National Cancer Institute®
Last Modified: August 1, 2002
UI - 11721427
AU - Guo L
TI - [Management of childhood acute leukemia with standard protocol for increasing the long-time disease free survival rate]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Jul;20(7):341-2
UI - 12116076
AU - Ziino O; Russo D; Orlando MA; Benigno V; Locatelli F; Arico M
TI - Symptomatic hypoglycemia in children receiving oral purine analogues for treatment of childhood acute lymphoblastic leukemia.
SO - Med Pediatr Oncol 2002 Jul;39(1):32-4
AD - Pediatric Hematology Oncology, Ospedale dei Bambini "G. Di Cristina, Palermo", Italy.
BACKGROUND: Antimetabolite-based continuation therapy is commonly used for childhood acute lymphoblastic leukemia (ALL) and hypoglycemia after prolonged fasting has been recently reported. We have found that spontaneous, symptomatic hypoglycemia (SH) may also occur in such patients. PROCEDURE: Between 1995 and 1999, patients treated according to the AIEOP-ALL-95 study received BFM-type intensive chemotherapy; mercaptopurine (6-MP) was given (60 mg/m(2)/days, orally for 14 days) during the second part of induction and during consolidation therapy (25 mg/m(2)/day, orally for 8 weeks); thioguanine (6-TG) was given during reinduction therapy with protocol II (60 mg/m(2)/day, orally for 14 days); continuation therapy consisted of a combination of 6-MP (50 mg/m(2)/day orally) and methotrexate (MTX, 20 mg/m(2)/weekly, i.m.). We reviewed the charts of all patients treated for childhood ALL at our two centers. This was done to assess the incidence and the characteristics of all episodes of SH: sweating, pallor, nausea, abdominal pain with or without transient alterations of alertness, in the presence of blood glucose level of under 60 mg/dl. RESULTS: Six of 86 patients (6.9%) developed 18 episodes of SH. Five were male, none was older than 5 years, and four were only 3 years old. SH episodes occurred during consolidation (n = 2), reinduction (n = 7), and continuation (n = 9) phases. CONCLUSIONS: SH is a rare complication associated with administration of the purine analogues, mercaptopurine and thioguanine to children with reduced fat storage and young age. Copyright 2002 Wiley-Liss, Inc.
UI - 12116084
AU - Swilley S; Strickland DK; Davila R; Levstik M; Ribeiro R; Hudson MM
TI - Hepatitis C infection during treatment for childhood cancer: pitfalls in diagnosis and management.
SO - Med Pediatr Oncol 2002 Jul;39(1):58-9
AD - University of Tennessee-Memphis, School of Medicine, Memphis, Tennessee.
UI - 12116090
AU - Chan GC; Chiang AK; Ha SY; Lau YL; Ong JB; Lee AC
TI - Asparaginase-induced acute parotitis: an uncommon and self-limiting complication.
SO - Med Pediatr Oncol 2002 Jul;39(1):73-4
UI - 12095569
AU - Halperin EC; Laurie F; Fitzgerald TJ
TI - An evaluation of the relationship between the quality of prophylactic cranial radiotherapy in childhood acute leukemia and institutional experience: a Quality Assurance Review Center-Pediatric Oncology Group study.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):1001-4
AD - Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. email@example.com
PURPOSE: The Pediatric Oncology Group Protocol 9404 was a prospective clinical trial of two forms of chemotherapy in childhood T-cell acute lymphoblastic leukemia and advanced stage T-cell lymphoblastic non-Hodgkin's lymphoma. The protocol called for prophylactic C1 whole brain external beam irradiation, 18 Gy in 2 Gy/fraction for 9 fractions. We hypothesized that a correlation would be found between the number of children irradiated on protocol by an institution and the compliance rate of that institution with radiotherapy quality assurance (QA) guidelines. We also hypothesized that QA compliance would improve as the study progressed. METHODS AND MATERIALS: We scored the radiation dose as a minor deviation from protocol guidelines if the dose to the prescription point differed from the protocol by 6-10%, and a major deviation if it differed from protocol by > 10%. Treatment volumes were scored as a minor deviation if the margins were less than specified or the fields were excessively large. A major deviation was defined as the transection of a potential leukemia-bearing volume such as would be caused by blocking the cribriform plate, optic nerve, or temporal lobe. When the treating physician submitted a treatment plan and simulator film at the initiation of therapy to the Quality Assurance Review Center (QARC), a rapid turn-around review of the plan and suggestions for improvement was provided. At the end of therapy, all simulator and port films were reviewed at the QARC. RESULTS: We reviewed the data from 353 patients treated at 73 institutions in the United States, Canada, and Europe. Of these patients, 2% (n = 7) were not assessable for QA because of incomplete information. Minor quality deviations were found in 27.7% of patients (n = 98) and major deviations in 7.9% (n = 28). The frequency of major deviations for institutions placing 1-4 patients on study was 11% vs. 5.5% for institutions placing > or =5 patients (p < 0.09). The frequency of minor deviations was 28.6% for institutions placing 1-4 patients on study vs. 27.1% for institutions placing >5 patients (p not significant). The frequency of major deviations fell over time (1996-1997, 15.5% vs. 1998-2001, 4.7%, p < 0.001). The frequency of minor deviations did not (1996-1997, 29.9% vs. 1998-2001, 26.9%, p not significant). CONCLUSION: For a relatively simple radiotherapy field, with clearly written protocol guidelines and rapid turn-around corrections from QARC, the rate of minor deviations was no different between institutions placing 1-4 patients on study and those placing > or =5. A trend (p < 0.09) was noted, however, for major deviations to decrease as a function of institutional experience, as well as over time (p < 0.001), supporting the validity of the hypothesis that pediatric clinical experience matters in QA for C1 whole brain leukemia radiotherapy.
