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National Cancer Institute®
Ultima Vez Modificado: 1 de abril del 2002
UI - 11862427
AU - Hempel G; Flege S; Wurthwein G; Boos J
TI - Peak plasma concentrations of doxorubicin in children with acute lymphoblastic leukemia or non-Hodgkin lymphoma.
SO - Cancer Chemother Pharmacol 2002 Feb;49(2):133-41
AD - Institut fur Pharmazeutische Chemie, Westfalische Wilhems-Universitat, Munster, Germany. firstname.lastname@example.org
PURPOSE: The peak plasma concentrations seem to play an important role in the toxicity of the anthracyclines. As there are only limited data in the literature about the distribution of doxorubicin in children, we assessed the peak plasma concentrations of doxorubicin in pediatric patients. PATIENTS AND METHODS: We collected 87 plasma samples at the end of infusion from 27 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) treated with 30 mg/m(2) doxorubicin as a 1- or 2-h infusion once weekly for four weeks in the ALL-BFM 95 or NHL-BFM 95 protocol. Plasma concentrations of doxorubicin were quantified by capillary electrophoresis, and the peak plasma levels for a uniform 2-h infusion were calculated. RESULTS: The geometric mean of all samples was 273 microg/l with a geometric coefficient of variation of 46.0%. This is in accordance with the peak plasma concentrations expected from simulations based on literature data from adults. High inter-individual as well as substantial intra-individual variability was observed. Girls had slightly higher peak plasma levels than boys. Age, weight, and body mass index as well as laboratory parameters had no influence on the peak plasma concentrations. No cumulation of doxorubicin during therapy was observed. CONCLUSION: The peak plasma concentrations are similar in adults and children for both the absolute values as well as the variability; this indicates that there are no major differences in the distribution of doxorubicin in children and adults.
UI - 11862429
AU - Muller HJ; Beier R; da Palma JC; Lanvers C; Ahlke E; von Schutz V;
TI - Gunkel M; Horn A; Schrappe M; Henze G; Kranz K; Boos J PEG-asparaginase (Oncaspar) 2500 U/m(2) BSA in reinduction and relapse treatment in the ALL/NHL-BFM protocols.
SO - Cancer Chemother Pharmacol 2002 Feb;49(2):149-54
AD - Department of Pediatric Hematology/Oncology, University of Munster, Germany. email@example.com
PURPOSE: As previous data had shown that only two-thirds of patients had the predicted activity time courses when PEG-asparaginase 1000 U/m(2) was used in reinduction after native E. coli asparaginase in induction treatment of acute lymphoblastic leukaemia (ALL), drug monitoring was performed with the use of a higher dose. METHODS: Because one-third of patients had insufficient serum asparaginase activity time courses after a single dose of 1000 U/m(2) PEG-asparaginase during reinduction treatment, a dose of 2500 U/m(2) PEG-asparaginase, which is the approved dosage in Germany, was used in 39 reinduction and 20 relapse patients to determine whether prolongation of the activity time course may be possible with this higher dose, and to look for significant differences between reinduction and relapse patients. RESULTS: After 1, 2 and 3 weeks, the mean activities were 1113 +/- 699 U/l, 231 +/- 259 U/l, and 13 +/- 35 U/l in the reinduction patients, and 1078 +/- 649 U/l, 165 +/- 195 U/l and 19 +/- 28 U/l in the relapse patients, respectively. There were a considerable number of patients with a substantially shortened activity time course in both groups. In 10 of 39 reinduction patients and in 7 of 24 doses during relapse treatment, only activities <100 U/l were found after 1 week with a further fast decline. No statistically significant differences between the two patient groups could be shown at any time-point. CONCLUSIONS: Comparison of these data with activities after 1000 U/m(2) PEG-asparaginase showed no prolongation of the time with activity in the therapeutic range with the higher dose. Therefore, for a longer duration of therapeutic activity, administration of further doses is mandatory.
