-
Pediatric Investigation Jun 2024It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A...
IMPORTANCE
It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor-titer ≥200 Bethesda Units (BU)/mL (LD-ITI-IS regimen) and LD-ITI combining with IS when SHA patients had inhibitor-titer ≥40 BU/mL (LD-ITI-IS regimen).
OBJECTIVE
To compare the efficacy of the LD-ITI-IS regimen with that of the LD-ITI-IS regimen for SHA patients with high-titer inhibitors.
METHODS
A prospective cohort study on patients receiving LD-ITI-IS compared to those receiving LD-ITI-IS from January 2021 to December 2023. Both received LD-ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD-ITI-IS regimen and ≥40 BU/mL in the LD-ITI-IS regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected.
RESULTS
We enrolled 30 patients on LD-ITI-IS and 64 patients on LD-ITI-IS, with similar baseline clinical characteristics. A lower IS-use rate was discovered in the LD-ITI-IS regimen compared to the LD-ITI-IS regimen (30.0% vs. 62.5%). The two regimens (LD-ITI-IS vs. LD-ITI-IS) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD-ITI-IS than for LD-ITI-IS (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor-titer 40-199 BU/mL, 10 non-IS-using (on LD-ITI-IS regimen) and 28 IS-using (on LD-ITI-IS regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months).
INTERPRETATION
In LD-ITI, IS are not necessary for inhibitor titer <200 BU/mL.
PubMed: 38910855
DOI: 10.1002/ped4.12429 -
BMC Pediatrics Jun 2024Serum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly...
BACKGROUND
Serum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly attributed to antibiotics, anticonvulsants, and anti-inflammatory agents.
CASE PRESENTATION
A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. She was evaluated by her pediatrician and started on a 7-day course of prednisone, as well as antihistamines. Her CBC, basic metabolic panel, liver function panel, Lyme titers, and urinalysis were all within normal limits. With concern for hypersensitivity reaction to medication, all medications were discontinued. Nine days after symptom onset, the patient was evaluated by an allergist, who confirmed her presentation was consistent with serum sickness-like reaction. Her symptoms resolved, and her medications were re-introduced sequentially over several months. Restarting UQora, however, triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free.
CONCLUSIONS
This case report describes the first documented case of serum sickness-like reaction caused by UQora (active ingredient D-mannose). D-mannose is a monosaccharide, and it is frequently promoted to prevent urinary tract infections. While the clinical features and timeline in this case were typical of serum sickness-like reaction, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of serum sickness-like reaction and the importance of prompt identification and management to enhance patient safety. Further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.
Topics: Humans; Female; Serum Sickness; Adolescent
PubMed: 38909179
DOI: 10.1186/s12887-024-04753-8 -
Oncology Letters Aug 2024Primary mantle cell lymphoma (MCL) in the gastrointestinal tract is rare, accounting for 4-9% of all reported cases of gastrointestinal non-Hodgkin lymphoma....
Primary mantle cell lymphoma (MCL) in the gastrointestinal tract is rare, accounting for 4-9% of all reported cases of gastrointestinal non-Hodgkin lymphoma. Furthermore, involvement of the entire gastrointestinal tract in MCL is rare. The present report describes an example of MCL characterized by numerous diffuse polypoid lesions along the whole digestive tract. In particular, there was a focus on the endoscopic presentation of the digestive tract. The patient initially received a treatment regimen of rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone. After two cycles of treatment, the regimen was changed to rituximab combined with etoposide, oxaliplatin and ifosfamide, with the addition of ibrutinib capsules. Patients with MCL have a poor prognosis; however, complete response can be achieved after treatment.
