National Cancer Institute®
Last Modified: March 1, 2002
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. email@example.com
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.
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. firstname.lastname@example.org
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.
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.
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.
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. email@example.com
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
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.
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.
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.
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.
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.
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.
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.
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
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
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.
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.
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. firstname.lastname@example.org
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.
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.
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. email@example.com
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.
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. firstname.lastname@example.org
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.
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.
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.
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.
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. email@example.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.
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.
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. firstname.lastname@example.org
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.
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
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.
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.
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.