UI - 11870560
AU - Hochhaus A
TI - [Selective tyrosine kinase inhibitor imatinib (STI571) in haematological and oncological disease]
SO - Dtsch Med Wochenschr 2002 Mar 1;127(9):451-6
AD - III. Medizinische Universitatsklinik, Fakultat fur Klinische Medizin Mannheim der Universitat Heidelberg, Germany. firstname.lastname@example.org
UI - 11882230
AU - Anghelescu DL; De Armendi AJ; Thompson JW; Sillos EM; Pui CH; Sandlund
TI - JT Vincristine-induced vocal cord paralysis in an infant.
SO - Paediatr Anaesth 2002 Feb;12(2):168-70
AD - Division of Anesthesia, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. email@example.com
We report the development of stridor and dysphagia in a 5-month-old-infant with acute lymphoblastic leukaemia after the administration of four weekly doses of vincristine during induction therapy. Because direct laryngoscopy revealed bilateral vocal cord paralysis, the patient underwent elective intubation. Extubation was performed 7 days later, after direct laryngoscopy confirmed recovery of vocal cord mobility. Vincristine-induced bilateral recurrent laryngeal nerve paralysis is a rare but potentially life-threatening complication. Therefore, it should be suspected when stridor is present, and clinicians should consider visualization of the airway to establish the cause of upper airway compromise in infants receiving vincristine.
UI - 11900213
AU - Weiser MA; O'Brien S; Thomas DA; Pierce SA; Lam TP; Kantarjian HM
TI - Comparison of two different schedules of granulocyte-colony-stimulating factor during treatment for acute lymphocytic leukemia with a hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) regimen.
SO - Cancer 2002 Jan 15;94(2):285-91
AD - Department of General Internal Medicine, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. firstname.lastname@example.org
BACKGROUND: Although the safety and efficacy of granulocyte-colony-stimulating factor (G-CSF) (filgrastim) in the treatment of hematologic malignancies has been well established, to the authors' knowledge the optimal timing of filgrastim administration during remission induction chemotherapy and consolidation chemotherapy has not been determined. The purpose of the current study was to determine whether a delay in the administration of filgrastim from Day 5 to Day 10 during chemotherapy with a hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) regimen resulted in a longer time to neutrophil or platelet count recovery or increased the incidence of infection. METHODS: One hundred ninety-nine patients who achieved complete disease remission after a single course of induction chemotherapy were considered for evaluation. Induction chemotherapy was with hyper-CVAD (fractionated cyclophosphamide, 300 mg/m2, twice daily for Days 1-3; doxorubicin, 50 g/m2, on Day 4; vincristine, 2 mg, on Days 4 and 11; and dexamethasone, 40 mg, on Days 1-4 and Days 11-14), which also was given in odd-numbered consolidation Courses 3, 5, and 7. Even-numbered courses (Courses 2, 4, 6, and 8) were comprised of methotrexate, 200 mg/m2, over 2 hours followed by 800 mg/m2 over 24 hours on Day 1; cytarabine, 3 g/m2, every 12 hours for 4 doses over 2 days (Days 2 and 3); and intravenous methylprednisolone, 50 mg, twice daily on Days 1-3 (MTX/ara-C regimen). Two sequential treatment groups were assessable based on timing of the filgrastim administration; 151 patients received filgrastim starting on Day 5 (D5) of induction chemotherapy and 48 patients received filgrastim starting on Day 10 (D10). RESULTS: Time to neutrophil recovery was shorter for the D5 group than for the D10 group during induction chemotherapy (18 days vs. 19 days; P = 0.04) and hyper-CVAD Courses 3 and 5 (12 days vs. 15 days during Course 3, P < 0.001; and 13 days vs. 16 days during Course 5, P = 0.002). There was no apparent significant difference between the two groups with regard to time to neutrophil recovery during the MTX/ara-C courses or the last hyper-CVAD course. Delay in the administration of filgrastim did not appear to result in an increase in time to platelet count recovery or in the incidence of infection; however, there was an increased incidence of mucositis during induction chemotherapy. CONCLUSIONS: For a hyper-CVAD and MTX/ara-C regimen, the results of the current study have shown that the administration of filgrastim can be delayed until Day 10 without increasing the risk of treatment-related morbidity during consolidation chemotherapy. During induction chemotherapy, delay in the administration of filgrastim may result in a slight increase in the time to neutrophil count recovery and risk of mucositis, but there is no apparent associated increase in the risk of infection.
