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NCI CANCERLIT® Search: Therapy of Acute Lymphocytic Leukemia - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
UI - 11843837
AU - Albertsen BK; Schroder H; Ingerslev J; Jakobsen P; Avramis VI; Muller
TI -
HJ; Carlsen NT; Schmiegelow K
Comparison of intramuscular therapy with Erwinia asparaginase and
asparaginase Medac: pharmacokinetics, pharmacodynamics, formation of
antibodies and influence on the coagulation system.
SO - Br J Haematol 2001 Dec;115(4):983-90
AD - Centre for Clinical Pharmacology, Department of Pharmacology, The
Bartholin Building, University of Aarhus, 8000 Aarhus C, Denmark.
bka@farm.au.dk
Asparaginase comes from different biological sources and the various
preparations have different pharmacokinetic properties, and their
tendency to induce side-effects is different. Erwinia asparaginase
(ASNase) has a shorter half-life than the Escherichia coli preparations,
and it has been reported to be less immunogenic than the E. coli
preparations and to induce fewer coagulation disorders. Children with
newly diagnosed acute lymphoblastic leukaemia (ALL) were included in
this study. Twenty-seven patients were treated with Erwinia ASNase
(induction therapy 30.000 IU/m2/d i.m. for 10 d, and re-induction
therapy 30.000 IU/m2 twice a week for 2 weeks) and 15 were treated with
ASNase Medac (induction therapy 1.000 IU/m2/d i.m. for 10 d, and
re-induction therapy 5.000 IU/m2 i.m. twice a week for 2 weeks). Blood
samples were drawn to determine enzyme activity, l-asparagine,
anti-asparaginase antibodies, and coagulation parameters. After i.m.
administration, Erwinia ASNase displayed a protracted absorption phase
compared to ASNase Medac. The mean bioavailability after i.m.
administration was 27% for Erwinia ASNase and 45% for ASNase Medac
respectively. Mean trough enzyme activities during induction therapy
were Erwinia ASNase 1748 IU/l and ASNase Medac 272 IU/l, and during
re-induction therapy Erwinia ASNase 83 IU/l and ASNase Medac 147 IU/l.
We conclude that in this setting, therapy with ASNase Medac resulted in
sufficient treatment during both phases of therapy, whereas treatment
with Erwinia ASNase resulted in unnecessarily intense therapy during the
induction phase and insufficient treatment during the re-induction
phase. There was no significant difference in the incidence of antibody
formation, and therapy with Erwinia ASNase resulted in a more pronounced
influence on the coagulation parameters than therapy with ASNase Medac.
2
UI - 11806983
AU - Lange BJ; Bostrom BC; Cherlow JM; Sensel MG; La MK; Rackoff W; Heerema
TI -
NA; Wimmer RS; Trigg ME; Sather HN; Children's Cancer Group
Double-delayed intensification improves event-free survival for children
with intermediate-risk acute lymphoblastic leukemia: a report from the
Children's Cancer Group.
SO - Blood 2002 Feb 1;99(3):825-33
AD - Division of Oncology, Children's Hospital of Philadelphia, PA, USA.
lange@email.chop.edu
Addition of a delayed-intensification (DI) phase after standard
induction/consolidation therapy was previously shown to improve outcome
for patients younger than 10 years of age with intermediate-risk acute
lymphoblastic leukemia (ALL). The current trial randomized 1204 patients
to regimens containing a single DI phase (405 patients), 2 DI phases
(DDI) (402 patients), or a single DI phase in conjunction with increased
vincristine and prednisone pulses during maintenance (DIVPI) (397
patients). Estimates of event-free survival (EFS) and survival at 6
years are 79% +/- 1% and 89% +/- 1%, respectively. EFS was improved on
DDI compared with either DI (log-rank P =.04; Kaplan-Meier [KM] P =.04;
relative risk [RR] = 1.38) or DIVPI (log-rank P =.04; KM P =.01; RR =
1.39).There was no difference in EFS for the DI and DIVPI regimens
(log-rank P =.96; KM P =.75). Survival estimates at 6 years were 87% (SD
= 2%) for DI; 91% (SD = 2%) for DDI; and 90% (SD = 2%) for DIVPI (P
=.17). Significant univariate risk factors for the overall cohort
included poor day-7 marrow response, black race, and age of at least 5
years. These data demonstrate that DDI improves EFS of patients younger
than 10 years of age with intermediate-risk ALL.
3
UI - 11806988
AU - Annino L; Vegna ML; Camera A; Specchia G; Visani G; Fioritoni G; Ferrara
TI -
F; Peta A; Ciolli S; Deplano W; Fabbiano F; Sica S; Di Raimondo F;
Cascavilla N; Tabilio A; Leoni P; Invernizzi R; Baccarani M; Rotoli B;
Amadori S; Mandelli F; GIMEMA Group
Treatment of adult acute lymphoblastic leukemia (ALL): long-term
follow-up of the GIMEMA ALL 0288 randomized study.
SO - Blood 2002 Feb 1;99(3):863-71
AD - Department of Cellular Biotechnology and Hematology, Universita degli
Studi La Sapienza, Via Benevento, 6-00161, Rome, Italy.
The GIMEMA ALL 0288 trial was designed to evaluate the impact of a 7-day
prednisone (PDN) pretreatment on complete remission (CR) achievement and
length, the influence of the addition of cyclophosphamide (random I) to
a conventional 4-drug induction on CR rate and duration, and whether an
early post-CR intensification (random II) by an 8-drug consolidation
could improve CR duration. Median follow-up of this study was 7.3 years.
patients registered, 778 were eligible. Their median age was 27.5 years;
73% had B-lineage acute lymphoblastic leukemia (ALL) and 22% had
T-lineage disease; 18% showed associated myeloid markers; 47 of 216
analyzed patients (22%) had Philadelphia chromosome-positive ALL.
