THE STORM (acute coronary Syndrome in paTients end Of life and Risk assesMent) study.

INTRODUCTION: Elderly patients with coexisting frailty and multiple comorbidities frequently present to the emergency department (ED). Because non-cardiovascular comorbidities and declining health status may affect their life expectancy, management of these patients should start in the ED. This study evaluated the role of Gold Standards Framework (GSF) criteria for identifying patients with acute coronary syndromes (ACS) approaching end of life. METHODS: All consecutive patients admitted to the ED and hospitalised with a diagnosis of ACS between May 2012 and July 2012 were included. According to GSF criteria, patients were labelled as positive GSF status when they met at least one general criterion and two heart disease criteria; furthermore, traditional cardiovascular risk scores (the Global Registry for Acute Coronary Events (GRACE) score and the Age, Creatinine and Ejection Fraction (ACEF) score) were calculated and WHOQOL-BREF was assessed. Mortality and repeat hospitalisation due to cardiovascular and non-cardiovascular causes were evaluated at 3-month and 12-month follow-up. RESULTS: From a total of 156 patients with ACS enrolled, 22 (14%) had a positive GSF. A positive GSF was associated with higher rate of non-cardiovascular events (22.7% vs 6.7%; p=0.03) at 3 months and higher rates of both cardiovascular and non-cardiovascular events (36% vs 16.4%; p=0.04 and 27.3% vs 6.7%; p=0.009, respectively) at 12 months. In multivariate analysis, an in-hospital GRACE score was a predictor of cardiovascular events, while a positive GSF independently predicted non-cardiovascular events. CONCLUSIONS: The GSF score independently predicts non-cardiovascular events in patients presenting with ACS and may be used along with traditional cardiovascular risk scores in choosing wisely the most appropriate treatment. The present results need to be externally validated on larger samples.

Prognostic relevance of cytometric quantitative assessment in patients with myelodysplastic syndromes.

OBJECTIVES: Morphology and cytogenetics are currently used to define prognosis in myelodysplastic syndromes (MDS). However, these parameters have some limits. Flow cytometry has been recently included in the diagnostic panel for MDS, and its prognostic significance is under evaluation. METHODS: Marrow aspirates from 424 MDS patients were analyzed by flow cytometry to evaluate the impact of bone marrow cell immunophenotype on overall survival (OS) and leukemia-free survival (LFS). The immature compartment of myeloblasts was analyzed by the quantitative expression of CD34 (<3% vs. ≥3%), CD117, and CD11b(-) /CD66b(-) (<5% vs. ≥5%); myeloid maturation was analyzed by the expression of CD11b(+) /CD66b(++) (<15% vs. ≥15%) and CD11b(+) /CD66b(+) (<25% vs. ≥25%). RESULTS: In univariate analysis, the expression of immaturity markers (CD34(+) , CD117(+) , and CD11b(-) /CD66b(-) ) was associated with shorter LFS and OS (P < 0.0001); higher expression of differentiation markers (CD11b(+) /CD66b(++) and CD11b(+) /CD66b(+) ) was associated with longer LFS (P < 0.0001 and P = 0.0002, respectively) and OS (P < 0.0001). In multivariate analysis, expression of CD34(+) (P = 0.007), CD117(+) (P = 0.013), and CD11b(+) /CD66b(++) (P = 0.023) retained independent prognostic value for OS, while only the expression of CD34(+) was a prognostic factor for LFS (P = 0.0003). Two different risk groups were defined according to the presence of 0-1 or ≥2 of these factors with significant different LFS and OS (P < 0.0001). This score showed prognostic value in predicting survival even in subanalysis according to IPSS and WHO subgroups. CONCLUSIONS: Flow cytometric analysis in MDS may provide meaningful prognostic information. Blast percentage expressed as CD117(+) or CD34(+) cells and the quantitative assessment of myeloid maturation showed prognostic value for survival.

HBV disease: HBsAg carrier and occult B infection reactivation in haematological setting.

HBV reactivation in patients with haematological malignancies undergoing chemoimmunotherapy is a serious and frequent complication. This is linked to either the high frequency of inactive HbsAg carriers and occult B infection among oncohaematological patients or the profound immunosuppression caused by high dose chemotherapy, monoclonal antibody therapy or auto- and allo-haematopoietic stem cell (HSC) transplantations. Identifying the patients at risk is mandatory in this clinical setting and prophylaxis with antiviral drugs or close monitoring may reduce and/or eliminate the HBV reactivation risk and the serious consequences. In general, preemptive anti-HBV therapy is more effective than treatment at reactivation. Prompt lamivudine prophylaxis should be given to HBsAg positive patients (inactive carriers) undergoing chemotherapy-immunochemotherapy and continued after cessation of immunosuppression even though long-term lamivudine therapy involves a risk of developing drug resistance. Use of newer anti-HBV agents may be considered. HBV reactivation has also been observed in occult B infection (HBcAb positive) and the optimal management of this group of patients requires special attention.

Treatment options in skeletal localizations of hairy cell leukemia: a systematic review on the role of radiation therapy.

Skeletal localizations are a rare complication in hairy cell leukaemia patients, with an estimated incidence of 3%. These lesions, mainly osteolytic, can occur at various sites and are almost always symptomatic. Localized radiation therapy (RT) has been extensively used as effective palliative treatment in such cases, with different total doses and fractionation schedules. In this article, a systematic review of all reported cases with osseous complications is presented, to underline the role of RT and to define the most appropriate approach in this subset of patients.

A case of bone involvement in hairy cell leukemia successfully treated with radiation therapy.

