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NCI CANCERLIT® Search: Therapy of Acute Lymphocytic Leukemia - January 2002
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Ultima Vez Modificado: 1 de enero del 2002
Table of Contents
1
UI - 11176579
AU - Pease CL; Horton TM; McClain KL; Kaplan SL
TI -
Aseptic meningitis in a child after systemic treatment with high dose
cytarabine.
SO - Pediatr Infect Dis J 2001 Jan;20(1):87-9
AD - Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030,
USA.
Cytarabine was temporally associated with aseptic meningitis syndrome in
an 8-year-old Hispanic girl being treated for acute lymphoblastic
leukemia.
2
UI - 11409148
AU - Steinbach WJ; Sandborg CI
TI -
Development of systemic lupus erythematosus following autologous bone
marrow transplant for acute lymphocytic leukemia.
SO - J Rheumatol 2001 Jun;28(6):1467-8
3
UI - 11410410
AU - Paolucci G; Vecchi V; Favre C; Miniero R; Madon E; Pession A; Rondelli
TI -
R; De Rossi G; Lo Nigro L; Porta F; Santoro N; Indolfi P; Basso G;
Conter V; Arico M; Associazione Italiana Ematologia Oncologia Pediatrica
(AIEOP)
Treatment of childhood acute lymphoblastic leukemia. Long-term results
of the AIEOP-ALL 87 study.
SO - Haematologica 2001 May;86(5):478-84
AD - Clinica Pediatrica dell'Universita di Bologna, Bologna, Italy.
study, based on the previous AIEOP-ALL-82. The aim of this new study was
to evaluate, for all risk groups: a) the efficacy of treatment
intensification achieved by adding a fourth drug (daunomycin) in the
induction phase and a 3-drug reinduction phase for all risk groups; b)
the impact of the addition of three doses of intrathecal methotrexate
during cranial radiotherapy and extended exposure to weekly high-dose
L-aspariginase during late intensification in high risk patients. We
report the long-term results of the AIEOP ALL-87 study. DESIGN AND
METHODS. From 1987 to 1991, a total of 632 eligible and evaluable
children (age 1 to < or =16 years) with non-B-cell acute lymphoblastic
leukemia (ALL), were enrolled and stratified as follows: standard risk
(SR, 79 patients, 12.5%) had WBC <10,000/mm3, age > or = 3 and <7 years,
and FAB L1 morphology. The high risk (HR, 175 patients, 27.7%) group
included patients with WBC > or =50,000/mm3 or FAB L3 morphology or T
immunophenotype or acute undifferentiated leukemia (AUL) or
leukemia-lymphoma syndrome. All the remaining patients formed the
intermediate risk group (IR, 378 patients, 59.8%). All patients received
a 4-drug induction therapy; intermediate-dose methotrexate was given to
HR patients; cranial radiotherapy was given to IR and HR patients, while
SR patients received extended intrathecal methotrexate; all patients
received a 3-drug reinduction phase; high dose L-asparaginase (HD-L-ASP;
E.Coli, Bayer) was given to HR patients; continuation therapy with
6-mercaptopurine, i.m. methotrexate, and monthly vincristine and
prednisone pulses was given to all patients. Treatment duration was 2
years. RESULTS. Six hundred and nineteen patients (97.9%) achieved
complete remission. The remission rate was 98.7% in the SR group, 98.1%
in the IR group, and 97.1% in the HR group. The overall 10-year survival
and event-free survival (EFS) rates (SE) are 74.7% (1.8) and 62.8% (2.0)
respectively; EFS rates by risk group are 67.5% (5.5) in SR, 62.8% (2.6)
in IR, and 61.9% (3.8) for HR. The 10-year EFS for all eligible patients
was 63.9% (1.9). INTERPRETATION AND CONCLUSIONS. When compared to the
results of the AIEOP-ALL-82 study, treatment intensification in the
ALL-87 study has improved long-term survival and EFS from 66.4% and
53.6% to 74.7% and 62.8%, respectively. Failures were mostly due to
marrow or extramedullary relapses suggesting that further treatment
intensification, as being used in current therapeutic strategies, is
appropriate, although patients relapsing after less intensive treatment
may have better chances of rescue. These results, although obtained in a
relatively large proportion of patients, in which infants were not
included, indicate that the addition of high-dose L-asparaginase to a
relatively non-intensive treatment may be of major benefit for HR
patients and that the addition of intrathecal methotrexate during CRT,
may improve the central nervous system-disease control with a marked
reduction of nervous system relapses.
4
UI - 11450870
AU - Carinder JE; Chua JD; Corales RB; Taege AJ; Procop GW
TI -
Rahnella aquatilis bacteremia in a patient with relapsed acute
lymphoblastic leukemia.
SO - Scand J Infect Dis 2001;33(6):471-3
AD - Department of Hematology and Medical Oncology Medicine, Cleveland Clinic
Foundation, OH 44195, USA.
Rahnella aquatilis infections are rare. We report the case of a 46-y-old
African-American male with relapsed acute lymphoblastic leukemia who had
R. aquatilis bacteremia after beginning reinduction chemotherapy. He was
treated for 4 weeks with piperacillin-tazobactam and gentamicin. He
recovered from the infection and had an allogenic bone marrow transplant
a month later.