Response to PDN pretreatment was observed in 65% of cases. CR was
achieved in 627 patients (82%). Resistant patients and induction death
rates were 11% and 7%, respectively. Random II was applied to 388
patients with CR; 201 had maintenance alone and 187 had consolidation
followed by maintenance. The relapse rate was 60%; isolated central
nervous system relapses were 8% of all CRs and 13% of all relapses.
Median survival (overall survival [OS]), continuous complete remission
(CCR), and disease-free survival (DFS) were 2.2, 2.4, and 2 years,
respectively. PDN pretreatment response resulted the main independent
factor influencing CR achievement, OS, CCR, and DFS; the addition of
cyclophosphamide in induction significantly influenced CR achievement in
a multivariate analysis. Neither induction intensification nor early
consolidation appeared to influence CCR and DFS duration. For the first
time PDN pretreatment response proved to be a powerful factor predicting
disease outcome in adult ALL patients.
4
UI - 11858371
AU - Tunc B; Oner AF; Hicsonmez G
TI -
The effect of short-course high-dose methylprednisolone on peripheral
blood CD34+ progenitor cells of children with acute leukemia during
remission induction therapy.
SO - Turk J Pediatr 2002 Jan-Mar;44(1):1-4
AD - Department of Pediatrics, Suleyman Demirel University Faculty of
Medicine, Isparta, Turkey.
This study was undertaken to determine the effect of short-course
high-dose methylprednisolone (HDMP) treatment on peripheral blood (PB)
CD34+ progenitor cells during remission induction treatment in 11
children with newly diagnosed acute leukemia (7 with ALL, 4 with AML)
whose bone marrow (BM) cells expressed fewer than 5% CD34 at the time of
diagnosis. All children who had no infection were given HDMP as a single
daily oral dose of 30 mg/kg for the first four days of induction
therapy. The number of CD34+ progenitor cells were determined by flow
cytometry before and after four days of HDMP treatment. While the number
of PB blast cells significantly decreased after only a four-day course
of HDMP treatment, the number of PB CD34+ progenitor cells increased in
all patients. In addition, after four days of HDMP treatment
polymorphonuclear leukocytes (PMN) and mononuclear cells (MNC) increased
significantly (p < 0.05). We suggest that the potential beneficial
effects of HDMP in the induction treatment of acute leukemia may occur
partly by the stimulation of PB CD34+ hematopoietic progenitor cells in
a short period of time.
5
UI - 11810044
AU - Nowicki M; Miskowiak B; Kaczmarek-Kanold M
TI -
Correlation between early treatment failure and Ki67 antigen expression
in blast cells of children with acute lymphoblastic leukaemia before
commencing treatment. A retrospective study.
SO - Oncology 2002;62(1):55-9
AD - Department of Paediatric Haematology and Oncology, Institute of
Paediatrics, Karol Marcinkowski University of Medical Sciences, Poznan,
Poland. mapar@eucalyptus.usoms.poznan.pl
OBJECTIVES: An attempt has been made to demonstrate the value of the
immunocytochemical assay of Ki67 antigen expression in blast cells in
children with acute lymphoblastic leukaemia (ALL) before initiation of
treatment and its correlation with early treatment failure. METHODS:
Bone marrow specimens were obtained before treatment from children
hospitalised in the years 1997-2000. A total of 60 children diagnosed
with ALL have been examined. Immunocytochemical staining for Ki67
expression was based on the ABC technique. RESULTS: Out of 45 children
assigned to the low risk group, the presence of Ki67 Ag was demonstrated
in 31 cases (68.8%). Out of 15 patients in the high risk group, Ki67 Ag
expression in blast cells was positive in 8 children (53.3%). The
fraction of immunopositive cells in these groups ranged from 19.8 to
81.3% compared to 5% in the control group. Early treatment failure was
observed in both groups and these were closely related to the lack of
Ki67 expression observed at the beginning of treatment. CONCLUSION: The
results indicate a possible connection between the Ki67 immunonegative
blast pattern and early leukaemia progression. It may also justify
routine determination of Ki67 Ag before the treatment of ALL is
initiated. Copyright 2002 S. Karger AG, Basel
6
UI - 11840289
AU - Liu T; Raetz E; Moos PJ; Perkins SL; Bruggers CS; Smith F; Carroll WL
TI -
Diversity of the apoptotic response to chemotherapy in childhood
leukemia.
SO - Leukemia 2002 Feb;16(2):223-32
AD - Center for Children at the Huntsman Cancer Institute, University of Utah
School of Medicine, Salt Lake City, UT, USA.
Apoptosis is the primary mechanism through which most chemotherapeutic
agents induce tumor cell death. The purpose of this study was to
determine the extent to which blasts from children with leukemia undergo
a uniform apoptotic death pathway in vivo. The expression of pro- and
anti-apoptotic proteins p53, p21, MDM-2, BCL-2, BCL-X(L), BCL-X(S), and
BAX, and caspase-3 activity was determined in circulating blasts
collected from the peripheral blood of children with leukemia prior to,
and at serial time points following chemotherapy. Culturing blasts ex
vivo for 12 h assessed spontaneous apoptosis and the increment induced
by chemotherapy. Baseline apoptosis varied between 3% and 29%.
Twenty-four hours following chemotherapy the increase in the percentage
of cells undergoing apoptosis ranged from <1% to 38%. Eleven of 20
patients who received initial treatment with a p53-dependent drug showed
an increase in p53 expression. In these patients, the levels of p53
target genes were also increased. A uniform pattern of BCL-2 family
protein expression was not observed and only a minority of samples
showed a change that would favor apoptosis. We conclude that that the
initial apoptotic response to chemotherapy in children with leukemia is
variable involving both p53-dependent and p53-independent pathways.