PubMed: 38903699
DOI: 10.3892/ol.2024.14496 -
Frontiers in Immunology 2024Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other... (Review)
Review
Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other causes including bone marrow suppression induced by chemotherapeutic agents, infection, and progression of cancer; drug-induced thrombocytopenia can easily be misdiagnosed or overlooked. Here, we present a case of an ovarian cancer patient with a history of mixed connective tissue disease who underwent surgery followed by treatment with paclitaxel, cisplatin, and bevacizumab. The patient developed acute isolated thrombocytopenia after the sixth cycle. Serum antiplatelet antibody testing revealed antibodies against glycoprotein IIb. After we analyzed the whole therapeutic process of this patient, drug-induced immune thrombocytopenia was assumed, and bevacizumab was conjectured as the most probable drug. Thrombocytopenia was ultimately successfully managed using recombinant human thrombopoietin, prednisone, and recombinant human interleukin-11. We provide a summary of existing literature on immune thrombocytopenia induced by bevacizumab and discuss related mechanisms and triggers for drug-induced immune thrombocytopenia. The present case underscores the potential of bevacizumab to induce immune-mediated thrombocytopenia, emphasizing the need for heightened vigilance towards autoimmune diseases or an autoimmune-activated state as plausible triggers for rare drug-induced immune thrombocytopenia in cancer therapy.
Topics: Female; Humans; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Mixed Connective Tissue Disease; Ovarian Neoplasms; Purpura, Thrombocytopenic, Idiopathic
PubMed: 38903494
DOI: 10.3389/fimmu.2024.1382964 -
Scientific Reports Jun 2024Previous studies showed tacrolimus monotherapy and dual therapy with tacrolimus and prednisone as effective treatment modalities in managing membranous nephropathy.... (Comparative Study)
Comparative Study
Previous studies showed tacrolimus monotherapy and dual therapy with tacrolimus and prednisone as effective treatment modalities in managing membranous nephropathy. However, few studies have compared these therapeutic regimens. The patients were divided into two groups based on the treatment regimen: (1) tacrolimus and prednisone dual therapy (T + P group, n = 67) treatment group; and (2) tacrolimus monotherapy (T group, n = 65) or the control group. Propensity matching method and subgroup analysis to eliminate the bias in the relationship between the treatment regimen and the outcomes. The mean remission times were 20.33 ± 2.75 weeks at T group and 9.50 ± 1.81 weeks at T + P group. The T group had a remission rates of 73.33, 76.66 and 66.66% at 12weeks, 24weeks and 48weeks, while the T + P group had a remission rate of 81.66, 86.66, 91.66%; At the follow-up of 48 weeks, the relapse rate for the T group was 21.66%, and that for the T + P group was 5%. The anti-PLA2R ab is positive and therapy may be the independent risk factors for predicting remission. Tacrolimus and low-dose prednisone dual therapy is efficacious in managing MN and lowers the recurrence rate in clinical practice.
Topics: Humans; Tacrolimus; Glomerulonephritis, Membranous; Prednisone; Male; Female; Middle Aged; Retrospective Studies; Drug Therapy, Combination; Immunosuppressive Agents; Adult; Treatment Outcome; Aged; Remission Induction
PubMed: 38902302
DOI: 10.1038/s41598-024-64661-w -
The New England Journal of Medicine Jun 2024The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but...
BACKGROUND
The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown.
METHODS
We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs. A phase 2 expansion in patients with germinal-center B-cell (GCB) and non-GCB DLBCL was performed. ViPOR was administered every 21 days for six cycles.
RESULTS
In phase 1b of the study, involving 20 patients (10 with DLBCL), a single dose-limiting toxic effect of grade 3 intracranial hemorrhage occurred, a result that established venetoclax at a dose of 800 mg as the recommended phase 2 dose. Phase 2 included 40 patients with DLBCL. Toxic effects that were observed among all the patients included grade 3 or 4 neutropenia (in 24% of the cycles), thrombocytopenia (in 23%), anemia (in 7%), and febrile neutropenia (in 1%). Objective responses occurred in 54% of 48 evaluable patients with DLBCL, and complete responses occurred in 38%; complete responses were exclusively in patients with non-GCB DLBCL and high-grade B-cell lymphoma with rearrangements of and or (or both). Circulating tumor DNA was undetectable in 33% of the patients at the end of ViPOR therapy. With a median follow-up of 40 months, 2-year progression-free survival and overall survival were 34% (95% confidence interval [CI], 21 to 47) and 36% (95% CI, 23 to 49), respectively.
CONCLUSIONS
Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.).
