-
Frontiers in Immunology 2024We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic... (Review)
Review
We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2019, resulting in complete remission. However, he was diagnosed in 2021 with several autoimmune disorders, including autoimmune hepatitis (AIH), Hashimoto's thyroiditis (HT), and autoimmune hemolytic anemia (AIHA). This is referred as multiple autoimmune syndrome (MAS), which is a rare occurrence after allo-HSCT, as previously noted in the literature. Despite being treated with glucocorticoids, cyclosporine A, and other medications, the patient did not fully recover. To address the glucocorticoid-refractory MAS, a four-week course of rituximab (RTX) at a weekly dose of 100mg was administered, which significantly improved the patient's condition. Thus, this case report underscores the importance of implementing alternative treatments in patients with post-transplant autoimmune diseases, who are glucocorticoid-refractory or glucocorticoid-dependent, and highlights the effectiveness of RTX as second-line therapy.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Male; Middle Aged; Glucocorticoids; Autoimmune Diseases; Transplantation, Homologous; Rituximab; Anemia, Hemolytic, Autoimmune; Drug Resistance
PubMed: 38707905
DOI: 10.3389/fimmu.2024.1366101 -
Orphanet Journal of Rare Diseases May 2024Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, leading to various complications and impairments in patients' health-related quality of life (HRQOL)....
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, leading to various complications and impairments in patients' health-related quality of life (HRQOL). Limited research has been conducted to evaluate the HRQOL of Chinese patients with PNH. Understanding the HRQOL in this specific population is crucial for providing effective healthcare interventions and improving patient' health outcomes. This study aimed to assess HRQOL of Chinese patients with PNH, and identify key determinants.
METHODS
A cross-sectional study was conducted during 2022 to recruit patients with PNH in China. The study population was recruited from PNH China, one of the largest public welfare PNH patient mutual aid organization in China. Data were collected via an online questionnaire including the EQ-5D-5L (5L), and social-demographic and clinical characteristics. Descriptive statistics were employed to summarize the characteristics of the participants and their HRQOL. Multiple linear and logistic regression analyses were adopted to explore key factors affecting HRQOL.
RESULTS
A total of 329 valid questionnaires were collected. The mean (SD) age of the patients was 35.3 (10.0) years, with 52.3% of them being male. The patients reported more problems in Anxiety/Depression (81.5%) and Pain/Discomfort (69.9%) dimensions compared to the other three 5L dimensions. The mean (SD) of 5L health utility score (HUS) and EQ-VAS score were 0.76 (0.21) and 62.61 (19.20), respectively. According to multiple linear regression, initial symptoms (i.e., Anemia [fatigue, tachycardia, shortness of breath, headache] and back pain) and complication of thrombosis were significant influencing factors affecting 5L HUS. Total personal income of the past year, initial symptom of hemoglobinuria and complication of thrombosis were significantly influencing factors of VAS score. Social-demographic and clinical characteristics, such as gender, income, and thrombosis, were also found to be significantly related to certain 5L health problems as well.
CONCLUSION
Our study manifested the HRQOL of PNH patients in China was markedly compromised, especially in two mental-health related dimensions, and revealed several socio-demographic and clinical factors of their HRQOL. These findings could be used as empirical evidence for enhancing the HRQOL of PNH patients in China.
Topics: Humans; Hemoglobinuria, Paroxysmal; Quality of Life; Male; Female; China; Adult; Cross-Sectional Studies; Middle Aged; Surveys and Questionnaires; Young Adult; Adolescent
PubMed: 38702811
DOI: 10.1186/s13023-024-03178-x -
BMC Oral Health May 2024Episil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in... (Comparative Study)
Comparative Study
BACKGROUND
Episil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in patients with head and neck cancer. However, reports on its use in patients with hematologic malignancies are scarce. Thus, we aimed to evaluate the efficacy of Episil for the treatment of oral mucositis in patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome.
METHODS
Between May 2018 and March 2019, a total of thirty-seven patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome who received Episil® for the treatment of oral mucositis were included in this study. All patients were treated at the Hiroshima Red Cross and Atomic-bomb Surgery Hospital. To determine the severity of oral mucositis, 22 out of the 37 patients were interviewed and compared objectively using the Common Terminology Criteria for Adverse Events, version 3.0. In addition, subjective measures of the effects of oral mucositis were assessed using an original evaluation protocol (a unique evaluation chart specific to the Department of Oral Surgery, Hiroshima Red Cross & Atomic-bomb Survivors Hospital).
