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NCI CANCERLIT® Search: Therapy of Acute Lymphocytic Leukemia - October 2001
National Cancer Institute®
Last Modified: November 21, 2001
Table of Contents
1
UI - 21417789
AU - Blanco JG; Dervieux T; Edick MJ; Mehta PK; Rubnitz JE; Shurtleff S;
TI -
Raimondi SC; Behm FG; Pui CH; Relling MV
Molecular emergence of acute myeloid leukemia during treatment for acute
lymphoblastic leukemia.
SO - Proc Natl Acad Sci U S A 2001 Aug 28;98(18):10338-43
AD - Department of Pharmaceutical Sciences, St. Jude Children's Research
Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
Therapy-related acute myeloid leukemias (t-AML) with translocations of
the MLL gene are associated with the use of topoisomerase II inhibitors.
We established the emergence of the malignant clone in a child who
developed t-AML with a t(11;19) (q23;p13.3) during treatment for acute
lymphoblastic leukemia (ALL). The MLL-ENL and the reciprocal ENL-MLL
genomic fusions and their chimeric transcripts were characterized from
samples collected at the time of t-AML diagnosis. We used PCR with
patient-specific genomic primers to establish the emergence of the
MLL-ENL fusion in serially obtained DNA samples. The MLL-ENL fusion was
not detectable in bone marrow at the time of ALL diagnosis or after 2
months of chemotherapy (frequency <8.3 x 10(-7) cells(-1)). The genomic
fusion was first detected in bone marrow after 6 months of treatment at
a frequency of one in 4,000 mononuclear bone marrow cells; the frequency
was one in 70 cells after 20 months of therapy. At the first detection
of MLL-ENL, the only topoisomerase II inhibitors the patient had
received were one dose of daunorubicin and two doses of etoposide. The
MLL-ENL fusion was not detectable in blood at the time of ALL diagnosis
or after 0.7, 2, 8, 10, and 12 months of therapy but was detectable in
blood at 16 months (one in 2.3 x 10(4) cells). Recombinogenic Alu
sequences bracketed the breakpoints in both fusions. These data indicate
that the malignant clone was not present before therapy, arose early
during chemotherapy, and was able to proliferate even during exposure to
antileukemic therapy.
2
UI - 21226344
AU - Hann I; Vora A; Harrison G; Harrison C; Martineau M; Moorman AV; Secker
TI -
Walker LM; Eden O; Hill F; Gibson B; Richards S; UK Medical Research
Council's Working Party on Childhood Leukaemia
Determinants of outcome after intensified therapy of childhood
lymphoblastic leukaemia: results from Medical Research Council United
Kingdom acute lymphoblastic leukaemia XI protocol.
SO - Br J Haematol 2001 Apr;113(1):103-14
AD - Department of Paediatric Haematology & Oncology, Great Ormond Street
Hospital, London, UK. Ian.Hann@gosh-tr.nthames.nhs.uk
The single most important prognostic determinant in childhood acute
lymphoblastic leukaemia (ALL) is effective therapy and changes in
therapy may influence the significance of other risk factors. The effect
of intensified therapy on the importance of currently recognized
phenotypic and genotypic determinants of outcome was assessed in 2090
children enrolled on the Medical Research Council United Kingdom acute
lymphoblastic leukaemia XI (MRC UKALL XI) protocol. Treatment allocation
was not determined by risk factors. Multivariate analysis confirmed the
dominant influence on prognosis of age, sex and presenting white cell
count (WCC). After allowing for these features, blast karyotype, d 8
marrow blast percentage and remission status at the end of induction
therapy were the only remaining significant predictors of outcome.
