63 research outputs found
Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosis
Aims:âTo evaluate the feasibility of the histopathological diagnosis of prefibroticâearly primary myelofibrosis (PM) as described in the World Health Organization (WHO) classification and to evaluate the clinical implications of prefibroticâearly PM in a series of patients previously diagnosed as having essential thrombocythemia (ET) according to the Polycythemia Vera Study Group criteria.
Methods and results:âWHO criteria were applied to bone marrow biopsy specimens by two pathologists who then reclassified 127 cases as 102 ET (80.3%), 18 prefibroticâearly PM (14.2%) and seven fibrotic PM (5.5%). In 45 cases (35%), the final diagnosis was only reached by consensus. The megakaryocytic criteria that best discriminated between ET and prefibroticâearly PM were an increased nucleoâcytoplasmic ratio, presence of cloudlike nuclei, hyperchromatic-dysplastic nuclei, paratrabecular megakaryocytes and tight clusters. A histological score discriminated between ET (score â€3) and PM (score â„6), but 21 cases showed an intermediate ambiguous score. No significant differences were observed at diagnosis and at follow-up (median time 93 months) for thrombosis, major haemorrhage, laboratory data, transformation into overt myeloid metaplasia and survival.
Conclusions: The distinction between ET and prefibroticâearly PM is impaired by subjectivity in pathological practice and is of questionable clinical relevance, at least when considering individual patients
Flow cytometry-evaluated platelet CD36 expression, reticulated platelets and platelet microparticles in essential thrombocythaemia and secondary thrombocytosis
International audienc
Outcome of Ph negative myeloproliferative neoplasms transforming to accelerated or leukemic phase
Myeloproliferative neoplasms (MPN) are chronic disorders that can sometimes evolve into accelerated or leukemic phases. We retrospectively identified 122 patients with such blastic phases. The overall median survival was four months: 10.2 months for patients treated with intensive treatments compared to three months for best supportive care (pâ=â.005). Azacytidine, intensive chemotherapies, or allogeneic stem cell transplantation gave the highest median survivals with 9, 10.2, and 19.4 months, respectively. Accelerated phases (AP) had a longer median survival compared to acute leukemia (4.8 months vs. 3.1 months; pâ=â.02). In this retrospective and observational study, we observe that the longest survivals are seen in patients eligible for intensive treatments. Azacytidine shows interesting results in patients non-fit for intensive chemotherapy. Supportive care should probably be restricted to elderly patients and those with unfavorable karyotype. An early diagnosis of AP could also result in a better survival rate
Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma
Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8Â months (range: 1.7-73.4Â months), median overall survival (OS) was 39.5Â months (95% confidence interval (95% CI): 18.3-60.7) and median progression-free survival (PFS) was 25.8Â months (95% CI: 5.2-46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate >â75% were associated with increased OS (pâ=â0.006 and pâ=â0.003, respectively) and PFS (pâ=â0.003 and pâ=â0.04, respectively) whereas comorbidities, defined by a CIRS-G score â„â8, were associated with decreased OS and PFS (pâ=â0.02 and pâ=â0.04, respectively). A high MSKCC score was associated with decreased OS (pâ=â0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (pâ=â0.02 and pâ=â0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials
Abnormal T-cell phenotype in episodic angioedema with hypereosinophilia (Gleich's syndrome): frequency, clinical implication and prognosis
BACKGROUND: Episodic Angioedema with eosinophilia (EAE, Gleich\u27s syndrome) is a rare disorder consisting of recurrent episodes of angioedema, hypereosinophilia and frequent elevated serum Immunoglobin M.
METHODS: We conducted a retrospective multicenter nationwide study regarding the clinical spectrum and therapeutic management of patients with EAE in France.
RESULTS: Thirty patients were included with a median age at diagnosis of 41 years [5-84]. The median duration of each crisis was 5.5 days [1-90] with swelling affecting mainly the face and the upper limbs. Total serum IgM levels were increased in 20 patients (67%). Abnormal T-cell immunophenotypes were detected in 12 patients (40%) among which 5 (17%) showed evidence of clonal TCR Îł gene rearrangement. Median follow-up duration was 53 months [31-99]. The presence of an abnormal T-cell population was the sole factor associated with a shorter time to flare (hazard ratio 4.15 [CI 95% 1.18-14.66; p=0.02). At last follow-up, 3 patients (10%) were able to withdraw all treatments and 11 (37%) were in clinical and biological remission with less than 10 mg of daily prednisone.
CONCLUSION: EAE is a heterogeneous condition that encompasses several disease forms. Although patients usually respond well to glucocorticoids, those with evidence of abnormal T-cell phenotype have a shorter time to flare
Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance
Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with Îș light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density
Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party
No studies have been reported so far on bridging treatment with idelalisib for patients with chronic lymphocytic leukemia (CLL) prior to allogeneic hematopoietic cell transplantation (alloHCT). To study potential carry-over effects of idelalisib and to assess the impact of pathway-inhibitor (PI) failure we performed a retrospective EBMT registry-based study. Patients with CLL who had a history of idelalisib treatment and received a first alloHCT between 2015 and 2017 were eligible. Data on 72 patients (median age 58 years) were analyzed. Forty percent of patients hadTP53(mut/del)CLL and 64% had failed on at least one PI. No primary graft failure occurred. Cumulative incidences of acute GVHD degrees II-IV and chronic GVHD were 51% and 39%, respectively. Estimates for 2-year overall survival (OS), progression-free survival (PFS), and cumulative incidences of relapse/progression (CIR) and non-relapse mortality NRM were 59%, 44%, 25%, and 31%. In univariate analysis, drug sensitivity was a strong risk factor. For patients who had failed neither PI treatment nor chemoimmunotherapy (CIT) the corresponding 2-year estimates were 73%, 65%, 15%, and 20%, respectively. In conclusion, idelalisib may be considered as an option for bridging therapy prior to alloHCT. Owing to the high risk for acute GVHD intensified clinical monitoring is warranted.Development and application of statistical models for medical scientific researc
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