tretinoin and Purpura--Thrombocytopenic--Idiopathic

All-trans retinoic acid (ATRA) application is a novel treatment approach for primary immune thrombocytopenia (ITP). This study aimed to evaluate the efficacy and safety of ATRA in the treatment of ITP. The databases of PubMed (MEDLINE), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Internet were searched on August 5, 2022, to find randomized controlled trials (RCTs) and observational studies. Five observational studies and four RCTs from China were included, and 760 Chinese patients were analyzed. In the five observational studies, the pooled overall response rate (ORR) and complete response rate (CRR) were 59.5% (95% confidence interval [CI], 52.4-66.4%) and 20.6% (95% CI, 14.3-27.6%), respectively. In the selected four RCTs, the pooled odds ratios for sustained response rate, ORR, and CRR were 3.00 (95% CI, 1.97-4.57; P < 0.01), 3.21 (95% CI, 2.15-4.78; P < 0.01), and 2.12 (95% CI, 1.17-3.86; P = 0.01), respectively. ATRA was associated with a reduction in relapse rate and salvage treatment rate (odds ratio, 0.30; 95% CI, 0.18-0.50; P < 0.01; 0.36; 95% CI, 0.23-0.56; P < 0.01, respectively). The pooled odds ratios for grade 1-2 dry skin, headache (or dizziness), and rash acneiform were 49.99 (95% CI, 16.05-155.67; P < 0.01), 1.75 (95% CI, 0.98-3.12; P = 0.06), and 0.37 (95% CI, 0.10-1.34; P = 0.13), respectively. This study suggests that ATRA may significantly improve the initial and long-term response of patients with ITP.

Topics: China; Chronic Disease; Humans; Purpura, Thrombocytopenic, Idiopathic; Remission Induction; Tretinoin

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.

Topics: Adrenal Cortex Hormones; Adult; Antineoplastic Agents; Drug Resistance; Drug Therapy, Combination; Female; Humans; Immunologic Factors; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Recurrence; Rituximab; Secondary Prevention; Tretinoin

Primary immune thrombocytopenia is a severe bleeding disorder. About 50-85% of patients achieve initial remission from first-line therapies, but optimal second-line treatment remains a challenge. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haemopoiesis, making it a possible treatment option. We aimed to evaluate the efficacy and safety of ATRA plus danazol versus danazol in non-splenectomised patients with corticosteroid-resistant or relapsed primary immune thrombocytopenia.. We did a multicentre, randomised, open-label, phase 2 study of adult patients (≥18 years) with primary immune thrombocytopenia from five different tertiary medical centres in China. Those eligible were non-splenectomised, resistant to corticosteroid treatment or relapsed, and had a platelet count less than 30 × 10. From June 1, 2012, to July 1, 2016, we screened 130 patients for eligibility; 34 were excluded and 96 were randomly assigned. 93 patients were included in the modified intention-to-treat analysis: 45 in the ATRA plus danazol group and 48 in the danazol group. At the 12-month follow-up, sustained response was achieved more frequently in patients receiving ATRA plus danazol than in those receiving danazol monotherapy (28 [62%] of 45 vs 12 [25%] of 48; odds ratio 4·94, 95% CI 2·03-12·02, p=0·00037). Only two grade 3 adverse events were reported: one (2%) patient receiving ATRA plus danazol with dry skin, and one (2%) patient receiving danazol monotherapy with liver injury. There was no grade 4 or worse adverse event or treatment-related death in either group.. Patients with primary immune thrombocytopenia given ATRA plus danazol had a rapid and sustained response compared with danazol monotherapy. This finding suggests that ATRA represents a promising candidate for patients with corticosteroid-resistant or relapsed primary immune thrombocytopenia.. National Natural Science Foundation of China, Beijing Natural Science Foundation, Beijing Municipal Science and Technology Commission, and the National Key Research and Development Program of China.