UI - 11849234
AU - Sanchez J; Serrano J; Gomez P; Martinez F; Martin C; Madero L; Herrera
TI - C; Garcia JM; Casano J; Torres A Clinical value of immunological monitoring of minimal residual disease in acute lymphoblastic leukaemia after allogeneic transplantation.
SO - Br J Haematol 2002 Mar;116(3):686-94
AD - Haematology and Bone Marrow Transplantation Department, University Hospital Reina Sofia, Cordoba, Spain. email@example.com
In this study, we used multiparameter flow cytometry to quantify minimal residual disease (MRD) in 165 serial bone marrow samples from 40 patients diagnosed with acute lymphoblastic leukaemia (ALL) who underwent allogeneic stem cell transplantation (allo-SCT) from siblings (n = 34) or unrelated donors (n = 6). Samples were prospectively taken from 24 patients before starting the conditioning regimen, at days +30, +60 and +90 and subsequently every 2-3 months. Samples from 16 patients in complete remission (CR) after allo-SCT were taken at least twice. Six of 24 patients harboured MRD (0.2-10% of mononuclear cells) at transplant and 18 were negative. Estimated disease-free survival for the MRD+ and MRD- groups at transplant was 33.3% and 73.5% respectively (P = 0.03). During follow-up, increasing MRD levels were detected in nine patients, a finding that preceded marrow relapse by 1-6 months. Two patients with stable low MRD levels remained in CR. When we used flow cytometry to test the effect of donor leucocyte infusions (DLI) in six patients, we observed that the only sustained remission was achieved when DLI was applied prior to overt relapse. We conclude that MRD by flow cytometry can rapidly assess tumoral burden before transplant to predict outcome, and can be clinically useful for the timing of DLI for increasing levels of leukaemia after transplant.
UI - 11920506
AU - Cortes J; Thomas D; Rios A; Koller C; O'Brien S; Jeha S; Faderl S;
TI - Kantarjian H Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia.
SO - Cancer 2002 Mar 1;94(5):1492-9
AD - Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. firstname.lastname@example.org
BACKGROUND: Patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma/leukemia have a poor prognosis and are frequently treated with low-intensity therapy. The authors investigated the feasibility and efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), a dose-intensive chemotherapy regimen, in patients with AIDS-associated Burkitt lymphoma/leukemia, as well as the possible impact of highly active antiretroviral therapy (HAART) in these patients. METHODS: Thirteen patients with AIDS-associated Burkitt lymphoma (six patients) or leukemia (acute lymphoblastic leukemia; seven patients) were treated with hyper-CVAD alternating with high-dose methotrexate and ara-C for a total of eight cycles. Nine patients received HAART from the start of induction chemotherapy (seven patients) or later in the course of chemotherapy (two patients). The median patient age was 43 years (range, 32-55). Nine patients were diagnosed with human immunodeficiency virus (HIV) infection at the time of diagnosis of Burkitt lymphoma/leukemia; the other 4 patients had been diagnosed with HIV infection for a median of 37 months (range, 18-137) prior to the diagnosis of Burkitt lymphoma/leukemia. The median absolute CD4 count from the 9 patients with evaluable counts was 77 cells/microL (range, 9-544); only one patient had a count > 200/microL. RESULTS: Twelve patients (92%) achieved a complete remission (CR) and one achieved a partial response (PR). Eight patients continued in CR after a median of 31 months (range, 7-45) at the time of writing. Five patients were alive and in CR over two years later. The median survival was 12 months, with 48% of patients alive after 2 years. Six of seven patients who received HAART from the start of chemotherapy were alive and in CR after a median of 29 months (range, 7-45). The four patients who did not receive HAART died. The regimen was universally myelosuppressive, but the toxicity profiles, recoveries from myelosuppression, and incidences of infectious complications were similar to that of non-HIV patients with Burkitt lymphoma/leukemia treated with the same regimen. CONCLUSIONS: Hyper-CVAD is an effective regimen for patients with AIDS-associated Burkitt lymphoma/leukemia, with acceptable toxicity. The combination of hyper-CVAD and HAART is associated with long-term survival in patients with the two diseases, which, until recently, were both considered invariably fatal and almost futile to treat medically. Copyright 2002 American Cancer Society.