7
UI - 11721390
AU - He H; Li C; Han M
TI -
[Acute lymphoblastic leukemia complicated with tumor lysis
syndrome--four cases report]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Jun;20(6):310-2
AD - Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC,
Tianjin 300020.
OBJECTIVE: To report four acute lymphoblastic leukemia(ALL) patients who
developed tumor lysis syndrome(TLS) after initial chemotherapy. METHODS:
The clinical features and blood biochemical changes of four patients
with TLS were analysed. RESULTS: TLS was characterized by hyperuricemia,
hyperkalemia, hyperphosphatemia and hypocalcemia. Three cases had renal
dysfunction and the other died of acute renal failure. After allopurinol
therapy and alkalinization of urine, the blood biochemical parameter
became normalization in all the three cases. CONCLUSIONS: TLS can be
effectively controlled by early recognition and administration of
allopurinol therapy and alkalinization of urine.
8
UI - 9632275
AU - Messina C; Cesaro S; Rondelli R; Rossetti F; Locatelli F; Pession A;
TI -
Miniero R; Dini G; Uderzo C; Dallorso S; Meloni G; Vignetti M; Andolina
M; Porta F; Amici A; Favre C; Basso G; Sotti G; Varotto S; Destro R;
Gazzola MV; Pillon M; Petris MG; Rabusin M; Scarzello G; et al
Autologous bone marrow transplantation for childhood acute lymphoblastic
leukaemia in Italy. AIEOP/FONOP-TMO Group. Italian Association of
Paediatric Haemato-Oncology.
SO - Bone Marrow Transplant 1998 May;21(10):1015-21
AD - Clinica Onco-Ematologia Pediatrica, Universita di Padova, Italy.
(101 males, 53 females; median age 10, range 3-21 years) with ALL and
registered for BMT by the AIEOP (Italian Association of Paediatric
Haemato-Oncology). All patients were in CR: 98 were in 2nd CR and 56
were in >2nd CR. Fifteen children (9.7%) died of transplant-related
mortality. Ninety-five patients (61.6%) relapsed at a median of 5 (range
1-42) months after ABMT. The 8-year EFS according to pre-BMT status was
34.6% (s.e. 4.9) for 2nd CR patients and 10.6% (s.e. 5.6) for patients
in >2nd CR. By univariate analysis, site of relapse (isolated
extramedullary (IE) vs BM: EFS = 68.5% vs 18.2%; P < 0.0001) and TBI
containing regimen (TBI vs no TBI: EFS = 48.1 vs 15.4%; P = 0.0023) were
significant factors for 2nd CR patients. When the 2nd CR subset with BM
involvement was analysed, TBI became insignificant (EFS = 25.4 vs
11.8%). No factors influenced EFS in patients in >2nd CR. By
multivariate analysis, site of relapse was the only significant factor
in 2nd CR patients (P < 0.0001). In conclusion, ABMT is an effective
treatment after one early IE relapse. Few patients can be rescued after
BM relapse.
9
UI - 9827986
AU - Lawson SE; Darbyshire PJ
TI -
Use of donor lymphocytes in extramedullary relapse of childhood acute
lymphoblastic leukaemia following bone marrow transplantation.
SO - Bone Marrow Transplant 1998 Oct;22(8):829-30
AD - Department of Haematology, Birmingham Children's Hospital NHS Trust, UK.
Relapse is the commonest cause of treatment failure following bone
marrow transplantation for malignant haematological disease. Treatment
options are limited and often unsuccessful, with remissions, if
achieved, being short-lived. Donor lymphocyte infusions have been used
in the treatment of relapsing CML for several years, with good results
being obtained. Use of this form of adoptive immunotherapy however, has
been much less successful in patients with acute leukaemias, with acute
lymphoblastic leukaemia appearing to be particularly resistant. We
report the successful use of a donor lymphocyte infusion in a patient
with isolated extramedullary relapse of acute lymphoblastic leukaemia
post bone marrow transplantation.
10
UI - 9877265
AU - Maldonado MS; Diaz-Heredia C; Badell I; Munoz A; Ortega JJ; Cubells J;
TI -
Otheo E; Olive T; Canals C; Perez-Oteyza J
Autologous bone marrow transplantation with monoclonal antibody purged
marrow for children with acute lymphoblastic leukemia in second
remission. Spanish Working Party for BMT in Children.
SO - Bone Marrow Transplant 1998 Dec;22(11):1043-7
AD - Ramon y Cajal Hospital, Madrid, Spain.
The purpose of this study was to evaluate the outcome of children with
acute lymphoid leukemia (ALL) in second remission who have undergone
high-dose chemotherapy and radiotherapy and autologous bone marrow
transplantation (ABMT) with monoclonal antibody purged marrow, and to
determine the main prognostic factors. From 1987 to 1992, 55 children
with ALL in second remission underwent ABMT. The conditioning regimen
consisted of total body irradiation (TBI) plus cyclophosphamide in 21
patients and TBI plus cyclophosphamide plus cytarabine or VP-16 in 28
patients; the remaining six patients were treated with chemotherapy
alone (cyclophosphamide and busulfan, and/or VP-16). The marrow was
purged using monoclonal antibodies and complement or magnetic
microspheres in all cases. All patients engrafted. Three patients (5%)
died early post transplant from infections. Twenty-six patients (47%)
relapsed (median 150 days); 26 patients (47%) are alive and in complete
remission (CR) at a median of 36 months. The Kaplan-Meier estimation
showed a probability of event-free survival (EFS) of 46 +/- 0.007%. In
the univariate analysis, first CR length and conditioning with TBI plus
two or more cytotoxic drugs were found to be the most significant
predictors of EFS. ABMT with purged marrow is a treatment modality which
offers a chance of cure in children with ALL after relapse, including
children who relapse early.