UI - 11911412
AU - Nomura K; Okamoto T; Nakao M; Ueda K; Akano Y; Fujita Y; Kobayashi M;
TI - Yokota S; Horiike S; Nishida K; Kusuzaki K; Taniwaki M Multiple bone lesions after allogeneic bone marrow transplantation in a patient with relapsed adult acute lymphoblastic leukemia: minimal residual disease analysis may predict extramedullary relapse.
SO - Leuk Lymphoma 2001 Nov-Dec;42(6):1305-8
AD - Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan. firstname.lastname@example.org
We describe a patient with acute lymphoblastic leukemia (ALL, L2) who relapsed with multiple bone lesions after allogeneic bone marrow transplantation (allo-BMT). Allo-BMT was performed from an HLA-identical sibling during the first hematological complete remission (CR). Minimal residual disease (MRD) assessed by polymerase chain reaction (PCR) with primers for T cell receptor delta (TCRdelta) gene became positive in the bone marrow sample on day 46 after allo-BMT. On day 113, the patient complained of a painful tumor at the right clavicle. The examination of biopsy specimen revealed infiltration of leukemic cells. After partial response was achieved by local radiotherapy, disseminated bone lesions were demonstrated by 99mTC scintigraphy scan, followed by bone marrow relapse on day 137. The patient died of cardiac tamponade on day 236 after Allo-BMT. MRD assessed by PCR assay for TCRdelta gene in the bone marrow is useful for the prediction of extramedullary as well as medullary relapse after BMT.
UI - 12043054
AU - Loennechen T; Lysaa RA; Giverhaug T; Sylte I; Mathiesen LE; Aarbakke J
TI - [New techniques for optimization of thiopurine therapy in leukemia and transplantation]
SO - Tidsskr Nor Laegeforen 2002 Apr 30;122(11):1107-10
AD - Avdeling for farmakologi Institutt for farmasi, Universitetet i Tromso 9037 Troms. email@example.com
BACKGROUND: The majority of chemotherapeutic agents are administered at fixed doses that are close to those maximally tolerated. MATERIAL AND METHODS: This review is based on current knowledge about the metabolism of thiopurines and the clinical implications of genetic polymorphism in thiopurine-S-methyltransferase (TPMT). RESULTS: Intracellularly thiopurines, e.g. 6-MP, are anabolized to cytotoxic 6-thioguanine nucleotides (6-TGN) that are incorporated into DNA and RNA. A competing pathway is S-methylation of 6-MP and its initial nucleotide metabolites by TPMT. In childhood acute lymphocytic leukaemia, high erythrocyte concentrations of 6-TGN correlate with the degree of leukopenia and a good prognosis, while low concentrations appear to be associated with higher risk of relapse. In most populations studied, approximately 10% have intermediate TPMT activity and 1/300 lacks TPMT activity due to one or two mutant TPMT alleles, respectively. INTERPRETATION: Phenotyping or genotyping may be used to identify patients as deficient or intermediate thiopurine metabolizers. This suggests that they should receive a profound or moderate reduction in dosage to avoid haematopoietic toxicity.
UI - 12133457
AU - Sun Z; Wang Z; Zhu W; Liu H; Liu X; Liu Z; Wang N; Pan L; Wu S; Wu J
TI - [Treatment of two case childhood acute lymphoblastic leukemia by HLA-mismatched unrelated umbilical cord blood transplantation]
SO - Zhonghua Xue Ye Xue Za Zhi 2002 Apr;23(4):198-201
AD - Anhui Provincial Hospital, Hefei 230001, China.
