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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past decade, advances in the treatment of childhood acute lymphoblastic leukemia (ALL) have continued, largely due to improved disease-free survival of poor-prognosis subgroups, improved sanctuary therapy, shortening of therapy duration, and salvage of relapsed patients with better chemotherapy regimens and with bone marrow transplantation. Nonetheless, more children continue to die of ALL than of any other childhood cancer. This review outlines central issues in the staging and treatment of ALL that should be addressed if the cure rate in childhood ALL is to be significantly improved. Present dilemmas in the staging of ALL include the following: lack of standardization of staging systems; complicated algorithms; variable application and interpretation of multivariate analyses; dynamic interactions between prognostic front end variables and subsequent treatment; ambiguity of prognostic factors that are predictive of outcome but biologically inexplicable; unsuccessful attempts to define a good-prognosis subgroup for the purpose of streamlining therapy to a minimum; and the interface between ALL and non-Hodgkin's lymphoma and myeloid leukemias. The remaining therapeutic problems include a lack of reliable in vitro tests of chemosensitivity and chemoresistance, inability to quantitate residual leukemia after remission induction or to detect drug-resistant clones of cells before they are clinically manifest, and delivery of optimum therapy and supportive care to all children with ALL.
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PMID:Acute lymphoblastic leukemia in children. Advances and prospectus. 240 96

To study the survival and prognostic factor of childhood acute lymphoblastic leukemia, 78 newly-diagnosed cases between January 1982 and June 1987 in National Taiwan University Hospital were reviewed and analyzed. They were stratified into two groups, i.e. standard-risk (SR) and high-risk (HR), according to their pre-treatment leukocyte count and age. Following induction therapy, 97% of the SR patients and 80% of the HR patients attained complete remission. In the SR group, the 2- and 3-year failure-free survival rates were 37% and 24%, with a median survival of 16 months. In the HR group, failure-free survival at the second and third year were 11% and 4%, respectively, with a median survival of 5.3 months. Three factors are strongly related to induction failure, i.e. high leukocyte counts (greater than 50*10(9)/1), massive hepatomegaly and large lymph nodes. Univariate analysis of failure-free survival showed six variables with significant detrimental effects on eventual outcomes, i.e. high leukocyte counts (greater than 50*10(9)/1), meningeal leukemia, marked lymphadenopathy, age younger than 2 years and older than 10 years, massive hepatomegaly (greater than 6 cm), and high LDH level (greater than 800 u/1). However, statistical survival models should also determine the joint effects of the prognostic factors so that the relative importance of each factor can be assessed. High initial leukocyte count, disclosed by multivariate analysis, was the single most important factor detrimental to the continuance of complete remission (P = 0.0004). Preliminary results also revealed poor compliance and early relapse in this study. Possible causes of early failure are discussed. Conceptual education for family members, as well as management with effective cytoreductive therapies are urgently needed.
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PMID:An analysis of risk factor and survival in childhood acute lymphoblastic leukemia. 263 11

During the past decade, advances in the treatment of childhood acute lymphoblastic leukemia (ALL) have continued. Progress is largely due to improved disease-free survival of poor-prognosis subgroups, improved sanctuary therapy, shortening of therapy duration, and salvage of relapsed patients by use of better chemotherapy regimens and bone marrow transplantation. Nonetheless, more children continue to die of ALL than of any other childhood cancer. This article reviews the progress and indicates remaining problems in the staging and treatment of ALL. Remaining problems include a lack of standardization between staging systems, variable application and interpretation of multivariate analysis, and occurrence of epiphenomenon. Also, to have statistical validity, clinical studies require numbers of patients larger than have been the case as results of treatment improve. Confusing also is the biological interface between ALL, non-Hodgkin's lymphoma, and the myeloid leukemias; the lack of reliable in vitro tests of chemosensitivity and chemoresistance; and the inability to quantitate residual leukemia after remission induction or to detect drug-resistant clones of cells before they are clinically manifest. Delivery of optimum therapy and supportive care to all children with ALL remains an elusive goal.
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PMID:Remaining problems in the staging and treatment of childhood lymphoblastic leukemia. 269 53

