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NCI CANCERLIT® Search: Therapy of Acute Lymphoblastic Leukemia - June 2002
National Cancer Institute®
Last Modified: June 1, 2002
- Hepatitis C infection and hepatocellular carcinoma after treatment of childhood cancer.
- No major cognitive impairment in young children with acute lymphoblastic leukemia using chemotherapy only: a prospective longitudinal study.
- Pediatric acute lymphoblastic leukemia: redefining outcomes.
- Antibody formation during intravenous and intramuscular therapy with Erwinia asparaginase.
- CNS late-effects after ALL therapy in childhood. Part III: neuropsychological performance in long-term survivors of childhood ALL:
- Pharmacokinetics of doxorubicin in children with acute lymphoblastic leukemia: multi-institutional collaborative study.
- Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia.
- Use of recombinant human deoxyribonuclease (DNase) for processing of a thawed umbilical cord blood transplant in a patient with relapsed acute
- In vitro drug resistance profile of Philadelphia positive acute lymphoblastic leukemia is heterogeneous and related to age: a report of
- Generalized vitiligo after lymphocyte infusion for relapsed leukaemia.
- Low relapse rate in children with acute lymphoblastic leukemia after risk-directed therapy.
- Childhood acute lymphoblastic leukaemia--current status and future perspectives.
- [Etiology and structure of infectious complications of cytostatic therapy in children with acute lymphoblastic leukemia and non-B-cell
- Daycare attendance and risk of childhood acute lymphoblastic leukaemia.
- Proliferation of myeloid lineage cells and apoptosis of lymphoblastic leukemic cells induced by short-course high-dose methylprednisolone in
- [Strategies for treatment of childhood leukemia]
- Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: outcomes of late effects on pituitary function and growth in
- Infants with acute lymphoblastic leukemia: no evidence for high methotrexate resistance.
- Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission.
- [Treatment of acute lymphoblastic leukemia in adults with seven-drug induction therapy and intensive consolidation with or without autologous
- [Exercise tolerance in patients after acute lymphoblastic leukemia treatment in childhood]
- BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk
- Bone marrow stroma-supported culture of T-lineage acute lymphoblastic leukemic cells predicts treatment outcome in children: a Pediatric
- Quantification of minimal residual disease in patients with e1a2 BCR-ABL-positive acute lymphoblastic leukemia using a real-time RT-PCR
- Assessment of minimal residual disease (MRD) in CBFbeta/MYH11-positive acute myeloid leukemias by qualitative and quantitative RT-PCR
- In vitro activity of glufosfamide in childhood acute leukemia.
- Adult T-cell leukemia-lymphoma during pregnancy.
- Acute graft-versus-host disease in the small intestine.
- Quantitative MRI assessment of leukoencephalopathy.
Table of Contents
1
UI - 11878782
AU - Strickland DK; Jenkins JJ; Hudson MM
TI -
Hepatitis C infection and hepatocellular carcinoma after treatment of
childhood cancer.
SO - J Pediatr Hematol Oncol 2001 Nov;23(8):527-9
AD - Department of Hematology-Oncology, St. Jude Children's Research
Hospital, Memphis, Tennessee 38105-2794, USA.
The results of preliminary reports of childhood cancer survivors with
hepatitis C infection (HCV) show that in none of these patients did the
disease progress to liver failure or hepatocellular carcinoma (HCC). The
authors describe two patients who were diagnosed with HCC more than 20
years after the treatment of childhood acute lymphocytic leukemia.
Serologic testing, done at the time HCC was diagnosed, found
HCV-directed antibodies, suggesting that chronic HCV infection
contributed to the development of the subsequent neoplasm.
Identification of infected patients will permit intervention to reduce
the risk of progressive liver disease and will also assist in defining
the risk of and variables contributing to progressive liver disease.
2
UI - 11990695
AU - Kingma A; Van Dommelen RI; Mooyaart EL; Wilmink JT; Deelman BG; Kamps WA
TI -
No major cognitive impairment in young children with acute lymphoblastic
leukemia using chemotherapy only: a prospective longitudinal study.
SO - J Pediatr Hematol Oncol 2002 Feb;24(2):106-14
AD - Department of Pediatrics, University Hospital Groningen, The
Netherlands. a.kingma@bkk.azg.nl
PURPOSE: To study, using serial neuropsychological assessment and
evaluation of school achievement, persistent neuropsychological late
effects in children treated for acute lymphoblastic leukemia (ALL) at a
young age with chemotherapy only. PATIENTS AND METHODS: Twenty
consecutive patients underwent three evaluations, including 12
psychometric measures beside IQ. The authors applied strict methodology
and a prospective-longitudinal design that started at diagnosis and
extended to a median follow-up of 7 years. This report focuses on the
outcome of the last evaluation. Test results were compared with healthy
controls and to patients with ALL treated on a previous
chemotherapy-only protocol. School achievement was evaluated in patients
and their siblings. RESULTS: At the last evaluation, significantly lower
test scores in patients compared with controls were found for only 2 of
14 cognitive measures (1 intelligence and 1 attention measure). No great
differences were seen between school achievement of patients and
siblings. Compared with the previous chemotherapy protocol, a better
outcome was seen in the current study group on two measures (one memory
and one attention measure). CONCLUSIONS: Children surviving ALL have no
major cognitive impairment after chemotherapy, including intrathecal and
high-dose intravenous methotrexate. The slightly better outcome in the
current group may indicate possible adverse effects of more
dexamethasone treatment in the previous group.
3
UI - 11990711
AU - Kadan-Lottick N; Neglia JP
TI -
Pediatric acute lymphoblastic leukemia: redefining outcomes.
SO - J Pediatr Hematol Oncol 2002 Feb;24(2):88
AD - Department of Pediatrics, University of Minnesota School of Medicine,
Minneapolis, USA.
4
UI - 11979454
AU - Albertsen BK; Schroder H; Jakobsen P; Avramis VI; Muller HJ; Schmiegelow
TI -
K; Carlsen NT
Antibody formation during intravenous and intramuscular therapy with
Erwinia asparaginase.
