Minimal residual disease in childhood B-lineage lymphoblastic leukemia. Persistence of leukemic cells during the first 18 months of treatment

BACKGROUND. Whether patients in clinical remission for acute lymphoblastic leukemia (ALL) continue to harbor leukemic cells is not known, because methods of detecting residual malignant cells have not been sufficiently sensitive. This information might be useful for predicting recurrence and determining the duration of therapy. METHODS. Using a sensitive new method--identifying complementarity-determining region III sequences with the polymerase chain reaction--we estimated the number of residual leukemic cells in the bone marrow of eight children with B-lineage lymphoblastic leukemia before and after remission. RESULTS. Induction chemotherapy produced a 3-to-4-log reduction in the number of leukemic cells. In all samples obtained up to 18 months after diagnosis, however, 0.004 to 2.6 percent of bone marrow nucleated cells were residual leukemic cells. Among the four patients studied more than 18 months after diagnosis, three had no detectable leukemic cells in marrow samples. Despite this, one of them, who was no longer receiving therapy, had a central nervous system relapse. In one patient receiving maintenance chemotherapy, there was a 60-fold increase in leukemic cells three months before bone marrow relapse. CONCLUSIONS. The complete disappearance of leukemic cells (or their reduction below our method's threshold of detection, 1 in 100,000 cells) may be necessary to achieve a cure of ALL. The quantification of residual leukemic cells in serial marrow aspirates during therapy may allow the early detection of relapse.     

Molecular diagnosis of cutaneous T-cell lymphoma: polymerase chain reaction amplification of T-cell antigen receptor beta-chain gene rearrangements.

The goal of our study was to molecularly diagnose CTCL, by cloning the T-cell antigen receptor beta chain (TCR-beta) gene rearrangement from the malignant T cells of a patient with Sézary syndrome, in order to generate a specific oligonucleotide probe capable of detecting CTCL cells through polymerase chain reaction (PCR) amplification. Total RNA isolated from peripheral blood lymphocytes was reverse transcribed and resultant first strand cDNA was PCR amplified utilizing a concensus primer to the TCR-beta variable region (V beta) and a 3' primer to the TCR-beta constant region (C beta). PCR reaction products were subcloned into a plasmid vector and sequenced. Sequence analysis revealed that the patient's in-frame TCR-beta gene rearrangement utilized V beta 6.4, D beta 1.1, J beta 2.2, and C beta 2.1 gene segments. Oligo-primers to V beta 6.4 and J beta 2.2 were utilized to PCR amplify genomic DNA taken from the patient's blood and involved skin. Screening the amplified DNA with an oligo-probe specific for the patient's V-D-J junctional sequences resulted in the detection of the patient-specific sequences. No sequences were detected from DNA from other malignant or benign infiltrates. Thus, we have defined a "molecular fingerprint" specific for a patient's malignant T-cells and can molecularly diagnose CTCL through PCR amplification.     

Amplified C lambda and c-abl genes are on the same marker chromosome in K562 leukemia cells.

The human leukemia cell line K562, derived from a patient with Philadelphia chromosome-positive chronic myelogenous leukemia, contains amplified c-abl oncogenes and unrearranged C lambda genes. Using in situ hybridization techniques, we have determined that the amplified c-abl and C lambda DNA sequences of K562 cells are both located on the same abnormal acrocentric marker chromosome, which may represent an altered Philadelphia chromosome.     

Terminal differentiation surface antigens of myelomonocytic cells are expressed in human promyelocytic leukemia cells (HL60) treated with chemical inducers

The expression of two surface antigens present on the cell membrane of both human granulocytes and monocytes was studied during the process of myelomonocytic differentiation using two monoclonal antibodies (B9.8.1 and B13.4.1). These surface antigens are not present on immature myeloid cells nor on nonmyeloid hematopoietic cells, but can be detected when the cells are terminally differentiated. Among the bone marrow cells, B13.4.1 binds to metamyelocytes and B9.8.1 to metamyelocytes and a fraction (30%) of myelocytes. HL60 human promyelocytic leukemia cells did not react with such monoclonal antibodies. However, when such cells were induced to differentiate in vitro into mature myeloid elements by treatment with retinoic acid or dimethyl sulfoxide, 70%--90% of the differentiated cells expressed both surface antigens. Cell sorting studies on these treated HL60 cells indicated that myelocytes and metamyelocytes were the most immature cells expressing such markers. Expression of the two surface antigens was also observed when HL60 cells were induced to differentiate into monocyte/macrophage cells by treatment with the tumor promoter 12-O- tetradecanoyl-phorbol-13-acetate. Thus, human promyelocytic leukemia cells induced to differentiate in vitro by treatment with specific chemical agents express membrane antigens in the same pattern as normal bone marrow myeloid cells at the corresponding stage of differentiation.     