5
UI - 11527196
AU - Prabakaran S; Senthilnathan SV; Venkatadesikalu M; Prasad N; Sridharan S
TI -
Adenocarcinoma of the colon as a second malignancy in a child.
SO - Pediatr Surg Int 2001 Jul;17(5-6):475-7
AD - Department of Paediatric Surgery, Institute of Child Health and Hospital
for Children, Chennai Medical College, Egmore, India.
Solid tumors as second malignancies are not common in children who have
been managed for lymphoproliferative disorders. We report a case of
adenocarcinoma (AC) of the colon as a second malignancy in a patient who
was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL).
In children, primary AC of the colon is very rare; colonic AC occurring
as a second malignancy in a child is rarer still. A case of AC of the
colon following chemotherapy for ALL has not yet been published.
6
UI - 11502486
AU - Chessells JM
TI -
The role of bone marrow transplantation in first remission of paediatric
all.
SO - Front Biosci 2001 Aug 1;6():G38-42
AD - Institute of Child Health & Great Ormond Street Hospital & Children NHS
Trust, University of London, 30 Guilford Street, London, WC1N 1EH,
United Kingdom. J.Chessells@ich.ucl.ac.uk
Although intensive chemotherapy has improved event-free survival for
most children with lymphoblastic leukaemia there remain up to 10% who
have not benefited from this approach. These include infants, children
with Ph1 positive leukaemia, with near-haploidy, and slow remitters in
most of whom event free survival remains below 40%. Evaluation of the
benefits of Bone Marrow Transplantation in high risk ALL is fraught with
difficulties and to date has not produced clear evidence of benefit. The
way forward lies in prospective evaluation of BMT in tightly defined
subsets of highest risk children, a task which will require
international collaboration.
7
UI - 11530813
AU - Sakata N; Yasui M; Kawa K
TI -
Pneumococcal arthritis affects performance status in patients with
chronic GVHD of the skin following allogeneic bone marrow
transplantation.
SO - Int J Hematol 2001 Jul;74(1):90-4
AD - Department of Pediatrics, Osaka Medical Center and Research Institute
for Maternal and Child Health, Japan. nsakata@mch.pref.osaka.jp
We encountered 2 patients with pneumococcal arthritis following bone
marrow transplantation (BMT). Both patients received grafts from
unrelated human lymphocyte antigen (HLA)-matched donors and had suffered
from chronic graft-versus-host disease (GVHD). One, a 10-year-old boy,
suffered from Epstein-Barr virus-related lymphoproliferative disease
(EB-LPD) and received oral 6-mercaptopurine and methotrexate to manage
lymphadenopathy. Twenty-four months after BMT and 7 months after the
onset of EB-LPD, pneumococcal arthritis occurred in both knee joints.
The other patient, a 10-year-old girl, received multiagent
immunosuppressive therapy for her chronic GVHD. At 51 months following
BMT, pneumococcal arthritis occurred in her left knee joint. Chronic
GVHD of the skin delayed the recovery from the arthritis in both
patients. This complication is quite rare but can be very serious, in
regard to the patient's performance status following BMT. Although
vaccination against pneumococcus or preventive antibiotics should be
administered to high-risk patients, early diagnosis and treatment may be
the best strategy for pneumococcal arthritis.
8
UI - 11571524
AU - Cornish J; Oakhill A
TI -
The management of relapsed acute lymphoblastic leukaemia.
SO - Bone Marrow Transplant 2001 Aug;28 Suppl 1():S9
AD - Bristol Royal Hospital for Sick Children, United Kingdom.
9
UI - 11564065
AU - Muller HJ; Beier R; Loning L; Blutters-Sawatzki R; Dorffel W; Maass E;
TI -
Muller-Weihrich S; Scheel-Walter HG; Scherer F; Stahnke K; Schrappe M;
Horn A; Lumkemann K; Boos J
Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase
medac) and hypersensitivity reactions in ALL-BFM 95 reinduction
treatment.
SO - Br J Haematol 2001 Sep;114(4):794-9
AD - Department of Paediatric Haematology/Oncology, University of Munster,
Germany. hmuller@uni-muenster.de
Repeated asparaginase treatment has been associated with
hypersensitivity reactions against the bacterial macromolecule in a
considerable number of patients. Immunological reactions may range from
anaphylaxis without impairment of serum asparaginase activity to a very
fast decline in enzyme activity without any clinical symptoms. Previous
investigations on a limited number of patients have shown high
interindividual variability of asparaginase activity time courses and
hypersensitivity reactions in about 30% of patients during reinduction
treatment. Therefore, monitoring of reinduction treatment was performed
prospectively in 76 children with newly diagnosed acute lymphoblastic
leukaemia (ALL). According to the ALL-Berlin-Frankfurt-Munster (BFM) 95
protocol, 10 000 U/m2 body surface area of native Escherichia coli
asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In
45/76 children, trough and peak activities were determined with every
dose, and also on d 4 and d 11 after the last administration. Data on
asparaginase activity were not available from the remaining 31 patients,
but information with regard to hypersensitivity reactions only was
given. Eighteen out of 76 patients (24%) suffered a clinical
hypersensitivity reaction; however, no silent inactivation was observed.
Activity in the therapeutic range of greater than 100 U/l for at least
14 d was determined in 43 of the 45 patients who were analysed for
enzyme activity.
10
UI - 11520582
AU - Bazarbachi A; Hermine O
TI -
Treatment of adult T-cell leukaemia/lymphoma: current strategy and
future perspectives.