SO - Med Pediatr Oncol 2002 May;38(5):310-6
AD - Department of Pharmacology, University of Aarhus, Aarhus, Denmark.
bka@farm.au.dk
BACKGROUND: Determination of the frequency of antibody formation during
first and second exposure to Erwinia asparaginase after i.v. and i.m.
administration. PROCEDURE: Thirty-nine children with newly diagnosed
acute lymphoblastic leukemia (ALL) were included in this prospective
study. Antibodies were determined (ELISA method) in plasma from these
patients on specific days during and after therapy with 30,000 IU/m(2)
i.v. or i.m. every day for ten days during the induction phase (first
exposure). For 19 children, antibodies were measured in plasma during
and after the re-induction phase (second exposure) following treatment
with 30,000 IU/m(2) i.v. or i.m. twice a week for two weeks (Mondays and
Thursdays). On the same days of therapy, enzyme activity
(spectrophotometric method) and the concentration of asparagine (HPLC)
was determined. RESULTS: During the first exposure, none of the patients
developed anti-Erwinia asparaginase antibodies. During the second
exposure, one patient (1 of 8 patients) treated intravenously developed
antibodies, which were associated with disappearance of enzyme activity
and reappearance of asparagine. Three of eleven patients developed
antibodies of pharmacokinetic importance after i.m. therapy. None of the
children had any clinical symptoms of hypersensitivity. CONCLUSIONS: The
formation of antibodies and subsequently altered pharmacokinetics of
Erwinia asparaginase seemed to be of importance only during a second
period of asparaginase therapy. Copyright 2002 Wiley-Liss, Inc.
5
UI - 11979456
AU - Langer T; Martus P; Ottensmeier H; Hertzberg H; Beck JD; Meier W
TI -
CNS late-effects after ALL therapy in childhood. Part III:
neuropsychological performance in long-term survivors of childhood ALL:
impairments of concentration, attention, and memory.
SO - Med Pediatr Oncol 2002 May;38(5):320-8
AD - Department of Pediatric Oncology, University Hospital for Children and
Adolescents, Erlangen, Germany.
PURPOSE: To date, the event free survival (EFS) after treatment of
childhood acute lymphoblastic leukemia (ALL) attains 80%. The survivor
group is growing steadily. Therefore, the primary purpose of our study
is to define the neuropsychological function and to describe which
central nervous system (CNS) functions are impaired following the German
ALL-BFM and COALL protocols for CNS-negative patients.Patients and
METHODS: In a cross-sectional multicenter study 121 subjects, long-term
survivors of childhood ALL in first continuous complete remission were
investigated. Seven years ago, the subjects were treated as standard or
medium risk patients according to ALL-BFM 81, ALL-BFM 83, or COALL 82
protocols, receiving comparable treatments. According to different
CNS-prophylaxes, two subgroups were compared in the study: the
non-cranially irradiated MTX-group (methotrexate-group) (n = 38) and the
cranially irradiated RT-group (radiotherapy-group) (with MTX i.th.) (n =
83). Intellectual and cognitive abilities of these groups were evaluated
using standardized psychometric techniques. The Kaufman factors Verbal
Comprehension, Perceptual Organisation and Freedom from Distractibility
were calculated. Demographical and clinical data collected at the time
of the diagnosis were compared between both groups. The different
prognoses for patients within both groups were taken into account using
a defined risk factor. Analysis of variance was conducted to relate
intellectual performance to age, gender, and CNS-treatment. RESULTS: The
RT-group exhibited a lower Full Scale IQ than the MTX-group (101.2 +/-
15.9 vs. 109.9 +/- 14.9, P = 0.031). Particularly for the Kaufman factor
Freedom from Distractibility the RT-group showed the lower scores (96.9
+/- 14.1 vs. 105.5 +/- 12.6, P = 0.037). Significant interactions
between gender and CNS prophylactic treatment were observed for Full
Scale IQ (P = 0.008), Verbal IQ (P = 0.012), Performance IQ (P = 0.024),
Verbal Comprehension (P = 0.004), and Perceptual Organisation (P =
0.032). CONCLUSIONS: Cranial irradiation in combination with MTX therapy
was associated with deficits in attention, concentration, and the
ability of sequencing and processing, measured by the Kaufman factor
Freedom from Distractibility. Our results support the strategy of
avoiding prophylactic CNS irradiation in low risk patients. Copyright
2002 Wiley-Liss, Inc.
6
UI - 11979457
AU - Frost BM; Eksborg S; Bjork O; Abrahamsson J; Behrendtz M; Castor A;
TI -
Forestier E; Lonnerholm G
Pharmacokinetics of doxorubicin in children with acute lymphoblastic
leukemia: multi-institutional collaborative study.
SO - Med Pediatr Oncol 2002 May;38(5):329-37
AD - University Children's Hospital, Uppsala, Sweden.
BACKGROUND: In adults, it has been shown that the pharmacokinetics of
doxorubicin are highly variable, despite standardization of the dose
based on body surface area (BSA). The purpose of this study was to
determine the plasma concentrations of doxorubicin and its active
metabolite doxorubicinol in children treated for acute lymphoblastic
leukemia (ALL). PROCEDURE: Children, 107 in number, aged 1.3-17.3 years,
were studied at Day 1 of induction therapy according to the current
Nordic protocol. Five infants, 3-9 months old, were also included.