11
UI - 10578164
AU - Au WY; Lie AK; Liang R; Kwong YL
TI -
Isolated extramedullary relapse of acute lymphoblastic leukaemia after
allogeneic bone marrow transplantation.
SO - Bone Marrow Transplant 1999 Nov;24(10):1137-40
AD - University Department of Medicine, Queen Mary Hospital, Hong Kong.
Isolated extramedullary relapse of acute lymphoblastic leukaemia (ALL)
with sparing of the marrow after allogeneic bone marrow transplantation
(BMT) is a rare occurrence, and the mechanisms underlying the selective
involvement of extramedullary sites remain undefined. These might be due
to relapse in sanctuary sites where the leukaemic cells are resistant to
chemotherapy, or a stronger putative graft-versus-leukaemia (GVL) effect
in the marrow as compared with peripheral tissues. We report two ALL
patients with repeated episodes of extramedullary relapse after BMT in
whom both mechanisms might be operating. In the first patient, the
marrow was in morphologic and molecular remission before isolated
leukaemic relapse in the central nervous system (CNS) occurred.
Subsequent secondary infiltration of leukaemic cells into the marrow was
only evident molecularly but not morphologically, implying that the
relapse had arisen in a sanctuary CNS site. In the second patient, a
first relapse in the marrow, which was induced into morphologic and
molecular remission by chemotherapy and donor lymphocyte infusion, was
followed by extramedullary relapses without any subsequent involvement
of the marrow. This suggested that factors, likely to be due to a GVL
effect, were stronger in the marrow than in peripheral tissues.
12
UI - 10734293
AU - Vaidya SJ; Atra A; Bahl S; Pinkerton CR; Calvagna V; Horton C; Milan S;
TI -
Shepherd V; Brain C; Treleaven J; Powles R; Tait D; Meller ST
Autologous bone marrow transplantation for childhood acute lymphoblastic
leukaemia in second remission - long-term follow-up.
SO - Bone Marrow Transplant 2000 Mar;25(6):599-603
AD - Paediatric Oncology, The Royal Marsden NHS Trust, Sutton, UK.
From 1984 to 1996, 31 consecutive children without sibling donors, aged
5-19 years (median 8) with acute lymphoblastic leukaemia (ALL) in second
complete remission (CR), received unpurged autologous bone marrow
transplantation (ABMT) after melphalan and single fraction total body
irradiation (TBI). ABMT was performed using fresh unmanipulated marrow
harvested after standard reinduction and consolidation therapy 2-11
months (median 5) after relapse. With a median survival of 2.9 years the
probability of survival for all patients in continuing second CR was
45.1% (95% CI, 24%-62%) after 5 years. Regimen-related and non-leukaemia
mortality was 7% (95% CI, 2%-26%). The longest time to second relapse
from ABMT was 3.1 years. Pituitary and gonadal dysfunction requiring
hormonal replacement therapy occurred in the majority of long-term
survivors. Twelve patients developed cataracts. ABMT with
melphalan/single fraction TBI has proved an effective anti-leukaemia
treatment with low regimen-related mortality but significant long-term
morbidity. The current approach of allogeneic BMT from an unrelated
donor when no sibling donor is available, following conditioning with
cyclophosphamide/ fractionated TBI has resulted in a reduced relapse
rate and improved short-term overall survival in the treatment of
relapsed childhood ALL. However, long-term results are awaited.
13
UI - 11108320
AU - Maldonado MS; Munoz A
TI -
Autologous bone marrow transplantation for childhood acute lymphoblastic
leukemia in second remission.
SO - Bone Marrow Transplant 2000 Nov;26(10):1136-7
14
UI - 11523412
AU - Savchenko VG; Parovichnikova EN; Isaev VG; Kulimova EP; Kucher RA;
TI -
Sokolov AN; Ustinova EN; Gribanova EO; Khoroshko ND; Pivnik AV;
Tikhonova LIu; Sarkisian GP; Domracheva EV; Maslova ER; Konstantinova
TS; Rekhtman GB; Lapin VA; Miliutina TI
[Treatment of acute lymphoblastic leukemia in adults as an unsolved
problem]
SO - Ter Arkh 2001;73(7):6-15
15
UI - 11844835
AU - Mortuza FY; Papaioannou M; Moreira IM; Coyle LA; Gameiro P; Gandini D;
TI -
Prentice HG; Goldstone A; Hoffbrand AV; Foroni L
Minimal residual disease tests provide an independent predictor of
clinical outcome in adult acute lymphoblastic leukemia.
SO - J Clin Oncol 2002 Feb 15;20(4):1094-104
AD - Department of Hematology, Royal Free and University College School of
Medicine, London, United Kingdom.
PURPOSE: Investigation of minimal residual disease (MRD) in childhood
acute lymphoblastic leukemia (ALL) using molecular markers has proven
superior to other standard criteria (age, sex, and WBC) in
distinguishing patients at high, intermediate, and low risk of relapse.
