Validation of the MD Anderson Prognostic Risk Model for patients with myelodysplastic syndrome

BACKGROUND:

The proposed MD Anderson Risk Model Score (MDAS) for myelodysplastic syndromes (MDS) refines outcome discrimination compared with the International Prognostic Scoring System (IPSS). We applied the MDAS to Moffitt Cancer Center (MCC) MDS patients to validate its prognostic utility.

METHODS:

This was a retrospective analysis of MDS cases, as defined by World Health Organization criteria, from the Moffitt database, with confirmatory chart review.

RESULTS:

A total of 775 patients evaluated between January 2001 and December 2009 were included. Patients were reclassified by MDAS as low (20.6%), intermediate‐1 (31%), intermediate‐2 (21%), high risk (16.1%), and unknown (11.2%). Median overall survival (OS) from diagnosis was 92, 49, 27, and 14 months for low, intermediate‐1, intermediate‐2, and high‐risk MDAS groups, respectively (P < .005). Median OS from referral was 61, 28, 15, and 8 months (P < .005), respectively. Among 484 patients classified by IPSS as low or intermediate‐1 risk, 25% were up‐staged as intermediate‐2 or high risk by MDAS; 4 prognostically distinct subgroups were identified among lower risk IPSS categories with median OS of 93, 53, 31, and 18 months (P < .005). Among 201 intermediate‐2 or high‐risk IPSS patients, 15.4% were down‐staged to intermediate‐1 by MDAS, with 3 groups identified by MDAS having median OS of 33, 23, and 14 months. Acute myeloid leukemia transformation rate was highest among high‐risk MDAS (50.4%). In Cox regression analysis, higher risk MDAS predicted inferior OS (hazard ratio 1.42; P < .005) independent of IPSS.

CONCLUSIONS:

Our data validated MDAS' prognostic value. MDAS is complementary to IPSS and refines prognostic precision. Cancer 2011;. © 2011 American Cancer Society.     

FIRST-DOSE RESPONSE TO ANGIOTENSIN-CONVERTING ENZYME INHIBITION IN CONGESTIVE CARDIAC FAILURE: A MALAYSIAN EXPERIENCE

Despite their proven value in reducing morbidity and mortality in different grades of heart failure, angiotensin converting enzyme (ACE) inhibitors continue to be underused. One reason for this is clinicians' apprehension of first-dose hypotension. We conducted a double-blind, randomised, placebo-controlled parallel group study to investigate the effect of various ACE inhibitors on first-dose hypotension. Eighty unselected patients were randomised into five treatment groups: placebo, captopril 6.25 mg, enalapril 2.5 mg, perindopril 2 mg and lisinopril 2.5 mg. Blood pressure was measured at baseline, half hourly for two hours and hourly for three hours after drug treatment. The maximum drops in mean arterial pressure (in mmHg ± SD) were placebo 5.89 ± 2.65, perindopril 5.29 ± 2.49, enalapril 13.28 ± 3.31, lisinopril 15.04 ± 5.74 and captopril 16.76 ± 5.74 (all p< 0.05 vs placebo except for perindopril). Perindopril, unlike the other ACE inhibitors studied, did not produce first-dose hypotension following its initiation in patients with congestive heart failure.     

Hemoglobin Nigeria (alpha-81 Ser replaced by Cys):a new variant associated with alpha-thalassemia

Hematologic evaluation of a Nigerian obstetrical patient disclosed the presence of sickle-cell trait as well as evidence of a hemoglobin alpha- chain abnormality. Hemoglobins containing the variant alpha-chain were isolated by DEAE-cellulose column chromatography, and analysis of the purified alpha-chain demonstrated a ser replaced by cys substitution at alpha-81. The abnormal alpha-chain represented approximately 45% of the total, and hemoglobins containing this alpha-chain appeared to have normal stability and functional properties. In addition to the abnormal hemoglobins that were identified in this patient, she also was found to have persistent microcytosis in the absence of iron deficiency, and the percentage of HbS in her erythrocytes was less than that usually present in individuals with sickle cell trait. These findings, together with a reduced alpha/beta globin synthesis ratio from her peripheral blood reticulocytes, indicated that the presence of alpha-thalassemia trait. Hematologic findings from members of the patients's family suggest that an alpha-thalassemia gene may be linked to that of the structurally abnormal alpha-chain.     

