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BACKGROUND: Large ß-globin gene cluster deletions (hereditary persistence of fetal hemoglobin [Hb] or ß-, δß-, γδß-, and ϵγδß-thalassemia), are associated with widely disparate phenotypes, including variable degrees of microcytic anemia and Hb F levels. When present, increased Hb A2 is used as a surrogate marker for ß-thalassemia. Notably, ϵγδß-thalassemias lack the essential regulatory locus control region (LCR) and cause severe transient perinatal anemia but normal newborn screen (NBS) results and Hb A2 levels. Herein, we report a novel deletion of the ϵ, Aγ, Gγ, and ψß loci with intact LCR, δ-, and ß-regions in 2 women and newborn twins. METHODS: Capillary electrophoresis (CE), high-performance liquid chromatography (HPLC), DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), gap-polymerase chain reaction (gap-PCR), and long-read sequencing (LRS) were performed. RESULTS: NBS showed an Hb A > Hb F pattern for both twins. At 20 months, Hb A2 was increased similarly to that in the mother and an unrelated woman. Unexplained microcytosis was absent and the twins lacked severe neonatal anemia. MLPA, LRS, and gap-PCR confirmed a 32 599 base pair deletion of ϵ (HBE1) through ψß (HBBP1) loci. CONCLUSIONS: This deletion represents a hemoglobinopathy category with a distinct phenotype that has not been previously described, an ϵγ-thalassemia. Both the NBS Hb A > F pattern and the subsequent increased Hb A2 without microcytosis are unusual. A similar deletion should be considered when this pattern is encountered and appropriate test methods selected for detection. Knowledge of the clinical impact of this new category will improve genetic counselling, with distinction from the severe transient anemia associated with ϵγδß-thalassemia.
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Hemoglobinopatias , Talassemia , Talassemia beta , Humanos , Feminino , Talassemia/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Hemoglobina Fetal/genética , Reação em Cadeia da Polimerase MultiplexRESUMO
Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counseling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms.
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Evolução Clonal , Neoplasias Hematológicas/genética , Adolescente , Adulto , Idoso , Anemia de Diamond-Blackfan/genética , Criança , Pré-Escolar , Síndrome Congênita de Insuficiência da Medula Óssea/genética , Anemia de Fanconi/genética , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: Myelodysplastic syndromes (MDS) are a class of clonal neoplastic disorders of largely unknown etiology, and published data remain inconclusive regarding the association between lifetime alcohol consumption and MDS risk. In these analyses, data from a population-based case-control study were used to investigate this association. METHODS: Eligible cases of MDS were identified through the Minnesota Cancer Reporting System; controls were matched by sex and age-decile. A central review process was used to confirm MDS diagnosis and classify subtypes. Unconditional and polytomous logistic regression were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Kaplan-Meier curves were used to compare survival by category of lifetime alcohol consumption. RESULTS: In total, 398 cases of MDS and 698 controls were included. Alcohol consumption at 23-30, 31-49, and 50-65 years of age, recent consumption 1 year before diagnosis/interview, and lifetime consumption were not found to be significantly associated with MDS in males (OR range 0.63-0.99) or females (OR range 0.58-1.70). Analysis by MDS subtype further suggested there was not a significant association between recent alcohol consumption and odds of disease by subtype (OR range 0.39-1.13). Lifetime alcohol consumption was not significantly associated with survival after diagnosis of MDS CONCLUSIONS: Previously reported associations between alcohol consumption and MDS risk were inconsistent. Results from our analyses by sex and disease subtype do not support alcohol as a significant contributor to risk of MDS.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Síndromes Mielodisplásicas , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
FLT3-internal tandem duplication occurs in 20-30% of acute myeloid leukemia and confers an adverse prognosis with its allelic ratio being a key risk stratifier. The US Food and Drug Administration recently approved FLT3 inhibitors midostaurin and gilteritinib in FLT3 mutation-positive acute myeloid leukemia. Historically, FLT3 was tested by fragment analysis, which has become the standard method endorsed by international guidelines. However, next generation sequencing is increasingly used at acute myeloid leukemia diagnosis given its ability to simultaneously evaluate multiple clinically informative markers. As FLT3-internal tandem duplication detection was known to be challenging by next generation sequencing and the results carry profound prognostic and therapeutic implications, it is important to thoroughly examine its performance in FLT3-internal tandem duplication detection and allelic ratio classification. In a comparative study with fragment analysis, we retrospectively reviewed our experience using a custom-designed, hybridization capture-based, targeted next generation sequencing panel. Among 7902 cases, FLT3-internal tandem duplication was detected in 335 with variable sizes (3-231 bp) and insertion sites. Fragment analysis was also performed in 402 cases, demonstrating 100% concordance in FLT3-internal tandem duplication detection. In 136 dual-tested, positive cases, 128/136 (94%) exhibited concordant high/low allelic ratio classifications. The remaining 6% showed borderline low allelic ratio by next generation sequencing. The two methods were concordant in FLT3-tyrosine kinase domain mutation detection at the hotspot D835/I836 targeted by fragment analysis. Furthermore, seven mutations which may benefit from FLT3 inhibitor therapy were detected by next generation sequencing, in regions not covered by fragment analysis. Our study demonstrates that using a hybridization capture-based chemistry and optimized bioinformatics pipeline, next generation sequencing can reliably detect FLT3-internal tandem duplication and classify its allelic ratio for acute myeloid leukemia risk stratification. Next generation sequencing also exhibits superior comprehensiveness in FLT3 mutation detection and may further improve personalized, targeted therapy in acute myeloid leukemia.