SO - Virus Res 2001 Oct 30;78(1-2):79-92
AD - Department of Internal Medicine, American University of Beirut, PO Box
113, 6044, Beirut, Lebanon. bazarbac@aub.edu.lb
Human T-cell leukaemia virus type I (HTLV-I) associated adult T-cell
leukaemia/lymphoma (ATL) carries a very poor prognosis due to an
intrinsic resistance of leukaemic cells to conventional or even high
doses of chemotherapy and to an associated severe immunosuppression.
Therefore, the potential role of conventional chemotherapy, high dose
chemotherapy with autologous or allogeneic bone marrow transplantation
remains to be defined. Important progress was achieved in the treatment
of ATL with the combination of zidovudine (AZT) and interferon-alpha
(IFN) which produces a high response rate in ATL patients with minimal
side effects. This treatment seems to prolong the survival of patients
much more than intensive chemotherapy. The success of this potentially
anti-retroviral approach in the treatment of ATL suggests the existence
of continuous HTLV-I replication in vivo. These encouraging results may
be improved by the use of higher doses of AZT and IFN combined with
other anti-retroviral agents. However, since cure seems still elusive,
new therapeutic approaches or new combinations are required. For
example, biological mediators such as retinoid acid, which induces
apoptosis of ATL cells in vitro, may reduce drug resistance and
stimulates immunity to restore anti-tumour activity against ATL cells.
Alternatively, immunotherapy with anti-interleukin-2 receptor monoclonal
antibodies or injection of cytotoxic T-cells directed against virus
antigens could be interesting approaches which may merit further
investigations in the near future. Finally, the recent demonstration
that the combination of arsenic trioxide (As) and IFN induces a specific
degradation of the viral transactivator Tax followed by cell cycle
arrest and apoptosis of HTLV-I positive cells may constitute a valuable
addition to ATL treatment.
11
UI - 11568905
AU - Reinders-Messelink HA; Schoemaker MM; Snijders TA; Goeken LN; Bokkerink
TI -
JP; Kamps WA
Analysis of handwriting of children during treatment for acute
lymphoblastic leukemia.
SO - Med Pediatr Oncol 2001 Oct;37(4):393-9
AD - Children's Cancer Center, University Hospital Groningen, 9700 RB
Groningen, The Netherlands. W.A.Kamps@bkk.azg.nl
BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL)
often complain about handwriting problems. PROCEDURE: Using a
computerized writing task, we have prospectively studied the processes
necessary for the production of handwriting movements in 11 children
(5-12 years old) during treatment for ALL. Children were tested at time
points closely related to the vincristine administration. RESULTS AND
CONCLUSIONS: Children treated for ALL drew slower, with longer pause
durations and increased drawing pressure. Children were able to overcome
the problems, except for a consistently increased drawing pressure. This
increased drawing pressure may be an attempt of the children to obtain
sufficient kinesthetic information and thus can be seen as an adequate
adaptation mechanism in case of peripheral neuropathy due to the
neurotoxic effects of vincristine. However, neurotoxic effects of other
cytostatic drugs cannot be excluded. Copyright 2001 Wiley-Liss, Inc.
12
UI - 11571715
AU - Press RD
TI -
Pharmacologic inhibition of the Bcr-Abl kinase with STI571: a novel,
safe, and effective therapy for chronic myeloid leukemia.
SO - Mol Diagn 2001 Sep;6(3):211-3
13
UI - 11579503
AU - Sato H; Goi K; Takahashi K; Nemoto A; Uno K; Inukai T; Sugita K;
TI -
Nakazawa S
[Cord blood transplantation with two mismatched HLA loci in a child with
acute lymphoblastic leukemia in second remission: follow-up of minimal
residual disease using a clone-specific probe]
SO - Rinsho Ketsueki 2001 Aug;42(8):633-8
AD - Department of Pediatrics, Yamanashi Medical University.
A 9-year-old girl with acute lymphoblastic leukemia in second remission
underwent cord blood transplantation (CBT) from an HLA-mismatched (2
loci by serotype, 3 loci by genotype) unrelated donor. The infused
nucleated cell count was 1.95 x 10(7)/kg. FK506 and mini-MTX were used
to prevent graft-versus-host disease (GVHD), but grade II acute GVHD
developed on the skin (stage III). The GVHD subsided after
administration of corticosteroid, but marked hyperglycemia developed,
which required transient insulin therapy for its control. Minimal
residual disease (MRD) was assessed using a clone-specific probe for the
JH region. MRD was positive before CBT, but became negative one month
after CBT. Now, at 14 months after CBT, the patient is in a disease-free
state without detectable MRD. These observations suggest that CBT with
two mismatched HLA loci can be performed safely, and that sequential
analysis of MRD is useful for evaluation of the disease status after
CBT.
14
UI - 11588763
AU - Mandrell BN; McCormick JN
TI -
Dapsone-induced methemoglobinemia in pediatric oncology patients: case
examples.
SO - J Pediatr Oncol Nurs 2001 Sep-Oct;18(5):224-8
AD - Nursing Education, St. Jude Children's Research Hospital, Memphis, TN
38105, USA.
