National Cancer Institute®
Last Modified: November 21, 2001
UI - 21417789
AU - Blanco JG; Dervieux T; Edick MJ; Mehta PK; Rubnitz JE; Shurtleff S;
TI - Raimondi SC; Behm FG; Pui CH; Relling MV Molecular emergence of acute myeloid leukemia during treatment for acute lymphoblastic leukemia.
SO - Proc Natl Acad Sci U S A 2001 Aug 28;98(18):10338-43
AD - Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
Therapy-related acute myeloid leukemias (t-AML) with translocations of the MLL gene are associated with the use of topoisomerase II inhibitors. We established the emergence of the malignant clone in a child who developed t-AML with a t(11;19) (q23;p13.3) during treatment for acute lymphoblastic leukemia (ALL). The MLL-ENL and the reciprocal ENL-MLL genomic fusions and their chimeric transcripts were characterized from samples collected at the time of t-AML diagnosis. We used PCR with patient-specific genomic primers to establish the emergence of the MLL-ENL fusion in serially obtained DNA samples. The MLL-ENL fusion was not detectable in bone marrow at the time of ALL diagnosis or after 2 months of chemotherapy (frequency <8.3 x 10(-7) cells(-1)). The genomic fusion was first detected in bone marrow after 6 months of treatment at a frequency of one in 4,000 mononuclear bone marrow cells; the frequency was one in 70 cells after 20 months of therapy. At the first detection of MLL-ENL, the only topoisomerase II inhibitors the patient had received were one dose of daunorubicin and two doses of etoposide. The MLL-ENL fusion was not detectable in blood at the time of ALL diagnosis or after 0.7, 2, 8, 10, and 12 months of therapy but was detectable in blood at 16 months (one in 2.3 x 10(4) cells). Recombinogenic Alu sequences bracketed the breakpoints in both fusions. These data indicate that the malignant clone was not present before therapy, arose early during chemotherapy, and was able to proliferate even during exposure to antileukemic therapy.
UI - 21226344
AU - Hann I; Vora A; Harrison G; Harrison C; Martineau M; Moorman AV; Secker
TI - Walker LM; Eden O; Hill F; Gibson B; Richards S; UK Medical Research Council's Working Party on Childhood Leukaemia Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol.
SO - Br J Haematol 2001 Apr;113(1):103-14
AD - Department of Paediatric Haematology & Oncology, Great Ormond Street Hospital, London, UK. Ian.Hann@gosh-tr.nthames.nhs.uk
The single most important prognostic determinant in childhood acute lymphoblastic leukaemia (ALL) is effective therapy and changes in therapy may influence the significance of other risk factors. The effect of intensified therapy on the importance of currently recognized phenotypic and genotypic determinants of outcome was assessed in 2090 children enrolled on the Medical Research Council United Kingdom acute lymphoblastic leukaemia XI (MRC UKALL XI) protocol. Treatment allocation was not determined by risk factors. Multivariate analysis confirmed the dominant influence on prognosis of age, sex and presenting white cell count (WCC). After allowing for these features, blast karyotype, d 8 marrow blast percentage and remission status at the end of induction therapy were the only remaining significant predictors of outcome. Organomegaly, haemoglobin concentration, French--American--British type, body mass index, presence of central nervous system disease at diagnosis, immunophenotype and presence of TEL/AML1 fusion gene (examined in a subset of 659 patients) either had no significant effect on outcome or were significant only in univariate analysis. Among karyotype abnormalities with an independent influence on prognosis, high hyperdiploidy (> 50 chromosomes) was shown to be favourable, whereas near haploidy (23--29 chromosomes), presence of the Philadelphia chromosome, t(4;11) and abnormalities affecting the short arm of chromosome 9 [abn (9p)] were adverse risk factors. Early responders to therapy, determined by residual marrow infiltration after 8 d of induction therapy, had a good outcome, while the small proportion of patients who did not achieve a complete remission by the end of induction therapy had a poor outcome. A third block of late intensification was shown to improve event-free survival by 8% at 5 years. The effect of these risk factors was not significantly different between those randomized to the third intensification block and those not randomized to a third block.
UI - 21345447
AU - Rios JA; Korones DN; Heal JM; Blumberg N
TI - WBC-reduced blood transfusions and clinical outcome in children with acute lymphoid leukemia.