Quality of life in dependent older adults living at home

The purpose of medical interventions today is to favor the duration of life and to assure its quality. For a proper evaluation of the quality of life (QoL) of the elderly, it is important to assess not only the health status, but also psychological, functional and existential domains. Up to now, QoL of the dependent older living at home does not seem to have received sufficient attention. This study is a population based, cross-sectional health survey, and tries to give a picture of the QoL conditions of a group of dependent elderly living at home, using a specifically designed structured interview. In addition to this interview the Activities of Daily Living (ADL) Index and the Zung rating scale for Anxiety and Depression (AD) were administered to a total of 167 elderly (60 males and 107 females). The most interesting results of the study are the following: (1) the definition of dependence is often worsen by cultural prejudices; (2) psychopathological factors show a deep negative effect on 'attitudes towards life' of the dependent elderly; (3) QoL of the dependent elderly people in this sample is mainly negatively influenced by the degree of depression. We believe that the 'QoL-oriented' therapeutic strategy should consider more articulated and multidisciplinary geriatric and psychosocial interventions in this population.     

Temperament and character profile of eating disorders: a controlled study with the Temperament and Character Inventory

OBJECTIVE: The question whether anorexia nervosa (AN) and bulimia nervosa (BN) are different disorders or the extremes of a psychopathologic spectrum still has no definite answer. A way to face this problem is to examine the personality traits underlying these disorders. METHOD: The Temperament and Character Inventory (TCI) was administered to 141 anorectics (70 Restrictor and 71 Binge-purging), to 102 bulimics, and to 100 controls. The Temperament and Character Inventory main scales are Novelty Seeking, Harm Avoidance, Reward Dependence, Persistence, Self-Directedness, Cooperativeness, and Self-Transcendence. RESULTS: The personality profiles that emerged are characterized by low Novelty Seeking, high Harm Avoidance, high Persistence, and low Self-Directedness in AN, and by high Novelty Seeking, high Harm Avoidance, and low Self-Directedness in BN. Binge-purging anorectics showed a personality profile midway between anorectics and bulimics. DISCUSSION: The dimensional study of personality through the TCI and its facets seems effective in discriminating the personality traits underlying the different subtypes of Eating Disorders. The hypothesis of an Eating Disorders spectrum and its clinical implications are discussed.     

Temperament and character in obese women with and without binge eating disorder

Obesity is a serious disorder and its treatment involves dietitians, psychologists, and psychiatrists, often with a poor outcome. The role of psychiatric issues in obesity is equivocal, and so is the fact whether emotional and behavioral disturbances are causes or consequences of an individual's overweight condition. We performed a study that included 120 obese women (59 with binge eating disorder [BED] and 61 with non-BED) according to specific selection criteria, and compared to 80 healthy controls. Body mass index (BMI) was calculated for all patients and they were assessed with the Temperament and Character Inventory (TCI). Despite the fact that obese patients with BED and without BED display a similar personality profile, those with BED show lower scores in Self-Directedness (SD). Both groups of obese patients differ from nonobese controls in Novelty Seeking (NS), Harm Avoidance (HA), Cooperativeness (C), and SD. SD seems to be the strongest predictor for the development of BED. The idea that two distinct groups of obese patients exist is supported. Moreover, as regards personality, a lower SD and a higher risk of Personality Disorders were found in obese BED patients. Different severities of overweight do not seem to relate to a specific personality susceptibility.     

Screening for lung cancer

The large clinical studies of lung cancer screening carried out more than 20 years ago were interpreted as evidence against screening. Those studies have been recently reassessed in the light of methodologic flaws in the randomization of subjects at risk for lung cancer. There is no evidence to support the former conclusion that screening is ineffective and the consequent official recommendation not to screen for lung cancer. The hypothesis of overdiagnosis of lung cancers diagnosed by screening is false. Clinical evidence supports the concept that the current dogma against screening for lung cancer is untrue. Indeed, the 5-year survival rate of patients with NSCLC detected in stage I and radically resected ranges from 60% to 80%. This rate is in sharp contrast to the 10% survival rate of stage I NSCLC not resected. About 90% of lung cancer cases are detected among smokers and former smokers; these well-known at-risk subjects should be offered a screening test with the goal of detecting the disease when it is in stage I. It is expected that the techniques for early detection of lung cancer will be refined and become more sensitive in the near future, so that it will be possible to detect an increasingly large proportion of lung cancers when they are truly in stage I (i.e., nonmetastatic) and curable by radical surgical resection. Low-dose helical CT scan is currently believed to represent a very useful technique for screening for lung cancer, with a higher sensitivity than chest radiograph screening. Chest radiography for lung cancer screening, however, is cheaper and ubiquitously available, and it should still be recommended if CT scan is locally unavailable. As underscored in a recent commentary in The Lancet, the existing public health policy discouraging the screening for lung cancer is in urgent need of reconsideration.