Over the last 25 years, significant advances have been made in
supportive care of the immunocompromised patient. One significant
advance is the use of trimethoprim-sulfamethoxazole (TMP-SMZ) in the
prevention of Pneumocystic carinii pneumonia (PCP). Although TMP-SMZ
remains the drug of choice for PCP prophylaxis, children who develop or
have a history of adverse reactions must be prescribed an alternative
treatment. In these instances, medications such as dapsone, aerosolized
pentamidine, or atovaquone are prescribed. This report discusses four
children with sulfa allergy who were prescribed dapsone and later
developed methemoglobinemia. Although methemoglobinemia is associated
with dapsone, there was no reference found regarding this link in the
pediatric oncology literature. The purpose of these clinical examples is
to alert the pediatric nurse and advanced practitioner to the
association of dapsone and methemoglobinemia. Copyright 2001 by
Association of Pediatric Oncology Nurses
15
UI - 11601198
AU - Ye H; Gu L
TI -
[Advances in the study of acute lymphocytic leukemia treated by large
dosage of methotrexate]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Feb;20(2):110-2
16
UI - 11598342
AU - Hollinger P; Zenhausern R; Schroth G; Mattle HP
TI -
MR findings in Balint's syndrome, following intrathecal methotrexate and
cytarabine therapy in adult acute lymphoblastic leukemia.
SO - Eur Neurol 2001;46(3):166-7
AD - Department of Neurology, University Hospital, Inselspital, Bern,
Switzerland.
17
UI - 11600602
AU - Lee EJ; Petroni GR; Schiffer CA; Freter CE; Johnson JL; Barcos M;
TI -
Frizzera G; Bloomfield CD; Peterson BA
Brief-duration high-intensity chemotherapy for patients with small
noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results
of cancer and leukemia group B study 9251.
SO - J Clin Oncol 2001 Oct 15;19(20):4014-22
AD - Department of Medicine, the Alvin and Lois Lapidus Cancer Institute,
Sinai Hospital, Baltimore, MD, USA.
PURPOSE: To define the activity and feasibility of brief-duration
high-intensity chemotherapy for adults with small noncleaved,
non-Hodgkin's lymphoma (SNC) and the L3 variant of acute lymphocytic
leukemia (L3 ALL). PATIENTS AND METHODS: Seventy-five adults with either
SNC or L3 ALL (median age, 44 years) were treated with an aggressive
regimen that consisted of one cycle of cyclophosphamide and prednisone
followed by cycles containing either ifosfamide or cyclophosphamide;
high-dose methotrexate, vincristine, dexamethasone, and either
doxorubicin or etoposide/cytarabine; or intrathecal triple therapy with
prophylactic CNS irradiation. RESULTS: All 24 patients with L3 ALL and
the 30 of 51 patients with SNC confirmed by central histologic review
were included in this analysis. Forty-three of 54 patients achieved
complete response (CR) (18 of 24 with ALL and 25 of 30 with SNC), and 28
are alive and in continuous CR with a median follow-up of 5.1 years.
Hematologic toxicity was profound, and nonhematologic toxicity was
notable, with 10 of 75 patients treated developing significant
neurologic toxicity consisting of transverse myelitis in five patients,
CNS toxicity in three, and severe peripheral neuropathy in two. All
patients who did not achieve CR died of the disease, and all recurrences
occurred within 16 months of the end of treatment. Responses and
toxicities were similar in the patients with both lymphoma and leukemia.
CONCLUSION: Aggressively delivered chemotherapy is potentially curative
in as many as half of patients with SNC and the L3 ALL variant. This
treatment regimen had considerable neurologic toxicity and has been
modified.
18
UI - 11673686
AU - Marie JP
TI -
Drug resistance in hematologic malignancies.
SO - Curr Opin Oncol 2001 Nov;13(6):463-9
AD - Department of Hematology and Medical Oncology, University Paris 6,
Paris, France. jean-pierre.marie@htd.ap-hop-paris.fr
Drug resistance eventually occurs in most hematologic malignancies
treated with chemotherapy. The mechanisms responsible for drug
resistance include expression of transporters of xenobiotics of the
adenosine triphosphate-binding cassette protein superfamily
(P-glycoprotein, multidrug resistance associated proteins, breast cancer
resistance protein), modifications of enzymes like deoxycytidine kinase,
and defects in chemotherapy-induced apoptosis. The efforts to overcome
this drug resistance have been focused, thus far, on modulation of
P-glycoprotein. Several compounds were manufactured for this purpose,
and phase III trials of PSC833, one of the most potent P-glycoprotein
inhibitors, are completed. The emergence of modulators with several
adenosine triphosphate-binding cassette protein targets, like GG120918
(inhibiting P-glycoprotein and breast cancer resistance protein) and
VX710 (inhibiting P-glycoprotein and multidrug resistance associated
protein 1), are of clinical interest in malignancies often expressing
several efflux pumps simultaneously. Another approach is the use of
"furtive" drugs like liposomal or nanoparticular anthracyclines.
19
UI - 11678787
AU - Albertsen BK; Schroder H; Jakobsen P; Muller HJ; Carlsen NT; Schmiegelow
TI -
K
Monitoring of Erwinia asparaginase therapy in childhood ALL in the
Nordic countries.
