT): ASCT as consolidation therapy (n=30) and observation (n=62). Clinical characteristics, treatment patterns, and survival outcomes were analyzed between the two groups. Univariate and Cox multivariate regression analyses were also performed to detect prognostic factors of survival.
RESULTS
With a median follow-up time of 41 months, the median overall survival (OS) of peripheral T-cell lymphoma patients treated with ASCT was not reached; the median progression-free survival (PFS) was 77.0 months, which was much higher than that of patients without ASCT (<0.003 for OS, p=0.015 for PFS). Subgroup analysis found that patients with high risks benefited more from ASCT. Combination with hemophagocytic lymphohistiocytosis (HLH) (<0.001), clinical stage more than III (=0.014), IPI score above 3 (=0.049), and bone marrow involvement (=0.010) were the independent prognostic factors significantly associated with worse OS and PFS. Additionally, pegylated liposomal doxorubicin (PLD)-containing chemotherapy regimen could bring a higher overall response rate (ORR) and prolong the survival of patients with PTCL who underwent ASCT.
CONCLUSION
ASCT may improve the long-term survival of patients with PTCL as consolidation therapy after achieving complete or partial remission of induction treatment, particularly for those with high risks. The chemotherapy regimen containing pegylated liposomal doxorubicin may induce deeper remission than traditional doxorubicin in PTCL. It is crucial to identify the specific groups most likely to benefit from upfront ASCT.
Topics: Humans; Lymphoma, T-Cell, Peripheral; Female; Male; Transplantation, Autologous; Middle Aged; Adult; Hematopoietic Stem Cell Transplantation; Consolidation Chemotherapy; Induction Chemotherapy; Antineoplastic Combined Chemotherapy Protocols; Remission Induction; Aged; Retrospective Studies; Young Adult; Treatment Outcome; Prognosis; Combined Modality Therapy
PubMed: 38799461
DOI: 10.3389/fimmu.2024.1382189 -
Medicina (Kaunas, Lithuania) May 2024Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man...
Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man presenting with bycitopenia and soft tissue infection. The bone marrow exhibited 3% abnormal cells. Immunophenotyping of these cells revealed the antigens CD45+ (dim), CD34+, CD117+, CD123+ (bright), HLA-DR+ (bimodal), CD56+ (bright), CD33+, CD13+, CD2+, and CD22+ (dim) and the partial expression of the CD10+, CD36+, and CD7+ antigens. All other myeloid, monocytic, and lymphoid antigens were negative. Genetic studies showed a complex karyotype and mutations in the TP53 and KRAS genes. On hospital admission, the patient showed a subcutaneous nodule on the right hand and left lower limb. Flow cytometry multiparameter (FCM) analysis showed the presence of 29% abnormal cells with the previously described immunophenotype. The patient was diagnosed with BPDCN. The patient was treated with broad-spectrum antibiotics for soft tissue infection, which delayed therapy for BPDCN. No steroids or chemotherapeutic or hypomethylating agents were administered. His blood cell counts improved and skin lesions disappeared, until the patient relapsed five months after achieving spontaneous remission. About 60% of abnormal cells were identified. No changes in immunophenotype or the results of genetic studies were observed. The patient underwent a HyperCVAD chemotherapy regimen for six cycles. Consolidation therapy was performed via allogeneic bone marrow transplantation with an HLA-unrelated donor. One year after the bone marrow transplant, the patient died due to the progression of his underlying disease, coinciding with a respiratory infection caused by SARS-CoV-2. In the available literature, SRs are often linked to infections or other stimulators of the immune system, suggesting that powerful immune activation could play a role in controlling the leukemic clone. Nevertheless, the underlying mechanism of this phenomenon is not clearly understood. We hypothesize that the immune system would force the leukemic stem cell (LSC) to undergo a state of quiescence. This loss of replication causes the LSC progeny to die off, resulting in the SR of BPDCN.