We assessed neuropsychologically 106 children with acute lymphoblastic leukemia (ALL) who had all received cranial irradiation for the prevention of central nervous system (CNS) leukemia 1-13 years previously. Children were assessed for adverse late effects of their therapy, using age-appropriate Wechsler measures of overall intellectual ability and supplementary tests. Forty-five siblings near in age to the patients were tested as controls. The patients who had had the most intensive central nervous system (CNS) prophylaxis were found to have a WISC-R Full Scale IQ 17 points lower than the sibling control group. Performance IQ was more affected than verbal IQ. The patients were more easily distracted and less able to concentrate. The severity of the aftereffects was related to younger age at the time of CNS prophylaxis and to a higher dose of cranial irradiation but not to time since CNS prophylaxis. CNS prophylaxis using a combination of cranial irradiation and intrathecal methotrexate has lowered the incidence of CNS relapse in childhood ALL but is associated with considerable long-term morbidity in survivors.
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PMID:Neuropsychological sequelae of central nervous system prophylaxis in survivors of childhood acute lymphoblastic leukemia. 270 13

Signals from many receptor-ligand interactions are mediated by enhancement of phospholipid hydrolysis which generates metabolic intermediates stimulating protein kinase C (PKC) and elevating cellular calcium. Pharmacologic agents such as phorbol 12, 13-dibutyrate (PDBu) and ionomycin selectively stimulate PKC and elevate intracellular calcium to directly stimulate downstream mechanisms critical to cell growth and function. This study examines the effects of PDBu, ionomycin, and rIL-2 on childhood ALL blasts of early B lineage with respect to various aspects of cell activation, including DNA synthesis, induction of non-MHC restricted tumoricidal activity, and changes in morphology and phenotype. Five childhood ALL samples were tested. A marked heterogeneity was seen among the ALL samples with respect to in vitro growth following manipulation with PDBu, ionomycin, and/or rIL-2, whereas normal peripheral blood lymphocytes (PBL) were consistently stimulated to grow with the combination of PDBu and ionomycin. Growth responsiveness did not appear to correlate with morphologic or phenotypic classification of the leukemia samples. Four of the five leukemia samples developed substantial non-MHC restricted cytotoxicity to K562 (natural killer cell (NK) sensitive) and Daudi (NK resistant) targets in response to rIL-2. This functional cytotoxic response correlated with morphologic changes in the cells and the appearance of granules. Phenotypic analyses of the ALL samples at the time of their peak cytotoxic function were consistent with the fresh ALL phenotype and showed no major change in cell populations. Three of the five ALL samples also retained rIL-2 induced cytotoxic capabilities when exposed simultaneously to the combination of PDBu and ionomycin, whereas rIL-2 induced tumoricidal activity in normal PBL and bone marrow cultures was inhibited by these reagents. These data show that morphologically and phenotypically similar ALL blasts have heterogeneous proliferative responses to the PKC and calcium modulators PDBu and ionomycin, as well as to rIL-2. Cytotoxic responses are also different from those of normal PBL and bone marrow cells with respect to kinetics and responsiveness to inducing agents. Thus current morphologic and phenotypic classifications of ALL may not adequately reflect the heterogeneity of this disorder as described here.
Leukemia 1989 Aug
PMID:Induction of tumoricidal activity and alterations of growth by interleukin-2 and manipulation of protein kinase C and cytosolic calcium in childhood acute lymphocytic leukemia cells. 278 55

We assessed the prognostic significance of leukemia cell cytogenetics by analyzing bone marrow aspirates obtained at time of diagnosis in 165 children on a single protocol for acute lymphoblastic leukemia (ALL). These children were assigned to six mutually exclusive cytogenetic categories as follows: (1) hyperdiploid, with 50 or more chromosomes (n = 35); (2) hyperdiploid, with 47 to 49 chromosomes (n = 11); (3) diploid (n = 42); (4) pseudodiploid (n = 34); (5) hypodiploid (n = 9); and (6) insufficient data (n = 34). At a median follow-up of 5 years, there were no statistically significant differences between any of these cytogenetic categories in either event-free or overall survival. Those children with chromosomal translocations (n = 26) appeared to fare the same as those lacking translocations (n = 105). The absence of karyotypic prognostic significance was observed not only within the overall group, but also when the results were stratified by standard-risk and high-risk status. Of the specific structural chromosome changes that we studied, only the Philadelphia chromosome (Ph) appeared to confer a poor prognosis, although there were too few such cases to achieve statistical significance. Although we did not detect the event-free survival differences that have been described previously in hyperdiploid, hypodiploid, and pseudodiploid childhood ALL, our findings must be viewed as preliminary given the small number of children in some of the cytogenetic categories. We think that the prognostic implications of these cytogenetic features might have been nullified by improvements in therapy.
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PMID:Prognostic implications of cytogenetic studies in an intensively treated group of children with acute lymphoblastic leukemia. 280 51