Topics: Adult; Danazol; Drug Therapy, Combination; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Odds Ratio; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Retreatment; Treatment Outcome; Tretinoin; Young Adult

Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. In adults, ITP is more likely to be chronic, requiring individualised treatment and management. Corticosteroids and splenectomy are the most common therapy for ITP. However, these routine approaches failed in these patients with chronic ITP. The aim of this study was to evaluate the efficacy of immunomodulatory therapy with all-trans retinoid acid (ATRA) in adult patients with chronic ITP.. ATRA therapy was applied in a total of 35 patients with chronic ITP who failed with standard dose corticosteroids and/or splenectomy. The response ratio and the change of the T cell subsets including Th1, Th2, Th17 and Treg, were evaluated.. Complete response and overall response were observed in 10 (28.6%) and 19 patients (54.3%), respectively. Compared with the control group, a significant decreased level of Treg cells, IL-10 and Foxp3 expression were found in ITP patients. ATRA therapy could significantly increase the percentage of Treg cell, IL-10 level and Foxp3 expression.. Our findings indicate that ATRA therapy could induce significant changes of Treg cells to induce response in patients with chronic ITP.

Topics: Adult; Chronic Disease; Female; Humans; Immunologic Factors; Interleukin-10; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Tretinoin

Topics: Dexamethasone; Drug Repositioning; Glucocorticoids; Humans; Immunologic Factors; Purpura, Thrombocytopenic, Idiopathic; Treatment Outcome; Tretinoin

Topics: Agammaglobulinaemia Tyrosine Kinase; Humans; Immunologic Factors; Platelet Count; Protein Kinase Inhibitors; Purpura, Thrombocytopenic, Idiopathic; Receptors, IgG; Receptors, Thrombopoietin; Signal Transduction; Syk Kinase; Tretinoin

Enhanced peripheral complement activation has long been considered as one of the major pathogenic elements of immune thrombocytopenia. A dysfunctional bone marrow microenvironment, especially with regards to mesenchymal stem cells, has been observed in patients with immune thrombocytopenia. However, the potential role of the complement system in the dysfunctional bone marrow microenvironment remains poorly understood. In this study, bone marrow samples from patients with immune thrombocytopenia were divided into two groups based on whether or not complement components were deposited on the surfaces of their mesenchymal stem cells. The mesenchymal cells from the group with complement deposition were less numerous, dysfunctional, had a reduced capacity to proliferate, and showed increased apoptosis as well as abnormal secretion of interleukin-1β and C-X-C motif chemokine ligand 12.

Topics: Animals; Apoptosis; Bone Marrow; Cell Differentiation; Complement Activation; Complement System Proteins; Disease Models, Animal; Gene Expression Profiling; Humans; Interleukin-1beta; Mesenchymal Stem Cells; Mice; Models, Biological; Protective Agents; Purpura, Thrombocytopenic, Idiopathic; Transcriptome; Tretinoin

Essentials M1/M2 imbalance is involved in many autoimmune diseases, and could be restored. The expressions and functions of M1 and M2 were investigated in an in vitro culture system. A preferred M1 polarization is involved in the pathogenesis of immune thrombocytopenia (ITP). High-dose dexamethasone or all-trans-retinoic acid restores M1/M2 balance in ITP patients.. Background Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune tolerance in antigen-presenting cells and cross-communication between antigen-presenting cells and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into proinflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and have diverse immunologic functions. Objectives To investigate the M1/M2 imbalance in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans-retinoic acid (ATRA) could restore this imbalance. Methods The numbers of M1 and M2 macrophages in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence. Monocyte-derived macrophages were cultured and induced with cytokines and drugs. The expression of M1 and M2 markers and functions of M1 and M2 macrophages before and after modulation by HD-DXM or ATRA were evaluated with flow cytometry and ELISA. Results There was preferred M1 polarization in ITP spleens as compared with healthy controls. Monocyte-derived macrophages from ITP patients had increased expression of M1 markers and impaired immunosuppressive functions. Either HD-DXM or ATRA corrected this imbalance by decreasing the expression of M1 markers and increasing the expression of M2 markers. Moreover, HD-DXM-modulated or ATRA-modulated macrophages suppressed both CD4

Topics: Adolescent; Adult; Aged; Biomarkers; Case-Control Studies; CD8-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Coculture Techniques; Cytokines; Dexamethasone; Female; Humans; Immunologic Factors; Lymphocyte Activation; Macrophage Activation; Macrophages; Male; Middle Aged; Phagocytosis; Phenotype; Purpura, Thrombocytopenic, Idiopathic; Spleen; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Treatment Outcome; Tretinoin; Young Adult

Topics: Adult; Danazol; Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Tretinoin