RESULTS
Out of 37 participants recruited in the study, 31 (84%) described the sensation of Episil® as very good or good. Moreover, the severity of mucositis was found to decrease after the use of Episil® in seven patients out of 22 (19%), particularly in those with mucositis at multiple sites. Participants' evaluations revealed pain relief and improvement in speech and feeding functions. Participants with grade 3 mucositis reported a greater improvement in pain relief, speech, and feeding functions than those with grade 2 mucositis.
CONCLUSIONS
This study suggests the efficacy of Episil® in treating oral mucositis in patients with hematologic malignancies, particularly in those with oral mucositis at multiple sites. In addition to pain relief, Episil® may improve speech and feeding functions.
Topics: Humans; Stomatitis; Male; Hematologic Neoplasms; Female; Middle Aged; Aged; Adult; Treatment Outcome; Aged, 80 and over
PubMed: 38698387
DOI: 10.1186/s12903-024-04233-6 -
Blood May 2024
Kewan T, Bahaj W, Durmaz A, et al. Validation of the Molecular International Prognostic Scoring System in patients with myelodysplastic syndromes. Blood. 2023;141(14):1768-1772.
Topics: Humans; Myelodysplastic Syndromes; Prognosis
PubMed: 38696199
DOI: 10.1182/blood.2024024464 -
JAAD Case Reports May 2024
PubMed: 38689864
DOI: 10.1016/j.jdcr.2024.02.016 -
Journal of Translational Medicine Apr 2024Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring...
Measurable residual disease monitoring by ddPCR in the early posttransplant period complements the traditional MFC method to predict relapse after HSCT in AML/MDS: a multicenter retrospective study.
BACKGROUND
Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously.
METHODS
Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse.
RESULTS
Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P < 0.001) and lower rates of relapse-free survival (RFS, 55.5% vs. 83.7%, P < 0.001) and overall survival (OS, 60.5% vs. 90.5%, P < 0.001). In multivariate analysis, ddPCR-MRD positivity of non-DTA genes was an independent adverse predictor for CIR (hazard ratio [HR], 4.02; P < 0.001), RFS (HR, 2.92; P = 0.002) and OS (HR, 3.12; P = 0.007). Moreover, the combination of ddPCR with multiparameter flow cytometry (MFC) can further accurately identify patients at high risk of relapse (F+/M+, HR, 22.44; P < 0.001, F+/M-, HR, 12.46; P < 0.001 and F-/M+, HR, 4.51; P = 0.003).
CONCLUSION
ddPCR-MRD is a feasible approach to predict relapse after allo-HSCT in AML/MDS patients with non-DTA genes and is more accurate when combined with MFC.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT06000306. Registered 17 August 2023 -Retrospectively registered ( https://clinicaltrials.gov/study/NCT06000306?term=NCT06000306&rank=1 ).
Topics: Humans; Hematopoietic Stem Cell Transplantation; Leukemia, Myeloid, Acute; Male; Female; Neoplasm, Residual; Middle Aged; Adult; Retrospective Studies; Myelodysplastic Syndromes; Recurrence; Polymerase Chain Reaction; Young Adult; Adolescent; Aged; Mutation
PubMed: 38689269
DOI: 10.1186/s12967-024-05114-w -
Molecular Cell May 2024Mutations in the RNA splicing factor gene SF3B1 are common across hematologic and solid cancers and result in widespread alterations in splicing, yet there is currently...
Mutations in the RNA splicing factor gene SF3B1 are common across hematologic and solid cancers and result in widespread alterations in splicing, yet there is currently no therapeutic means to correct this mis-splicing. Here, we utilize synthetic introns uniquely responsive to mutant SF3B1 to identify trans factors required for aberrant mutant SF3B1 splicing activity. This revealed the G-patch domain-containing protein GPATCH8 as required for mutant SF3B1-induced splicing alterations and impaired hematopoiesis. GPATCH8 is involved in quality control of branchpoint selection, interacts with the RNA helicase DHX15, and functionally opposes SURP and G-patch domain containing 1 (SUGP1), a G-patch protein recently implicated in SF3B1-mutant diseases. Silencing of GPATCH8 corrected one-third of mutant SF3B1-dependent splicing defects and was sufficient to improve dysfunctional hematopoiesis in SF3B1-mutant mice and primary human progenitors. These data identify GPATCH8 as a novel splicing factor required for mis-splicing by mutant SF3B1 and highlight the therapeutic impact of correcting aberrant splicing in SF3B1-mutant cancers.