SO - Transfusion 2001 Jul;41(7):873-7
AD - Transfusion Medicine Unit, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
BACKGROUND: WBC reduction offers a variety of benefits to patients requiring multiple transfusions during induction therapy for childhood acute lymphoid leukemia (ALL), including reductions in febrile transfusion reactions, HLA alloimmunization, and CMV transmission. One potential benefit is a reduction in the deleterious effects of transfusion immunomodulation. In the surgical setting, transfusion immunomodulation has been linked to increases in postoperative infections and decreases in host cellular immunity that are mitigated by WBC reduction of transfused blood. STUDY DESIGN AND METHODS: A retrospective review was conducted of the medical records of 68 consecutive children undergoing induction therapy for newly diagnosed ALL from 1988 through 1995, a period whose midpoint is 1991, the year WBC reduction was introduced in this hospital. RESULTS: WBC reduction of platelet and RBC transfusions was associated with fewer days with fever (mean, 5.7 days [no WBC reduction] and 2.1 days [WBC reduction]; p = 0.012) and days with positive microbial cultures (mean, 1.5 [no WBC reduction] and 0.71 [WBC reduction]; p = 0.0055). There were more high-risk ALL patients in the group receiving WBC-reduced transfusions. CONCLUSION: Allogeneic WBCs in transfused blood may cause impairment of host defenses against microbial infection during induction therapy for childhood ALL.
UI - 21426545
AU - Uzunel M; Mattsson J; Jaksch M; Remberger M; Ringden O
TI - The significance of graft-versus-host disease and pretransplantation minimal residual disease status to outcome after allogeneic stem cell transplantation in patients with acute lymphoblastic leukemia.
SO - Blood 2001 Sep 15;98(6):1982-4
AD - Department of Clinical Immunology, Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden. firstname.lastname@example.org
Relapse is the major cause of treatment failure after allogeneic stem cell transplantation (SCT) in patients with acute lymphoblastic leukemia. Minimal residual disease (MRD) was analyzed before SCT in 30 patients with acute lymphoblastic leukemia. The aim was to determine whether the level of MRD before transplantation was correlated with outcome. Fifteen patients were found to have high-level MRD (10(-2) to 10(-3)), 10 had low-level MRD (< 10(-3)), and 5 were MRD(-). Among MRD(-) patients the probability of relapse was 0 in 5, which was less than in MRD(+) patients (13 of 25) (P =.05). No major difference was found between the high- and low-level MRD(+) groups. Among the MRD(+) patients, only 2 of 11 with acute and chronic graft-versus-host disease had a relapse, versus 11 of 14 without (P =.005). In conclusion, for patients entering transplantation while they have residual disease, a combination of acute and chronic graft-versus-host disease may be needed to decrease the risk of relapse after SCT.
UI - 21464093
AU - Xinjia F; Matano S; Amitani S; Terahata S; Furusyo H; Yamamoto M;
TI - Sugimoto T [Low-dose etoposide in a patient with adult T-cell leukemia/lymphoma who had severe complications]
SO - Gan To Kagaku Ryoho 2001 Sep;28(9):1269-72
AD - Dept. of Hematology, Tonami General Hospital.
A 76-year-old female had been followed in our hospital for dissecting aneurysm, cardiac failure, and cerebral infarction. Inguinal histopathologic diagnosis of the biopsied lymph node was diffuse pleomorphic type non-Hodgkin's lymphoma with T-cellular phenotype, and the patient was referred to our department. She had human T-lymphotropic virus type I seropositivity, and PCR of the pX lesion disclosed a monoclonal band. She was ultimately diagnosed as having adult T-cell leukemia/lymphoma (ATL/L, stage IV). Since she had many severe complications, she was given low-dose etoposide (LD-ETP, 50 mg/day). Atypical cells disappeared from the blood, and lymphadenopathy regressed. No major adverse reaction was observed after LD-ETP. She continued to receive intermittent LD-ETP, but she developed pneumonia in lymphomatous lesions. These findings suggest that LD-ETP is a well tolerable and effective treatment in patients with ATL/L even if there are severe complications.
UI - 21446742
AU - Kingma A; van Dommelen RI; Mooyaart EL; Wilmink JT; Deelman BG; Kamps WA
TI - Slight cognitive impairment and magnetic resonance imaging abnormalities but normal school levels in children treated for acute lymphoblastic leukemia with chemotherapy only.
SO - J Pediatr 2001 Sep;139(3):413-20
AD - Department of Pediatrics, Division of Pediatric Oncology/Hematology, University Hospital Groningen, Groningen, The Netherlands.