SO - Br J Clin Pharmacol 2001 Oct;52(4):433-7
AD - Centre for Clinical Pharmacology, University of Aarhus, Aarhus, Denmark.
bka@farm.au.dk
AIMS: Evaluation of L-asparaginase therapy in the NOPHO-92 ALL-protocol
(treatment protocol of acute lymphoblastic leukaemia of the Nordic
Society of Paediatric Haematology and Oncology, initiated in 1992) after
intravenous and intramuscular administration of Erwinia asparaginase
during induction and re-induction therapy. METHODS: Forty children with
newly diagnosed acute lymphoblastic leukaemia received Erwinia
asparaginase (30 000 IU/m2 i.v. or i.m.) during induction therapy (every
day for 10 days), and 19 children received Erwinia asparaginase (30 000
IU/m2 i.v. or i.m.) during re-induction therapy (twice a week for 2
weeks). Within the treatment periods asparaginase trough activity (using
a spectrophotometric assay) was determined on specific days. The goal of
therapy is complete L-asparagine depletion, which asparaginase
activities above 100 IU l(-1) have been shown to ensure. Therefore
determination of L-asparagine (using a h.p.l.c. method) was performed
only in plasma samples with asparaginase activities below 100 IU l(-1).
RESULTS: During induction therapy 92.2% of the trough enzyme activities
were above 500 IU l(-1) for the i.v.-treated patients, and 92.4% of the
trough enzyme activities were above 500 IU l(-1) for the i.m.-treated
patients. During re-induction therapy 64.7% of the trough enzyme
activities were below 100 IU l(-1) in the i.v.-treated group, and 73.3%
of the trough enzyme activities were below 100 IU l(-1) in the
i.m.-treated group. For trough enzyme activities below 100 IU l(-1)
L-asparagine depletion was complete in two thirds of the samples.
CONCLUSIONS: In the NOPHO-92 ALL-protocol L-asparaginase treatment
during induction therapy was unnecessarily intense, but during the
re-induction phase it appeared inadequate.
20
UI - 11680979
AU - Umeda K; Lin YW; Watanabe K; Adachi S; Usami I; Akiyama Y; Kubota M;
TI -
Nakahata T
[Hematopoietic stem cell transplantation with
busulfanthiotepa-cyclophosphamide conditioning for pediatric patients
with high-risk acute lymphoblastic leukemia]
SO - Rinsho Ketsueki 2001 Sep;42(9):685-90
AD - Department of Pediatrics, Graduate School of Medicine, Kyoto University.
Twelve children with high-risk acute lymphoblastic leukemia underwent
stem cell transplantation (SCT) with a conditioning regimen consisting
of busulfan, cyclophosphamide and thiotepa. Eight of them underwent SCT
while in complete remission (CR) and the other 4 while not in CR. Three
children underwent HLA-matched related bone marrow transplantation
(BMT), 7 HLA-matched unrelated BMT, 1 HLA one-locus-mismatched unrelated
cord blood cell transplantation, and 1 autologous peripheral blood stem
cell transplantation. Grade II-IV acute GVHD was observed in 3 of the 11
allo-SCT cases, while chronic GVHD was seen in 3 of 9 evaluable cases.
None of the 12 cases showed thrombotic microangiopathy, and
veno-occlusive disease (VOD) was observed in 3. Nine of the patients are
alive and disease-free 6-45 months after diagnosis. The event-free
survival rate at 3 years was 72.2% for the 12 patients, including 8 of
the 9 who received SCT during CR, and 2 of the 4 who did so while not in
CR. The other 3 patients died: 2 of disease progression and 1 of VOD
with pneumonia. All of those who died had undergone unrelated BMT.
21
UI - 11680981
AU - Noda M; Takeuchi Y; Tsujimoto T; Takimoto Y; Okita H
TI -
[Pneumatosis intestinalis after allogeneic bone marrow transplantation
for acute lymphocytic leukemia]
SO - Rinsho Ketsueki 2001 Sep;42(9):696-700
AD - Department of Internal Medicine, National Otake Hospital.
A 45-year-old man was diagnosed as having acute lymphocytic leukemia
and allogeneic BMT from his HLA-identical sister was performed on
November 13, 1997. He developed acute GVHD (grade II), but quickly
recovered after methyl-PSL pulse therapy. On June 5, 1998--day 202 after
BMT--abdominal pain developed. X-ray and CT examinations showed
pneumatosis intestinalis, pneumoperitoneum, pneumomediastinum and
abdominal free air. We performed oxygen administration and methyl-PSL
pulse therapy, and this quickly improved the symptoms. Corticosteroid
and chronic GVHD were thought to be the causative factors of pneumatosis
intestinalis in this case. Although pneumatosis intestinalis is
relatively rare, it is one of the important potential complications that
can occur after allogeneic BMT.
22
UI - 11704796
AU - Okano A; Shimazaki C; Ochiai N; Hatsuse M; Takahashi R; Ashihara E;
TI -
Inaba T; Fujita N; Noda Y; Nakagawa M
Subcutaneous infection with Mycobacterium fortuitum after allogeneic
bone marrow transplantation.
SO - Bone Marrow Transplant 2001 Oct;28(7):709-11
AD - Second Department of Medicine, Kyoto Prefectural University of Medicine,
465 Kawaramachi-Hirokoji, Kami-gyoku, Kyoto, 602-8566, Japan.
Reports of cases of mycobacterial infections after SCT are rare. We
report a 30-year-old female with a cutaneous infection of Mycobacterium
fortuitum 30 months after allogeneic bone marrow transplantation for
acute lymphoblastic leukemia. The patient was successfully treated with
surgical debridement followed by oral minocycline and clarithromycin.