The aim of our study was to determine whether MRD investigation is
valuable in predicting outcome in Philadelphia-negative adult patients
with ALL. PATIENTS AND METHODS: MRD was assessed in 85 adult patients
with B-lineage ALL by semiquantitative immunoglobulin H gene analysis on
bone marrow samples collected during four time bands in the first 24
months of treatment. Fifty patients received chemotherapy only and 35
patients received allogeneic (n = 19) or autologous (n = 16) bone marrow
transplantation (BMT) in first clinical remission. The relationship
between MRD status and clinical outcome was investigated and compared
with age, sex, immunophenotype, and presenting WBC count. RESULTS:
Fisher's exact test established a statistically significant concordance
between MRD results and clinical outcome at all times. Disease-free
survival (DFS) rates for MRD-positive and -negative patients and
log-rank testing established that MRD positivity was associated with
increased relapse rates at all times (P <.05) but was most significant
at 3 to 5 months after induction and beyond. MRD status after allogeneic
BMT rather than before was found to be an important predictor of outcome
in 19 adult patients with ALL tested. In patients receiving autologous
BMT (n = 16), the MRD status before BMT was more significant (P =.005).
CONCLUSION: The association of MRD test results and DFS was independent
of and greater than other standard predictors of outcome and is
therefore important in determining treatment for individual patients.
16
UI - 11594709
AU - Kounami S; Douno S; Matsubara H; Takayama J; Ohira M
TI -
Olfactory neuroblastoma as a second malignant neoplasm in a patient
previously treated for childhood acute leukemia.
SO - Pediatr Hematol Oncol 2001 Oct-Nov;18(7):459-63
AD - Department of Pediatrics, National Cancer Center Hospital, Tokyo, Japan.
Various kinds of second malignant neoplasms after sucessful treatment
for childhood acute leukemia have been reported. The authors describe an
unusual case of an olfactory neuroblastoma in a patient previously
treated for childhood acute leukemia including autologous bone marrow
transplantation. The prophylactic cranial irradiation and the total body
irradiation during autologous bone marrow transplantation may have
induced the development of their patient's olfactory neuroblastoma.
Although a second primary olfactory olfactory neuroblastoma is rare is
rare, it should be added to the list of second malignant neoplasms in
the sinonasal region.
17
UI - 11878573
AU - Felice M S; Zubizarreta P A; Alfaro E M; Sackmann-Muriel F
TI -
Childhood acute lymphoblastic leukemia: prognostic value of initial
peripheral blast count in good responders to prednisone.
SO - J Pediatr Hematol Oncol 2001 Oct;23(7):411-5
AD - Hematology/Oncology Department, Hospital de Pediatria SAMIC Prof. Dr.
Juan P. Garrahan, Buenos Aires, Argentina. mfelice@dd.com.ar
PURPOSE: To assess the value of initial peripheral blast count in
patients with acute lymphoblastic leukemia (ALL) and prednisone good
1995, 403 consecutive patients with newly diagnosed ALL were enrolled in
the authors' protocol 1-ALL90-BFM/HPG. Prednisone good response was
defined as a blast count of less than 1,000/microL and a prednisone poor
response (PPR) as a blast count of at least 1,000/microL, both in
peripheral smears, after 7 days of oral prednisone (60 mg/m2 per day)
and one intrathecal dose of methotrexate. In the PGR group, patients
were divided into two subgroups: patients who had less than 1,000
blasts/microL at diagnosis and those with at least 1,000 blasts/microL
at diagnosis. RESULTS: Three-hundred thirty-seven patients (90%) had PGR
and 37 had (10%) PPR. At 5-year follow-up, event-free survival estimates
were 67 +/- 3.8% and 38 +/- 8% for PGR and PPR, respectively (P =
0.0001). In the PGR group, 114 patients (34%) had an initial blast count
of less than 1,000/microL and 223 (66%) had an initial blast count of at
least 1,000/microL. The authors compared the clinical and laboratory
characteristics of these subgroups at diagnosis and outcome and detected
significant differences in white cell count, incidence of T
immunophenotype, and presence of mediastinal or spleen enlargement.
However, there were no differences in response to induction treatment,
death in complete remission, relapses, or event-free survival
probability. CONCLUSIONS: In the PGR group, regardless of the initial
blast count, both subgroups had the same outcome. The PGR group with an
initial blast count of at least 1,000/microL had significantly higher
white cell counts. T markers, and mediastinal or spleen enlargement at
diagnosis. Response to prednisone is a practical, inexpensive, and good
prognostic factor in childhood ALL.
18
UI - 11878575
AU - Porea T J; Dreyer Z E; Bricker J T; Mahoney D H Jr
TI -
Evaluation of left ventricular function in asymptomatic children about
to undergo anthracycline-based chemotherapy for acute leukemia: an
outcome study.
SO - J Pediatr Hematol Oncol 2001 Oct;23(7):420-3
AD - Division of Pediatric Hematology-Oncology, Texas Children's Hospital,
Baylor College of Medicine, Houston, USA.
BACKGROUND: Cardiac toxicity is a well-recognized potential complication
of anthracycline use. Children treated with anthracyclines undergo
several cardiac screening procedures before therapy, but the usefulness
of these pretherapy cardiac studies has never been evaluated. The
authors examined whether induction chemotherapy in patients with
high-risk acute lymphoblastic leukemia (ALL) was altered based on a
pretherapy left ventricular shortening fraction (SF). PATIENTS AND
METHODS: Medical records of 134 children registered on treatment
protocols of the Pediatric Oncology Group for high-risk B-precursor and
T-cell ALL between 1987 and 1998 were reviewed. Demographic information
consisting of age at diagnosis, sex, and past cardiac history was
collected, as were the results of all echocardiographic evaluations for
SF and actions taken based on these evaluations. The outcome measured
was whether any changes were made in induction therapy based on initial
SF. In addition, secondary SF results obtained at the cumulative
anthracycline dose range of 90 to 150 mg/m2 were studied to determine
whether modifications of future chemotherapy were made after this
limited exposure. RESULTS: Three of 128 children (2.3%) without a
previous cardiac history had an initial SF on their pretherapy
echocardiogram that prompted additional evaluation but no change in
therapy. A secondary analysis of SF in 85 children who completed
anthracycline doses of 90 to 150 mg/m2 was performed. There were three
(3.5%) with abnormal study results who were evaluated further. Again, no
changes were made in the anthracycline doses based on these findings. No
cardiac dysfunction occurred among these six patients during later
follow-up. CONCLUSIONS: In the absence of a previous cardiac history or
signs and symptoms or cardiac disease, pretherapy evaluation of left
ventricular function may not be indicated in children about to undergo
anthracycline-based treatment of acute leukemia. The timing of
initiation of cardiac evaluation remains unclear, but these results
suggest that even at a cumulative dose of 90 to 150 mg/m2, studies to
determine left ventricular function do not yield data sufficient to
warrant a change in the clinical management of these patients.
