NCI CANCERLIT^® Search: Therapy of Acute Lymphocytic Leukemia - September 2001

Last Modified: November 1, 2001

[Changes in gonadal function in post-pubertal male survivors of acute lymphoblastic leukemia and Hodgkin's disease]
Isolation frequency and antimicrobial susceptibility of Pseudomonas aeruginosa bloodstream infections in neutropenic patients with acute leukemia.
Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.
Hematopoietic growth factors in patients receiving intensive chemotherapy for malignant disorders: studies of granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and Flt-3 ligand (Flt3L).
Effect of glucocorticoid therapy on energy intake in children treated for acute lymphoblastic leukemia.
Real-time quantitative PCR for detection of minimal residual disease before allogeneic stem cell transplantation predicts outcome in children with acute lymphoblastic leukemia.
Intrathecal chemotherapy with antineoplastic agents in children.
A mechanism of apoptosis induced by all-trans retinoic acid on adult T-cell leukemia cells: a possible involvement of the Tax/NF-kappaB signaling pathway.
[Leukemia treatment results have improved, but prognosis is still questionable]
Late effects in long-term survivors of ALL in childhood: experiences from the SPOG late effects study.
A parent's perspective: providing compassionate and effective care.
Severe persistent neuropsychiatric toxicity after a human leucocyte antigen-non-identical peripheral blood stem cell transplantation (total body irradiation, etoposide, thiotepa) and interleukin 2-based experimental therapy for poor prognosis relapse acute lymphoblastic leukaemia.

CancerMail from the National Cancer Institute

1
UI - 21062261
AU - Soriano Guillen L; Munoz Calvo MT; Pozo Roman J; Contra Gomez T; Buno Soto M; Argente Oliver J
TI - [Changes in gonadal function in post-pubertal male survivors of acute lymphoblastic leukemia and Hodgkin's disease]
SO - An Esp Pediatr 2000 Oct;53(4):318-23
AD - Secciones de Endocrinologia y Oncologia Pediatricas. Hospital Universitario Nino Jesus. Universidad Autonoma. Madrid.
AIM: To study gonadal function in male patients surviving acute lymphoblastic leukemia (ALL) or Hodgkins disease (HD). PATIENTS AND METHODS: Thirteen postpubertal males were studied (Tanner stage V), 9 with ALL and 4 with HD, who had received polychemotherapy during the pre-puberal period. The control group was composed of 13 male volunteers of similar ages and with complete pubertal development. Testicular size, spermiogram, serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) before and after stimulus with gonadotropin-releasing hormone (GnRH), and serum testosterone levels were determined. The germinal epithelium was believed to be damaged when at least one of the following criteria was present: 1) oligospermia/azoospermia, 2) increase in serum FSH levels before or after GnRH, or 3) reduction in testicular volume. Lesions in Leydig's cells were thought to exist when serum testosterone levels were reduced or when serum LH levels, before or after stimulus, increased. RESULTS: Patients with HD presented clear alterations in germinal function and, to a lesser degree, in the function of Leydig's cells. Significant differences compared with the control group (p < 0.001) were found in peak FSH (19.7 +/- 18 vs 4.8 +/- 1.8 microUI/mL), peak LH (49.2 +/- 31 vs 33.4 +/- 10.0 microUI/mL), serum testosterone (4.1 +/- 0.6 vs 5.9 +/- 0.3 ng/mL) and testicular volume (16.6 +/- 2.8 vs 22.5 +/- 2.4 mL). Of the four patients with HD, three presented azoospermia and one oligospermia. No significant differences in any of the clinical or biochemical parameters studied were found in patients surviving ALL compared with the control group, but two of the nine patients studied presented oligospermia. CONCLUSIONS: The chemotherapy protocols used in the treatment of HD and ALL produced a high incidence of germinal cell damage and subclinical alterations in the Leydig's cell function in males with HD. In patients with ALL, the germinal line was only mildly affected. Prepubertal state does not protect the testes from the harmful effects of chemotherapy.