UI - 11767129
AU - Schroder H; Agger KE; Rosthoj S; Carlsen NT; Schmiegelow K
TI - Antibacterial prophylaxis with trimethoprim-sulfamethoxazole during induction treatment for acute lymphoblastic leukemia.
SO - Dan Med Bull 2001 Nov;48(4):275-7
AD - Department of Pediatrics, University Hospital of Aarhus.
BACKGROUND AND PURPOSE: Children with acute lymphoblastic leukemia are treated with intensive chemotherapy resulting in profound immuno suppression. Therefore treatment with trimethoprim-sulfamethoxazole (TMP-SMX) may be used for prophylaxis against infections both with bacteria and Pneumocystis carinii in some departments. The use of TMP-SMX for prophylaxis during the induction therapy is not uniform in the four departments of pediatric oncology in Denmark. This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy. MATERIAL AND METHODS: Between January 1st 1992 and December 31st 1997, 210 children were diagnosed with ALL in Denmark. Based on a retrospective review of the medical charts the number of children with fever (>38 degrees C), the number of febrile days, days of antibiotic treatment and the number of positive blood cultures were registered for every febrile episode. RESULTS: One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) v 60/76 (79%), p <0,01), and significantly fewer children who received TMP/SMX prophylaxis had positive blood cultures before start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p<0.001)). Nineteen different species were isolated from the blood stream before start of antibiotic treatment. In the non-prophylaxis group there was a preponderance of isolates with Staph. aureus, Str. pneumoniae, E. coli and P. aeruginosa. There was no difference in the mortality between the two groups (p=0.44).There were no cases of P carinii pneumonia in the period of induction therapy. CONCLUSION: TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteremias and febrile illness.
UI - 11836166
AU - Ribera JM; Ortega JJ; Oriol A; Granada I; Hernandez-Rivas JM; Parody R;
TI - Bethencourt C; Rivas C; Bastida P; del Potro E; Gonzalez-Valentin ME; Moreno MJ; Besalduch J; Fernandez-Calvo J; Tormo M; Arias J; Molines A; Sanz MA; Maldonado J; Milla F; Feliu E; San Miguel JF; PETHEMA Group, Spanish Society of Hematology Prognostic value of karyotypic analysis in children and adults with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 trial.
SO - Haematologica 2002 Feb;87(2):154-66
AD - Hematology Department and Hematopoietic Progenitor Transplant Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. email@example.com
BACKGROUND AND OBJECTIVES: Cytogenetic analysis is one of the most reliable prognostic factors in acute lymphoblastic leukemia. The objective of this study was to analyze the prognostic value of cytogenetic analysis in children and adults with high-risk acute lymphoblastic leukemia (HR-ALL) included in a prospective multicenter trial. DESIGN AND METHODS: One hundred and thirty patients (44 children and 86 adults) with HR-ALL included in the PETHEMA ALL-93 trial had an adequate cytogenetic study after review. Cytogenetic subgroups were established according to the cancer and acute leukemia group B criteria (unfavorable: 11q23, t(9;22), -7 and +8; normal; miscellaneous: the remaining chromosome abnormalities) and their main clinicobiological features were compared. Univariable and multivariable analyses for complete remission (CR) attainment, event-free survival (EFS) and overall survival (OS) were performed. RESULTS: The mean SD age was 26 14 years. Two were infants (<1 year), 42 were children and 86 adults (19-50 years). The cytogenetic study was normal in 44 (34%) cases. The most frequent chromosomal rearrangement was t(9;22)(q34;q11) (34 cases, 26%, 30 adults), followed by 11q23 (12 cases, 9% -8 children-, including t(4;11)(q21;q23) in 8, 7 children). Patients with t(9;22) were older than the remaining cases, whereas those with 11q23 rearrangements were younger and had higher WBC counts. Multivariable analyses showed two associated factors in adults with a lower frequency of CR and a shorter EFS and OS: t(9;22) and slow response to therapy (assessed by a percentage of blast cells higher than 10% in bone marrow study on day 14). For children with very high-risk ALL, only slow response to therapy (assessed by the presence of blast cells in peripheral blood on day 8) was associated with a negative impact on CR, EFS and OS. INTERPRETATION AND CONCLUSIONS: In adult patients with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 protocol, cytogenetic analysis at diagnosis is a useful independent prognostic marker. The poorest prognosis for patients with t(9;22) justifies the development of specific treatments for these patients. In this small subgroup of children with very high-risk ALL no cytogenetic characteristics was found to influence the results of therapy, slow response to therapy being the only prognostic factor.