Plasma samples were drawn 23 hr after the start of a 24-hr infusion of
doxorubicin 40 mg/m(2), and analyzed by reversed-phase liquid
chromatography. RESULTS: There was a more than 10-fold difference
between patients in dose normalized plasma concentration of doxorubicin,
median 62.8 ng/ml, range 22.6-334 ng/ml. The doxorubicin concentrations
differed significantly between age groups (P = 0.003). Children aged 4-6
years had the highest doxorubicin concentrations, median 77.9 ng/ml,
followed by 2-4-year-old children, median 64.3 ng/ml. Both younger and
older children had median values of about 50 ng/ml. Patients with white
blood cell (WBC) count > 50 x 10(9)/L at diagnosis had significantly
lower doxorubicin concentrations, median 55.3 ng/ml, than those with WBC
count < 10 x 10(9)/L, median 64.4 ng/ml (P = 0.015). There was no
difference in doxorubicin concentration between boys and girls. No
correlation was found between doxorubicin levels and serum
aminotransferases or serum creatinine. The concentration of
doxorubicinol was 13% (median value) of that of doxorubicin. Four
infants, 7-9 months old, had plasma clearance between 350-431
ml/min/m(2), which is in the same range as in older children. A
3-month-old infant had a clearance of 181 ml/min/m(2). CONCLUSIONS: The
age groups who had the highest doxorubicin concentrations, (2-)
4-6-year-old children, are known to make up a large proportion of
standard risk ALL cases with good prognosis. The correlation between
doxorubicin plasma levels and clinical effect needs further study. The
influence of age, body composition, and tumor burden on the
pharmacokinetics of antineoplastic drugs should also be further
explored, aiming at improvements in the current dosing regimen based on
BSA. Copyright 2002 Wiley-Liss, Inc.
7
UI - 12011123
AU - Linker C; Damon L; Ries C; Navarro W
TI -
Intensified and shortened cyclical chemotherapy for adult acute
lymphoblastic leukemia.
SO - J Clin Oncol 2002 May 15;20(10):2464-71
AD - Bone Marrow Transplant Program, Medical Center, University of California
San Francisco, 400 Parnassus Avenue, Rm. A502, San Francisco, CA
94143-0324, USA. linkerc@medicine.ucsf.edu
PURPOSE: To assess the efficacy and toxicity of a new treatment program
of intensified and shortened cyclical chemotherapy (protocol 8707) in
adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS:
Previously untreated adults < or = 60 years old with ALL were treated
with a four-agent induction chemotherapy regimen. This was followed by
cyclical postremission therapy with high-dose cytarabine/etoposide;
high-dose methotrexate/6-mercaptopurine; and daunorubicin, vincristine,
prednisone, and asparaginase. Maintenance chemotherapy with oral
methotrexate and 6-mercaptopurine was continued for 30 months. CNS
prophylaxis was given with intrathecal methotrexate in addition to the
systemic chemotherapy indicated above. RESULTS: Seventy-eight of 84
patients (93%) achieved complete remission. With a median follow-up of
5.6 years, 5-year event-free survival (EFS) of all remission patients is
52%. Patients with high-risk features including adverse cytogenetics,
failure to achieve remission with the first cycle of chemotherapy, and
B-precursor disease with WBC counts more than 100,000/microL all
relapsed unless taken off study for transplantation. For patients
without these high-risk features, 5-year EFS was 60%. Compared with our
previous treatment regimen, results appear to be improved for patients
with standard-risk B-precursor disease (5-year EFS, 66% v 34%; P =.01).
CONCLUSION: Intensified and shortened chemotherapy may improve the
outcome for patients with ALL with B-precursor disease lacking high-risk
features. Further trials of this regimen are warranted.
8
UI - 11904746
AU - Eichler H; Beck C; Bernard F; Bugert P; Kluter H
TI -
Use of recombinant human deoxyribonuclease (DNase) for processing of a
thawed umbilical cord blood transplant in a patient with relapsed acute
lymphoblastic leukemia.
SO - Ann Hematol 2002 Mar;81(3):170-3
AD - Institute of Transfusion Medicine and Immunology, Red Cross Blood
Service of Baden-Wurttemberg-Hessen, College of Clinical Medicine
Mannheim, University of Heidelberg, Mannheim, Germany.
h.eichler@blutspende.de
This case report describes for the first time the use of a recombinant
human enzyme deoxyribonuclease (rhDNase) containing solution for the
processing of a thawed umbilical cord blood (UCB) unit prior to
successful transplantation to avoid cell losses by clotting phenomena. A
6-year-old boy received an unrelated 2/6 HLA antigen mismatched UCB
transplant for high-risk Burkitt type acute lymphoblastic leukemia. The
UCB unit was provided as a volume-reduced sample after buffy coat
separation with a final volume of 36 ml. To avoid the loss of nucleated
cells due to cell clumping during thawing procedure cells were washed
with a solution containing the rhDNase. No visible clotting of the
resuspended unit occurred, and the patient was transplanted with
2.9x10(7) nucleated cells/kg body weight without any acute or chronic
side effects due to rhDNase. On day +35, PCR analysis of bone marrow
aspirate showed complete chimerism, and the child engrafted with an
absolute neutrophil count greater than 0.5x10(9)/l on day +47. Platelet
transfusion independence was achieved on day +120. In conclusion, the
supplementation of rhDNase to the washing and resuspension solutions of
a thawed UCB unit is effective to prevent cell losses prior to
transplantation. However, further investigations must be performed to
confirm the safety of this procedure.
9
UI - 11984797
AU - Ramakers-van Woerden NL; Pieters R; Hoelzer D; Slater RM; den Boer ML;
TI -
Loonen AH; Harbott J; Janka-Schaub GE; Ludwig WD; Ossenkoppele GJ; van
Wering ER; Veerman AJ; Dutch and German Leukemia Study Groups
In vitro drug resistance profile of Philadelphia positive acute
lymphoblastic leukemia is heterogeneous and related to age: a report of
the Dutch and German Leukemia Study Groups.
SO - Med Pediatr Oncol 2002 Jun;38(6):379-86
AD - Department of Pediatric Hematology, VU University Medical Center,
Amsterdam, The Netherlands. ramakersvanwoerden@VUmc.nl
BACKGROUND: The t(9;22)(q34;q11) translocation leading to the
Philadelphia (Ph) chromosome resulting in BCR-ABL gene fusion is
associated with a poor prognosis in acute lymphoblastic leukemia (ALL).