OBJECTIVES: To investigate persistent neuropsychologic late effects in children treated for acute lymphoblastic leukemia at a young age with chemotherapy only by means of serial neuropsychologic assessments (NPAs), magnetic resonance imaging (MRI) of the brain, and evaluation of school levels. STUDY DESIGN: Consecutive patients (n = 17) had 2 extensive NPAs (12 psychometric measures) after cessation of therapy. Test results were compared with those of both healthy control subjects and 28 previously treated children who received cranial irradiation. MRI findings were related to test scores. School levels were evaluated in the patients and their healthy siblings. RESULTS: Initial participation (n = 17) and availability of the study group after 8 years of follow-up were 100%. Significant group differences between patients who received chemotherapy and healthy control subjects were found for memory and fine-motor functioning. The 17 patients combined showed 16 deficits on various test measures. MRI abnormalities were seen in 6 children, but these did not correlate with cognitive performance. No differences in school levels were seen when the patients who received chemotherapy were compared with their siblings. The current nonirradiated patients demonstrated significantly better test results and significantly fewer learning disabilities and MRI abnormalities than did the previously irradiated group. CONCLUSION: Treatment with chemotherapy only may be associated with some cognitive impairment. However, these children attained normal school levels.
UI - 21371225
AU - Ma R; Liu F; Yang J
TI - [Clinical study on effect of Fuzheng Kangbai Granule on long-term survival of patients with acute leukemia]
SO - Zhongguo Zhong Xi Yi Jie He Za Zhi 1998 May;18(5):276-8
AD - Department of Hematology, Xiyuan Hospital, China Academy of TCM, Beijing 100091.
OBJECTIVE: To observe the effect of Fuzheng Kangbai Granule (FZKBG) on event free interval (EFI) and over survival (OS) of patients with acute leukemia, and to study the mechanism of FZKBG. METHODS: FZKBG was used in 90 cases of completely remitted acute leukemia, immune functions of patients before and after using FZKBG were measured. RESULTS: Five year EFI and OS were 64.2% and 77.2% of 90 cases of completely remitted acute leukemia, and the immune functions after using FZKBG have improved significantly. CONCLUSIONS: FZKBG could increase the EFI and OS of patients with acute leukemia, and the improved immune functions may play a role in increasing 5 year EFI and OS.
UI - 21066421
AU - Espy KA; Moore IM; Kaufmann PM; Kramer JH; Matthay K; Hutter JJ
TI - Chemotherapeutic CNS prophylaxis and neuropsychologic change in children with acute lymphoblastic leukemia: a prospective study.
SO - J Pediatr Psychol 2001 Jan-Feb;26(1):1-9
AD - Department of Psychiatry, Southern Illinois University, Carbondale, IL 62901-6503, USA. email@example.com
OBJECTIVE: To determine whether prophylactic CNS chemotherapy for childhood acute lymphoblastic leukemia is associated with declines in neuropsychological abilities. METHODS: Growth curve analysis was used to examine neuropsychological outcome and treatment-related change in children (N = 30) who were treated at two childhood cancer centers. A comprehensive test battery was administered at baseline (8 months), 2, 3, and 4 years postdiagnosis (age at diagnosis M = 5.90 years, SD = 4.2C). RESULTS: Results indicated modest declines in arithmetic, visual motor integration, and verbal fluency. Intrathecal and systemic treatment was related to poorer visual motor integration at 4 years postdiagnosis and a faster rate of decline in visual motor integration skills across the observation period than intrathecal treatment alone. Arithmetic proficiency at 4 years after diagnosis was related to maternal education, but the rate of decline was not. Verbal fluency was unrelated to demographic or treatment variables. CONCLUSIONS: These findings suggest that neuropsychological outcome and declines are related to both demographic and treatment characteristics depending on the cognitive domain examined.
UI - 99065270
AU - Nysom K; Holm K; Michaelsen KF; Hertz H; Muller J; Molgaard C
TI - Bone mass after treatment for acute lymphoblastic leukemia in childhood.