UI - 11328289
AU - Hann I; Vora A; Harrison G; Martineau M; Moorman AV; Secker Walker LM;
TI - 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 - 11896112
AU - Furman WL; Stewart CF; Kirstein M; Kepner JL; Bernstein ML; Kung F;
TI - Vietti TJ; Steuber CP; Becton DL; Baruchel S; Pratt C Protracted intermittent schedule of topotecan in children with refractory acute leukemia: a pediatric oncology group study.
SO - J Clin Oncol 2002 Mar 15;20(6):1617-24
AD - Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. firstname.lastname@example.org
PURPOSE: To determine dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of a protracted, intermittent schedule of daily 30-minute infusions of topotecan (TPT) for up to 12 consecutive days, every 3 weeks, in children with refractory leukemia. PATIENTS AND METHODS: Forty-nine children were enrolled onto this phase I trial (24 with acute nonlymphoblastic leukemia [ANLL] and 25 with acute lymphoblastic leukemia [ALL]). TPT dosage was escalated from 2.0 to 5.2 mg/m(2)/d for 5 days and 2.4 mg/m(2)/d from 7 days to the same dose for 9 and 12 days in cohorts of three to six patients when no DLT was identified. TPT pharmacokinetics were studied in 33 children once or twice (first and last doses in patients who received TPT for > 7 days). RESULTS: Seventy assessable courses of TPT were administered to 49 children who had refractory leukemia. DLTs were typhlitis, diarrhea, and mucositis, and the MTD was 2.4 mg/m(2)/d for 9 days in this group of heavily pretreated children. In 33 patients, the median TPT lactone clearance after the first dose was 19.2 L/h/m(2) (range, 9.4 to 45.9 L/h/m(2)) and did not change during the course. There were significant responses (one complete response [CR] and four partial responses [PR] in patients with ANLL and one CR and two PRs in patients with ALL), and all but one were at dosages of TPT given for at least 9 days. CONCLUSION: The MTD was 2.4 mg/m(2)/d for 9 days. Further testing is warranted of TPT's schedule dependence in children with leukemia.
UI - 11822985
AU - Kaleita TA
TI - Central nervous system-directed therapy in the treatment of childhood acute lymphoblastic leukemia and studies of neurobehavioral outcome: Children's Cancer Group trials.
SO - Curr Oncol Rep 2002 Mar;4(2):131-41
AD - Department of Psychiatry and Biobehavioral Sciences and The UCLA Neuro-Oncology Program, UCLA School of Medicine, 300 Medical Plaza, Los Angeles, CA 90095-6967, USA. tkaleit email@example.com
Long-term survival rates in childhood acute lymphoblastic leukemia (ALL) have improved due, in part, to the introduction and subsequent refinements in central nervous system (CNS)-directed therapy. Studies of cognitive, motor, and behavioral functioning, which characterize the patterns and severity of CNS sequelae, are being used increasingly as measurable treatment endpoints. This paper summarizes the advances in CNS-directed therapy derived from Children's Cancer Group randomized therapeutic trials. Results from neurobehavioral outcome studies built upon these trials are also presented. A section of this review is focused on CNS-directed treatments and the neurodevelopmental outcomes of infants diagnosed with ALL, an especially high-risk patient subset. Future studies of neurobehavioral outcome are briefly elaborated in the context of current chemotherapy approaches used in the treatment of childhood ALL.
