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1.
Ann Hematol ; 101(6): 1163-1172, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35412083

RESUMEN

The thrombopoietin mimetic eltrombopag (EPAG) is efficacious in clinical trials of newly diagnosed moderate (M), severe (S) and very severe (vS) aplastic anaemia (AA). Its use in routine practice and resource-constrained settings is not well described. Twenty-five men and 38 women at a median age of 54 (18-86) years with newly diagnosed AA treated consecutively in a 7-year period with EPAG (N = 6), EPAG/cyclosporine (CsA) (N = 33) and EPAG/CsA/anti-thymocyte globulin (ATG) (N = 24) were analyzed. Because EPAG was not reimbursed, peak doses ranged from 25 to 200 mg/day depending on affordability. EPAG/CsA-treated patients were older (median age: 61 years) with less severe AA (MAA, N = 15; SAA, N = 14; vSAA, N = 4), whereas EPAG/CsA/ATG-treated patients were younger (median age: 44 years) with more severe AA (MAA, N = 2; SAA, N = 12, vSAA, N = 10). The overall/trilineage response rates were 83%/50% for EPAG-treated patients; 79%/42% for EPAG/CsA-treated patients and 75%/63% for EPAG/CsA/ATG-treated patients. Adverse events included grade 1 liver derangement (N = 7) and grade 1 dyspepsia (N = 3). The 5-year overall survivals/failure-free survivals were 62%/80% for the entire cohort; 55%/75% for EPAG/CsA-treated patients and 82%/78% for EPAG/CsA/ATG-treated patients. EPAG showed robust efficacy in AA in routine practice. However, EPAG dosage and combinations remain to be optimized for AA of different severities.


Asunto(s)
Anemia Aplásica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Aplásica/inducido químicamente , Anemia Aplásica/tratamiento farmacológico , Suero Antilinfocítico/uso terapéutico , Benzoatos/efectos adversos , Ciclosporina/uso terapéutico , Femenino , Humanos , Hidrazinas/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Pirazoles , Resultado del Tratamiento , Adulto Joven
2.
Bone Marrow Transplant ; 59(5): 660-669, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38383715

RESUMEN

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10-7) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10-5) and ASCT (p = 4.8 × 10-4) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10-8, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10-4), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10-4) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.


Asunto(s)
Bortezomib , Mieloma Múltiple , Trasplante Autólogo , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Mieloma Múltiple/tratamiento farmacológico , Bortezomib/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Trasplante de Células Madre Hematopoyéticas/métodos , Pronóstico
3.
Ther Adv Hematol ; 13: 20406207221082043, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35465644

RESUMEN

Introduction: Bortezomib has been reported to favourably impact the outcomes of t(4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown. Methods: To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence in situ hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), t(14;16), t(4;14), and +1q. Presence of +1q was defined as the presence of at least three copies of 1q21 at the cut off level of 20% of bone marrow plasma cells. Results: +1q identified in 167 (66.8%) and associated with t(4;14) and high lactate dehydrogenase (LDH). +1q was not associated with response rate but shorter event-free survival (EFS) (median EFS 35 vs 55 months, p = 0.05) and overall survival (OS) (median OS 74 vs 168 months, p = 0.00025). Copy number and clone size did not impact survival. Multivariate analysis showed +1q was an independent adverse factor for OS together with International Staging System (ISS)3, high LDH, del(17p) and t(4;14). When a risk score of 1 was assigned to each independent adverse factor, OS was shortened incrementally by a risk score from 0 to 4. Post-relapse/progression survival was inferior in those with +1q (median 60 vs 118 months, p = 0.000316). Autologous stem cell transplantation (ASCT) improved OS for those with +1q (median OS 96 vs 49 months, p = 0.000069). Conclusion: +1q is an adverse factor for OS in MM uniformly treated with bortezomib-based induction but was partially mitigated by ASCT. A risk scoring system comprising +1q, LDH, high-risk FISH, and ISS is a potential tool for risk stratification in MM.

4.
Med Teach ; 30(5): e125-30, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18576182

RESUMEN

BACKGROUND: Brainstem death (BSD), defined as the irreversible loss of consciousness, brainstem reflexes and the capacity to breathe, is not an uncommon scenario seen in the day to day practice of medical personnel. Upon the diagnosis of BSD, controversial issues of withdrawing life-supporting treatments and organ procuring for transplantation inevitably arise. This study evaluated the knowledge, acceptance and perception of BSD amongst medical students in Hong Kong. METHODS: A total of 126 medical students completed a self-administered questionnaire. Ten questions were used to assess their knowledge of BSD and this was correlated with their responses in three hypothetical vignettes. RESULTS: The mean score of the subjects' knowledge was 6.03 out of 10. Less than half (48.8%) of the subjects' knew that BSD is different from persistent vegetative state while 49.2% and 36.3% knew that BSD is accepted as death medically and legally in Hong Kong, respectively. When 'diagnosed' with BSD, 63.7%, 46.8% and 52.4% of the subjects would agree to the withdrawal of life-support from themselves, their most-loved one/family member and a stranger, respectively. Subjects with better knowledge and those who thought that doctors may tend to diagnose BSD to save resources or procure organs for transplantation were more ready to accept the withdrawal of life-support. CONCLUSIONS: We concluded that knowledge of BSD amongst medical students was unsatisfactory and that urgent actions should be taken to remedy the situation. A better knowledge of BSD positively influenced the decision-making on withdrawing life-support and that adequate information regarding the outcome of BSD should be provided. On the other hand, the perception of doctors' intentions behind diagnosing BSD has no direct influence on the decision-making. More emphasis is required on medical education, including a specific emphasis in the undergraduate lecture curriculum and bedside exposure to BSD diagnosis and subsequent counselling of patients' family members.


Asunto(s)
Muerte Encefálica/diagnóstico , Tronco Encefálico/fisiopatología , Conocimiento , Percepción , Estudiantes de Medicina/psicología , Estudios Transversales , Toma de Decisiones , Femenino , Hong Kong , Humanos , Masculino , Encuestas y Cuestionarios , Privación de Tratamiento
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