Mycobacterial infections should be considered in SCT patients with
undiagnosed refractory chronic cutaneous infection, and surgical
debridement is useful for the diagnosis and treatment of such
infections.
23
UI - 11722407
AU - Donadieu J; Hill C
TI -
Early response to chemotherapy as a prognostic factor in childhood acute
lymphoblastic leukaemia: a methodological review.
SO - Br J Haematol 2001 Oct;115(1):34-45
AD - Service de Biostatistique et d'epidemiologie, Institut Gustave Roussy,
Villejuif, France. jean.donadieu@trs.ap-hop-paris.fr
Published studies of the prognostic value of the early response to
induction treatment in childhood acute lymphoblastic leukaemia (ALL)
were analysed. Three criteria were used to judge the early treatment
response: persistence of peripheral blasts (PPB) or of bone marrow
blasts (PBMB) during induction therapy and minimal residual disease
(MRD) after completion of induction therapy. Studies with more than 50
patients, published between 1980 and 2000, were reviewed. Among 13 659
distinct articles published on ALL, we identified only 43 applicable
studies. Within- and between-laboratory variations were evaluated in
only one study. Treatment modalities differed among, and sometimes
within, studies. The cut-off points used in the statistical analyses
were never discussed, and in many studies appeared to be selected after
multiple tests. The proportion of missing data was > 30% in almost all
studies of MRD, as a result of technical difficulties and not missing
samples. PPB and PBMB were associated with shorter survival in,
respectively, 13 out of 14 and 15 out of 16 studies. Detection of MRD
was associated with poor outcome in 12 of the 13 studies. Because none
of the parameters used to measure the early response to induction
therapy for childhood ALL have been properly assessed as prognostic
factors, we conclude that they should be considered only as candidate
prognostic indicators pending more thorough studies.
24
UI - 11718088
AU - Huang W; Zhang B; Yao S
TI -
[Clinical efficacy of double autologous hematopoietic stem cell
transplantation in the treatment of adult acute lymphoblastic leukemia]
SO - Zhonghua Xue Ye Xue Za Zhi 2001 Aug;22(8):399-402
AD - Hematology Department, PLA General Hospital of China, Beijing 100853,
China.
OBJECTIVE: To evaluate the clinical efficacy of double autologous
hematopoietic stem cell transplantation (DAHSCT) in adult acute
lymphoblastic leukemia and analyse the affecting factors. METHODS:
Thirteen adult acute lymphoblastic leukemia (ALL) patients received the
first AHSCT in 12 months after complete remission (CR). The first
conditioning regimen was Vp16,600-1000 mg or Ara-C 2-4 g/m2, CTX 120
mg/kg, total body irradiation(TBI) 7.5-9.0 Gy and in 6 patients BCNU 125
mg was added. All the patients received the second AHSCT in 4 to 10
months after the first AHSCT. The second conditioning regimen was
Vp16,600-1000 mg or Ara-C 2-4 g/m2, Mel 140 mg/m2, CTX 120 mg/kg.
RESULTS: All engrafted patients had rapid hematopoietic reconstitution.
There was no AHSCT related death. The median follow-up duration was 837
days. Seven of the 13 DAHSCT patients were alive. The 3 year
disease-free survival (DFS) was (53.8 +/- 7.7)%. Those who had more
lymphoblasts in bone marrow at the second AHSCT than that at the first
AHSCT had greater probability of relapse. CONCLUSION: It suggested that
DAHSCT could be used as an important treatment owing to its low AHSCT
related death and relatively long DFS.
25
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.
26
UI - 11418367
AU - Ortega JJ; Ribera JM; Oriol A; Bastida P; Gonzalez ME; Calvo C; Egurbide
TI -
I; Hernandez Rivas JM; Rivas C; Alcala A; Besalduch J; Macia J; Gardella
S; Carnero M; Lite JM; Casanova F; Martinez M; Fontanillas M; Feliu E;
San Miguel JF; PETHEMA Group, Spanish Society of Hematology. Programa
para el Estudio y Tratamiento de las Hemopatias Malignas
Early and delayed consolidation chemotherapy significantly improves the
outcome of children with intermediate risk acute lymphoblastic leukemia.
Final results of the prospective randomized PETHEMA ALL-89 TRIAL.
SO - Haematologica 2001 Jun;86(6):586-95
AD - Haematology Department, Hospital Universitari Germans Trias i Pujol,
Badalona, Spain. jmribera@ns.hugtip.scs.es
BACKGROUND AND OBJECTIVES: To evaluate the impact of early and delayed
consolidation chemotherapy on the outcome of children with acute
lymphoblastic leukemia (ALL) stratified according to risk groups. DESIGN
AND METHODS: From 1989 to 1994, 195 children (< or = 15 years old)
diagnosed as having ALL (ALL-L3 excluded) in 15 Spanish hospitals
entered the prospective, randomized PETHEMA ALL-89 trial. Patients were
stratified into low-risk (LR), intermediate-risk (IR) and high-risk (HR)
groups according to their initial features and the rate of response to
induction therapy. LR-ALL patients were randomized to receive or not
early consolidation chemotherapy (C-1). After receiving C-1, IR patients
were randomized to receive or not delayed consolidation chemotherapy
(C-2). HR patients received C-1 and C-2 chemotherapy. Standard
maintenance chemotherapy was administered to all patients for 2 years.