Organomegaly, haemoglobin concentration, French--American--British type,
body mass index, presence of central nervous system disease at
diagnosis, immunophenotype and presence of TEL/AML1 fusion gene
(examined in a subset of 659 patients) either had no significant effect
on outcome or were significant only in univariate analysis. Among
karyotype abnormalities with an independent influence on prognosis, high
hyperdiploidy (> 50 chromosomes) was shown to be favourable, whereas
near haploidy (23--29 chromosomes), presence of the Philadelphia
chromosome, t(4;11) and abnormalities affecting the short arm of
chromosome 9 [abn (9p)] were adverse risk factors. Early responders to
therapy, determined by residual marrow infiltration after 8 d of
induction therapy, had a good outcome, while the small proportion of
patients who did not achieve a complete remission by the end of
induction therapy had a poor outcome. A third block of late
intensification was shown to improve event-free survival by 8% at 5
years. The effect of these risk factors was not significantly different
between those randomized to the third intensification block and those
not randomized to a third block.
3
UI - 21345447
AU - Rios JA; Korones DN; Heal JM; Blumberg N
TI -
WBC-reduced blood transfusions and clinical outcome in children with
acute lymphoid leukemia.
SO - Transfusion 2001 Jul;41(7):873-7
AD - Transfusion Medicine Unit, Department of Pathology and Laboratory
Medicine, University of Rochester Medical Center, 601 Elmwood Avenue,
Rochester, NY 14642, USA.
BACKGROUND: WBC reduction offers a variety of benefits to patients
requiring multiple transfusions during induction therapy for childhood
acute lymphoid leukemia (ALL), including reductions in febrile
transfusion reactions, HLA alloimmunization, and CMV transmission. One
potential benefit is a reduction in the deleterious effects of
transfusion immunomodulation. In the surgical setting, transfusion
immunomodulation has been linked to increases in postoperative
infections and decreases in host cellular immunity that are mitigated by
WBC reduction of transfused blood. STUDY DESIGN AND METHODS: A
retrospective review was conducted of the medical records of 68
consecutive children undergoing induction therapy for newly diagnosed
ALL from 1988 through 1995, a period whose midpoint is 1991, the year
WBC reduction was introduced in this hospital. RESULTS: WBC reduction of
platelet and RBC transfusions was associated with fewer days with fever
(mean, 5.7 days [no WBC reduction] and 2.1 days [WBC reduction]; p =
0.012) and days with positive microbial cultures (mean, 1.5 [no WBC
reduction] and 0.71 [WBC reduction]; p = 0.0055). There were more
high-risk ALL patients in the group receiving WBC-reduced transfusions.
CONCLUSION: Allogeneic WBCs in transfused blood may cause impairment of
host defenses against microbial infection during induction therapy for
childhood ALL.
4
UI - 21426545
AU - Uzunel M; Mattsson J; Jaksch M; Remberger M; Ringden O
TI -
The significance of graft-versus-host disease and pretransplantation
minimal residual disease status to outcome after allogeneic stem cell
transplantation in patients with acute lymphoblastic leukemia.
SO - Blood 2001 Sep 15;98(6):1982-4
AD - Department of Clinical Immunology, Karolinska Institute at Huddinge
University Hospital, Huddinge, Sweden. mehmet.uzunel@impi.ki.se
Relapse is the major cause of treatment failure after allogeneic stem
cell transplantation (SCT) in patients with acute lymphoblastic
leukemia. Minimal residual disease (MRD) was analyzed before SCT in 30
patients with acute lymphoblastic leukemia. The aim was to determine
whether the level of MRD before transplantation was correlated with
outcome. Fifteen patients were found to have high-level MRD (10(-2) to
10(-3)), 10 had low-level MRD (< 10(-3)), and 5 were MRD(-). Among
MRD(-) patients the probability of relapse was 0 in 5, which was less
than in MRD(+) patients (13 of 25) (P =.05). No major difference was
found between the high- and low-level MRD(+) groups. Among the MRD(+)
patients, only 2 of 11 with acute and chronic graft-versus-host disease
had a relapse, versus 11 of 14 without (P =.005). In conclusion, for
patients entering transplantation while they have residual disease, a
combination of acute and chronic graft-versus-host disease may be needed
to decrease the risk of relapse after SCT.
5
UI - 21464093
AU - Xinjia F; Matano S; Amitani S; Terahata S; Furusyo H; Yamamoto M;
TI -
Sugimoto T
[Low-dose etoposide in a patient with adult T-cell leukemia/lymphoma who
had severe complications]
SO - Gan To Kagaku Ryoho 2001 Sep;28(9):1269-72
AD - Dept. of Hematology, Tonami General Hospital.