19
UI - 11878576
AU - Oeffinger K C; Buchanan G R; Eshelman D A; Denke M A; Andrews T C;
TI -
Germak J A; Tomlinson G E; Snell L E; Foster B M
Cardiovascular risk factors in young adult survivors of childhood acute
lymphoblastic leukemia.
SO - J Pediatr Hematol Oncol 2001 Oct;23(7):424-30
AD - Department of Family Practice and Community Medicine, The University of
Texas Southwestern Medical Center at Dallas, 75390-9067, USA.
kevin.oeffinger@email.swmed.edu
PURPOSE: To assess cardiovascular risk factors (CVRF) in young adult
survivors of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND
METHODS: Twenty-six subjects (median age, 20.9 years; median interval
since completion of therapy, 13.3 years) were evaluated. Ten
participants had received cranial irradiation (CRT), whereas 16 had
received only chemotherapy. Primary outcome measures included body mass
index (BMI), blood pressure, fasting lipoprotein, glucose, and insulin
levels. Secondary measures included insulin-like growth factor-1 (IGF-1)
and IGF binding protein-3 levels, physical activity index, a 7-day
dietary recall, tobacco product use, and measurement of the intima-media
thickness (IMT) of the common carotid artery. RESULTS: Sixty-two percent
(16/26) of participants had at least one CVRF potentially related to
their cancer treatment (obesity, dyslipidemia, increased blood pressure,
or insulin resistance), with 30% (7/26) having more than two CVRF.
Thirty-one percent (8/26) of subjects were obese (BMI > or = 30).
Subjects who were treated with CRT (BMI, 30.4 +/- 6.7) had an increased
BMI (P = 0.039) in comparison with those who received only chemotherapy
(BMI, 25.4 +/- 5.1). Triglyceride and very low-density lipoprotein C
levels were significantly higher in those treated with CRT (P = 0.027
and 0.022, respectively). The IGF-1 was inversely correlated with IMT
(total group, -0.514, P = 0.009; females only, -0.729, P = 0.003).
CONCLUSIONS: Young adult survivors of childhood ALL, especially those
treated with CRT, are at risk for obesity and dyslipidemia, insulin
resistance, hypertension, and cardiovascular disease. Further
investigation of these risks is warranted.
20
UI - 11831066
AU - Ottmann OG; Wassmann B; Hoelzer D
TI -
[Therapy of Philadelphia chromosome positive acute lymphatic leukemia
(Ph+ ALL) with an inhibitor of abl-tyrosine kinase (Glivec)]
SO - Med Klin 2002 Jan 15;97 Suppl 1():16-21
AD - Abteilung Hamatologie/Onkologie, Medizinische Klinik III der
Johann-Wolfgang-Goethe-Universitat Frankfurt/Main.
ottmann@em.uni-frankfurt.de
BACKGROUND: Ph+/bcr-abl positive ALL has the worst prognosis of all
subgroups of ALL; only a small minority of patients are cured with
currently established treatment regimens. The central pathogenetic role
of the constitutively activated and deregulated abl-tyrosine kinase that
is a direct consequence of the bcr-abl rearrangement opens the
possibility of treating this disease using a molecularly targeted
approach. The recent development of the selective abl-tyrosine kinase
inhibitor Glivec (formerly STI571) opens the opportunity of blocking the
signal transduction pathways critically involved in bcr-abl induced
leukemogenesis. TREATMENT RESULTS AND CONCLUSIONS: Glivec exerts a
significant anti-leukemic effect in patients with Ph+ ALL, with a
remarkably favorable toxicity profile. This enables transfer of a subset
of the responding patients to a potentially curative allogeneic stem
cell transplantation. Despite promising initial therapeutic effects,
treatment with Glivec alone is not able to achieve cures in the majority
of patients with relapsed or refractory Ph+ ALL. The earlier
administration of Glivec in patients with "de novo" ALL as well as
combining it with other treatment modalities is likely to improve
treatment results. The identification of specific resistance mechanisms
towards Glivec should provide valuable information regarding the
development of clinical strategies to circumvent resistance. Glivec can
already be considered an important element in the treatment of Ph+ ALL,
although the most effective ways of employing this novel agent remain to
be established.
21
UI - 11841456
AU - Al-Kasim FA; Thornley I; Rolland M; Lau W; Tsang R; Freedman MH;
TI -
Saunders EF; Calderwood S; Doyle JJ
Single-centre experience with allogeneic bone marrow transplantation for
acute lymphoblastic leukaemia in childhood: similar survival after
matched-related and matched-unrelated donor transplants.
SO - Br J Haematol 2002 Feb;116(2):483-90
AD - Division of Haematology/Oncology, The Hospital for Sick Children,
Toronto, Ontario, Canada.