We report the case of a 63-year-old man with a clearly established diagnosis of hairy cell leukemia, treated with multiple lines of chemotherapy, who complained of localized pain in the left humerus. Radiological findings showed a dystrophic-blastic area within the humeral head. Fine-needle biopsy confirmed the hypothesis of bone involvement of hairy cell leukemia. The patient underwent radiotherapy at a dose of 25 Gy, obtaining a complete clinical response with resolution of pain and a partial recovery of the normal radiological structure of the humerus after 2 months. In addition to the case report, we present a short review of the literature focusing on the role of radiotherapy in this subset of patients.

Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders.

In this study we investigated telomere restriction fragment (TRF) length in a panel of mature B-cell lymphoproliferative disorders (MBCLDs) and correlated this parameter with histology and histopathogenesis in relation to the germinal center (GC). We assessed 123 MBCLD samples containing 80% or more tumor cells. TRF length was evaluated by Southern blot analysis using a chemiluminescence-based assay. GC status was assessed through screening for stable and ongoing somatic mutations within the immunoglobulin heavy-chain genes. Median TRF length was 6170 bp (range, 1896-11 200 bp) and did not correlate with patient age or sex. TRF length was greater in diffuse large cell lymphoma, Burkitt lymphoma, and follicular lymphoma (medians: 7789 bp, 9471 bp, and 7383 bp, respectively) than in mantle cell lymphoma and chronic lymphocytic leukemia (medians: 3582 bp and 4346 bp, respectively). GC-derived MBCLDs had the longest telomeres, whereas those arising from GC-inexperienced cells had the shortest (P < 10(-9)). We conclude that (1) TRF length in MBCLD is highly heterogeneous; (2) GC-derived tumors have long telomeres, suggesting that minimal telomere erosion occurs during GC-derived lymphomagenesis; and (3) the short TRF lengths of GC-inexperienced MBCLDs indicates that these neoplasms are good candidates for treatment with telomerase inhibitors, a class of molecules currently the subject of extensive preclinical evaluation.

Patients with high-risk aggressive lymphoma treated with frontline intensive chemotherapy and autografting: evidence of marked differences in outcome between patients with age-adjusted International Prognostic Index scores 2 and 3.

BACKGROUND: The goal of the current study was to evaluate the impact of presentation with an age-adjusted International Prognostic Index (aaIPI) score of 2 or 3 on patients with high-risk aggressive lymphoma who are treated with frontline intensive chemotherapy and autografting. METHODS: Sixty-nine consecutive patients (median age, 40 years) with either B-cell (n = 60) or non-B-cell (n = 9) aggressive lymphoma were treated with high-dose sequential (HDS) chemotherapy and peripheral blood progenitor cell (PBPC) autografting. The patients who were examined had poor prognoses, with aaIPI scores of 2 (n = 37) or 3 (n = 32). The original treatment regimen, sequential delivery of cyclophosphamide, methotrexate, and etoposide, followed by PBPC autografting (o-HDS), was used in the first 32 patients; the program was intensified by the addition of a course of high-dose cytosine arabinoside (C-HDS) in the next 37 patients. RESULTS: There were 4 toxicity-related deaths-2 in each aaIPI subgroup (treatment-related mortality, 5.8%). The complete remission rate was significantly higher among patients with an aaIPI score of 2 (n = 32 [86%]) compared with those with an aaIPI score of 3 (n = 13 [41%]; P < 0.001). Patients with an aaIPI score of 2 had significantly better outcomes than did patients with an aaIPI score of 3 in terms of both overall survival (78% vs. 34% at 8 years; P < 0.001) and event-free survival (72% vs. 28% at 8 years; P < 0.001). Similar results were observed when the analysis was limited to the 60 patients with B-cell-derived lymphoma. No significant differences in outcome between patients receiving o-HDS and patients receiving C-HDS were observed. Multivariate analysis demonstrated that an aaIPI score of 3 was the only parameter that was significantly associated with poor overall and event-free survival. CONCLUSIONS: Age-adjusted International Prognostic Index score is applicable to patients with aggressive lymphoma who are treated with frontline intensive chemotherapy and autografting. In addition, upfront use of HDS chemotherapy appears to be beneficial to patients with an aaIPI score of 2 but not to those with an aaIPI score of 3.

Significant correlation between the degree of WT1 expression and the International Prognostic Scoring System Score in patients with myelodysplastic syndromes.

PURPOSE: To determine whether pattern of WT1 gene expression is a useful marker for establishing prognosis and tracking disease progression in patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: We performed a quantitative assessment of the WT1 transcript amount by real-time quantitative polymerase chain reaction (RQ-PCR) in 173 samples (131 bone marrow samples and 42 peripheral-blood samples) from 131 patients with MDS (79 patients with refractory anemia [RA], 31 with RA with excess blasts [RAEB], 18 with secondary acute myeloid leukemia [s-AML] evolved from MDS, and three with deletion of 5q as the sole cytogenetic abnormality). Values obtained were correlated with the blast percentage and International Prognostic Scoring System (IPSS) score. RESULTS: Sixty-five percent of BM and 78% of PB samples for RA and 100% of BM and PB samples of RAEB and s-AML expressed WT1 transcript amounts greater than the level observed in healthy volunteers. The degree of WT1 expression was highly correlated with the type of MDS, was much higher in RAEB and s-AML compared with RA, and increased during disease progression. Moreover, a significant correlation was found between WT1 expression levels, blast cell percentage, and the presence of cytogenetic abnormalities. Therefore, we found a significant correlation between the amount of WT1 transcripts and the IPSS score, which currently represents the most reliable risk index of disease progression available for MDS patients. CONCLUSION: WT1 is a useful molecular marker for risk assessment in MDS patients.