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1.
Blood Adv ; 7(9): 1672-1681, 2023 05 09.
Article in English | MEDLINE | ID: mdl-36375042

ABSTRACT

Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders that are challenging with regard to diagnosis and clinical management. To study the similarities and differences between these disorders, we undertook a multicenter international study of one of the largest case series (CNL, n = 24; aCML, n = 37 cases, respectively), focusing on the clinical and mutational profiles (n = 53 with molecular data) of these diseases. We found no differences in clinical presentations or outcomes of both entities. As previously described, both CNL and aCML share a complex mutational profile with mutations in genes involved in epigenetic regulation, splicing, and signaling pathways. Apart from CSF3R, only EZH2 and TET2 were differentially mutated between them. The molecular profiles support the notion of CNL and aCML being a continuum of the same disease that may fit best within the myelodysplastic/myeloproliferative neoplasms. We identified 4 high-risk mutated genes, specifically CEBPA (ß = 2.26, hazard ratio [HR] = 9.54, P = .003), EZH2 (ß = 1.12, HR = 3.062, P = .009), NRAS (ß = 1.29, HR = 3.63, P = .048), and U2AF1 (ß = 1.75, HR = 5.74, P = .013) using multivariate analysis. Our findings underscore the relevance of molecular-risk classification in CNL/aCML as well as the importance of CSF3R mutations in these diseases.


Subject(s)
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative , Leukemia, Neutrophilic, Chronic , Myelodysplastic-Myeloproliferative Diseases , Humans , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/diagnosis , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/genetics , Leukemia, Neutrophilic, Chronic/diagnosis , Leukemia, Neutrophilic, Chronic/genetics , Epigenesis, Genetic , Myelodysplastic-Myeloproliferative Diseases/genetics , Mutation
2.
Article in English | MEDLINE | ID: mdl-15024360

ABSTRACT

OBJECTIVES: The aim of the study was to determine the recurrence rate of denture stomatitis and persistence of Candida in 22 patients (5 male and 17 female, mean age 71 years) over a 3-year period. STUDY DESIGN: Denture hygiene practice, denture cleanliness, and the presence of palatal erythema were assessed for each patient at the start of the study (baseline). The oral cavity was sampled for yeasts by imprint culture and denture discs. Ten patients received a capsular form of itraconazole (100 mg twice daily for 15 days) and 12 patients were provided with 100 mg of itraconazole in the form of a mouthwash (10 mL twice daily), which was then swallowed. No further antifungal treatment was administered to any of the patients. Clinical and microbiological assessments were repeated for each patient at 6 months and 3 years after the original appointment. Yeasts were identified by colony color on CHROMagar Candida, germ-tube formation, and API-32C profiling. Selected isolates were then typed by inter-repeat polymerase chain reaction (IR PCR). RESULTS: Candida albicans was isolated at baseline from all patients either alone (12 patients) or in combination with another species (10 patients). Other yeast species recovered were C glabrata (5 patients), C tropicalis (1 patient), C guilliermondii (1 patient), C krusei (1 patient), C parapsilosis (1 patient), C kefyr (1 patient), and Saccharomyces cerevisiae (2 patients). Candida albicans and/or C glabrata were recovered from 11 of the 22 patients after 6 months or 3 years. A complete and consistent change of yeast species from baseline was observed in 6 patients after 6 months and at 3 years. The remaining 5 patients were yeast-free at the follow-up assessments. PCR fingerprinting of C albicans and C glabrata indicated strain persistence over 6 months in 10 patients and in 4 patients after 3 years. A switch in strain type occurred for 1 patient after 6 months and for 3 patients after 3 years. CONCLUSIONS: The recurrence of denture stomatitis in patients who maintained a high standard of denture cleanliness was low. Although itraconazole was beneficial in reducing the fungal load, there may be strain persistence or subsequent recolonization of the oral cavity by a broader range of potentially less sensitive yeast species.


Subject(s)
Antifungal Agents/therapeutic use , Candida/drug effects , Candidiasis, Oral/drug therapy , Itraconazole/therapeutic use , Stomatitis, Denture/drug therapy , Aged , Aged, 80 and over , Antifungal Agents/administration & dosage , Candida/classification , Candida albicans/growth & development , Candida glabrata/growth & development , Candida tropicalis/growth & development , Capsules , Chromogenic Compounds , Denture Cleansers/therapeutic use , Female , Follow-Up Studies , Humans , Itraconazole/administration & dosage , Male , Middle Aged , Mouthwashes/therapeutic use , Oral Hygiene , Recurrence , Stomatitis, Denture/microbiology
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