A 76-year-old female had been followed in our hospital for dissecting
aneurysm, cardiac failure, and cerebral infarction. Inguinal
histopathologic diagnosis of the biopsied lymph node was diffuse
pleomorphic type non-Hodgkin's lymphoma with T-cellular phenotype, and
the patient was referred to our department. She had human T-lymphotropic
virus type I seropositivity, and PCR of the pX lesion disclosed a
monoclonal band. She was ultimately diagnosed as having adult T-cell
leukemia/lymphoma (ATL/L, stage IV). Since she had many severe
complications, she was given low-dose etoposide (LD-ETP, 50 mg/day).
Atypical cells disappeared from the blood, and lymphadenopathy
regressed. No major adverse reaction was observed after LD-ETP. She
continued to receive intermittent LD-ETP, but she developed pneumonia in
lymphomatous lesions. These findings suggest that LD-ETP is a well
tolerable and effective treatment in patients with ATL/L even if there
are severe complications.
6
UI - 21346272
AU - Maeda Y
TI -
[ATRA therapy for adult T-cell leukemia]
SO - Rinsho Ketsueki 2001 May;42(5):376-9
7
UI - 21446742
AU - Kingma A; van Dommelen RI; Mooyaart EL; Wilmink JT; Deelman BG; Kamps WA
TI -
Slight cognitive impairment and magnetic resonance imaging abnormalities
but normal school levels in children treated for acute lymphoblastic
leukemia with chemotherapy only.
SO - J Pediatr 2001 Sep;139(3):413-20
AD - Department of Pediatrics, Division of Pediatric Oncology/Hematology,
University Hospital Groningen, Groningen, The Netherlands.
OBJECTIVES: To investigate persistent neuropsychologic late effects in
children treated for acute lymphoblastic leukemia at a young age with
chemotherapy only by means of serial neuropsychologic assessments
(NPAs), magnetic resonance imaging (MRI) of the brain, and evaluation of
school levels. STUDY DESIGN: Consecutive patients (n = 17) had 2
extensive NPAs (12 psychometric measures) after cessation of therapy.
Test results were compared with those of both healthy control subjects
and 28 previously treated children who received cranial irradiation. MRI
findings were related to test scores. School levels were evaluated in
the patients and their healthy siblings. RESULTS: Initial participation
(n = 17) and availability of the study group after 8 years of follow-up
were 100%. Significant group differences between patients who received
chemotherapy and healthy control subjects were found for memory and
fine-motor functioning. The 17 patients combined showed 16 deficits on
various test measures. MRI abnormalities were seen in 6 children, but
these did not correlate with cognitive performance. No differences in
school levels were seen when the patients who received chemotherapy were
compared with their siblings. The current nonirradiated patients
demonstrated significantly better test results and significantly fewer
learning disabilities and MRI abnormalities than did the previously
irradiated group. CONCLUSION: Treatment with chemotherapy only may be
associated with some cognitive impairment. However, these children
attained normal school levels.
8
UI - 21371225
AU - Ma R; Liu F; Yang J
TI -
[Clinical study on effect of Fuzheng Kangbai Granule on long-term
survival of patients with acute leukemia]
SO - Zhongguo Zhong Xi Yi Jie He Za Zhi 1998 May;18(5):276-8
AD - Department of Hematology, Xiyuan Hospital, China Academy of TCM, Beijing
100091.
OBJECTIVE: To observe the effect of Fuzheng Kangbai Granule (FZKBG) on
event free interval (EFI) and over survival (OS) of patients with acute
leukemia, and to study the mechanism of FZKBG. METHODS: FZKBG was used
in 90 cases of completely remitted acute leukemia, immune functions of
patients before and after using FZKBG were measured. RESULTS: Five year
EFI and OS were 64.2% and 77.2% of 90 cases of completely remitted acute
leukemia, and the immune functions after using FZKBG have improved
significantly. CONCLUSIONS: FZKBG could increase the EFI and OS of
patients with acute leukemia, and the improved immune functions may play
a role in increasing 5 year EFI and OS.