PROCEDURE: We studied the relation between t(9;22), determined by
karyotype, fluorescence in situ hybridization (FISH) or polymerase chain
reaction (PCR), and in vitro drug resistance, measured by the MTT assay,
in precursor B-cell ALL at diagnosis. The findings in twenty-one
Ph-positive (Ph+) childhood common/precursorB (c/preB) cases were
compared with 254 Ph-negative (Ph-) ALL cases. RESULTS: A large range of
LC(50) values was found within the Ph+ patients. Moreover, LC(50) values
did not differ significantly between Ph+ and Ph- samples for
prednisolone, dexamethasone, L-asparaginase, vincristine,
anthracyclines, thiopurines, epipodophyllotoxins, and 4H00-ifosfamide,
even after matching for important prognostic features (age, white blood
cell count (WBC), and immunophenotype). Adult Ph+ (n = 12) ALL was more
resistant to prednisolone (> 270-fold, P = 0.030), and displayed an
overall tendency to resistance when compared to matched cases of Ph- (n
= 15) adult precursor B-cell ALL. Within Ph+ ALL, in vitro prednisolone
resistance increased significantly with age (P = 0.006). The expression
of lung resistance protein (LRP), but not P-glycoprotein (P-gp) or
multidrug resistance protein (MRP), was significantly higher in all Ph+
patients. CONCLUSIONS: Both childhood and adult Ph+ precursor B-cell ALL
samples display a heterogeneous in vitro resistance profile, with
relatively sensitive and resistant cases. The adult Ph+ samples,
however, are generally more resistant compared to matched Ph- controls,
reaching significance for prednisolone. The correlation of prednisolone
resistance with age within the Ph+ cases might help explain the poorer
prognosis of adult Ph+ ALL. Copyright 2002 Wiley-Liss, Inc.
10
UI - 11899125
AU - Au WY; Yeung CK; Chan HH; Lie AK
TI -
Generalized vitiligo after lymphocyte infusion for relapsed leukaemia.
SO - Br J Dermatol 2001 Dec;145(6):1015-7
AD - Department of Medicine, Queen Mary Hospital, University of Hong Kong.
auwing@hotmail.com
Vitiligo is an autoimmune disease caused by T-lymphocyte-mediated
destruction of melanocytes. We describe two patients with generalized
vitiligo caused iatrogenically after donor lymphocyte infusion (DLI) for
leukaemia relapse over 3 years after bone marrow transplantation (BMT).
Neither the sibling donor nor the recipient had vitiligo or other
autoimmune diseases, and vitiligo did not occur after the first BMT. DLI
was accompanied by skin graft-versus-host disease in both cases, which
was controlled with immunosuppression. However, over several months,
progressive generalized and persistent skin depigmentation occurred in
both patients. Peripheral blood molecular studies showed the complete
disappearance of host haematolymphopoiesis. The specific destruction of
melanocytes in both patients was therefore probably mediated by new
alloreactive lymphocytes infused from the donors.
11
UI - 11902303
AU - Tzortzatou-Stathopoulou F; Papadopoulou AL; Moschovi M; Botsonis A;
TI -
Tsangaris GT
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.
12
UI - 11902549
AU - Pui CH; Campana D; Evans WE
TI -
Childhood acute lymphoblastic leukaemia--current status and future
perspectives.
SO - Lancet Oncol 2001 Oct;2(10):597-607
AD - Leukaemia/Lymphoma Division, Fahad Nassar Al-Rashid Chair of Leukaemia
Research at St Jude Children's Research Hospital, Memphis, TN 38105,
USA. ching-hon.pui@stjude.org
The current cure rate of 80% in childhood acute lymphoblastic leukaemia
attests to the effectiveness of risk-directed therapy developed through
well-designed clinical trials. In the past decade there have been
remarkable advances in the definition of the molecular abnormalities
involved in leukaemogenesis and drug resistance. These advances have led
to the development of promising new therapeutic strategies, including
agents targeted to the molecular lesions that cause leukaemia. The
importance of host pharmacogenetics has also been recognised. Thus,
genetic polymorphisms of certain enzymes have been linked with host
susceptibility to the development of de novo leukaemia or
therapy-related second cancers. Furthermore, recognition of inherited
differences in the metabolism of antileukaemic agents has provided
rational selection criteria for optimal drug dosages and scheduling.
Treatment response assessed by measurements of submicroscopic leukaemia
(minimal residual disease) has emerged as a powerful and independent
prognostic indicator for gauging the intensity of therapy. Ultimately,
treatment based on biological features of leukaemic cells, host
genetics, and the amount of residual disease should improve cure rates
further.
13
UI - 11949261
AU - Peshikova MV; Dolgushin II; Rusanova NN
TI -
[Etiology and structure of infectious complications of cytostatic
therapy in children with acute lymphoblastic leukemia and non-B-cell
non-Hodgkin lymphomas]
SO - Zh Mikrobiol Epidemiol Immunobiol 2002 Jan-Feb;(1):70-1
AD - State Medical Academy, Chelyabinsk, Russia.
A retrospective analysis of medical histories with acute lymphoblast
leucosis and non-B-cell non-Hodgkin lymphomas made it possible to reveal
infectious complications of cytostatic therapy in 100% of children,
namely: sepsis (0.3%), unidentified infection (12%), local infection
(87.7%). Infectious complications of the cytopenic nature were localized
mainly in the upper sections of the gastrointestinal tract and in upper
respiratory tract. Bacterial infectious complications caused by
opportunistic microorganisms with the prevalence of Gram positive flora,
resistant to cephalosporins of generations I and II, occurred most
frequently.
14
UI - 11986774
AU - Ma X; Buffler PA; Selvin S; Matthay KK; Wiencke JK; Wiemels JL; Reynolds
TI -
P
Daycare attendance and risk of childhood acute lymphoblastic leukaemia.
SO - Br J Cancer 2002 May 6;86(9):1419-24
AD - Division of Public Health Biology and Epidemiology, University of
California-Berkeley, California, CA 94720-7360, USA.