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Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Leucemia Mieloide Aguda/genética , Mutação , Sequências de Repetição em Tandem , Tirosina Quinase 3 Semelhante a fms/genética , Biologia Computacional , Predisposição Genética para Doença , Humanos , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Clinical trials and treatment guidelines for myelodysplastic syndrome depend on several prognostic scoring systems to stratify patients by risk. These include different variables: the degree of cytopenia, percentage of bone marrow blasts, and cytogenetics. Little is known about the impact of bone marrow blasts in patients with adverse cytogenetics. In this retrospective study, we analyzed 536 patients with high-grade myelodysplastic syndrome to examine the differences in survival for patients with different percentages of bone marrow blasts. The median overall survival in patients with ≥ 5% marrow blasts was not statistically different from that for patients with < 5% marrow blasts; however, the former group had a higher risk of progression to acute myeloid leukemia (p < 0.001). Therefore, cytogenetics is the most important factor in our prognostic tools to determine survival outcomes for patients with myelodysplastic syndrome, and patients with high-risk disease have poor prognosis irrespective of their marrow blasts percentage.
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Crise Blástica , Medula Óssea , Síndromes Mielodisplásicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Crise Blástica/metabolismo , Crise Blástica/mortalidade , Crise Blástica/patologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
A novel unstable Gγ-globin variant, Hb F-Wentzville [Gγ24(B6)GlyâGlu; HBG2: c.74G>A, (p.Gly25Glu)], was identified in a young infant who required a single transfusion of erythrocytes for hemolytic anemia. This is the first reported γ-globin variant affecting the highly conserved glycine residue at helical position B6. In the tertiary structure of hemoglobin (Hb), glycine at B6 is in close proximity to another invariant glycine residue at E8. Prior studies have shown that replacement of the B6 or E8 glycine residues with bulkier amino acids disrupts packing between the B and E helices, resulting in Hb instability. Thus, Hb F-Wentzville is analogous to the following unstable ß-globin B6 variants: Hb Savannah (HBB: c.74G>T, p.Gly24Val), Hb Riverdale-Bronx (HBB: c.73G>C, p.Gly24Arg), and Hb Moscva (HBB: c.74G>A, p.Gly24Asp).
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Anemia Hemolítica/genética , Hemoglobina Fetal/genética , Mutação , gama-Globinas/genética , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/patologia , Cromatografia Líquida de Alta Pressão , Eletroforese Capilar , Expressão Gênica , Heterozigoto , Humanos , Lactente , Masculino , Estabilidade Proteica , Análise de Sequência de DNA , gama-Globinas/deficiênciaRESUMO
OBJECTIVE: Little prospective data regarding factors determining patient outcomes in myelodysplastic syndromes (MDS) are available. To establish features of early mortality in MDS, we compare characteristics of patients dying within 1 year of diagnosis with those surviving longer. METHODS: We prospectively enrolled adults with a new MDS diagnosis in a population-based case-control study. Logistic regression was used to calculate odds ratios and 95% confidence intervals for potential predictors of early mortality. Subgroup analyses were conducted within the following groups: high-/very-high-risk IPSS-R; very-low-/low-/intermediate-risk IPSS-R; treated patients; and supportive care only patients. RESULTS: We observed early mortality in those with abnormal cytogenetics (OR: 3.36, 95% CI: 1.52-7.46), three or greater cytogenetic abnormalities (OR: 3.48, 95% CI: 1.51-7.99), treatment at a community medical center (versus academic) (OR: 2.55, 95% CI: 1.18-5.47), and with 2-3 concurrent medical comorbidities (OR: 2.14, 95% CI: 1.08-4.22). Similarly, in subgroup analyses, abnormal cytogenetics remained the main predictor of early mortality. CONCLUSION: Complex cytogenetics and prognostic risk category have been associated with early mortality without intervention. Our data confirm these associations in a large, prospectively followed cohort and highlight the significance of cytogenetic abnormalities and complexity regardless of IPSS-R risk categorization or treatment.