9
UI - 21066421
AU - Espy KA; Moore IM; Kaufmann PM; Kramer JH; Matthay K; Hutter JJ
TI -
Chemotherapeutic CNS prophylaxis and neuropsychologic change in children
with acute lymphoblastic leukemia: a prospective study.
SO - J Pediatr Psychol 2001 Jan-Feb;26(1):1-9
AD - Department of Psychiatry, Southern Illinois University, Carbondale, IL
62901-6503, USA. kespy@siumed.edu
OBJECTIVE: To determine whether prophylactic CNS chemotherapy for
childhood acute lymphoblastic leukemia is associated with declines in
neuropsychological abilities. METHODS: Growth curve analysis was used to
examine neuropsychological outcome and treatment-related change in
children (N = 30) who were treated at two childhood cancer centers. A
comprehensive test battery was administered at baseline (8 months), 2,
3, and 4 years postdiagnosis (age at diagnosis M = 5.90 years, SD =
4.2C). RESULTS: Results indicated modest declines in arithmetic, visual
motor integration, and verbal fluency. Intrathecal and systemic
treatment was related to poorer visual motor integration at 4 years
postdiagnosis and a faster rate of decline in visual motor integration
skills across the observation period than intrathecal treatment alone.
Arithmetic proficiency at 4 years after diagnosis was related to
maternal education, but the rate of decline was not. Verbal fluency was
unrelated to demographic or treatment variables. CONCLUSIONS: These
findings suggest that neuropsychological outcome and declines are
related to both demographic and treatment characteristics depending on
the cognitive domain examined.
10
UI - 99065270
AU - Nysom K; Holm K; Michaelsen KF; Hertz H; Muller J; Molgaard C
TI -
Bone mass after treatment for acute lymphoblastic leukemia in childhood.
SO - J Clin Oncol 1998 Dec;16(12):3752-60
AD - Section of Paediatric Haematology, The Juliane Marie Centre,
Rigshospitalet, Copenhagen, Denmark. nysom@dadlnet.dk
PURPOSE: To study bone mass after childhood acute lymphoblastic leukemia
(ALL) and determine if reduced bone mass is related to previous therapy
or endocrine status at follow-up. PATIENTS AND METHODS: We studied 95
survivors of childhood ALL who were in first remission a median of 11
years (range, 3 to 23 years) after diagnosis and who had never been
irradiated outside a cranial field. The bone mass was measured by
dual-energy x-ray absorptiometry. The results were compared with data on
396 local controls. RESULTS: Adjusted for sex and age, the mean
whole-body bone mineral content (BMC) and bone mineral areal density
(BMDA) were both significantly reduced (0.4 SDs less than the predicted
mean value). This was mainly caused by reduced bone mass in the 33
participants who were aged 19 years or older at follow-up. In these
young adults, the mean height for age, bone area for height, and BMC for
bone area were all significantly reduced. This indicated that the
reduced whole-body bone mass was caused by both reduced bone size and
reduced size-adjusted bone mass. Reduced bone size was related to
previous cranial irradiation. Reduced size-adjusted bone mass was not
significantly related to age at diagnosis or at follow-up, length of
follow-up, cranial irradiation, cumulative dose of methotrexate or
corticosteroids, or endocrine status at follow-up. CONCLUSION: The
whole-body bone mass was reduced 11 years after diagnosis of childhood
ALL. If these abnormalities remain, survivors of childhood ALL will have
an increased risk for osteoporotic fractures later in life.
11
UI - 21281051
AU - Nysom K; Holm K; Hertz H; Muller J; Fleischer Michaelsen K; Molgaard C
TI -
Bone mass after treatment for acute lymphoblastic leukemia in childhood.
SO - J Clin Oncol 2001 Jun 1;19(11):2970-1
12
UI - 92029758
AU - Ruccione K; Kramer RF; Moore IK; Perin G
TI -
Informed consent for treatment of childhood cancer: factors affecting
parents' decision making.