The relationship between daycare/preschool ("daycare") attendance and
the risk of acute lymphoblastic leukaemia was evaluated in the Northern
California Childhood Leukaemia Study. Incident cases (age 1-14 years)
were rapidly ascertained during 1995-1999. Population-based controls
were randomly selected from the California birth registry, individually
matched on date of birth, gender, race, Hispanicity, and residence,
resulting in a total of 140 case-controls pairs. Fewer cases (n=92, 66%)
attended daycare than controls (n=103, 74%). Children who had more total
child-hours had a significantly reduced risk of ALL. The odds ratio
associated with each thousand child-hours was 0.991 (95% confidence
interval (CI): 0.984-0.999), which means that a child with 50 thousand
child-hours (who may have, for example, attended a daycare with 15 other
children, 25 h per week, for a total duration of 30.65 months) would
have an odds ratio of (0.991)(50)=0.64 (95% CI: 0.45, 0.95), compared to
children who never attended daycare. Besides, controls started daycare
at a younger age, attended daycare for longer duration, remained in
daycare for more hours, and were exposed to more children at each
daycare. These findings support the hypothesis that delayed exposure to
common infections plays an important role in the aetiology of childhood
acute lymphoblastic leukaemia, and suggest that extensive contact with
other children in a daycare setting is associated with a reduced risk of
acute lymphoblastic leukaemia. Copyright 2002 Cancer Research UK
15
UI - 12026198
AU - Yildiran A; Erduran E; Tekelioglu Y; Dilber E; Gedik Y
TI -
Proliferation of myeloid lineage cells and apoptosis of lymphoblastic
leukemic cells induced by short-course high-dose methylprednisolone in
patients with acute lymphoblastic leukemia.
SO - Turk J Pediatr 2002 Apr-Jun;44(2):116-21
AD - Department of Pediatrics, Ondokuz Mayis University Faculty of Medicine,
Samsun, Turkey.
In this paper, we investigated the effects of short-course high-dose
methylprednisolone (HDMP) treatment on the proliferation of myeloid
lineage cells and on apoptosis of blast cells in eight children with
acute lymphoblastic leukemia (ALL). The patients were given the HDMP
treatment (30 mg/kg/d, perorally) before 9:00 a.m. for seven days. Bone
marrow (BM) aspiration was done at days 0 and 3 of the HDMP treatment in
all patients and at the 7th day of the HDMP treatment in six patients.
Bone marrow blast cells had gradually decreased after the HDMP treatment
by the 7th day. There were statistically significant differences between
the mean percentages of BM blast cells at days 0 and 3, days 0 and 7,
and at days 3 and 7 (p<0.05). The mean percentages of blast cell
apoptosis at the 3rd day was significantly higher than at days 0 and 7,
and apoptosis at day 0 was significantly lower than at the 7th day
(p<0.05). The mean percentages of BM myeloid lineage cells at the 7th
day was significantly higher than at days 0 and 3 (p<0.05), and the mean
percentage at day 0 was significantly lower than at the 3rd day
(p<0.05). These findings indicate that short-course HDMP treatment
causes apoptosis on lymphoblasts and increases the proliferation of
myeloid lineage cells in children with ALL.
16
UI - 12043195
AU - Tsukimoto I
TI -
[Strategies for treatment of childhood leukemia]
SO - Rinsho Ketsueki 2002 Apr;43(4):223-6
17
UI - 11992395
AU - Hata M; Ogino I; Aida N; Saito K; Omura M; Kigasawa H; Toyoda Y;
TI -
Tachibana K; Matsubara S; Inoue T
Prophylactic cranial irradiation of acute lymphoblastic leukemia in
childhood: outcomes of late effects on pituitary function and growth in
long-term survivors.
SO - Int J Cancer 2001;96 Suppl():117-24
AD - Department of Radiology, Yokohama City University, School of Medicine,
Yokohama, Japan. mhata@syd.odn.ne.jp
It is well known that prophylactic cranial irradiation is highly
effective in preventing central nervous system (CNS) relapse of acute
lymphoblastic leukemia (ALL). Nevertheless, there have been very few
reports on the late effects, especially pituitary function and growth,
in long-term survivors who were treated with 18 Gy cranial irradiation
in childhood. The subjects consisted of 35 children with ALL who were
treated with prophylactic 18 Gy cranial irradiation at Kanagawa
patients received cranial irradiation after first attaining complete
remission with induction chemotherapy, according to the treatment
protocols prescribed by the Tokyo Children's Leukemia Study Group
(TCLSG) and Tokyo Children's Cancer Study Group (TCCSG). Their ages at
the time of cranial irradiation ranged from 2.2-15.0 years (mean 6.8).
We evaluated their pituitary functions by measuring their pituitary
hormone values 0.7-11.3 years (mean 6.0) after cranial irradiation and
their growth by analyzing their height standard deviation score (SDS) at
diagnosis of ALL and their final height SDS at the mean follow-up period
of 8.2 years after cranial irradiation. Height SDS is defined as the
difference between the patient's height and the mean height of their age
and sex, divided by the standard deviation of their age and sex. Eight
of 35 patients had ALL relapse, involving the bone marrow in seven
patients and the CNS in only one. Six of the eight patients with relapse
died 1.5-6.6 years after cranial irradiation and the other two patients
were salvaged by further intensive therapies. The remaining 27
relapse-free patients have survived for 1.4-15.8 years (mean 10.1) after
cranial irradiation. Twenty-six of the 29 survivors are long-term
survivors of more than 5 years. Although there was one patient with an
abnormal result in each value of growth hormone (GH),
adrenocorticotropic hormone (ACTH), and prolactin (PRL), and two
patients with abnormal results in thyroid-stimulating hormone (TSH)
values, none of the patients had clinical symptoms of pituitary hormone
abnormality and none required hormone supplements. The final height SDS
decreased significantly compared with the height SDS at diagnosis of ALL
in the long-term survivors (P = 0.001) and the height SDS of the
patients who had received cranial irradiation at a young age tended to
decrease gradually (P = 0.019). However, no patient showed severe growth
failure. It is considered that prophylactic 18 Gy cranial irradiation
plus chemotherapy for ALL in childhood can effectively prevent CNS
relapse and is unlikely to produce clinically significant late effects,
although it may cause slight pituitary hormone abnormality. Copyright
2002 Wiley-Liss, Inc.
18
UI - 11986959
AU - Ramakers-van Woerden NL; Pieters R; Rots MG; van Zantwijk CH; Noordhuis
TI -
P; Beverloo HB; Peters GJ; van Wering ER; Camitta BM; Pui CH; Relling
MV; Evans WE; Veerman AJ
Infants with acute lymphoblastic leukemia: no evidence for high
methotrexate resistance.