Seventy percent of children with acute lymphoblastic leukaemia (ALL) who
may benefit from bone marrow transplant (BMT) lack a human leucocyte
antigen (HLA)-matched related donor (MRD). For these children, BMT from
a matched unrelated donor (MUD) represents a therapeutic option. We
reviewed the course of 62 children with ALL who received fully matched
marrow allografts at our institution between 1990 and 1998: 36 with MRDs
and 26 with MUDs. Clinical characteristics were similar in the two
groups. The interval from attainment of pre-BMT complete remission to
transplant was significantly longer in the MUD group. Conditioning
(etoposide/total body irradiation) and graft-versus-host disease (GVHD)
prophylaxis regimens were the same for all patients, and all received T
cell-replete bone marrow. There was no significant difference in
probability of engraftment, or time to engraftment, in the two groups.
MUD BMT recipients had a significantly greater incidence of grade II-IV
acute GVHD (58% versus 24% in the MRD group; P = 0.02), and demonstrated
a trend towards more chronic GVHD (39% versus 15%; P = 0.06). Three
years post BMT, the probabilities of transplant-related mortality were
33 +/- 11% and 20 +/- 8% in MUD and MRD groups respectively (P = 0.38);
the probabilities of relapse were 28 +/- 12% and 41 +/- 9% respectively
(P = 0.19). Lansky or Karnofsky performance scores in event-free
survivors were 90-100 in 87% of the MUD group and 83% of the MRD group.
With a median follow up of 38 months (range, 3-97), 3-year event-free
survival was 49 +/- 11% and 47 +/- 9% in the MUD and MRD BMT groups
respectively (P = 0.71). These results suggest that MUD BMT is a
valuable therapy for children with ALL in whom BMT is indicated, and
underscore the importance of efforts aimed at expediting unrelated donor
searches for patients lacking a MRD.
22
UI - 11721377
AU - Ke X; Yang Y; Zhao X
TI -
[An analysis of autologous peripheral stem cell transplantation for
hematological malignancies]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Nov;20(11):586-8
AD - Third Hospital, Beijing Medical University, Beijing 100083.
OBJECTIVE: To summarize the data of autologous peripheral stem cell
transplantation (APBSCT) for 49 hematological malignancies patients.
METHODS: Forty-nine patients, 18 with acute myeloid leukemia, (AML) 10
acute lymphoblastic leukemia(ALL), 14 multiple myeloma(MM), 6
non-Hodgkin's lymphoma(NHL) and 1 myelodysplastic syndrome(MDS RAEB-t)
received APBSCT were retrospectively analyzed. RESULTS: Comparing to
conventional chemotherapy, APBSCT can prolong the patients' disease-free
survival(DFS) and overall survival (OS). The 3 and 5-year OS rates were
74.78% and 83.33% for AML/NHL; 38% and 19% for MM; 40% and 0 for ALL,
respectively. The time of hematopoietic reconstitution was influenced by
G-CSF administration significantly. The mean time of neutrophil
recovering to 0.5 x 10(9)/L after APBSCT was +17.7 days in no G-CSF
group, and +11.14 days in G-CSF group. Up to now, of the 49 patients, no
APBSCT related death occur, 23 have died and 22 of them died of relapse.
The most common transplantation related complications were fever, liver
dysfunction and hypopotassemia, all of which can be cured by proper
treatment. CONCLUSION: APBSCT can be safely performed in hematological
malignancies.
23
UI - 11721378
AU - Wang Y; Jiang H; Xie X
TI -
[Comparative pharmacokinetic study of two different ways of using
L-asparaginase as the main drug in combination chemotherapy]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Nov;20(11):589-91
AD - Shanghai Pediatric Medical Center, Shanghai Second Medical University,
Shanghai 200092.
OBJECTIVE: To search for a safer and more effective way of using
L-asparaginase as the main drug in combination protocol. METHOD: Twenty
children with lymphoid malignancies were randomly divided into two
groups: Group A and Group B, for L-asparaginase therapy. Group A:
Leunase 6,000 KU/m2, continuous intravenous injection every day for 8
times; Group B: Leunase 6,000 KU/m2, continuous intravenous injection
every other day for 8 times. Blood samples were collected every day for
group A and every other day for group B and serum L-asparaginase and
L-asparagine levels were tested. RESULTS: 1. The pre-treatment mean
value of serum L-asparaginase in group A was significantly higher than
that in group B (P < 0.01). The levels of L-asparaginase in group A
tended to increase day by day during the therapeutic course while those
in group B without increasing tendency. 2. The L-asparagine levels and
their dynamic changes were not significantly different between the two
groups (P > 0.05). CONCLUSION: The administration of Leunase by
continuous intravenous injection every other day is a much safer and
effective protocol and worthy of recommendation.
24
UI - 11899125
AU - Au W Y; Yeung C K; Chan H H; Lie A K
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.
25
UI - 11878782
AU - Strickland D K; Jenkins J J; Hudson M M
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.
26
UI - 11836715
AU - Warner JT; Evans WD; Webb DK; Gregory JW
TI -
Body composition of long-term survivors of acute lymphoblastic
leukaemia.