UI - 11745246
AU - Hsu CP; Yang CC; Hsueh SF; Peng CC; Fu HH; Yang SD
TI - Suppression of proline-directed protein kinase F(A) potentiates apoptotic induction and greatly enhances chemosensitivity in human acute lymphoblastic leukemia cells.
SO - Cancer 2001 Oct 1;92(7):1753-8
AD - Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
BACKGROUND: Previously, the authors reported that specific antisense suppression of overexpressed proline-directed protein kinase (PDPK) F(A) enhances the chemosensitivity of various clinical anticancer drugs up to > 100-fold in human prostate carcinoma cells, suggesting an association of PDPK F(A) with drug resistance in human malignancies. METHODS: In this report, by using a similar approach, the authors demonstrate further that the suppression of PDPK F(A) enhances even more dramatically the chemosensitivity of clinically used anticancer drugs in various types of human acute lymphoblastic leukemia (ALL) cells. RESULTS: Compared with parental and control transfected cells, transduced ALL cells (both Jurkat and CCRF-CEM cells) with low levels of PDPK F(A) displayed an enhanced sensitivity to vincristine, vinblastine, paclitaxel, methotrexate, doxorubicin, and daunorubicin. Estimation of the 50% inhibitory concentration (IC(50)) index further revealed that the transduced cells displayed up to > 3000-fold drug sensitivity, and there was a correlation between suppressed levels of PDPK F(A) and drug sensitivity. A mechanistic study further revealed that the enhanced chemosensitivity in transduced ALL cells was due mainly to the potentiation of apoptotic induction. CONCLUSIONS: Taken together, the results demonstrate that the suppression of overexpressed PDPK F(A) greatly enhances the chemosensitivity of various clinical anticancer drugs in both types of human ALL cells, providing initial evidence for an important role of this PDPK in controlling multidrug resistance of ALL. Copyright 2001 American Cancer Society.
UI - 11902303
AU - Tzortzatou-Stathopoulou F; Papadopoulou A L; Moschovi M; Botsonis A;
TI - Tsangaris G T Low relapse rate in children with acute lymphoblastic leukemia after risk-directed therapy.
SO - J Pediatr Hematol Oncol 2001 Dec;23(9):591-7
AD - First Department of Pediatrics, University of Athens, Aghia Sophia Children's Hospital, Greece. firstname.lastname@example.org
PURPOSE: Even though acute lymphoblastic leukemia (ALL) responds well to chemotherapy, relapse remains the major problem. This study documents relapse and survival rates in 85 consecutive children (33 at good risk, 52 at high risk) with ALL diagnosed in 1991 to 1996. PATIENTS AND METHODS: Until 1993, the New York II protocol for the high-risk group and a combination of UKALL XI (induction) and R blocks of ALL-REZ BFM-87 (intensification) regimens for patients at good risk were used. To reduce toxicity, the protocols were subsequently modified. Consolidation treatment was the same for both groups, consisting of a lower cytarabine dose and methotrexate removal, whereas intensification was changed only for the high-risk group using the BB block of the NHL-BFM-90 protocol. The bone marrow clearance of leukemia was assessed on day 22, and minimal residual disease was detected using polymerase chain reaction analysis of Ig heavy-chain gene rearrangements. RESULTS: Seventy patients had common precursor B lineage ALL, six had pre-B-ALL, eight had T-ALL, and one had B-ALL. Two patients never achieved remission and died. Six patients died of consolidation-related complications. Four more patients died, two during induction and two during maintenance therapy. Two other children had relapse (2.3%), both of whom were treated with the earlier protocols and then underwent bone marrow transplantation. Four more children with morphologically complete remission showed minimal residual disease (which reached the levels of 1 leukemic cell among 10(2)-10(4) normal cells) with the use of clone-specific probes at several points of the study intervals, but never had relapse. The 5-year overall and event-free survival rates were 86% and 83%, respectively. The 5-year overall survival rates for good-risk and high-risk groups were 94% and 81%; the corresponding event-free rates were 91% and 78%. The 5-year event-free survival rate in the patients at high risk was significantly higher after the protocol change (90% vs. 65%, P = 0.04). CONCLUSIONS: The modification proved to be effective in diminishing the therapeutic toxicity and improving the efficacy, mainly for the high-risk group.
