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NCI CANCERLIT® Search: Therapy of Acute Lymphocytic Leukemia - April 2002
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Table of Contents
1
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. hempege@uni-muenster.de
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.
2
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. muellerb@mailer.uni-marburg.de
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.
3
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. hochhaus@uni-hd.de
4
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. doralina.anghelescu@stjude.org
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.
5
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. maweiser@mdanderson.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.
6
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. joaquin.sanchez@cheerful.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.
7
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. jcortes@mdanderson.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.
8
UI - 10979367
AU - Rosner F
TI -
Therapeutic efficacy of amulets.
SO - Isr Med Assoc J 2000 Aug;2(8):643
9
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.
10
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.
jmribera@ns.hugtip.scs.es
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.
11
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.
12
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. wayne.furman@stjude.edu
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.
13
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 a@ucla.edu
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.
14
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.
15
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. ftzortzatou@hotmail.com
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.
16
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.
norbert-claude.gorin@sat.ap-hop-paris.fr
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.
17
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.
18
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. m.greaves@icr.ac.uk
19
UI - 11924274
AU - Nysom K
TI -
[Late effects after treatment of childhood leukemia. The Danish Society
of Pediatrics]
SO - Ugeskr Laeger 2002 Mar 18;164(12):1651
AD - nysom@dadlnet.dk
20
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.
21
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.
22
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.
pam_mcgrath@bigpond.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.
23
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. lvichai@ratree.psu.ac.th
24
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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