High doses of intravenous methotrexate and 12 triple intrathecal doses
were given as prophylaxis against central nervous system (CNS) disease.
RESULTS:The mean (and standard deviation) age was 6 (4) years and 120
patients were males. Fourteen patients had early pre-B-ALL, 149 common
or pre-B-ALL, and 32 T-ALL. Complete remission (CR) was attained in 189
patients (97%), 11 of whom (6%) had a slow response. Risk group
stratification after CR was: LR 89, IR 50 and HR 56 patients (including
a subset of 26 patients at very high risk). Ten-year event-free survival
(EFS) and overall survival (OS) probabilities for the whole series were
58% (95% CI: 52-64%) and 69% (61-77), respectively, with a median
follow-up of 8.7 years. Dividing the patients according to risk group,
the 10-year EFS and OS probabilities in the LR group were 71% (63-79)
and 86% (80-92), respectively; in the IR group 69% (57-81) and 76%
(64-88), respectively, and in the HR group 30% (18-42) and 44% (32-57),
respectively. For LR patients receiving C-1, EFS and OS were 79% (57-92)
and 90% (82-98), respectively, versus 62% (48-76) and 66% (51-81) in
patients not receiving C-1 (p= 0.06). For IR patients, EFS and OS were
significantly improved in those receiving early and delayed
consolidation (EFS 87% (74-88) vs. 52% (41-70), and OS 92% (87-97) vs.
61% (51-71)(p=0.036). Prognostic factors for EFS identified in
multivariable analyses were: age >10 years in the LR group (OR 3.5, 95%
CI 1.3-9.5, p=0.01), and treatment with C-2 in IR patients (OR 5.0, 95%
CI 1.4-17.8, p=0.01). The CNS relapse rate was 4% for all the series
(including the HR subset). Tolerance to treatment was good.
INTERPRETATION AND CONCLUSIONS: In this study, early consolidation
seemed to improve the prognosis of children with LR-ALL, but differences
in EFS were not significant. Delayed consolidation had a favorable
influence on the outcome of IR-ALL. CNS preventive treatment without
cranial irradiation was effective in all the groups of ALL patients.
27
UI - 11746248
AU - Acar H; Caliskan U; Demirel S; Largaespada DA
TI -
Micronucleus incidence and their chromosomal origin related to therapy
in acute lymphoblastic leukemia (ALL) patients: detection by
micronucleus and FISH techniques.
SO - Teratog Carcinog Mutagen 2001;21(5):341-7
AD - Department of Medical Genetics, Selcuk University, Medical Faculty,
Konya, Turkey. yaseminsena@hotmail.com
Micronucleus assay and dual color-fluorescence in situ hybridization
(DC-FISH), using centromere-specific and whole chromosome-specific
painting probes, are considered a useful screening test to determine the
incidence of micronucleus, their origin and contents. The patients with
acute lymphoblastic leukemia (ALL), who had undergone chemotherapy, were
analysed before and after treatment with vincristine, methotrexate,
daunomycin, prednisone, and asparaginase. The incidence of micronuclei
after the antileukemic agent treatment was significantly higher than
before the treatment. Application of DC-FISH using a combination of
whole chromosome-specific painting probes and the same
chromosome-specific alpha-satellite centromeric probe showed that there
were no significant differences in the micronucleus incidence for any
specific chromosome (chromosomes 7, 8, 11, 17, X, and Y). There were no
significant differences between the incidence of centromere-positive
micronuclei and the incidence of centromere-negative micronucleus. We
concluded that antileukemic agents induced the somatic genetic damage
but this damage is not related to any specific chromosome studied.
Copyright 2001 Wiley-Liss, Inc.
28
UI - 11745870
AU - Mori T; Manabe A; Tsuchida M; Hanada R; Yabe H; Ohara A; Saito T;
TI -
Nakazawa S
Allogeneic bone marrow transplantation in first remission rescues
children with Philadelphia chromosome-positive acute lymphoblastic
leukemia: Tokyo Children's Cancer Study Group (TCCSG) studies L89-12 and
L92-13.
SO - Med Pediatr Oncol 2001 Nov;37(5):426-31
AD - Department of Pediatrics, Social Insurance Saitama Chuo Hospital, Tokyo,
Japan.
BACKGROUND: The prognosis of Philadelphia chromosome-positive acute
lymphoblastic leukemia (Ph(+) ALL) is generally poor and reports from
large studies are scarce. We evaluated the efficacy of allogeneic bone
marrow transplantation (allo-BMT) for children with this type of
leukemia. PROCEDURE: The chemotherapy regimens consisted of an induction
phase and very intensive consolidation followed by a reinduction phase
and late intensification treatment. The selection of treatment
modalities such as chemotherapy, allo-BMT, or autologous transplantation
was made by each institute. The principal endpoint was the outcome of
children with Ph(+) ALL according to the treatment options. RESULTS:
Thirty-two patients (4.3%) were diagnosed as Ph(+) ALL out of the 741
cases of ALL consecutively enrolled in two protocols of the Tokyo
Children's Cancer Study Group (TCCSG) from 1989 to 1994. Thirty patients
(93.8%) were induced into complete remission (CR). Of these 30 patients,
eight children electively received allo-BMT in the first CR. Six of
these patients are in continuous remission at a median follow-up of 58
(range 48-105) months after the diagnosis. One patient died following
recurrence and another patient died of graft vs. host disease. Three
patients treated with autologous BMT or peripheral blood stem cell
transplantation in the first CR experienced a subsequent relapse. In the
remaining 19 patients, 13 patients were treated with very high-risk
chemotherapy alone and all relapsed within 28 months. One patient was
excluded from the analysis because he was treated with standard-risk
chemotherapy until relapse. The other five patients were also excluded
from the analysis because Philadelphia chromosome was not detected until
they relapsed. None of the relapsed patients survived in spite of
treatment including allo-BMT. In multivariate analysis, only allo-BMT
remained as an independent factor for good prognosis. CONCLUSIONS: The
only way to cure children with Ph(+) ALL was allo-BMT in this study and
its outcome seemed promising. Copyright 2001 Wiley-Liss, Inc.