SO - J Clin Oncol 1998 Dec;16(12):3752-60
AD - Section of Paediatric Haematology, The Juliane Marie Centre, Rigshospitalet, Copenhagen, Denmark. firstname.lastname@example.org
PURPOSE: To study bone mass after childhood acute lymphoblastic leukemia (ALL) and determine if reduced bone mass is related to previous therapy or endocrine status at follow-up. PATIENTS AND METHODS: We studied 95 survivors of childhood ALL who were in first remission a median of 11 years (range, 3 to 23 years) after diagnosis and who had never been irradiated outside a cranial field. The bone mass was measured by dual-energy x-ray absorptiometry. The results were compared with data on 396 local controls. RESULTS: Adjusted for sex and age, the mean whole-body bone mineral content (BMC) and bone mineral areal density (BMDA) were both significantly reduced (0.4 SDs less than the predicted mean value). This was mainly caused by reduced bone mass in the 33 participants who were aged 19 years or older at follow-up. In these young adults, the mean height for age, bone area for height, and BMC for bone area were all significantly reduced. This indicated that the reduced whole-body bone mass was caused by both reduced bone size and reduced size-adjusted bone mass. Reduced bone size was related to previous cranial irradiation. Reduced size-adjusted bone mass was not significantly related to age at diagnosis or at follow-up, length of follow-up, cranial irradiation, cumulative dose of methotrexate or corticosteroids, or endocrine status at follow-up. CONCLUSION: The whole-body bone mass was reduced 11 years after diagnosis of childhood ALL. If these abnormalities remain, survivors of childhood ALL will have an increased risk for osteoporotic fractures later in life.
UI - 21281051
AU - Nysom K; Holm K; Hertz H; Muller J; Fleischer Michaelsen K; Molgaard C
TI - Bone mass after treatment for acute lymphoblastic leukemia in childhood.
SO - J Clin Oncol 2001 Jun 1;19(11):2970-1
UI - 92029758
AU - Ruccione K; Kramer RF; Moore IK; Perin G
TI - Informed consent for treatment of childhood cancer: factors affecting parents' decision making.
SO - J Pediatr Oncol Nurs 1991 Jul;8(3):112-21
Both the treatment for childhood cancer and the legal requirements for gaining parents' consent to treatment have become increasingly complex. The purpose of the exploratory investigation reported here was to identify influential circumstances surrounding the consent process in the pediatric setting, to describe the relationship of parental anxiety to these factors, and to delineate related practice and research implications. Twenty-eight parents of children entered on one of four protocols for the treatment of newly diagnosed acute lymphoblastic leukemia at the Childrens Hospital Los Angeles and the University of California San Francisco were asked to complete two questionnaires within 48 hours after consenting to treatment: the State-Trait Anxiety Index and the Parent Informed Consent Questionnaire. Results of the study confirmed clinical experience that parents are given complex information and asked to make decisions about their child's life in a highly anxious state. Although participants were generally satisfied with the informed consent process 48 hours after signing a consent form, further research is needed to document how well parents understand and remember key information, as well as the influence of time, experience, and changes in state anxiety on their perceptions of the adequacy of the consent process. In current clinical practice, simple strategies can be applied to improve the informed consent process for families of children with cancer.
UI - 94301076
AU - Jenney M
TI - Limitation of therapy in the treatment of childhood cancer: toxicity versus cure.
SO - Lancet 1994 Jul 23;344(8917):210-1
AD - Department of Pediatrics, University of Minnesota, Minneapolis.
UI - 95245790
AU - Enskar K
TI - Ethical aspects of judging the alternative treatment of children with cancer.
SO - Nurs Ethics 1995 Mar;2(1):51-62
In recent decades the improved treatment of childhood cancer has increased the proportion of children being cured. However, the intensive treatment required also implies a heavy burden for the children and their families. The purpose of this article is to judge the ethical aspects of different treatment regimens used for children with cancer by means of a case study. The analysis is based on the ethical model by Beauchamp and Childress. The assessment is based on every person, or group of persons, involved and is on the principles of autonomy, nonmaleficence, beneficence and justice. The analysis shows that intensification of treatment of children with cancer is ethically justified from a deontological point of view. The consequences are more difficult to anticipate from a utilitarian perspective.
UI - 96268676
AU - Entwistle VA; Watt IS; Bradbury R; Pehl LJ
TI - Media coverage of the Child B case.
SO - BMJ 1996 Jun 22;312(7046):1587-91
AD - NHS Centre for Reviews and Dissemination, University of York. email@example.com
The case of a girl with leukaemia, known as Child B, hit the headlines who counselled against further treatment and took Cambridge and Huntingdon Health Authority to court for refusing to fund chemotherapy and a second bone transplant for her in the private sector. British national newspapers varied greatly in the way they covered the case. Some paid little attention to clinical considerations and presented the case as an example of rationing based on financial considerations. Their selective presentations meant that anyone reading just one newspaper would have received only limited and partial information. If members of the public are to participate in debates about treatment decisions and health care rationing, means other than the media will need to be found to inform and involve them.
UI - 96403418
AU - Spike J; Greenlaw J
TI - Case consultation: when to invoke state agencies to treat: the cases of a minor and a mentally disabled adult.
SO - J Law Med Ethics 1996 Spring;24(1):65-9
UI - 21314728
AU - Landier W
TI - Childhood acute lymphoblastic leukemia: current perspectives.