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Síndromes Mielodisplásicas/epidemiologia , Idoso , Estudos de Casos e Controles , Aberrações Cromossômicas , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Razão de Chances , Vigilância da População , Prognóstico , Fatores SocioeconômicosRESUMO
Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non-Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS-R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population-based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc.
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DNA Mitocondrial/genética , Haplótipos/genética , Mitocôndrias/genética , Síndromes Mielodisplásicas/genética , Polimorfismo Genético/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Etnicidade , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , PrognósticoRESUMO
The clinical and laboratory characteristics of patients with non-syndromic, autosomal dominant thrombocytopenia secondary to germ line ANKRD26 mutations appear to be heterogeneous. Except for a targeted molecular genotyping approach, there is no distinct clinical or laboratory phenotype that has been specifically associated with this particular gene mutation. Such heterogeneity could be due to variations in mutation and genetic background in different families. To understand the phenotypic heterogeneity, we thoroughly studied one affected family using the International Society for Thrombosis and Haemostasis bleeding assessment tool and both clinically validated standard and esoteric platelet testing (electron microscopy (EM) and flow cytometry). We found that decreased platelet aggregation with arachidonic acid and epinephrine agonists was common in affected family members. EM studies demonstrated persistent borderline low mean dense granules per platelet, decreased alpha granules and an increased canalicular network pattern in all affected members. Since these characteristics are subtle or non-pathognomonic, molecular testing for ANKRD26 mutation remains the most reliable test to render a diagnosis and should be considered when evaluating a patient or family with congenital thrombocytopenia, particularly if there is a history of myeloid neoplasms.
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Mutação , Proteínas Nucleares/genética , Fenótipo , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Adolescente , Adulto , Idoso , Alelos , Plaquetas/metabolismo , Plaquetas/ultraestrutura , Família , Feminino , Estudos de Associação Genética , Testes Genéticos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pessoa de Meia-Idade , Linhagem , Agregação Plaquetária , Contagem de Plaquetas , Adulto JovemRESUMO
OBJECTIVE: To describe trends in chlamydia positivity from 2007 to 2011 among heterosexual people tested for chlamydia at selected clinics that provide services to people at high risk in Victoria, Australia. DESIGN: The Victorian Primary Care Network for Sentinel Surveillance is a prospective system that collates pathology results from laboratories and demographic and behavioural data from a questionnaire. SETTING: Two sexual health clinics and six other primary care clinics that target young people and women at high risk. PARTICIPANTS: All clients tested for chlamydia at sentinel clinics. Individuals aged less than 16 years, sex workers, or those reporting any same-sex sexual partners in the past 12 months were excluded from the analysis. MAIN OUTCOME MEASURES: Chlamydia positivity trends were assessed using three-level random-effects Poisson regression, with clinic and subject treated as nested random factors. Models were offset for total number of tests and adjusted for relevant covariates. RESULTS: Between 2007 and 2011, chlamydia positivity among 31 682 tests in women increased from 5.1% to 6.3%, and positivity among 23 771 tests in men increased from 7.4% to 8.2%. Adjusting for age, country of birth, number of sex partners, condom use, and presence of symptoms, chlamydia positivity increased between 2007 and 2011 significantly among women (incidence rate ratio [IRR], 1.29; 95% CI, 1.11-1.50) and non-significantly among men (IRR, 1.07; 95% CI, 0.92-1.23). Over time, a decrease in reported inconsistent condom use was also observed in both men and women; however, men became more likely to report more than one partner in the past year. CONCLUSION: We identified a concerning increase in chlamydia positivity over time, particularly among young women.