SO - Leukemia 2002 May;16(5):949-51
19
UI - 11964277
AU - Bunin N; Carston M; Wall D; Adams R; Casper J; Kamani N; King R; the
TI -
National Marrow Donor Program Working Group
Unrelated marrow transplantation for children with acute lymphoblastic
leukemia in second remission.
SO - Blood 2002 May 1;99(9):3151-7
AD - National Marrow Donor Program, Minneapolis, MN, USA.
bunin@email.chop.edu
Allogeneic bone marrow transplantation (BMT) may be curative for more
patients than chemotherapy for the child with relapsed acute
lymphoblastic leukemia. This study reviewed the outcomes of 363 children
with acute lymphoblastic leukemia in second remission who received
unrelated donor BMT from 1988 to 2000 in order to define prognostic
factors that affect leukemia-free survival (LFS). Median patient age was
9 years (range, 0-19 years), and median follow-up 29 was months (range,
0-125 months). The median duration of first remission was 24 months
(range, 0-109 months). Prognostic factors, including age, duration of
first remission, HLA matching, and graft-versus-host (GVH) disease, were
analyzed using both univariate and multivariate analyses. Overall
survival was 38%, and LFS was 36% at 5 years. LFS was significantly
worse for patients 15 years or older (log-rank, P =.009). HLA matching
was associated with improved LFS. Acute GVH disease developed in 71%,
with 29% having grades III-IV. The incidence of chronic GVH disease was
39% for patients who survived more than 80 days and was significantly
higher for female patients receiving marrow from female donors (P
=.0009). Transplantation-related mortality was 42% and was associated
with HLA mismatches, age 15 years and older, and first remission less
than 12 months. The 5-year estimate for relapse was 22%, with first
remission at least 6 months associated with a lower risk. Results of
unrelated donor BMT appear similar to multi-institutional studies of
matched related donor BMT, and this approach appears to be curative for
many patients. However, innovative approaches are needed for patients
with initial remissions of less than 6 months and for older teenagers.
20
UI - 12046256
AU - Doubek M; Mayer J; Koristek Z; Protivankova M; Brychtova Y; Oborilova A;
TI -
Kral Z; Klabusay M; Tomiska M; Buchtova I; Vorlicek J
[Treatment of acute lymphoblastic leukemia in adults with seven-drug
induction therapy and intensive consolidation with or without autologous
stem cell transplantation followed by maintenance therapy. Experience of
a single center]
SO - Cas Lek Cesk 2002 Mar 1;141(4):122-6
AD - Interni hematoonkologicka klinika LF MU a FN, Brno. mdoubek@fnbrno.cz
BACKGROUND: During the last few years, improvement in prognosis of the
adult acute lymphoblastic leukaemia (ALL) has been modest. The
probability of leukemia-free survival is 20-40%. Philadelphia-chromosome
positive (BCR-ABL positive) ALL has the worse prognosis. A single centre
experience with treatment of ALL in adults is reported. METHODS AND
de novo adult ALL (7 T-lineage ALL, 7 B-lineage ALL, 1 null ALL) begin
their treatment with the seven-drug induction regimen (in phase I,
daunorubicin, vincristine, L-asparaginase, i.v., and prednisone, p.o.;
in phase II, 6-mercaptopurine, p.o., cytosine arabinoside and
cyclophosphamide, i.v.) and central nervous system (CNS) prophylaxis
(methotrexate and CNS irradiation in patients without total body
irradiation in conditioning regimen), with intensive consolidation
(three times high-dose methotrexate and high-dose-cytarabine, i.v.), and
with/out autologous peripheral blood stem cell transplantation (PBSCT)
followed by maintenance chemotherapy (6-mercaptopurine and methotrexate,
p.o.). Seven patients received autologous PBSCT. Median patient age was
30 years. Three patients were BCR-ABL positive at diagnosis. With median
follow-up 14 month (range 0.1-46 month), seven (4 T-lineage ALL, 2
B-lineage ALL, 1 null ALL) out of 15 patients are alive in remission
(four of them receiving autologous PBSCT). Causes of death were relapse
(n = 3), chemotherapy related toxicity (n = 2), infection (n = 1), and
acute myeloid leukaemia developed 10 months after autologous PBSCT (n =
1). All BCR-ABL positive patients died. CONCLUSIONS: Chemotherapy alone
and autologous PBSCT with maintenance therapy may be curative for adult
patients with ALL. We can recommend these treatment options for patients
without risk factors in particular.
21
UI - 11928552
AU - Ostanski M; Sonta-Jakimczyk D
TI -
[Exercise tolerance in patients after acute lymphoblastic leukemia
treatment in childhood]
SO - Wiad Lek 2001;54(11-12):650-5
AD - Katedry i Kliniki Hematologii Dzieciecej i Chemioterapii w Zabrzu.
The purpose of the presented study was to define the exercise tolerance
in patients after acute lymphoblastic leukemia (ALL) treatment in
childhood. Three groups of persons were examined: group A: 20 children,
aged 7-19 years (mean 12.4 y), examined immediately after ALL therapy
completion, with cumulative anthracycline (ATC) doses administered
155.8-300 mg/m2 and dexrazoxane, as cardioprotectant, group B: 36
patients, aged 12-24 years (mean 15.9), being 3-5 years after ALL
treatment, who received ATC in cumulative doses 148.6-416.7 mg/m2,
without cardioprotection, group C: 28 healthy volunteers, aged 9-25
years (mean 17.3), as controls. All the examined patients belonged to
NYHA functional class I. In all subjects the exercise treadmill test was
performed according to modified Bruce protocol. The parameters analysed
were: MET--number of metabolic effort units achieved at the test,
HRmax--maximal heart rate during exercise, %HRmax--percent of maximal HR
for given patient's age achieved during the STdep--depression of ST
segment in electrocardiography (ECG) immediately after the maximal
exercise. During the exercise members of all 3 groups achieved the
required HRmax without serious complaints and ECG abnormalities.