The oral cavity in leprosy: what clinicians need to know

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a bacillus that has a tropism for skin and peripheral nerves. Leprosy treatment is based on a multidrug therapy established by the World Health Organization in 1982 and, despite its widespread use, Brazil ranks second worldwide in numbers of cases. Oral involvement in leprosy has been poorly described in the literature, and few studies have shown that although the bacillus is found in mucosa, specific leprosy lesions are rare and affect patients with advanced stages of the disease. This review aimed to assess the literature on oral manifestations in leprosy and the aspects involving oral cavity in leprosy pathogenesis.     

Plasma/serum levels of flt3 ligand are low in normal individuals and highly elevated in patients with Fanconi anemia and acquired aplastic anemia

The flt3 ligand is a growth factor that stimulates the proliferation of hematopoietic progenitor and stem cells. We established a sensitive enzyme-linked immunosorbent assay (ELISA) to measure the concentration of flt3 ligand in plasma or serum from normal individuals, as well as in patients with hematopoietic disorders. Concentrations of flt3 ligand in plasma or serum from normal individuals were quite low: only 12% (7 of 60) of normal individuals had flt3 ligand levels above 100 pg/mL (the limit of detection). In contrast, 86% (19 of 22) of samples from patients with Fanconi anemia and 100% (eight of eight) of samples from patients with acquired aplastic anemia had plasma or serum levels above 100 pg/mL. Mean plasma or serum concentrations (calculated by assigning a value of 0 pg/mL to any sample reading below the level of detection) were as follows: normal volunteers, 14 pg/mL; patients with Fanconi anemia, 1,331 pg/mL; and patients with acquired aplastic anemia, 460 pg/mL. Concentrations of flt3 ligand in blood are, therefore, specifically elevated to a level that may be physiologically relevant in hematopoietic disorders with a suspected stem cell component. The elevated flt3 ligand concentrations in these individuals may be part of a compensatory hematopoietic response to boost the level of progenitor cells.     

In vitro analysis of the interactions between preadipocytes and endothelial cells in a 3D fibrin matrix

The volume‐persistent survival of transplanted adipose tissue in vivo relies on early vascularization, due to an otherwise early induction of apoptosis of the centrally located cells. Thus, one way to enable the early formation of a capillary network resulting in a sufficient perfusion of the transplanted construct might be the co‐transplantation of autologous preadipocytes with endothelial cells. To investigate preadipocyte–endothelial cell interaction, three‐dimensional proliferation‐ and angiogenesis assays were performed in vitro. Proliferation rates of co‐cultured endothelial cells and preadipocytes suspended in a fibrin matrix were elucidated by Alamarblue assays. The spheroid angiogenesis model was applied for analyzing the effects of vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF) (produced by preadipocytes) as well as the impact of cell‐cell interaction between preadipocytes and endothelial cells and fibrin matrix on endothelial cell migration. Preadipocytes proliferated in fibrin glue, whereas endothelial cells underwent apoptosis. By co‐culturing, both cell types demonstrated an increased proliferation rate. Preadipocytes provoked migration of endothelial cells. Blocking bFGF and/or VEGF led to a significant decrease of migration. Changes in fibrin structure were followed by migration of single cells instead of sprouting. An appropriate fibrin matrix as well as already differentiated endothelial cells are necessary for preadipocytes to develop their angiogenic activity via bFGF and VEGF.     

Cladribine,cytarabine, filgrastim,and mitoxantrone (CLAG-M) compared to standard induction in acute myeloid leukemia from myelodysplastic syndrome after azanucleoside failure

For patients with acute myeloid leukemia from antecedent myelodysplastic syndrome particularly after azanucleoside treatment failure, outcome is poor. Here, we conducted a case-control study in these patients to compare the efficacy of CLAG-M induction (28 patients) versus standard 3 + 7 induction chemotherapy (24 patients). Response rates (P = 0.014) and median overall survival (P = 0.025) were 64% and 202 days (95% CI 37–367 days) versus 29% and 86 days (95% CI 36–136) in the CLAG-M and 3 + 7 cohorts, respectively. Median overall survival was 202 (95% CI 37–367 days) versus 86 days (95% CI 36–136) (P = 0.025), respectively. CLAG-M has encouraging activity in this patient group.