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Infecções por Chlamydia/epidemiologia , Adolescente , Adulto , Infecções por Chlamydia/diagnóstico , Feminino , Heterossexualidade , Humanos , Masculino , Vigilância da População , Prevalência , Atenção Primária à Saúde , Análise de Regressão , Vitória/epidemiologia , Adulto JovemAssuntos
Leucemia Eritroblástica Aguda/classificação , Síndromes Mielodisplásicas/classificação , Feminino , Humanos , Leucemia Eritroblástica Aguda/mortalidade , Masculino , Síndromes Mielodisplásicas/mortalidade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Organização Mundial da SaúdeAssuntos
Aberrações Cromossômicas , Células Clonais/patologia , Síndromes Mielodisplásicas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tamanho Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Background: Epidermal growth factor receptor (EGFR) inhibitors cause cutaneous toxicity in over 90% of patients. Conceivably, healthcare providers could overlook such toxicity in African American/Black patients because of a darker complexion. This qualitative study sought to learn about such cutaneous signs and symptoms and, if present, to report them in patients' own words. Methods: Any patient who self-identified as African American/Black and who had been prescribed an EGFR inhibitor was eligible. The current report focuses on patients' responses to the following question, "What have you noticed since starting your cancer treatment (the EGFR inhibitor), any particular symptoms or reactions, positive or negative?" All interview data were audio-recorded, transcribed, and then independently coded and analyzed by two investigators. Results: Fifteen patients are the focus of this report, and all described cutaneous toxicity. Patients appeared troubled by the cosmetic aspect of these drug-induced skin changes, including their acneiform appearance, describing "little pimples with little, little pus in it." Notable were comments on hyperpigmentation, "I'm a black person but . became darker." Furthermore, patients experienced physical symptoms: "it itches;" "it's like you stuck a pin in it;" "stinging;" and "burning;". Conclusion: Although cutaneous toxicity from EGFR inhibitors might be more difficult to visualize among darkly complected patients, the graphic descriptions offered in this qualitative study underscore the need for clinicians to heighten their awareness of such toxicity in African American/Black patients.
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Negro ou Afro-Americano , Receptores ErbB , Pele , Humanos , Administração Cutânea , Receptores ErbB/antagonistas & inibidores , Pele/efeitos dos fármacos , /efeitos adversosRESUMO
PURPOSE: Although a few previous studies have reported positive associations between adult myeloid leukemia and a history of certain medical conditions, the etiology of most cases remains largely unknown. Our purpose was to examine associations between certain medical conditions and adult myeloid leukemia. METHODS: Using logistic regression, we evaluated associations between 16 self-reported medical conditions and myeloid leukemia in a case-control study of 670 cases [including 420 acute myeloid leukemia (AML) and 186 chronic myelogenous leukemia (CML)] and 701 population-based controls. RESULTS: We observed significant positive associations between AML and ulcerative colitis (odds ratio (OR) = 3.8; 95 % confidence interval (CI), 1.1-13) and between CML and peptic ulcer (OR = 2.0; 95% CI, 1.1-3.8). A personal cancer history increased both AML (OR = 2.6; 95% CI, 1.7-3.9) and CML (OR = 3.5; 95% CI, 2.0-5.8) risk even after excluding individuals who reported prior radiation and/or chemotherapy treatment. CONCLUSION: Certain inflammatory medical conditions and a personal history of cancer, independent from therapy, are associated with an increased risk of myeloid leukemia.
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Nível de Saúde , Leucemia Mieloide/etiologia , Inquéritos e Questionários , Doença Aguda , Adulto , Idoso , Estudos de Casos e Controles , Colite Ulcerativa/complicações , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Úlcera Péptica/complicações , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Early conversations about patients' goals and values improve care, but clinicians struggle to conduct them. The systems-based Serious Illness Care Program (SICP) helps clinicians have more, better, and earlier conversations. Central to this approach is a clinician conversation guide for patient encounters. While the SICP works for practicing clinicians, it has not been tested with medical trainees. INTERVENTION: We adapted the SICP training to emphasize assessing prognostic awareness and responding to emotion. We developed a 2.5-hour SICP workshop for medical students and medical interns that included large- and small-group work, practice with an actor, and interdisciplinary clinician facilitators. We trained 81 students and 156 interns and obtained anonymous quantitative and qualitative feedback. OUTCOMES: Eighty-six percent of students and 91% of residents rated the session as "very good" or "excellent" and >90% of all learners would either recommend this training or intended to apply this to their practice. Post-session learner confidence increased in all communication skills. Learners said the training provided a helpful framework and useful language for these conversations. Resident documentation of serious illness conversations in the medical record increased dramatically during the year following training commencement. CONCLUSIONS: Grounded in principles of adult learning theory, this training was rated highly by trainees and resulted in demonstrable practice change. These early learners were more flexible and willing to try this approach than practicing clinicians who tend to resist or revert to old habits. A Guide represents a new paradigm for teaching communication skills and is valued by early learners.