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine lymphosarcoma. Much speculation continues to be directed at the role of BLV in human leukemia. To test this hypothesis rigorously, a case-control study of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma was conducted between December 1983 and February 1986. Cases (less than or equal to 16 years at diagnosis) derived from patients diagnosed at the primary institutions and affiliated hospitals were matched (age, sex, and race) with regional population controls. DNA samples from bone marrow or peripheral blood from 157 cases (131 acute lymphoblastic leukemia, 26 non-Hodgkin's lymphoma) and peripheral blood from 136 controls were analyzed by Southern blot technique, under highly stringent conditions, using cloned BLV DNA as a probe. None of the 157 case or 136 control DNA samples hybridized with the probe. The high statistical power and specificity of this study provide the best evidence to date that genomic integration of BLV is not a factor in childhood acute lymphoblastic leukemia/non-Hodgkin's lymphoma.
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PMID:No involvement of bovine leukemia virus in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma. 283 51

Analysis of the results of United Kingdom Acute Lymphoblastic Leukaemia (UKALL) trials since 1972 showed that no improvement in remission or survival had been achieved over the 7 years up to 1979 for 1470 patients in trials UKALL II to VI. UKALL VII (1979-80) gave somewhat better results for a small group of good-prognosis patients. However, UKALL VIII, introduced in 1980, produced a 15-20% increase in 4-year disease-free survival compared with the best results of previous studies, despite a higher frequency of treatment-induced morbidity and mortality. Factors possibly contributing to this highly significant difference include the policy of continuing therapy without interruption during induction, a long course of intramuscular asparaginase over 3 weeks, full-dose mercaptopurine and co-trimoxazole during central-nervous-system prophylaxis, and the use of sustained maximum tolerated oral doses of mercaptopurine and methotrexate maintenance. An intensive sustained approach to chemotherapy in childhood ALL is needed, especially in the early stages of treatment.
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PMID:Improvement in treatment for children with acute lymphoblastic leukaemia. The Medical Research Council UKALL trials, 1972-84. Report to the Council by the Working Party on Leukaemia in Childhood. 286 39

The best therapy for children with acute lymphoblastic leukaemia (ALL) who have an initial bone marrow relapse and subsequently achieve second remission is controversial. Some findings suggest that bone marrow transplantation (BMT) is better than chemotherapy whereas others do not. An analysis of 871 children treated by BMT or chemotherapy showed that outcome was correlated with risk factors at diagnosis and with length of first remission. BMT seemed superior in patients who relapsed within 18 months of first remission while on maintenance chemotherapy. BMT was not demonstrably superior in patients who relapsed more than 18 months after first remission. The choice of treatment in childhood ALL must be based on prognostic variables at diagnosis and on the circumstances of the relapse.
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PMID:Which treatment for childhood acute lymphoblastic leukaemia in second remission? 288 Feb 24

Cell kinetics were studied in 124 patients with acute lymphoblastic leukaemia (ALL) by flow cytometry, comparing cell cycle characteristics between adults (57 cases) and children (67 cases). S, G2 + M and the low protein content fraction of G1 (LPC fraction) were determined and studied in relation to other clinical and biological features. No difference was found between adults and children in the distribution of these variables. The proliferative rates according to organomegaly, leukocytosis, the FAB cytological groups and the immunological groups did not present any significant differences between the two groups of patients. However, cell cycle did seem to have a very different prognostic value for adults and for children. G2 + M was a strong prognostic indicator for childhood ALL: duration of CR and survival were significantly longer when G2 + M was higher (P less than 0.01). In adults, survival was longer for intermediary (between 3.8 and 5.8%) and high (over 7.2%) G2 + M values (P less than 0.01). The negative correlation between S and G2 + M observed in adults and the absence of correlation in children raise the possibility of differences in duration of the different phases for the two groups and perhaps an accumulation of cells in G2 or tetraploidy in some cases.
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PMID:Cell kinetics in acute lymphoblastic leukaemia: comparative analysis between adults and children. 293 Jul 6


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