2
UI - 21227799
AU - Fanci R; Paci C; Pecile P
TI - Isolation frequency and antimicrobial susceptibility of Pseudomonas aeruginosa bloodstream infections in neutropenic patients with acute leukemia.
SO - J Chemother 2001 Apr;13(2):213-5

3
UI - 21241458
AU - Matsuzaki A; Ishii E; Nagatoshi Y; Eguchi H; Koga H; Yanai F; Inada H; Nibu K; Tamai Y; Akiyoshi K; Nakayama H; Hara T; Take H; Miyazaki S; Okamura J
TI - Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.
SO - Int J Hematol 2001 Apr;73(3):369-77
AD - Division of Child Health, School of Health Sciences, Kyushu University, Fukuoka, Japan. matsuzaki@shs.kyushu-u.ac.jp
We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.

4
UI - 21292754
AU - Bruserud O; Foss B; Petersen H
TI - Hematopoietic growth factors in patients receiving intensive chemotherapy for malignant disorders: studies of granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and Flt-3 ligand (Flt3L).
SO - Eur Cytokine Netw 2001 Apr-Jun;12(2):231-8
AD - Department of Medicine, Haukeland University Hospital and the University of Bergen, N-5021 Bergen, Norway.
The levels of hematopoietic growth factors in patients receiving intensive chemotherapy for malignant disorders were investigated using a variety of approaches. Firstly, serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF and Flt3-ligand (Flt3L) were examined in acute leukemia patients with treatment-induced cytopenia and complicating bacterial infections. Increased serum levels of both G-CSF and Flt3-ligand (Flt3L) were detected when these patients developed therapy-induced leukopenia, whereas GM-CSF levels were low or undetectable. Development of complicating bacterial infections then increased the serum levels of both G- and GM-CSF, and the Flt3L levels remained high during the infections. Secondly, release of growth factors was characterized for clonogenic T cells that remained in the circulation of acute leukemia patients with chemotherapy-induced cytopenia. CD4(+) and CD8(+) T cells from these patients released high levels of GM-CSF, relatively low levels of IL-3 secretion having been detected, and only a minority of the clones released detectable amounts of Flt3L. Thus, circulating T cells may contribute to the high systemic growth factor levels in cytopenic patients. Thirdly, plasma levels of GM-CSF and interleukin-3 (IL-3) were examined in patients with malignant disorders who received chemotherapy plus G-CSF for stem cell mobilization. Increased levels of GM-CSF and Flt3L were detected both in the patients' plasma and in the stem cell grafts. Despite the increased growth factor levels in neutropenic patients with complicating infections, the occurrence of febrile neutropenia did not have a major impact on normal hematopoietic reconstitution (i.e. duration of treatment-induced neutropenia) after intensive chemotherapy for acute myelogenous leukemia.

5
UI - 21394095
AU - Reilly JJ; Brougham M; Montgomery C; Richardson F; Kelly A; Gibson BE
TI - Effect of glucocorticoid therapy on energy intake in children treated for acute lymphoblastic leukemia.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3742-5
AD - Department of Human Nutrition, University of Glasgow, Yorkhill Hospitals, Glasgow, Scotland G3 8SJ. jjr2y@climed.gla
Despite a widespread belief that glucocorticoid therapy is associated with positive energy balance and excess weight gain there is a dearth of quantitative evidence about its effects and the underlying mechanisms of any effects. The primary aim of the present study was to quantify the effect of dexamethasone and prednisone treatment on energy intake in children treated for childhood acute lymphoblastic leukemia. A secondary aim was to test for differences in excess weight gain between patients treated using the 2 glucocorticoids. We measured energy intake in 26 patients (mean +/- SD age, 6.3 +/- 2.3 yr) during a 5-d period "on" steroids and again in the week before steroid treatment. Changes in body mass index from diagnosis to 1 and 2 yr postdiagnosis were expressed as SD scores. Steroid treatment was associated with a significant increase in energy intake of approximately 20% (mean paired difference, 1.7 MJ/d; SD, 2.8; 95% confidence interval, 0.7-2.8 MJ/d), with no significant difference between the 2 steroids. The mean change in body mass index SD score was +0.38 (SD, 1.10; P < 0.05) to 1 yr and +0.68 (SD, 1.38; P < 0.05) to 2 yr, with no significant difference between the 2 groups of patients. Glucocorticoid treatment in childhood acute lymphoblastic leukemia increases energy intake markedly, and this effect contributes to the excess weight gain and obesity characteristic of patients being treated for acute lymphoblastic leukemia.