Examined persons in group A,B and C presented with effort levels (MET),
%HRmax, STdep that did not differ significantly. Only HRmax in groups A
and C were higher than that achieved by members of group B.
22
UI - 12040440
AU - Kamps WA; Bokkerink JP; Hakvoort-Cammel FG; Veerman AJ; Weening RS; van
TI -
Wering ER; van Weerden JF; Hermans J; Slater R; van den Berg E; Kroes
WG; van der Does-van den Berg A
BFM-oriented treatment for children with acute lymphoblastic leukemia
without cranial irradiation and treatment reduction for standard risk
patients: results of DCLSG protocol ALL-8 (1991-1996).
SO - Leukemia 2002 Jun;16(6):1099-111
AD - Dutch Childhood Leukemia Study Group, The Hague, The Netherlands.
Modern treatment strategies, consisting of intensive chemotherapy and
cranial irradiation, have remarkably improved the prognosis for children
with acute lymphoblastic leukemia. However, patients with a potential
for cure are at risk of severe acute and late adverse effects of
treatment. Furthermore, in 25-30% of patients treatment still fails. The
objectives of the DCLSG study ALL 8 were to decrease the toxicity and to
increase the effectivity of BFM-oriented treatment. Decrease of toxicity
was aimed at by confirmation of the results of the previous DCLSG study
ALL-7, showing that the majority (94%) of children with ALL can
successfully be treated with BFM-oriented therapy without cranial
irradiation, and by reduction of treatment for standard risk (SRG)
patients. To increase the cure rate in medium risk (MRG) patients the
efficacy of high doses of intravenous 6-mercaptopurine (HD-6MP) during
protocol M and in SRG patients the efficacy of high doses of
L-asparaginase (HD-L-ASP) during maintenance treatment was studied in
randomized studies. Patient stratification and treatment were identical
to protocol ALL-BFM90, with the following differences: no prophylactic
cranial irradiation, SRG patients received only phase 1 of protocol I.
Four hundred and sixty-seven patients entered the protocol: 170 SRG, 241
MRG and 56 HRG patients. The 5 years event-free survival rate for all
patients was 73% (s.e. 2%); for SRG, MRG and HRG patients 85% (s.e. 3%),
73% (s.e. 3%) and 39% (s.e. 7%), respectively. In patients >1 year of
age at diagnosis unfavorable prognostic factors were male sex, >25%
blasts in the bone marrow at day 15 and initial white blood cell count
(WBC) >50 x 10(9)/l. The cumulative risk of CNS relapse rate was 5%
(s.e. 1%) at 5 years. These results confirm that the omission of cranial
irradiation in BFM-oriented treatment does not jeopardize the overall
good treatment results, nor does early reduction of chemotherapy in SRG
patients. No benefit was observed from treatment intensification with
HD-L-ASP in SRG patients, nor from HD-6MP in MRG patients.
23
UI - 12040442
AU - Winter SS; Sweatman J; Shuster JJ; Link MP; Amylon MD; Pullen J; Camitta
TI -
BM; Larson RS
Bone marrow stroma-supported culture of T-lineage acute lymphoblastic
leukemic cells predicts treatment outcome in children: a Pediatric
Oncology Group study.
SO - Leukemia 2002 Jun;16(6):1121-6
AD - University of New Mexico Health Sciences Center, Department of
Pediatrics, Albuquerque, NM, USA.
Significant predictors of treatment outcome are poorly defined for
patients with T-lineage acute lymphoblastic leukemia (T-ALL). A high WBC
at diagnosis, which has traditionally been a predictor of poor response
in T-ALL, has considerably weakened prognostic significance in the face
of modern, more intensive chemotherapy. To test the hypothesis that bone
marrow stroma-supported leukemic cell recovery might identify children
at high risk for relapse, we measured the ex vivo recovery of T-ALL
lymphoblasts from 29 newly diagnosed patients using a stromal cell
co-culture assay. In all cases the T-ALL lymphoblasts showed an increase
in recovery of T-ALL cells (RTC), ranging from 4 to 343%, in comparison
to samples maintained without stroma. Since we were blinded to patient
outcome in this case-control study, we then correlated patient outcome
with RTC. The RTC for 18 patients in complete continuous remission (CCR)
for greater than 4 years was stochastically larger than for the 11
patients who eventually relapsed (P = 0.011, by the two-sided Wilcoxon
test). Furthermore, 100% of patients with an RTC of more than 26% had a
CCR greater than 4 years while 78% of the patients with an RTC of less
than 25% relapsed within 4 years. This is the first report to show that
higher lymphoblast recovery may predict a more favorable outcome for
children with T-ALL. A prospective study is needed to test whether
stroma-supported leukemic cell recovery might serve as a basis for
assigning risk-adjusted therapy.
24
UI - 12040449
AU - Yokota H; Tsuno NH; Tanaka Y; Fukui T; Kitamura K; Hirai H; Osumi K;
TI -
Itou N; Satoh H; Okabe M; Nakahara K
Quantification of minimal residual disease in patients with e1a2
BCR-ABL-positive acute lymphoblastic leukemia using a real-time RT-PCR
assay.
SO - Leukemia 2002 Jun;16(6):1167-75
AD - Department of Laboratory Medicine, Graduate School of Medicine, The
University of Tokyo, Tokyo, Japan.
Using a real-time RT-PCR method, we analyzed the expression of e1a2
BCR-ABL mRNA in bone marrow samples from 13 patients with e1a2
BCR-ABL-positive acute lymphoblastic leukemia (ALL) at different time
points during chemotherapy and after bone marrow transplantation (BMT).