SO - J Pediatr Oncol Nurs 1991 Jul;8(3):112-21
Both the treatment for childhood cancer and the legal requirements for
gaining parents' consent to treatment have become increasingly complex.
The purpose of the exploratory investigation reported here was to
identify influential circumstances surrounding the consent process in
the pediatric setting, to describe the relationship of parental anxiety
to these factors, and to delineate related practice and research
implications. Twenty-eight parents of children entered on one of four
protocols for the treatment of newly diagnosed acute lymphoblastic
leukemia at the Childrens Hospital Los Angeles and the University of
California San Francisco were asked to complete two questionnaires
within 48 hours after consenting to treatment: the State-Trait Anxiety
Index and the Parent Informed Consent Questionnaire. Results of the
study confirmed clinical experience that parents are given complex
information and asked to make decisions about their child's life in a
highly anxious state. Although participants were generally satisfied
with the informed consent process 48 hours after signing a consent form,
further research is needed to document how well parents understand and
remember key information, as well as the influence of time, experience,
and changes in state anxiety on their perceptions of the adequacy of the
consent process. In current clinical practice, simple strategies can be
applied to improve the informed consent process for families of children
with cancer.
13
UI - 94301076
AU - Jenney M
TI -
Limitation of therapy in the treatment of childhood cancer: toxicity
versus cure.
SO - Lancet 1994 Jul 23;344(8917):210-1
AD - Department of Pediatrics, University of Minnesota, Minneapolis.
14
UI - 95245790
AU - Enskar K
TI -
Ethical aspects of judging the alternative treatment of children with
cancer.
SO - Nurs Ethics 1995 Mar;2(1):51-62
In recent decades the improved treatment of childhood cancer has
increased the proportion of children being cured. However, the intensive
treatment required also implies a heavy burden for the children and
their families. The purpose of this article is to judge the ethical
aspects of different treatment regimens used for children with cancer by
means of a case study. The analysis is based on the ethical model by
Beauchamp and Childress. The assessment is based on every person, or
group of persons, involved and is on the principles of autonomy,
nonmaleficence, beneficence and justice. The analysis shows that
intensification of treatment of children with cancer is ethically
justified from a deontological point of view. The consequences are more
difficult to anticipate from a utilitarian perspective.
15
UI - 96268676
AU - Entwistle VA; Watt IS; Bradbury R; Pehl LJ
TI -
Media coverage of the Child B case.
SO - BMJ 1996 Jun 22;312(7046):1587-91
AD - NHS Centre for Reviews and Dissemination, University of York.
vael@york.ac.uk
The case of a girl with leukaemia, known as Child B, hit the headlines
who counselled against further treatment and took Cambridge and
Huntingdon Health Authority to court for refusing to fund chemotherapy
and a second bone transplant for her in the private sector. British
national newspapers varied greatly in the way they covered the case.
Some paid little attention to clinical considerations and presented the
case as an example of rationing based on financial considerations. Their
selective presentations meant that anyone reading just one newspaper
would have received only limited and partial information. If members of
the public are to participate in debates about treatment decisions and
health care rationing, means other than the media will need to be found
to inform and involve them.
16
UI - 96403418
AU - Spike J; Greenlaw J
TI -
Case consultation: when to invoke state agencies to treat: the cases of
a minor and a mentally disabled adult.
SO - J Law Med Ethics 1996 Spring;24(1):65-9
17
UI - 21314728
AU - Landier W
TI -
Childhood acute lymphoblastic leukemia: current perspectives.
SO - Oncol Nurs Forum 2001 Jun;28(5):823-33; quiz 834-5
AD - City of Hope National Medical Center, Duarte, CA, USA. wlandier@coh.org
PURPOSE/OBJECTIVES: To provide an overview of childhood acute
lymphoblastic leukemia (ALL), including epidemiology, clinical
presentation, diagnostic classification, prognostic factors, current
treatment, long-term sequelae, and nursing management. DATA SOURCES:
Journal articles, books, and clinical experience. DATA SYNTHESIS:
Childhood ALL is a heterogeneous disorder, and current treatment is
tailored to risk factors (e.g., initial white blood count, cytogenetic
properties of the leukemic blasts). Risk-directed therapy ensures that
children with a higher risk of relapse receive more intensive treatment,
whereas those with lower risk disease receive less toxic therapy with
decreased potential for treatment-related morbidity. Quality of life in
long-term survivors is a significant issue. Late sequelae of treatment
can include neurocognitive difficulties, endocrine dysfunction,
secondary malignancies, and cardiomyopathy. CONCLUSIONS: With
risk-directed therapy, cure rates for childhood ALL continue to improve.
At least 80% of children diagnosed with ALL today are expected to
survive their disease. IMPLICATIONS FOR NURSING PRACTICE: Nurses caring
for children with ALL can have a significant impact on the children's
overall health, from diagnosis through long-term follow-up. Nursing
interventions encompass the domains of physical and psychosocial care,
as well as patient and family education. Assisting the child and family
to maintain normalcy in the face of chronic illness, as well as
fostering the family's hope for the future and their belief in the
child's potential for survival, are key nursing strategies that promote
the child's growth, development, and psychological health.
18
UI - 21323341
AU - Wiela-Hojenska A; Gorczynska E; Orzechowska-Juzwenko K; Golebiowski W;
TI -
Hurkacz M; Boguslawska-Jaworska J
Metabolic functions of the liver during chemotherapy in children with
acute lymphoblastic leukemia.
SO - Int J Clin Pharmacol Ther 2001 Jun;39(6):246-50
AD - Department of Clinical Pharmacology, Wroclaw Medical University, Poland.
OBJECTIVE: The purpose of the present work was estimation of liver
function using the phenazone test and commonly used biochemical tests in
children with acute lymphoblastic leukemia (ALL) during anticancer
treatment. METHODS: Observations were carried out in the same 21
patients with ALL before the beginning of chemotherapy, after Protocol I
and after Protocol M of the antileukemic treatment carried out according
to the program BFM 86. RESULTS: The applied chemotherapy inhibited
phenazone elimination. Both phenazone half-life and metabolic clearance
rate were significantly different in patients after treatment with
anticancer drugs, especially with high-dose of methotrexate (MTX), from
those in patients before the beginning of chemotherapy (p < 0.001).
Moreover, after MTX administration transaminases activity and serum
bilirubin concentration were significantly higher than before treatment
(p < 0.05). CONCLUSION: Our results showed that in children with acute
lymphoblastic leukemia, anticancer chemotherapy decreased liver
metabolic capacity. Particularly, high-dose methotrexate treatment
altered the elimination of phenazone by inhibiting the activity of
hepatic mixed function oxidase system. This change may lead to an
increase in toxicity of active drugs which are metabolized by this
enzyme system. In addition, altered activity of liver metabolic function
can impair transformation of prodrugs to active forms. It should be
considered in selection of individual drug dosages. The objective
estimation of the type and degree of liver dysfunction can only be
achieved by the combination of a quantitative phenazone dynamic test and
static biochemical tests.
19
UI - 21532732
AU - Eckert C; Biondi A; Seeger K; Cazzaniga G; Hartmann R; Beyermann B;
TI -
Pogodda M; Proba J; Henze G
Prognostic value of minimal residual disease in relapsed childhood acute
lymphoblastic leukaemia.
SO - Lancet 2001 Oct 13;358(9289):1239-41
Molecular monitoring by quantitative PCR techniques of residual
leukaemia cells during the first phases of treatment can predict outcome
in children with acute lymphoblastic leukaemia. We did a retrospective
study of 30 children who had been treated according to the ALL-REZ BFM
trials to assess whether amount of minimal residual disease during the
first stages of treatment for relapsed acute lymphoblastic leukaemia
could predict outcome. In children with minimal residual disease of less
than 10(-3) at day 36, probability of event-free survival was 0.86 (95%
CI 0.77-0.95), compared with 0 in children with minimal residual disease
of 10(-3) or greater (p<0.001). Our results suggest that information
about molecular response to treatment can be used to predict long-term
outcome in relapsed childhood acute lymphoblastic leukaemia.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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