Clinical features and outcome in childhood T-cell leukemia-lymphoma according to stage of thymocyte differentiation: a Pediatric Oncology Group Study

The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment.     

Risk factors for avascular bone necrosis in systemic lupus erythematosus

OBJECTIVE: To study the predictive factors for avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE). METHOD: The records of 38 SLE patients who developed clinically apparent AVN during the course of their disease were reviewed. Information on clinical presentation, corticosteroid usage and autoantibody profiles was obtained, and comparison was made between these patients and 143 consecutive control SLE patients who did not have AVN. RESULTS: The point prevalence of AVN in our SLE population was 12%. Patients with AVN, when compared with controls, had a significantly higher incidence of neurological disease (39% vs 14%; P < 0.001) and Cushingoid body habitus after steroid treatment (79% vs 53%; P = 0.004). The highest cumulative prednisolone dose in 1 and 4 months was significantly higher in the AVN group than the controls (1.8 vs 1.1 and 4.5 vs 2.8 g, respectively; P < 0.01 in both) and showed a linear trend with the incidence of AVN (chi2 test for trend, P < 0.01 in both). Lupus anticoagulant was associated with AVN (P = 0.02, odds ratio 2.88 [1.14- 7.28]). Logistic regression analysis revealed that the highest cumulative prednisolone dose administered in 4 months, the maximum and mean daily prednisolone dosage, and the lupus anticoagulant were independent risk factors for AVN. CONCLUSIONS: Corticosteroid remains the major predisposing factor for AVN in SLE. Patients who require an initial high-dose steroid for disease control are at risk of AVN, especially if they are positive for the lupus anticoagulant or develop Cushingoid habitus after steroid treatment. High-risk patients should be closely monitored so that early AVN can be diagnosed by sensitive techniques such as magnetic resonance imaging and radioisotope bone scanning.      

delta-Aminolevulinate dehydratase in human erythroleukemia cells: an immunologically distinct enzyme

Physicochemical and immunologic properties of delta-aminolevulinate (ALA) dehydratase in human K562 erythroleukemia cells were examined. ALA dehydratase activity was found to increase in K562 cells after treatment with butyric acid or selenium oxide. Enzyme activity in untreated K562 cells was comparable to that in normal adult erythrocytes but was increased three- to six-fold in K562 cells treated with 1.2 mmol/L butyric acid or 0.03 mmol/L selenium oxide. The Michaelis-Menten constant (Km), the inhibitor constant (Ki), and elution profile by diethylaminoethyl (DEAE) cellulose chromatography were similar for ALA dehydratase from K562 cells and normal human adult and human fetal erythrocytes. However, ALA dehydratase from K562 cells did not react with a monospecific rabbit antibody against ALA dehydratase purified from normal adult erythrocytes, although the antibody reacted with the enzyme from normal adult and fetal red cells. These findings indicate that ALA dehydratase in K562 cells is immunologically distinct from the normal enzyme.     

Independent Origin of Plasmodium falciparum Antifolate Super-Resistance,Uganda, Tanzania,and Ethiopia

Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine–pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004–2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles derived from 1 lineage that was distinct from those in Uganda and Tanzania. Uganda and Tanzania triple mutants derived from the previously characterized southeastern Africa double-mutant lineage. The A581G mutation has occurred multiple times on local Pfdhps double-mutant backgrounds; however, a novel microsatellite allele incorporated into the Tanzania lineage since 2004 illustrates the local expansion of emergent triple-mutant lineages.     

A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain

Background

In resource-poor settings, cold chain requirements present barriers for vaccine delivery. We evaluated the immunogenicity and safety of tetanus toxoid (TT) vaccine in “Controlled Temperature Chain” (CTC; up to 40 °C for <30 days before administration), compared to standard cold chain (SCC; 2–8 °C). Prior to the study, stability parameters of TT–CTC were shown to meet international requirements.

Methods

A cluster randomized, non-inferiority trial was conducted in Moïssala district, Chad, December 2012–March 2013. Thirty-four included clusters were randomized to CTC or SCC. Women aged 14–49 years, eligible for TT vaccination and with a history of ≤1 TT dose, received two TT doses 4 weeks apart. Participants were blinded to allocation strategy. Tetanus antibody titers were measured using standard ELISA at inclusion and 4 weeks post-TT2. Primary outcome measures were post-vaccination seroconversion and fold-increase in geometric mean concentrations (GMC). Non-inferiority was by seroconversion difference (TT_SCC − TT_CTC) <5% and ratio of GMCs (TT_SCC/TT_CTC) <1.5. Adverse events were monitored at health centers and at next contact with participants.

Results

A total of 2128 women (CTC = 1068; SCC = 1060) were recruited. Primary intention to vaccinate analysis included 1830 participants; 272 of these were included in the seroconversion analysis. Seroconversion was reached by >95% of participants; upper 95%CI of the difference was 5.6%. Increases in GMC were over 4-fold; upper 95%CI of GMC ratio was 1.36 in the adjusted analysis. Few adverse events were recorded.

Conclusions

This study demonstrates the immunogenicity and safety of TT in CTC at <40 °C for <30 days. The high proportion of participants protected at baseline results in a reduction of power to detect a 5% non-inferiority margin. However, results at a 10% non-inferiority margin, the comparable GMC increases and vaccine's stability demonstrated in the preliminary phase indicate that CTC can be an alternative strategy for TT delivery in situations where cold chain cannot be maintained.     

经肛门内镜显微手术切除直肠肿瘤

目的评价经肛门内镜显微手术(TEM)切除直肠绒毛状腺瘤和早期直肠癌的应用效果。方法分析我院总结1995年11月至2001年12月27例TEM手术的临床资料。结果本组患者肿瘤直径中位值2.5cm,肿瘤下缘与齿状线距离(8.9±3.4)cm,肿瘤侵犯直肠周径范围(35.7±17.5)%。平均手术时间(109±46)min。平均住院日4.5d。无围手术期死亡。手术并发症有尿潴留、暂时性大便失禁和慢性阻塞性肺病(COPD)复发。术中2例切穿至腹腔,即刻内镜下修补成功。切缘100%瘤细胞阴性。病理示直肠绒毛状腺瘤14例、直肠腺癌13例,后者包括pTis2例,pT16例和pT25例。直肠癌腔内超声肿瘤T分期符合率为84.6%。5例pT2中2例中转前切除术,1例接受术后放疗,2例无附加任何治疗。平均随访18个月,所有病例无局部复发。死亡2例,但无复发迹象。结论TEM易行且安全,是直肠绒毛状腺瘤和部分T1直肠癌的治愈性手术,也可作为T2直肠癌的姑息性治疗手段。     

经肛门内镜显微手术治疗直肠绒毛状腺瘤和早期直肠癌31例

目的探讨经肛门内镜显微手术（transanal endoscopicmic rosurgery，TEM）治疗直肠绒毛状腺瘤和早期直肠癌的疗效。方法1995年11月～2003年12月，我院行TEM治疗直肠肿瘤31例。全麻下根据肿瘤位置选择合适的体位，经肛门插入特殊的手术直肠镜，保持CO2充气状态，在立体视镜和腔镜系统下，采用针形电刀或5mm超声刀将直肠肿瘤完整切除（黏膜下或全层切除），手术创口在腔内连续缝合。结果31例直肠肿瘤均获完整切除，切缘均阴性。手术时间45～220min，平均95min；术中出血量0～180ml，平均40ml。手术并发症：暂时性排气失控2例，急性尿潴留1例，慢性阻塞性气道疾病急性发作1例，因服用阿斯匹林而出现继发性出血1例。术后病理分期：pT0期16例，pTis期2例，pT1期7例，pT2和pT3期各3例。31例随访2～92个月，平均23个月，肿瘤无原位复发。结论TEM是治疗直肠绒毛状腺瘤和早期直肠癌的一种安全、有效的微创手术方法。