6
UI - 21406933
AU - van der Velden VH; Joosten SA; Willemse MJ; van Wering ER; Lankester AW; van Dongen JJ; Hoogerbrugge PM
TI - Real-time quantitative PCR for detection of minimal residual disease before allogeneic stem cell transplantation predicts outcome in children with acute lymphoblastic leukemia.
SO - Leukemia 2001 Sep;15(9):1485-7

7
UI - 21253887
AU - Ruggiero A; Conter V; Milani M; Biagi E; Lazzareschi I; Sparano P; Riccardi R
TI - Intrathecal chemotherapy with antineoplastic agents in children.
SO - Paediatr Drugs 2001;3(4):237-46
AD - Division of Paediatric Oncology, Catholic University, Rome, Italy.
Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. Intrathecal MTX administered sequentially with systemic high dose MTX infusion prolongs therapeutic cerebral spinal fluid (CSF) levels of the drug. Prolonged therapeutic CSF levels can also be achieved by giving repeated small intrathecal doses of MTX over an extended period in selected patients, with an implanted Ommaya reservoir. In the CSF, the metabolic inactivation of Ara-C is significantly lower than in plasma with a CSF clearance similar to the rate of CSF bulk flow. A slow-release formulation of Ara-C may be given intrathecally, resulting in a prolonged cytotoxic concentration in the CSF. CNS relapse and neurotoxicity in patients with acute lymphoblastic leukaemia, especially younger children, may be reduced by using age-related dosing of intrathecal MTX and Ara-C. Hydrocortisone is used in combination with MTX and Ara-C for so-called 'triple intrathecal chemotherapy' in the treatment of meningeal leukaemia. Intrathecal thiotepa does not appear to be advantageous over systemic administration in patients with brain and meningeal leukaemia. Monoclonal antibodies, reactive with tumour-associated antigens, can be used as delivery systems for chemotherapeutic agents and radionuclides. However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a fatal outcome.

8
UI - 21145711
AU - Nawata H; Maeda Y; Sumimoto Y; Miyatake J; Kanamaru A
TI - A mechanism of apoptosis induced by all-trans retinoic acid on adult T-cell leukemia cells: a possible involvement of the Tax/NF-kappaB signaling pathway.
SO - Leuk Res 2001 Apr;25(4):323-31
AD - Third Department of Internal Medicine, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan
In this study, five single clones were randomly established by limiting dilution method from each of the HTLV-I positive T cell lines - HUT 102 and ATL-2, and examined for the all-trans retinoic acid (ATRA) sensitivity, respectively. For each clone, we found a significant correlation between the reduction in 3[H]-thymidine incorporation and the reduction in CD25 expression (r=0.701, P<0.05) following treatment with 10(-5) M ATRA for 48 h. Agarose gel electrophoresis revealed DNA fragmentation of the cell lines treated with ATRA, indicative of apoptosis. These results suggested that the tax gene in the HTLV-I genome might be a key molecule involved in cell proliferation and CD25 expression. Thereafter, we transfected the tax gene in the expression vector (pCMV-Tax-neo) into the HTLV-I(-) T cell line Jurkat and examined the effects of ATRA on cell growth. The results showed that ATRA sensitivity was acquired by the Jurkat cells transfected with the tax gene expression vector, but not in those transfected with the control vector. We also observed NF-kappaB transcriptional activity on Jurkat cells transfected with the tax gene by CAT assay in the presence or absence of ATRA. NF-kappaB transcriptional activity was decreased significantly on Jurkat cells transfected with the tax gene after ATRA treatment. Taken together, these results indicate that ATRA may affect or block the Tax/NF-kappaB signaling pathway in ATL cells.

