Molecular characteristics and chromatin texture features in acute promyelocytic leukemia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background: Acute promyelocytic leukemia is a cytogenetically well defined entity. Nevertheless, some features observed at diagnosis are related to a worse outcome of the patients. Methods: In a prospective study, we analyzed peripheral (PB) leukocyte count, immunophenotype, methylation status of CDKN2B, CDKN2A and TP73; FLT3 and NPM1 mutations besides nuclear chromatin texture characteristics of the leukemic cells. We also examined the relation of these features with patient's outcome. Results: Among 19 cases, 4 had a microgranular morphology, 7 presented PB leukocytes >10x10(9)/l, 2 had FLT3-ITD and 3 had FLT3-TKD (all three presenting a methylated CDKN2B). NPM1 mutation was not observed. PB leukocyte count showed an inverse relation with standard deviation of gray levels, contrast, cluster prominence, and chromatin fractal dimension (FD). Cases with FLT3-ITD presented a microgranular morphology, PB leukocytosis and expression of HLA-DR, CD34 and CD11b. Concerning nuclear chromatin texture variables, these cases had a lower entropy, contrast, cluster prominence and FD, but higher local homogeneity, and R(2)45, in keeping with more homogeneously distributed chromatin. In the univariate Cox analysis, a higher leukocyte count, FLT3-ITD mutation, microgranular morphology, methylation of CDKN2B, besides a higher local homogeneity of nuclear chromatin, a lower chromatin entropy and FD were associated to a worse outcome. All these features lost significance when the cases were stratified for FLT3-ITD mutation. Methylation status of CDNK2A and TP73 showed no relation to patient's survival. Conclusion: in APL, patients with FLT3-ITD mutation show different clinical characteristics and have blasts with a more homogeneous chromatin texture. Texture analysis demonstrated that FLTD-ITD was accompanied not only by different cytoplasmic features, but also by a change in chromatin structure in routine cytologic preparations. Yet we were not able to detect chromatin changes by nuclear texture analysis of patients with the FTLD-TKD or methylation of specific genes.7Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2007/54686-0]CNPq [302277/2009-9, 307270/2010-6, 402022/2010-6

An exemplary secondary physical education teacher-coach: An ecological comparison

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Exploring the work of an exemplary dual role professional: a teacher-coach case study

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An exemplary secondary physical education teacher-coach: An ecological comparison

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Cutaneous adverse reaction to 2-chlorodeoxyadenosine with histological flame figures in patients with chronic lymphocytic leukaemia

Introduction 2-Chlorodeoxyadenosine (cladribine or 2-CdA) is a purine analogue that has been used successfully in hairy cell leukaemia (HCL). Moreover, it has been increasingly used to treat chronic lymphoproliferative syndromes and paediatric acute myeloid leukaemia. Cutaneous side-effects associated with this drug have seldom been described in cases of HCL. Patients and methods We describe three patients with chronic lymphocytic leukaemia that presented generalized skin eruptions after treatment with 2-CdA. Results All patients had advanced disease, receiving 2-CdA as a second or third line chemotherapy. Skin lesions were severe and chemotherapy had to be discontinued. Histological examination of skin biopsies showed an eosinophil-rich infiltrate with flame figures, similar to what is observed in Wells' syndrome (eosinophilic cellulitis). Corticosteroids were effective to control the eruptions. Conclusions Cutaneous adverse reactions associated with 2-CdA have seldom been observed in the treatment of HCL. However, as this purine analogue has been used in more advanced cases these may be more frequent and severe. The pathophysiology of these lesions is unclear, but it is probably related to drug-induced change in T-cell imbalance in severely immunosuppressed patients.18553854

Middle school students' prior knowledge of physical activity and physical education before an assessment initiative for teacher development

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Primary myelofibrosis: risk stratification by IPSS identifies patients with poor clinical outcome

OBJECTIVES: To evaluate whether risk scores used to classify patients with primary myelofibrosis and JAK-2 V617F mutation status can predict clinical outcome. METHODS: A review of clinical and laboratory data from 74 patients with primary myelofibrosis diagnosed between 1992 and 2011. The IPSS and Lille scores were calculated for risk stratification and correlated with overall survival. RESULTS: A V617F JAK2 mutation was detected in 32 cases (47%), with no significant correlation with overall survival. The patients were classified according to the scores: Lille - low, 53 (73.%); intermediate, 13 (18%); and high, 5 (7%); and IPSS – low, 15 (26%); intermediate-1, 23 (32%); intermediate-2, 19 (26%); and high, 15 (31%). Those patients presenting a higher risk according to the IPSS (high and intermediate-2) had a significantly shorter overall survival relative to the low risk groups (intermediate-1 and low) (p = 0.02). CONCLUSIONS: These results emphasize the importance of the IPSS prognostic score for risk assessment in predicting the clinical outcome of primary myelofibrosis patients

Brazilian Experience Using High-Dose Sequential Chemotherapy Followed by Autologous Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Purpose: We evaluate the effectiveness and toxicity of high-dose sequential chemotherapy (HDS) as salvage therapy in patients with advanced-stage Hodgkin lymphoma. Patients and Methods: We performed a retrospective analysis on 77 patients receiving HDS between 1998 and 2006. Patients enrolled were in disease progression or relapsed disease, or did not achieve a complete remission after first-line treatment. HDS consisted of the sequential administration of cyclophosphamide and granulocyte colony-stimulating factor with stem cell harvesting, followed by methotrexate plus vincristine and etoposide. Results: The majority of patients had stage III/IV (64%) and B symptoms (71.4%). Disease status improvement after HDS was observed in 24 of 57 patients (42%) previously in disease progression or relapse. HDS-related deaths occurred in 8 of 77 patients (10.4%). Four patients (5.2%) developed acute myeloid leukemia/myelodysplastic syndrome. Overall, disease-free and progression-free survival was 27%, 57%, and 25%, respectively. Conclusion: Despite the treatment-related mortality, HDS is feasible, with satisfactory response rates, even in patients with poor prognosis.96449454Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP