Sixty transfusion-dependent thalassemic patients were studied by simultaneous measurement of circulating thyroid hormones, basal thyroid-stimulating hormone (TSH) and TSH response to thyrotropin-releasing hormone with the aim of evaluating the frequency of hypothyroidism in such patients, and the relationship between hypothyroidism and compliance with treatment and iron overload. Thyroid failure was present in 31 of the 60 patients. A correlation was found between impairment of thyroid functions, duration of chronic hypoxia and the activities of various transaminases. The results of this study emphasize the importance of early evaluation of thyroid function in thalassemic patients and suggest that anemia and hypoxia may potentiate the toxicity of iron deposition in endocrine glands.
CD 10-positive lymphoid cells are of interest because they are the most immature recognizable B cells and because they are usually present in acute lymphocytic leukemia (ALL) [l]. Although the presence of CD10-positive lymphoid cells has been considered an early marker of relapse in off-therapy ALL children [2], studies dealing with CDlO antigen intensity in such patients are virtually absent. In fact, fluorescence intensity of CDlO-positive cells is heterogeneous. It has previously been shown that normal CD 10-positive cells display a lower mean CDlO antigen density than do cells from most cases of CDIO-positive ALL [3]. This separation, however, is far from absolute.Ten off-therapy ALL children in continued remission formed the basis of this study aimed at investigating the presence of bone marrow (BM) CDlO-positive cells. There were 4 males and 6 females. Median age at the diagnosis of ALL was 7 years (range: 5-12 years). As far as antileukemic therapy is concerned, all patients were treated according to the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) protocols. At the time of the BM study, all had remained disease-free for 1-12 months (median: 7 months) from the discontinuation of therapy. In each patient, BM aspirates were analyzed by flow cytometry with fluorescein-labeled monoclonal antibodies.The results of BM cell phenotyping were as follows [mean % (range)]: CD3 = 28.9 (16.9-56); CD4 = 12.6 (8.4-11.6); CD8 = 16 (6.8-30); CD2 = 26.3 (5.9-66.6); HLA-DR = 62.9 (44-74.3); CD19 = 49.2 (1 1.4-72.7); CD20 = 43.2 (11-67.6); CDlO (weakly) = 40 (32.1-58.5); CDlO (strongly) = 2.1 (1.5-3.2); CD34 = 9.7 (4.5-16. I).The FACS profile from a representative patient stained for CDlO is shown in Figure 1. The histogram suggests the presence of cell subpopulations with weak and strong fluorescence. The inflection point between the peaks occurred approximately at the value of 100 in a scale of 250 channels of fluorescence intensity. By setting a cutoff at this value we defined two subpopulations of CD1O-positive cells that differ with respect to their fluorescence intensity, with mean specific fluorescence 0 1991 Wiley-Liss, Inc. 119.7 2 12.6 and 86.5 -t 10.9 for cells displaying strong and weak CDlO antigen density, respectively.Our results demonstrate that strongly CD10-positive BM subpopulation, similar to that shown by CD10-positive ALL, can be found in off-therapy ALL children without clinical or hematological evidence of relapse. This feature suggests the immaturity of the strongly CD1O-positive lymphoid cells. Further studies should address the proper role of this observation with regard to the outcome of disease.
In this retrospective multicentric study, we report on early deaths (ie, those that occurred during the first month of treatment) in a total of 943 newly diagnosed ALL pediatric patients registered from 1976 to 1981 at 21 centers of the AIL- AIEOP . Objectives of this study were as follows: (1) to verify the incidence and the cause of early death in a wide population of children with ALL and (2) to elucidate factors associated with early death and therefore to identify "high-risk" groups of patients. Out of the 943 ALL patients, 39 (4.1%) early deaths were registered. Main causes were infection, 20 patients (51.3%); hemorrhage, 11 patients (28.3%); uric acid nephropathy, 2 patients (5.1%); cardiac failure, 3 patients (7.6%); syndrome of inappropriate antidiuretic hormone secretion, 1 patient. Two patients died during the first week of unknown cause. Thirteen factors measured at diagnosis and possibly influencing the early death rate were analyzed. Using the chi-square test, only three of these factors (age, mediastinum status, surface markers) appear to have any significant influence on the early death rate. We also tried to determine how therapy influences this process by analyzing variations in the early death rate, other factors being equal. Significant differences in the early death rates were encountered in AIEOP protocols using different induction regimens.
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