Topics: Humans; Male; Adult; Dendritic Cells; Remission, Spontaneous; Immunophenotyping; Hematologic Neoplasms
PubMed: 38792990
DOI: 10.3390/medicina60050807 -
Medicina (Kaunas, Lithuania) Apr 2024The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the... (Observational Study)
Observational Study
The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the effectiveness of anti-H1, omalizumab, montelukast, and systemic glucocorticoids is rarely reported in the pediatric population. There is a wide variation in the rate of remission of chronic urticaria between studies. The aim of this study is to enhance our understanding of pediatric chronic urticaria. This study enrolled 37 children with chronic urticaria aged from 0 to 18 years. Demographic parameters, medical history, clinical features, laboratory data and treatment information were collected. Children were treated with the recommended dosage of second-generation H1-antihistamines, which was increased by up to twofold. Omalizumab was added for refractory anti-H1 patients. A three-day course with systemic glucocorticoids was administered for severe exacerbations. Montelukast was administered to some children. : Wheals without angioedema were common. Chronic urticaria was spontaneous in 32 children (86.48%), inducible in 2 (5.41%), induced by a parasite in 1 and vasculitic in 2. Treatment of the potential causes of chronic urticaria was of no benefit, except for eradication of Dientamoeba fragilis. Chronic urticaria was resolved within three years in 45.9% of cases. Allergic diseases were present in nine children (24.32%) and autoimmune diseases were present in three (8.11%). All children were treated with anti-H1 at the licensed dose or at a higher dose. A partial or complete response to anti-H1 was observed in 29 (78.38%) patients. Montelukast showed no benefit. All children treated with omalizumab responded. Systemic glucocorticoids were successfully used to treat exacerbations. Our findings indicate that laboratory tests should not be routinely performed in children with chronic urticaria without clinical suspicion. However, comorbidities such as thyroid autoimmune disease and coeliac disease are suggested to be monitored over the chronic urticaria course. These clinical conditions could be diagnosed from the diagnostic framework of chronic urticaria. Increasing the dosage of anti-H1 and omalizumab was effective in children resistant to standard treatment but we still need further studies to generate a standard patient-centered treatment.
Topics: Humans; Child; Female; Male; Child, Preschool; Adolescent; Chronic Urticaria; Infant; Sulfides; Cyclopropanes; Quinolines; Acetates; Omalizumab; Histamine H1 Antagonists; Glucocorticoids; Anti-Allergic Agents; Infant, Newborn; Chronic Disease; Urticaria
PubMed: 38792886
DOI: 10.3390/medicina60050704 -
Journal of Clinical Medicine May 2024Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are...
Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV) (+440 mL at 36 months, < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety.
PubMed: 38792553
DOI: 10.3390/jcm13103013 -
Biomedicines Apr 2024In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is...
BACKGROUND
In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest.
OBJECTIVE
We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration.
METHODS
In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria.
RESULTS
According to the criteria, 39-52% of patients experienced complete remission in the first year, increasing to 51-73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization.
CONCLUSIONS
Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission.
PubMed: 38790922
DOI: 10.3390/biomedicines12050960 -
Brain Sciences Apr 2024Major depressive disorder (MDD) is frequently chronic and relapsing. The use of maintenance or continuation transcranial magnetic stimulation (TMS) has received clinical...
BACKGROUND
Major depressive disorder (MDD) is frequently chronic and relapsing. The use of maintenance or continuation transcranial magnetic stimulation (TMS) has received clinical and some research support.
OBJECTIVE
To conduct a case series study to report the outcomes of once-weekly (OW) or once-fortnightly (OF) continuation TMS in a real-life setting.
METHODS
We offered OW or OF TMS sessions to patients with MDD in remission or partial remission/relapse.
RESULTS
Ten patients received OW TMS and four received OF TMS, for 8 to 46 weeks. No patients in either group who were in remission or partial remission at baseline experienced a relapse. Improvements in HAMD6 and CGI-S scores were statistically significant or of borderline significance for the total sample and the OW group.