Topics: RNA Splicing Factors; Humans; Animals; Phosphoproteins; Mutation; Hematologic Neoplasms; Mice; RNA Splicing; DEAD-box RNA Helicases; Hematopoiesis; HEK293 Cells; Introns; RNA Helicases; RNA-Binding Proteins
PubMed: 38688280
DOI: 10.1016/j.molcel.2024.04.006 -
Cureus Mar 2024Patients with myelodysplastic syndrome (MDS) often need platelet transfusions to address thrombocytopenia. The risk of alloimmunization, particularly in Rhesus (Rh)...
Patients with myelodysplastic syndrome (MDS) often need platelet transfusions to address thrombocytopenia. The risk of alloimmunization, particularly in Rhesus (Rh) incompatibility between donors and recipients during platelet transfusions, is heightened, especially with whole blood-derived pooled platelets as opposed to apheresis platelets. Although the occurrence of alloimmunization from platelet transfusions is minimal, there is an ongoing debate about whether Rh immune globulin (RhIg) should be administered to Rhesus D (RhD)-negative recipients of RhD-positive platelet units. We present a unique case of anti-D alloimmunization in a 56-year-old patient with underlying MDS following multiple platelet transfusions but never received packed cell transfusion or anti-D immunoglobulin. Some studies advocate for RhIg administration in specific scenarios and for certain patient populations. This case underscores the importance of considering Rhesus compatibility or administering anti-D immunoglobulin in cases where frequent platelet transfusions are required.
PubMed: 38681415
DOI: 10.7759/cureus.57165 -
Cancers Apr 2024Myelodysplastic syndromes/neoplasms (MDSs) encompass a range of hematopoietic malignancies, commonly affecting elderly individuals. Molecular alterations in the... (Review)
Review
Myelodysplastic syndromes/neoplasms (MDSs) encompass a range of hematopoietic malignancies, commonly affecting elderly individuals. Molecular alterations in the hematopoietic stem cell compartment drive disease pathogenesis. Recent advancements in genomic profiling have provided valuable insights into the biological underpinnings of MDSs and have expanded therapeutic options, particularly for specific molecularly defined subgroups. This review highlights the diagnostic principles, classification updates, prognostic stratification systems, and novel treatments, which could inform future clinical trials and enhance the management of adult MDS patients, particularly for specific molecularly defined subgroups.
PubMed: 38672645
DOI: 10.3390/cancers16081563 -
Cancers Apr 2024Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. It is diagnosed in patients with a platelet count below 100,000 per... (Review)
Review
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. It is diagnosed in patients with a platelet count below 100,000 per cubic millimeter in whom other causes of thrombocytopenia have been ruled out, and its diagnosis is generally one of exclusion. Clinical manifestations of patients may vary from asymptomatic disease to mild mucocutaneous or life-threatening bleeding. Glucocorticoids are used as first-line treatment for ITP, while other second-line medications, mainly thrombopoietin-receptor agonists (TPO-RA) and rituximab, are given to patients in whom ITP does not remit, or relapses soon after glucocorticoid treatment. Refractoriness of ITP strongly questions its diagnosis and necessitates a thorough clinical and laboratory work-up to decide whether that is the case of refractory ITP or a misdiagnosis. The aim of this review is to summarize the conditions associated with isolated thrombocytopenia and highlight the characteristics of confusing cases. Even though the case of a myelodysplastic syndrome presented with isolated thrombocytopenia (MDS-IT) is relatively rare and not well-established in the literature, it constitutes one of the most predominant misdiagnoses of refractory ITP. MDS-IT patients are thought to present with multilineage dysplasia, normal karyotype and low risk prognostic score, based on IPSS-R. It has been shown that a significant proportion of MDS-IT patients are misdiagnosed as having the more common ITP. Therefore, it is crucial that in confusing cases of persistent thrombocytopenia a detailed diagnostic work-up is applied-including evaluation of peripheral-blood smear, bone marrow examination and cytogenetic testing-to avoid unnecessary therapy delay.
PubMed: 38672544
DOI: 10.3390/cancers16081462