29
UI - 10759711
AU - Lawson SE; Harrison G; Richards S; Oakhill A; Stevens R; Eden OB;
TI -
Darbyshire PJ
The UK experience in treating relapsed childhood acute lymphoblastic
leukaemia: a report on the medical research council UKALLR1 study.
SO - Br J Haematol 2000 Mar;108(3):531-43
AD - Department of Haematology, Birmingham Children's Hospital, Birmingham,
UK. isaac.lawson@btinternet.com
We have examined the toxicity and overall outcome of the Medical
Research Council UKALL R1 protocol for 256 patients with relapsed
childhood acute lymphoblastic leukaemia (ALL). Second remission was
achieved in over 95% of patients. Two patients died during induction and
seven patients died of resistant disease. The overall actuarial
event-free survival (EFS) at 5 years for all patients experiencing a
first relapse was 46% (95% CI 40-52). Duration of first remission, site
of relapse, age at diagnosis and sex emerged as factors of prognostic
significance. Five-year EFS was only 7% for children relapsing in the
bone marrow within 2 years of diagnosis, but was 77% for those relapsing
without bone marrow involvement > 2.5 years from diagnosis. All analyses
in this report are by treatment received. For those receiving
chemotherapy alone, the 5-year EFS was 48%; for autologous bone marrow
transplantation (BMT), the 5-year EFS was 47%; for unrelated donor BMT,
it was 52%; and for related donor BMT, the 5-year EFS was 45%. The
groups, however, were not comparable with respect to risk factor
profile, and therefore direct comparison of EFS is misleading.
Adjustment for time to transplant and prognostic factors was used to
reduce the effects of biases between treatment groups, but did not
suggest benefit for any particular treatment. There was failure of our
planned randomization scheme in this trial with only 9% of those
eligible being randomized, which highlights the difficulties in running
randomized trials especially in patients who have relapsed from a
previous trial. The optimal treatment for relapsed ALL therefore remains
uncertain. Alternative approaches are clearly needed for those with
early bone marrow relapse if outcome is to improve.
30
UI - 10986059
AU - Mattano LA Jr; Sather HN; Trigg ME; Nachman JB
TI -
Osteonecrosis as a complication of treating acute lymphoblastic leukemia
in children: a report from the Children's Cancer Group.
SO - J Clin Oncol 2000 Sep 15;18(18):3262-72
AD - Kalamazoo Center for Medical Studies, Michigan State University, USA.
PURPOSE: To determine the incidence, risk factors, and morbidity for
osteonecrosis (ON) in children with acute lymphoblastic leukemia (ALL)
treated with intensive chemotherapy including multiple, prolonged
courses of corticosteroid. PATIENTS AND METHODS: The occurrence of
symptomatic ON was investigated retrospectively in 1, 409 children ages
1 to 20 years old receiving therapy for high-risk ALL on Children's
Cancer Group (CCG) protocol CCG-1882. RESULTS: ON was diagnosed in 111
patients (9.3% +/- 0.9%, 3-year life-table incidence). The incidence was
higher for older children (> or = 10 years: 14.2% +/- 1.3% v < 10 years:
0.9% +/- 0.4%; P: <.0001), especially females 10 to 15 years old and
males 16 to 20 years old (19.2% +/- 2.3% and 20.7% +/- 4.7%,
respectively). In patients 10 to 20 years old, the incidence of ON was
higher for females versus males (17.4% +/- 2.1% v 11.7% +/- 1.6%,
respectively; P: =.03) and for patients randomized to receive two 21-day
dexamethasone courses versus one course (23.2% +/- 4.8% v 16.4% +/-
4.3%, respectively; P: =.27). Among ethnic groups, whites had the
highest incidence and blacks the lowest, with other groups intermediate
(16.7% +/- 1.4% v 3.3% +/- 2.3% v 6.7% +/- 2.2%, respectively; P:
=.003). There was no difference in event-free survival in patients with
or without ON. ON was diagnosed within 3 years of starting ALL therapy
in all but one patient, involved weight-bearing joint(s) in 94% of
patients, and was multifocal in 74% of patients. Symptoms of pain and/or
immobility were chronic in 84% of patients, with 24% having undergone an
orthopedic procedure and an additional 15% considered candidates for
surgery in the future. CONCLUSION: Children ages 10 to 20 years who
receive intensive ALL therapy, including multiple courses of
corticosteroid, are at significant risk for developing ON.
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