SO - Oncol Nurs Forum 2001 Jun;28(5):823-33; quiz 834-5
AD - City of Hope National Medical Center, Duarte, CA, USA. firstname.lastname@example.org
PURPOSE/OBJECTIVES: To provide an overview of childhood acute lymphoblastic leukemia (ALL), including epidemiology, clinical presentation, diagnostic classification, prognostic factors, current treatment, long-term sequelae, and nursing management. DATA SOURCES: Journal articles, books, and clinical experience. DATA SYNTHESIS: Childhood ALL is a heterogeneous disorder, and current treatment is tailored to risk factors (e.g., initial white blood count, cytogenetic properties of the leukemic blasts). Risk-directed therapy ensures that children with a higher risk of relapse receive more intensive treatment, whereas those with lower risk disease receive less toxic therapy with decreased potential for treatment-related morbidity. Quality of life in long-term survivors is a significant issue. Late sequelae of treatment can include neurocognitive difficulties, endocrine dysfunction, secondary malignancies, and cardiomyopathy. CONCLUSIONS: With risk-directed therapy, cure rates for childhood ALL continue to improve. At least 80% of children diagnosed with ALL today are expected to survive their disease. IMPLICATIONS FOR NURSING PRACTICE: Nurses caring for children with ALL can have a significant impact on the children's overall health, from diagnosis through long-term follow-up. Nursing interventions encompass the domains of physical and psychosocial care, as well as patient and family education. Assisting the child and family to maintain normalcy in the face of chronic illness, as well as fostering the family's hope for the future and their belief in the child's potential for survival, are key nursing strategies that promote the child's growth, development, and psychological health.
UI - 21323341
AU - Wiela-Hojenska A; Gorczynska E; Orzechowska-Juzwenko K; Golebiowski W;
TI - Hurkacz M; Boguslawska-Jaworska J Metabolic functions of the liver during chemotherapy in children with acute lymphoblastic leukemia.
SO - Int J Clin Pharmacol Ther 2001 Jun;39(6):246-50
AD - Department of Clinical Pharmacology, Wroclaw Medical University, Poland.
OBJECTIVE: The purpose of the present work was estimation of liver function using the phenazone test and commonly used biochemical tests in children with acute lymphoblastic leukemia (ALL) during anticancer treatment. METHODS: Observations were carried out in the same 21 patients with ALL before the beginning of chemotherapy, after Protocol I and after Protocol M of the antileukemic treatment carried out according to the program BFM 86. RESULTS: The applied chemotherapy inhibited phenazone elimination. Both phenazone half-life and metabolic clearance rate were significantly different in patients after treatment with anticancer drugs, especially with high-dose of methotrexate (MTX), from those in patients before the beginning of chemotherapy (p < 0.001). Moreover, after MTX administration transaminases activity and serum bilirubin concentration were significantly higher than before treatment (p < 0.05). CONCLUSION: Our results showed that in children with acute lymphoblastic leukemia, anticancer chemotherapy decreased liver metabolic capacity. Particularly, high-dose methotrexate treatment altered the elimination of phenazone by inhibiting the activity of hepatic mixed function oxidase system. This change may lead to an increase in toxicity of active drugs which are metabolized by this enzyme system. In addition, altered activity of liver metabolic function can impair transformation of prodrugs to active forms. It should be considered in selection of individual drug dosages. The objective estimation of the type and degree of liver dysfunction can only be achieved by the combination of a quantitative phenazone dynamic test and static biochemical tests.
UI - 21532732
AU - Eckert C; Biondi A; Seeger K; Cazzaniga G; Hartmann R; Beyermann B;
TI - Pogodda M; Proba J; Henze G Prognostic value of minimal residual disease in relapsed childhood acute lymphoblastic leukaemia.
SO - Lancet 2001 Oct 13;358(9289):1239-41
Molecular monitoring by quantitative PCR techniques of residual leukaemia cells during the first phases of treatment can predict outcome in children with acute lymphoblastic leukaemia. We did a retrospective study of 30 children who had been treated according to the ALL-REZ BFM trials to assess whether amount of minimal residual disease during the first stages of treatment for relapsed acute lymphoblastic leukaemia could predict outcome. In children with minimal residual disease of less than 10(-3) at day 36, probability of event-free survival was 0.86 (95% CI 0.77-0.95), compared with 0 in children with minimal residual disease of 10(-3) or greater (p<0.001). Our results suggest that information about molecular response to treatment can be used to predict long-term outcome in relapsed childhood acute lymphoblastic leukaemia.
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