The detection limit of the method, assessed using serial dilutions of
ALL/MIK cells, was found to be 1:10(5), similar to what is observed for
the conventional RT-nested PCR method. The e1a2 BCR-ABL values were
normalized with respect to those of the housekeeping gene GAPDH. The
decrease in the e1a2 BCR-ABL/GAPDH ratio after remission induction
chemotherapy reflects well the response to chemotherapy and consequently
correlates with the prognosis. Although molecular remission was achieved
by chemotherapy alone, some patients relapsed, and the e1a2
BCR-ABL/GAPDH ratios in these cases progressively increased to the
levels seen prior to hematological relapse. Long-term hematological
complete remission (more than 30 months) could be achieved in cases in
which a more than 4.0 log decrease in the e1a2 BCR-ABL/GAPDH ratio was
obtained by chemotherapy alone, and BMT was then performed. In
conclusion, real-time RT-PCR allows for an evaluation of the kinetics of
e1a2 BCR-ABL/GAPDH expression during the various phases of chemotherapy
or after BMT and may be effective for the indication and control of
disease relapse in Ph-positive ALL patients.
25
UI - 12040450
AU - Guerrasio A; Pilatrino C; De Micheli D; Cilloni D; Serra A; Gottardi E;
TI -
Parziale A; Marmont F; Diverio D; Divona M; Lo Coco F; Saglio G
Assessment of minimal residual disease (MRD) in CBFbeta/MYH11-positive
acute myeloid leukemias by qualitative and quantitative RT-PCR
amplification of fusion transcripts.
SO - Leukemia 2002 Jun;16(6):1176-81
AD - Dipartimento di Scienze Cliniche e Biologiche, Universita di Torino,
Orbassano, Torino, Italy.
The inv(16)(p13q22) chromosomal rearrangement associated with FAB M4Eo
acute myeloid leukemia (AML) subtype is characterized by the presence of
the CBFbeta/MYH11 fusion transcript that can be used to detect minimal
residual disease (MRD). However, qualitative RT-PCR studies of MRD have
so far produced conflicting results and seem of limited prognostic
value. We have evaluated retrospectively MRD in a large series of
CBFbeta/MYH11-positive patients employing both qualitative and
quantitative (real-time PCR) approaches. 186 bone marrow samples from 36
patients were examined with a median follow-up of 27.5 months; 15
patients relapsed during follow-up. In qualitative studies, carried out
by 'nested' RT-PCR assay, all patients in complete remission (CR)
immediately after induction/consolidation therapy were found to be PCR
positive. However, follow-up samples at later time points were
persistently negative (except one case) in patients remaining in
continuous CR (CCR) for more than 12 months. 16 patients were evaluated
by quantitative real-time PCR assay: CBFbeta/MYH11 transcript copy
number was normalized for expression of the housekeeping gene ABL,
expressed as fusion gene copy number per 10(4) copies of ABL. A 2-3 log
decline in leukemic transcript copy number was observed after
induction/consolidation therapy. After achieving CR, the mean copy
number was significantly higher in patients destined to relapse compared
to patients remaining in CCR (151 vs 9, P < 0.0001 by Mann-Whitney
test). Moreover, in CCR patients, the copy number dropped below the
detection threshold after the treatment protocol was completed and
remained undetectable in subsequent MRD analysis in accordance with
results obtained by qualitative RT-PCR. On the contrary, in the seven
patients who relapsed, the copy number in CR never declined below the
detection threshold; thus a cut-off value discriminating these two
groups of patients could be established. The findings of our study, if
confirmed, might confer an important predictive value to quantitative
real-time PCR determinations of MRD in patients with inv(16) leukemia.
26
UI - 12017297
AU - Styczynski J; Wysocki M; Kurylak A; Juraszewska E; Malinowska I;
TI -
Stanczak E; Ploszynska A; Stefaniak J; Mazur B; Szczepanski T; Ras M
In vitro activity of glufosfamide in childhood acute leukemia.
SO - Anticancer Res 2002 Jan-Feb;22(1A):247-50
AD - Katedra i Klinika Pediatrii, Hematologii i Onkologii, Bydgoszcz, Poland.
jan_styczynski@kki.net.pl
Glufosfamide is a new agent for cancer chemotherapy. The objective of
the study was the comparison of the in vitro drug resistance profile of
glufosfamide with other oxazaphosphorines in 106 samples of childhood
acute leukemia by means of the MTT assay. The following drugs were
tested: glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide,
mafosfamide cyclohexylamine salt, prednisolone, vincristine,
L-asparaginase, daunorubicin and cytarabine. In the group of initial
Acute Lymphoblastic Leukemia (ALL) samples, equivalent cytotoxicity
values for glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide and
mafosfamide were 5.95, 9.92, 4.60 and 3.90 microg/ml, respectively. In
comparison to initial ALL samples, the relative resistance for
glufosfamide and 4-HOO-ifosfamide in relapsed ALL samples were 1.9
(p=0.049) and 1.3 (ns), and in initial Acute Myeloblastic Leukemia (AML)
samples, respectively, 31 (p<0.001) and 5 (p=0.001). All
oxazaphosphorines showed highly significant cross-resistance. In
conclusion, in vitro activity of glufosfamide is comparable to
ifosfamide. Glufosfamide shows high activity against lymphoblasts both
on diagnosis and on relapse, however it cannot circumvent resistance to
other oxazaphosphorines.
27
UI - 12075070
AU - Safdar A; Johnson N; Gonzalez F; Busowski JD
TI -
Adult T-cell leukemia-lymphoma during pregnancy.
SO - N Engl J Med 2002 Jun 20;346(25):2014-5
28
UI - 11979255
AU - Watanabe N; Okazaki K; Yazumi S; Nishi T; Matsuura M; Chiba T
TI -
Acute graft-versus-host disease in the small intestine.
SO - Gastrointest Endosc 2002 May;55(6):716
AD - Kyoto University, Kyoto, Japan.
29
UI - 11979570
AU - Reddick WE; Glass JO; Langston JW; Helton KJ
TI -
Quantitative MRI assessment of leukoencephalopathy.
SO - Magn Reson Med 2002 May;47(5):912-20
AD - Department of Diagnostic Imaging, St. Jude Children's Research Hospital,
Memphis, Tennessee 38105-2794, USA. gene.reddick@stjude.org
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