9
UI - 21360534
AU - Siimes MA
TI - [Leukemia treatment results have improved, but prognosis is still questionable]
SO - Duodecim 1997;113(7):677-82
AD - University of Helsinki, Helsinki, Finland.

10
UI - 21243943
AU - von der Weid N; Swiss Pediatric Oncology Group (SPOG)
TI - Late effects in long-term survivors of ALL in childhood: experiences from the SPOG late effects study.
SO - Swiss Med Wkly 2001 Apr 7;131(13-14):180-7
AD - Swiss Pediatric Oncology Group (SPOG), Medizinische Universitats-Kinderklinik, Inselspital, Bern, Switzerland. nvdweid@insel.ch
With the use of more intensive regimens including prophylactic CNS treatment, the prognosis of children with ALL has dramatically improved over the last three decades. The aim of this cross-sectional, nationwide study was to comprehensively assess long-term toxicity in ALL survivors, with special attention given to neuropsychological morbidity, and to look for possible differences in cognitive outcome between children having received prophylactic cranial irradiation and those not having received it. Between 1994 and 1996, long-term survivors of ALL were assessed in a multi-center setting according to a standardized protocol which included, besides usual clinical and laboratory investigations, a comprehensive endocrine work-up. Additionally, children having received anthracyclines were checked for possible late cardio-toxicity with echocardiography and ECG. Intellectual performance was evaluated with standardized neuropsychological tests (age-adapted versions of the Wechsler test). One-hundred and fifty patients were eligible for the study. The median age at diagnosis was 5 years and at evaluation 16 years, for a median follow-up of 10 years. Thirty-five patients had cranial irradiation as part of the prophylactic CNS treatment. One-hundred and forty (93%) of the 150 eligible patients were completely evaluated in terms of global long-term toxicity: 117 (83%) long-term survivors had no (n = 61) or only minimal (n = 56) late toxicity; 19 (14%) suffered from moderate impairments; 4 (3%) showed severe somatic or neuropsychological sequelae. Intellectual performance could be assessed in 147 (98%) of the 150 eligible patients. The mean global, verbal and non-verbal IQs (103, 105 and 101 respectively) of the ALL survivors as a group were comparable with those found in the general population. The results of the comparison between children having and those not having received prophylactic cranial irradiation showed: 1) significantly higher scores in chemotherapy-only treated patients, both for the global and the verbal performances; 2) significantly poorer results in specific items of the Wechsler test (short-term verbal memory, arithmetics, concentration/speed of processing) in irradiated children. These findings which show the deleterious role of cranial irradiation correlate well with many other reports found in the literature. However, they could have been influenced by the significantly longer time interval observed between therapy and evaluation in our irradiated patients. Prospective studies are needed to further characterize the potential neuropsychological hazards of chemotherapy and their evolution over time.

11
UI - 21386706
AU - McDonald V
TI - A parent's perspective: providing compassionate and effective care.
SO - Hosp Q 1999-2000 Winter;3(2):20-4

12
UI - 21421130
AU - Classen CF; Schulz AS; Debatin KM; Friedrich W
TI - Severe persistent neuropsychiatric toxicity after a human leucocyte antigen-non-identical peripheral blood stem cell transplantation (total body irradiation, etoposide, thiotepa) and interleukin 2-based experimental therapy for poor prognosis relapse acute lymphoblastic leukaemia.
SO - Br J Haematol 2001 Aug;114(2):487-9