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Cuidados Críticos , Estudantes de Medicina , Adulto , Comunicação , Estado Terminal/terapia , Documentação , Humanos , Estudantes de Medicina/psicologiaRESUMO
BACKGROUND: Autoimmune diseases and hematopoietic malignancies are known to cluster within individuals, suggesting intertwined etiologies. A limited number of studies have evaluated pre-existing medical conditions as risk factors for myelodysplastic syndromes (MDS). We evaluated associations between autoimmune disease and other medical conditions and risk of MDS. METHODS: Cases were identified through the Minnesota Cancer Reporting System. Controls were identified through the Minnesota State driver's license/identification card list. History of autoimmune disease and other medical conditions was based on self-report; proxy interviews were not conducted. Unconditional logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CI). RESULTS: We included 395 cases and 694 controls. Cases were significantly more likely to report a diagnosis of any autoimmune disease when compared with controls (aOR=1.41, 95% CI: 1.05-1.89) after adjustment for age, sex, education, NSAID use, exposure to benzene and body mass index. When we evaluated specific autoimmune conditions, a statistically significant association was observed for hypothyroidism (aOR=2.16, 95% CI: 1.39-3.34) and odds ratios were elevated for inflammatory bowel disease (aOR=1.75) and systemic lupus erythematosus (SLE; aOR=3.65), although these associations did not reach statistical significance. Presence of an autoimmune condition did not impact overall survival (p = 0.91). CONCLUSION: Our results validate previous findings of an association between autoimmune disease and MDS. Further studies are required to determine whether this association is due to shared etiology, treatment for autoimmune diseases, or altered immune surveillance or bone marrow damage caused by the autoimmune condition.
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Doenças Autoimunes , Síndromes Mielodisplásicas , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Estudos de Casos e Controles , Humanos , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/etiologia , Razão de Chances , Fatores de RiscoRESUMO
OBJECTIVES: Patients with clonal cytopenia of undetermined significance (CCUS) are at increased risk of developing myeloid neoplasia (MN). We evaluated whether a simple flow cytometry immunophenotyping (FCIP) assay could differentiate the risk of development of MN in patients with CCUS. METHODS: Bone marrow aspirates were assessed by FCIP panel in a cohort of 80 patients identified as having CCUS based on next-generation sequencing or cytogenetics from March 2015 to May 2020, with available samples. Flow cytometric assay included CD13/HLA-DR expression pattern on CD34-positive myeloblasts; CD13/CD16 pattern on maturing granulocytic precursors; and aberrant expression of CD2, CD7, or CD56 on CD34-positive myeloblasts. Relevant demographic, comorbidity, and clinical and laboratory data, including the type and extent of genetic abnormalities, were extracted from the electronic health record. RESULTS: In total, 17 (21%) patients with CCUS developed MN over the follow-up period (median survival follow-up, 28 months [95% confidence interval, 19-31]). Flow cytometry immunophenotyping abnormalities, including the aberrant pattern of CD13/HLA-DR expression, as detected at the time of the diagnosis of CCUS, were significantly associated with risk of developing MN (hazard ratio, 2.97; P = .006). Additional FCIP parameters associated with the development of MN included abnormal expression of CD7 on myeloblasts and the presence vs absence of any FCIP abnormality. CONCLUSIONS: A simple FCIP approach that includes assessment of CD13/HLA-DR pattern on CD34-positive myeloblasts can be useful in identifying patients with CCUS at higher risk of developing MN.
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Antígenos CD13 , Antígenos HLA-DR , Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Antígenos CD13/genética , Hematopoiese Clonal , Citometria de Fluxo , Células Precursoras de Granulócitos , Antígenos HLA-DR/genética , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Contagem de Leucócitos , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genéticaRESUMO
OBJECTIVE: Over 50% of cancer patients who are treated with epidermal growth factor receptor (EGFR) inhibitors develop a papulopustular rash that involves the face, neck, and upper torso. However, because relatively few previous reports have focused on the full ramifications of this drug-induced side effect, this qualitative study was undertaken. METHODS: Fifteen patients who had either an active or previous rash from these agents participated in scripted interviews. All interviews were transcribed and examined by means of a qualitative methodologic approach. RESULTS: Four major themes emerged: (1) actual physical discomfort was associated with the rash; (2) patients were concerned about their appearance; (3) despite initial denial, patients did suffer social isolation; and (4) high medical morbidity was associated with the rash. Patients voiced concerns such as: (1) 'Especially when I try to sleep, I can feel the itch and burn all over '; (2) 'My face looks so bad that if I go to see my friends and they say, 'What happened to you.' I am self conscious about that'; (3) 'I just told them they would be better off just calling me, don't come visit '; and (4) 'I went to the hospital for my face they made a bandage to put all over [my] face . [I] just had a little nose hole, a mouth hole and holes for eyes.'. CONCLUSION: Rash from EGFR inhibitors can have a major negative impact upon cancer patients.