UI - 11796917
AU - Gorin NC
TI - Autologous stem cell transplantation in acute lymphocytic leukemia.
SO - Stem Cells 2002;20(1):3-10
AD - Department of Hematology, Hopital Saint-Antoine, Paris, France. email@example.com
Autologous stem cell transplantation (ASCT) as well as allogeneic stem cell transplantation and conventional chemotherapy (CT) are less effective at treating acute lymphocytic leukemia (ALL) than acute myelocytic leukemia (AML). Chemoresistance and late relapses are hallmarks of ALL. In this context, the question of whether ASCT is superior to CT remains unanswered. In vitro marrow purging using monoclonal antibodies is not routinely used. This review summarizes the results of ASCT for adult and childhood ALL. Statistics from the European Group for Blood and Marrow Transplantation reveal a transplant-related mortality at 5 years of 11% +/- 1%, a relapse incidence of 60% +/- 2%, and a leukemia-free survival (LFS) and overall survival (OS) of 36% +/- 2% and 42% +/- 2%, respectively in 1,366 adults autografted in first remission (CR1). In 269 children, the LFS and OS were 50% +/- 3% and 54% +/- 3%, respectively. There was no evidence in favor of purging the autograft in vitro. In contrast, multicentric and single-institution studies have found better results in adults autografted in CR1, with LFS at 5 years from 46% to 64%, possible efficacy of marrow in vitro purging with mafosfamide (LFS 52%), and improvement in outcome with additional measures post-ASCT, such as maintenance chemotherapy (LFS 57%). Further, as already observed for AML, analyses by risk groups suggest that ASCT may essentially benefit good- but not poor-risk patients. For patients with the Ph1/bcr-abl translocation, the role of STI571 anti-tyrosine kinase for in vivo purging before stem cell harvesting is being investigated.
UI - 11929036
AU - Ray M; Marwaha RK; Trehan A
TI - Chemotherapy related fatal neurotoxicity during induction in acute lymphoblastic leukemia.
SO - Indian J Pediatr 2002 Feb;69(2):185-7
AD - Division of Pediatric Hematology-Oncology, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Neurotoxicity is a common complication during cancer chemotherapy. It is estimated that 3-10% of children with acute lymphoblastic leukemia (ALL) experience acute, transient neurotoxicity during induction chemotherapy. Fatal acute neurotoxicity is rarely encountered. Neurological evaluation of children with ALL at diagnosis and during treatment is of value in order to diagnose neurological complications early so that appropriate intervention can be adopted. This communication describes the profile of two children with unexpected, acute fatal neurologic toxicity during induction chemotherapy for ALL.
UI - 11823363
AU - Greaves M
TI - Childhood leukaemia.
SO - BMJ 2002 Feb 2;324(7332):283-7
AD - Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB. firstname.lastname@example.org
UI - 11951089
AU - Chan KW
TI - Acute lymphoblastic leukemia.
SO - Curr Probl Pediatr Adolesc Health Care 2002 Feb;32(2):40-9
AD - Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas., USA.
Acute leukemia is the most common childhood malignancy, representing 30% of all cancer in American children under the age of 15 years and 12% of cancer cases in those ages 15 to 19 years old. In the United States, approximately 2500 new cases are diagnosed annually; 80% of these are acute lymphoblastic leukemia, 15% are acute myelogenous leukemia, and 5% belong to the chronic leukemia category.(1) The survival rates of children with acute leukemia have increased dramatically in the last 40 years.(2-5) The most success in outcome has occurred in acute lymphoblastic leukemia, although improvement is also being reported in acute myelogenous leukemia in the past few years. Progress comes from treatment strategy modifications on the basis of observations made in sequential large-scale therapeutic trials, an approach that serves as a paradigm for research in other malignant diseases.