OBJECTIVE: To explore the hematopoietic and immunologic reconstitution and transplantation-related complications of HLA one locus mismatched unrelated umbilical cord blood transplantation for the treatment of hematological malignancies. METHODS: Two children with acute lymphoblastic leukemia received HLA-mismatched unrelated umbilical cord blood transplantation. The conditioning regimens were BU-CTX (case 1) and BU-CTX plus BCNU (case 2). GVHD prophylaxis regimen consisted of cyclosporine (CsA) and mycophenolate mofetil (MMF). The patients received 14.6 x 10(7) nucleated cells/kg with 7.24 x 10(5) CD(34)(+) cells/kg and 16.24 x 10(7) nucleated cells/kg with 21.11 x 10(5) CD(34)(+) cells/kg, respectively. RESULTS: The two recipients, ANC > 0.5 x 10(9)/L occurred at day 27 and day 17, BPC > 50 x 10(9)/L at day 53 and day 46, the peripheral blood counts normalization at day 60 and day 52, the immune function normalization at day 134 and day 122 and the DNA fingerprinting showing engraftment at day 19 and day 17, respectively. The donor-recipient pair of case 1 was male to female, and the chromosome karyotype of recipients bone marrow and peripheral blood cells showed 100%, 46, XY cells at day 49. Grade II acute graft versus host disease (aGVHD) occurred at day 26 (case 1) and day 21 (case 2). The two recipients have survived for 353 days and 256 days. CONCLUSION: The hematopoietic and immunologic reconstitution in umbilical cord blood transplantation were earlier and more durable. The transplantation-related complications were less and aGVHD were milder.
UI - 12166264
AU - Nakanishi N; Kojima K; Ueda N; Moritaka T
TI - [A case of bronchiolitis obliterans after allogeneic bone marrow transplantation for acute lymphocytic leukemia]
SO - Nihon Kokyuki Gakkai Zasshi 2002 May;40(5):408-11
AD - Department of Medicine, Ehime Prefecture Central Hosptial, Matsuyama, 790-0024, Japan.
A case of bronchiolitis obliterans after allogeneic bone marrow transplantation (BMT) for acute lymphocytic leukemia in an 18-year-old woman with both acute and chronic graft-versus-host disease is described. About 160 days after BMT she started complaining of a non-productive cough and exertional dyspnea. Pulmonary function testing revealed obstructive respiratory dysfunction. High-resolution CT (HRCT) scan of the lungs showed areas of parenchymal hypoattenuation with air-trapping, which was more emphasized with expiratory HRCT. She had many of the risk factors for bronchiolitis obliterans, such as total body irradiation, pretreatment with cyclophosphamide, chronic graft-versus-host disease and a low IgG level. Her symptoms were progressive and bronchiectasis developed. She died of respiratory failure 3.5 years after BMT. Bronchiolitis obliterans is an important complication of BMT which the clinician must take into account.
UI - 12145682
AU - Lauten M; Matthias T; Stanulla M; Beger C; Welte K; Schrappe M
TI - Association of initial response to prednisone treatment in childhood acute lymphoblastic leukaemia and polymorphisms within the tumour necrosis factor and the interleukin-10 genes.
SO - Leukemia 2002 Aug;16(8):1437-42
AD - Hannover Medical School, Children's Hospital, Department of Paediatric Haematology and Oncology, Hannover, Germany.
Plasma levels of TNF and IL-10 have been associated with therapy outcome in haematological malignancies and are influenced by genetic variation due to germline polymorphisms within the TNF and IL-10 genes. Different TNF and IL-10 genetic polymorphisms might therefore also correlate with clinical outcome in childhood acute lymphoblastic leukaemia (ALL). We analysed the association of TNF and IL-10 polymorphisms with response to initial treatment and risk of relapse in 135 children with ALL, treated according to Berlin-Frankfurt-Munster (BFM) protocols. Our data showed a protective effect from prednisone poor response in patients with the IL-10 G/G genotype, whereas no association of the risk of relapse and IL-10 genotype was found. In the total study group, subjects expressing the TNF2 allele neither showed a statistically significant general association with prednisone response nor with risk of relapse compared to subjects homozygous for the TNF1 allele. Nevertheless, we did find a higher risk of relapse in poor prednisone responders expressing the TNF2 allele compared to poor prednisone responders not expressing the TNF2 allele. We conclude that IL-10 genotype might influence prednisone response in patients with childhood ALL, whereas TNF genotype seems to influence the risk of relapse in high risk ALL patients.
UI - 12138643
AU - Telek B; Rejto L; Kiss A; Batar P; Remenyi G; Rak K; Udvardy M
TI - [Experience with fludarabine treatment and review of the literature]
SO - Orv Hetil 2002 Jun 16;143(24):1459-65
AD - Debreceni Orvos- es Egeszsegtudomanyi Centrum, II. Belgyogyaszati Klinika, Hematologiai Tanszek.