SO - Med Pediatr Oncol 2002 Mar;38(3):165-72
AD - Department of Paediatrics, John Radcliffe Hospital, Oxford, UK.
justin.warner@orh.anglox.nhs.uk
BACKGROUND: Long-term quality of life is of growing importance in
children previously treated for malignancy. Obesity defined indirectly
from indices of height and weight, has been described in long-term
survivors of acute lymphoblastic leukaemia (ALL) and hypothesised to be
a consequence of previous cranial irradiation. PROCEDURE: In this study,
measures of whole and regional body composition using skinfold and dual
energy X-ray absorptiometry (DEXA) measurements have been made in 35
long-term survivors of ALL who had received cranial irradiation and
chemotherapy. To assess the influence of cranial irradiation, results
were compared with those obtained in 21 children treated for other
malignancies, who received chemotherapy alone and with 31 healthy
sibling controls. RESULTS: Girls treated for ALL were significantly
fatter than those treated for other malignancies or healthy control
siblings whether measured by skinfold thickness (median (range) 37.4%
(17.9-41.3) vs. 24.6% (19.1-35.0) and 28.8% (19.6-43.1), respectively,
P<0.01) or DEXA (33.5% (20.5-42.8) vs. 25.5% (16.5-31.0) and 24.5%
(18.8-53.6), respectively, P<0.01). Boys treated for ALL were not
significantly fatter than boys in the other two groups. Measures of
whole body percent fat derived from DEXA were persistently less than
those derived from skinfold measurements with a mean (95% CI) difference
of 2.4% (1.7-3.1, P<0.001) for all groups combined. In ALL survivors,
using regression equations for skinfold thicknesses derived from
controls with DEXA as the 'gold standard' method, fat mass was
significantly overestimated. CONCLUSION: Female survivors of ALL are
significantly fatter than those of other malignancies and healthy
sibling controls. Caution should be observed in the application of
published equations, derived from the normal population, for the
calculation of body composition in children treated for ALL. The
mechanism of onset of obesity remains unclear, but is probably
multifactorial and related to previous cranial irradiation. Copyright
2002 Wiley-Liss, Inc.
27
UI - 11846309
AU - Soker M; Dikici B; Devecioglu C; Ece A; Haspolat K
TI -
Interferon-alpha treatment as a possible cause of relapse in a child
with precursor B acute lymphoblastic leukemia.
SO - J Pediatr Hematol Oncol 2001 May;23(4):256-7
28
UI - 11876615
AU - Yahya H I; Al-Allawi N A; Mattar Y
TI -
Acute Lympoblastic Leukaemia in seventy Iraqi adults: clinical and
haematological findings and outcome of therapy.
SO - Indian J Cancer 2000 Jun-Sep;37(2-3):85-90
AD - Dept of Medicine, College of Medicine, University of Baghdad and its
teaching Hospitals, Iraq.
Studies on acute Leukaemia from developing and Asian countries are
scarce, and generally reflect poorer outcomes of therapy compared to
their Western counterparts. This study was undertaken to address the
latter issue in Iraqi adults with Acute Lymphoblastic Leukaemia (ALL).
It included seventy unselected Iraqi adults (aged 14-60years), diagnosed
as ALL in Baghdad Teaching Hospital, Baghdad, during the period between
included patients were generally comparable with those reported from the
West, except for the lower median age. The patients were scheduled to
receive a modified intensive chemotherapy protocol, and had an overall
complete remission rate of 84.3%, and all overall median survival of 24
months. Nineteen patients were still alive in complete remission after a
median follow-up of 67 months, and the estimated five year disease free
survival was 27.2%. The above finding compare favourably with Western
studies and are among the more favourable reports from Asian countries.
The study also includes a discussion of the problems facing
haematologists in the management of ALL in this part of the world.
29
UI - 11721423
AU - Wu B; Sun J; Meng F
TI -
[Allogeneic peripheral stem cell transplantation (PBSCT) for
hematological malignancies]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Aug;20(8):420-3
AD - Nanfang Hospital, First Military Medical University, Guangzhou 510515.
OBJECTIVE: To evaluate the efficacy of allo-PBSCT in hematological
malignancies. METHODS: Sixteen patients with hematological malignancies
were treated by allo-PBSCT, started from march 1997. Five of them were
ALL (CR1 4, CR2 1), 2 ANLL (CR1), 8 CML(CP 5, AP 3), and one NHL(PR).
The median age was 33(18-49) years. Conditioning regimen was TBI 9-10 Gy
+ CTX 120 mg/kg, or TBI 10 Gy + CTX 120 mg/kg + Vp16 500 mg. A
combination of cyclosporine and methotrexate was administered to prevent
acute GVHD. All donors received G-CSF 5 micrograms.kg-1.d-1 for 5 to 6
days. One or three leukapheresis procedures were performed by CS 3000
plus blood cell separator to collect a median mononuclear cells of 9 x
10(8)/kg recipient weight [range(5.79-13.7) x 10(8)/kg], including a
median CD34+ cells 13.9 x 10(6)/kg [range(5.69-49.00) x 10(6)/kg].
RESULTS: All patients were engrafted and hematopoietic reconstitution
was rapid: neutrophils achieving 0.5 x 10(9)/L on day 12 (range, 10-15),
platelets > 30 x 10(9)/L on day 13 (range, 8-24). More than grade II
aGVHD occurred in 3(18.7%), and localized cGVHD in 3 patients. Leukemia
relapse occurred in one patients. The median follow-up duration was 13
months. Eleven patients were alive in disease-free situation.
CONCLUSION: Allo-PBSCT can rapidly reconstitute hematopoiesis with
incidences of aGVHD and cGVHD not more than that in BMT.
30
UI - 11721425
AU - Wang M; Han M; Feng S
TI -
[Comparison of clinical outcome between allogeneic peripheral blood stem
cell transplantation and bone marrow transplantation]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Aug;20(8):427-30
AD - Institute of Hematology, CAMS and PUMC, Tianjin 300020.
OBJECTIVE: To compare the clinical outcome of allogeneic peripheral
blood stem cell transplantation(PBSCT) with that of bone marrow
transplantation(BMT). METHODS: Twenty-six patients received allo-BMT and
1998. Conditioning regimens were CY 120 mg/kg plus STBI 9-10 Gy or BU 16
mg/kg or Mel 140-160 mg/m2 plus CY 120 mg/kg. RESULTS: Twenty-three
patients of PBSCT and 24 of BMT group engrafted successfully.
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