UI - 11953850
AU - Perrillat F; Clavel J; Auclerc MF; Baruchel A; Leverger G; Nelken B;
TI - Philippe N; Schaison G; Sommelet D; Vilmer E; Hemon D Day-care, early common infections and childhood acute leukaemia: a multicentre French case-control study.
SO - Br J Cancer 2002 Apr 8;86(7):1064-9
AD - Institut National de la Sante et de la Recherche Medicale, Inserm U170, 16 avenue Paul Vaillant Couturier, 94807 Villejuif, France.
We conducted a case-control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers. The interviews included questions on early common infections, day-care attendance, breast-feeding, birth order and infantile diseases. Odds ratios were estimated using an unconditional regression model including the stratification variables, parental socio-economic status and perinatal characteristics. Birth order was not associated with childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A statistically-significant inverse association was observed between childhood leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4-1.0)), repeated early common infections (> or = 4 per year before age two, odds ratio=0.6 (0.4-1.0)), surgical procedures for ear-nose-throat infections before age two (odds ratio=0.5 (0.2-1.0)) and prolonged breast-feeding (> or = 6 months, odds ratio=0.5 (0.2-1.0)). In the multivariate model including day-care attendance, early common infections and breast-feeding, results concerning breast-feeding remained unchanged. A statistically significant interaction between day-care attendance and repeated early common infections was observed. When the interaction was taken into account, the simple effects of day-care and early common infections disappeared (odds ratio=1.1 (0.5-2.3) and odds ratio=0.8 (0.5-1.3), respectively) while the joint effect of day-care attendance and early common infections was negatively associated with childhood leukaemia (odds ratio=0.3 (0.1-0.8)). All the above associations were observed both for acute lymphoblastic leukaemia and acute non-lymphoblastic leukaemia. Our results support Greaves' hypothesis, even though they are not specific of common leukaemia.
UI - 11862504
AU - McGrath P; Pitcher L
TI - 'Enough is enough': qualitative findings on the impact of dexamethasone during reinduction/consolidation for paediatric acute lymphoblastic leukaemia.
SO - Support Care Cancer 2002 Mar;10(2):146-55
AD - Leukaemia Foundation's Psycho-social Research Program, Studies in Religion, School of History, Philosophy, Religion and Classics, University of Queensland, St Lucia Q 4072, Australia. email@example.com
The results of a longitudinal study conducted with children undergoing treatment for acute lymphoblastic leukaemia (ALL) and their families in Brisbane, Australia, indicate that the emotional impact of one of the protocol drugs, dexamethasone, is acutely distressing. The findings presented cover the second interviews with the parents and children of the first 11 ALL families to have completed the re-consolidation stage of treatment. The results indicate that the negative impact of this drug is particularly severe during the reconsolidation stage, when families are exhausted with coping with the intensity of treatment. Thus, the administration of dexamethasone is a critical point in the pathway of care for children with ALL. The emotional consequences of the drug are profoundly disturbing, not only for the child, but for the whole family. The findings indicate that the period when dexamethasone is being administered is an important time for providing families with emotional support and information about likely sequelae of treatment. Because of guilt and self-doubt parents will not necessarily seek help, even if it is greatly needed. Recommendations are provided as to possible ways of reducing the distressing impact of the administration of this pharmaceutical intervention.
UI - 11920793
AU - Laosombat V; Wongchanchailert M; Sattayasevana B; Wiriyasateinkul A;
TI - Watana-Arepornchai S The treatment of children with acute lymphoblastic leukemia in Thailand.
SO - Med Pediatr Oncol 2002 Apr;38(4):266-8
AD - Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand. firstname.lastname@example.org
UI - 11920807
AU - Ozsahin H; Fluss J; McLin V; Wacker P; Miralbell R; Helg C
TI - Rituximab with interleukin-2 after autologous bone marrow transplantation for acute lymphocytic leukemia in second remission.
SO - Med Pediatr Oncol 2002 Apr;38(4):300-1
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