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Female; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Sulfonamides; Aged; Male; Bridged Bicyclo Compounds, Heterocyclic; Lenalidomide; Piperidines; Adult; Antibodies, Monoclonal, Humanized; Prednisone; Adenine; Aged, 80 and over; Recurrence; Pyrazoles; Pyrimidines; Molecular Targeted Therapy; Progression-Free Survival
PubMed: 38899693
DOI: 10.1056/NEJMoa2401532 -
Kidney International Reports Jun 2024Postmarketing data on outcomes of avacopan use in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are lacking.
INTRODUCTION
Postmarketing data on outcomes of avacopan use in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are lacking.
METHODS
We performed a multicenter retrospective analysis of 92 patients with newly diagnosed or relapsing AAV who received therapy with avacopan. The coprimary outcome measures were clinical remission at 26 and 52 weeks. We use descriptive statistics and univariate logistic regression to assess outcomes and predictors of remission, respectively.
RESULTS
Of the 92 patients, 23% (n = 21) had a baseline estimated glomerular filtration rate (eGFR) < 15 ml/min per 1.73 m and 10% on kidney replacement therapy at baseline. Among those with kidney involvement, mean (SD) enrollment eGFR was 33 (27) ml/min per 1.73 m with a mean (SD) change of +12 (25) and +20 (23) ml/min per 1.73 m at weeks 26 and 52, respectively. In addition to avacopan, 47% of patients received combination therapy of rituximab and low-dose cyclophosphamide, and 14% of patients received plasma exchange (PLEX). After induction, the median (interquartile range [IQR]) time to start avacopan was 3.6 (2.1-7.7) weeks, and the median time to discontinue prednisone after starting avacopan was 5.6 (3.3-9.5) weeks. Clinical remission was achieved in 90% of patients at week 26 and 84% of patients at week 52. Of the patients, 20% stopped avacopan due to adverse events, with the most common being elevated serum aminotransferases (4.3%).
CONCLUSION
A high rate of remission and an acceptable safety profile were observed with the use of avacopan in the treatment of AAV in this postmarketing analysis, including the populations excluded from the ADVOCATE trial.
PubMed: 38899183
DOI: 10.1016/j.ekir.2024.03.022 -
Revista Iberoamericana de Micologia Jun 2024Paracoccidioidomycosis is a neglected tropical disease caused by fungi of the genus Paracoccidioides. A wide range of symptoms is related to the disease; however, lungs...
BACKGROUND
Paracoccidioidomycosis is a neglected tropical disease caused by fungi of the genus Paracoccidioides. A wide range of symptoms is related to the disease; however, lungs and skin are the sites predominantly affected. The disease is mostly seen in people living in rural areas in Latin America.
CASE REPORT
We present a pediatric case of severe disseminated paracoccidioidomycosis that slowly responded to the antifungal treatment. Within three months, symptoms evolved into hepatosplenomegaly, necrotic cervical and abdominal lymph nodes, and splenic abscess. Clinical response to amphotericin B deoxycholate and itraconazole was slow, resulting in pleural and peritoneal cavity effusions, heart failure and shock. Amphotericin B deoxycholate was replaced by the liposomal formulation, with no response. Subsequently, prednisone was added to the treatment, which led to improvement in the clinical response. Serological Paracoccidioides antibody titers were atypical, with very low titers in the critical phase and significant increase during the convalescence phase. The infection was finally cleared up with amphotericin B deoxycholate, liposomal amphotericin B and the use of corticosteroids. Paracoccidioidomycosis serology was non-reactive two years post-discharge.
CONCLUSIONS
Due to the intense inflammatory response triggered by Paracoccidioides cells, giving low-dose prednisone for a short period of time modulated the inflammatory response and supported antifungal treatment.
PubMed: 38897873
DOI: 10.1016/j.riam.2024.04.001 -
EJHaem Jun 2024Multiple myeloma remains an incurable cancer mostly affecting older adults and is characterized by a series of remission inductions and relapses. This study aims to...
Long-term follow-up of outcomes including progression-free survival 2 in patients with transplant-ineligible multiple myeloma in the real-world practice: A multi-institutional report from the Canadian Myeloma Research Group (CMRG) database.