INTRODUCTION: Fludarabine is the most commonly used purine analog, its mechanism of action is complex. Fludarabine inhibits DNA synthesis, acts on non-dividing (G0 phase) cells influencing apoptosis. PATIENTS, RESULTS, CONCLUSIONS: In our institute 47 patients were treated with fludarabine or fludarabine based combination chemotherapy. Fludarabine was given in 19 patients with chronic lymphocytic leukaemia (CLL), complete remission (CR) was achieved in one case, partial remission (PR) was obtained in 10 patients. Fludarabine was more effective in patients who received less intensive chemotherapy prior to fludarabine therapy and in those patients who had less advanced diseases. Elderly patients (over sixty years of age) also responded to fludarabine therapy. Fludarabine and cyclophosphamide combination (FCy) were used in three lymphocytic lymphoma patients, two of them obtained PR, in the third case the disease progressed. Fludarabine + mitoxantrone (Novantrone) + dexamethasone (FND) regimen was administered in nine patients who were previously heavily treated (one patient with B-CLL, one with T-CLL, one with peripheral T-cell lymphoma and six with indolent B-cell lymphoma). More patients and longer follow up is needed to determine the efficacy of FCy and FND protocol. FLAG-IDA (fludarabine, high dose Ara-C, granulocyte colony-stimulating factor, idarubicin) was applied in 16 acute leukaemia patients with poor prognosis including therapy refractory and relapsing cases. Three CR and two PR, one CR and three PR was achieved in nine patients with acute myeloid leukaemia and in seven patients with acute lymphoid leukaemia, respectively. For this reason, despite the short period of remission, this regimen can be recommended to patients who are candidate for stem cell transplantation.
UI - 11697438
AU - Kamaluddin M; McNally P; Breatnach F; O'Marcaigh A; Webb D; O'Dell E;
TI - Scanlon P; Butler K; O'Meara A Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies.
SO - Acta Paediatr 2001 Oct;90(10):1204-7
AD - Department of Haematology Oncology, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland.
Eight consecutive paediatric patients with acute lymphoblastic leukaemia (ALL) (n = 7) and T-cell non-Hodgkin's lymphoma (NHL) (n = 1) presenting within a 5-wk interval were started on a standard induction protocol which included weekly treatment with vincristine for 4 wk. Itraconazole was commenced as antifungal prophylaxis, 1-21 d after the first injection of vincristine. Within 2 to 4 wk, enhanced vincristine neurotoxicity was noted in all patients, abdominal cramps and constipation occurred most frequently, and one patient developed a bowel perforation associated with paralytic ileus. Hyponatraemia associated with SIADH was observed in three patients and four patients developed seizures. An additional patient with B cell NHL developed seizures 5 d after an injection of vincristine. Recovery was complete in all patients and ranged from 2 d to 15 wk. CONCLUSION: The extent and consistency of adverse effects documented in this study support the recommendation that concurrent administration of vincristine and itraconazole should be avoided.
UI - 12091331
AU - Arico M; Valsecchi MG; Conter V; Rizzari C; Pession A; Messina C;
TI - Barisone E; Poggi V; De Rossi G; Locatelli F; Micalizzi MC; Basso G; Masera G Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II.
SO - Blood 2002 Jul 15;100(2):420-6
AD - Onco-Ematologia Pediatrica, Ospedale dei Bambini G. Di Cristina, Palermo, Italy. firstname.lastname@example.org
One hundred ninety-eight children and adolescents were entered in the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-ALL95 study for high-risk acute lymphoblastic leukemia (ALL). Inclusion criteria were poor response to initial prednisone/intrathecal methotrexate (prednisone-poor response [PPR]), resistance to induction therapy, translocation t(9;22), infants with the t(4;11), or CD10(-) ALL. The event-free survival (EFS) rate at 4 years was 56.5% (SE, 3.9%) for the entire group. The overall EFS rate in the current study was significantly better (P =.002) than that obtained in a comparable group of patients treated in the early 1990s in the AIEOP-ALL91 study. In particular, patients with PPR had a 4-year EFS of 61.1% (SE, 4.4%) versus 42.8% (SE, 5.4%) in the ALL 91 study (P =.008). Among PPR patients, those who were PPR-only (60.1%)-that is, they achieved CR and were negative for t(9;22) and t(4;11) translocations-had the best outcomes with this intensive treatment, even when additional adverse features (hyperleukocytosis, T phenotype) were present (4-year EFS, 70.1%; SE, 4.7%). We attribute this improvement to the replacement of 6 alternating blocks of non-cross-resistant drugs with an 8-drug reinduction regimen (Berlin-Frankfurt-Muenster [BFM] protocol II), repeated twice, in the context of a standard BFM-type intensive chemotherapy for high-risk ALL. This modified therapy may lead to high cure rates for patients defined as at high risk for intrinsic resistance to corticosteroids only.
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