CONCLUSIONS
This naturalistic, open-label observational study indicates that OW TMS is effective as maintenance therapy in MDD, while also offering some support for OF TMS maintenance in preventing relapse.
PubMed: 38790394
DOI: 10.3390/brainsci14050415 -
Diabetology & Metabolic Syndrome May 2024Mesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in...
Evaluation of type 1 diabetes' partial clinical remission after three years of heterologous adipose tissue derived stromal/stem cells transplantation associated with vitamin D supplementation.
BACKGROUND
Mesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in patients with type 1 diabetes (T1D). Intervention with these agents after onset of T1D could favor the development of a remission phase, with potential clinical impact. We aimed to compare the presence of clinical remission (CR), glycemic control and daily insulin requirement at 6, 12, 18, 24 and 36 months after the diagnosis of T1D using IDAA1c in patients who received therapy with adipose tissue-derived mesenchymal stem cell (ASC) infusion and vitamin D supplementation and a control group.
METHODS
This retrospective cohort study analyzed data from the medical records of patients with T1D diagnosed between 15 and 40 years. Partial CR was defined as an IDAA1c index < 9. Patients in the intervention group received an infusion of adipose tissued-derived mesenchymal stem cells (ASCs) within 3 months after diagnosis and supplementation with 2000 IU of cholecalciferol for 1 year, started on the day following the infusion. Partial CR was also determined using the ISPAD criteria, to assess its agreement with IDAA1c.
RESULTS
A total of 28 patients were evaluated: 7 in the intervention group (group 1) and 21 in the control group (group 2). All patients in group 1 evolved with partial CR while only 46.7% of patients in group 2 had this outcome. Group 1 had a higher frequency of CR when evaluated with IDAA1c and ISPAD criteria. The mean duration of CR varied between the two criteria. Although HbA1c was similar between groups during follow-up, group 1 had a lower total daily insulin requirement (p < 0.005) at all time points. At 36 months, group 1 used 49% of the total daily insulin dose used by group 2 with similar glycemic control.
CONCLUSION
The intervention with infusion of ASC + vitamin D supplementation was associated with partial CR at 6 months. Although there were no differences in CR established by the IDAA1c and ISPAD criteria after three years of follow-up, patients who underwent intervention had nearly the half insulin requirement of controls with conventional treatment, with similar glycemic control.
TRIAL REGISTRATION
37001514.0.0000.5257.
PubMed: 38790009
DOI: 10.1186/s13098-024-01302-2 -
Medicine May 2024Inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue tumor. Many IMTs are positive for anaplastic lymphoma kinase (ALK) with ALK gene fusion; other...
INTRODUCTION
Inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue tumor. Many IMTs are positive for anaplastic lymphoma kinase (ALK) with ALK gene fusion; other gene mutations have also been reported, which indicates a key role for genetic testing and the development of target therapy to optimize treatment strategies.
PATIENT CONCERNS
We report 2 patients who obtained clinical benefits following targeted treatment with ensartinib.
DIAGNOSIS
The first patient was diagnosed as IMT, with TFG-ROS1 fusion gene mutation. The second patient was IMT harboring the ALK-STRN fusion gene mutation.
INTERVENTIONS
We performed gene testing for these 2 patients. According to the test result, both patients received ensartinib 225 mg QD as targeted therapy for a 30-day cycle.
OUTCOMES
The first patient achieved partial remission and maintained a stable state for 14.7 months. The second patient was treated for 10 months and reached complete remission after 5 months and is currently still benefiting from treatment. Treatment-related side effects were mild in both patients.
CONCLUSION
Our cases provided some new insights and approaches for the clinical diagnosis and treatment of IMT.
Topics: Humans; Female; Male; Neoplasms, Muscle Tissue; Adult; Anaplastic Lymphoma Kinase; Middle Aged; Soft Tissue Neoplasms; Antineoplastic Agents
PubMed: 38787978
DOI: 10.1097/MD.0000000000038136