Multiple myeloma remains an incurable cancer mostly affecting older adults and is characterized by a series of remission inductions and relapses. This study aims to evaluate the outcomes in newly diagnosed transplant-ineligible patients using bortezomib/lenalidomide-based regimens in the Canadian real world as well as their outcomes in the second line. The Canadian Myeloma Research Group Database (CMRG-DB) is a national database with input from multiple Canadian Centres with now up to 8000 patients entered. A total of 1980 transplant ineligible patients were identified in the CMRG-DB between the years of 2007-2021. The four most commonly used induction regimens are bortezomib/melphalan/prednisone (VMP) (23%), cyclophosphamide/bortezomib/dexamethasone (CyBorD) (47%), lenalidomide/dexamethasone (Rd) (24%), and bortezomib/lenalidomide/dexamethasone (VRd) (6%). After a median follow-up of 30.46 months (0.89-168.42), the median progression-free survival (mPFS) and median overall survival (mOS) of each cohort are 23.5, 22.9, 34.0 months, and not reached (NR) and 64.1, 51.1, 61.5 months, and NR respectively. At the time of data cut-off, 1128 patients had gone on to second-line therapy. The mPFS2 based on first-line therapy, VMP, CyBorD, Rd, and VRd is 53.3, 48.4, 62.7 months, and NR respectively. The most common second-line regimens are Rd (47.4%), DRd (12.9%), CyBorD (10.3%), and RVd (8.9%) with a mPFS and a mOS of 17.0, 31.1, 15.4, and 14.0 months and 34.7, NR, 47.6, 33.4 months, respectively. This study represents the real-world outcomes in newly diagnosed transplant-ineligible myeloma patients in Canada. The spectra of therapy presented here reflect the regimens still widely used around the world. While this is sure to change with anti-CD38 monoclonal antibodies now reflecting a new standard of care in frontline therapy, this cohort is reflective of the type of multiple myeloma patient currently experiencing relapse in the real-world setting.
PubMed: 38895063
DOI: 10.1002/jha2.894 -
CNS Neuroscience & Therapeutics Jun 2024We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+)...
BACKGROUND
We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG).
METHODS
This single-center prospective cohort study was based on patients from an MG registry study in China and conducted from February 10, 2021 to March 31, 2022. Adult refractory patients with AChR-Ab+ gMG were assigned to tocilizumab or conventional immunotherapy groups. The primary efficacy outcome was the mean difference of MG activities of daily living (MG-ADL) change at weeks 4, 8, 12, 16, 20, 24 corresponding to that at the baseline between the two groups. A generalized estimating equation model was used for the primary outcome analysis. Safety was assessed based on adverse events.
RESULTS
Of 34 eligible patients, 20 (mean [standard deviation] age, 53.8 [21.9] years; 12 [60.0%] female) received tocilizumab and 14 received conventional immunotherapy (45.8 [18.0] years; 8 [57.1%] female). The tocilizumab group had greater reduction in MG-ADL score at week 4 (adjusted mean difference, -3.4; 95% CI, -4.7 to -2.0; p < 0.001) than the conventional immunotherapy group, with significant differences sustained through week 24 (adjusted mean difference, -4.5; 95% CI, -6.4 to -2.6; p < 0.001). At week 24, the proportion of patients achieving higher levels of MG-ADL (up to 7-point reduction) and QMG (up to 11-point reduction) scores improvement was significantly greater with tocilizumab. Tocilizumab had acceptable safety profiles without severe or unexpected safety issues.
CONCLUSION
Tocilizumab is safe and effective in improving the MG-ADL score and reducing prednisone dose in refractory AChR-Ab+ gMG, suggesting tocilizumab has the potential to be a valuable therapeutic option for such patients.
Topics: Humans; Antibodies, Monoclonal, Humanized; Female; Middle Aged; Male; Myasthenia Gravis; Adult; Aged; Prospective Studies; Treatment Outcome; Cohort Studies; Activities of Daily Living; Immunotherapy; Registries
PubMed: 38894580
DOI: 10.1111/cns.14793