National Cancer Institute®
Last Modified: May 1, 2002
UI - 11960347
AU - Mikhail FM; Serry KA; Hatem N; Mourad ZI; Farawela HM; El Kaffash DM;
TI - Coignet L; Nucifora G AML1 gene over-expression in childhood acute lymphoblastic leukemia.
SO - Leukemia 2002 Apr;16(4):658-68
AD - Department of Clinical Pathology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
The present study was conducted on a series of 41 Egyptian children with newly diagnosed acute lymphoblastic leukemia (ALL) to investigate TEL and AML1 abnormalities. The TEL-AML1 fusion was observed in six patients both by RT-PCR and FISH analyses, with a frequency of 22.2% among the B-lineage group, whereas TEL deletion was seen by FISH analysis in seven patients (17.1%). By FISH analysis, nine patients (22%) showed evidence of extra AML1 copies. In five of these patients the extra copies were due to non-constitutional trisomy 21, whereas in the remaining four cases they were due to tandem AML1 copies on der(21), as evidenced by metaphase FISH. Unexpectedly however, enhanced AML1 expression levels were seen by real-time quantitative RT-PCR in 18 out of the 41 ALL patients (43.9%). This high level of AML1 expression could be an important factor contributing to the pathogenesis and progression of childhood ALL. One key mechanism for over-expression seems to be the extra copies of AML1, but other mechanisms may involve an alteration of the activity of the AML1 promoter. Here, we also report two novel findings. The first is an intragenic deletion of TEL exon 7 in a case of T cell ALL. This deletion creates a frame-shift and results in a truncated protein lacking the C-terminus that includes the ETS domain. This shorter TEL is presumably unable to bind DNA. The second finding is a rearrangement of AML1 in a case of T cell ALL due to t(4;21)(q31;q22). This is the first reported chromosomal translocation where AML1is rearranged in childhood T cell ALL.
UI - 11960348
AU - Jabber Al-Obaidi MS; Martineau M; Bennett CF; Franklin IM; Goldstone AH;
TI - Harewood L; Jalali GR; Prentice HG; Richards SM; Roberts K; Harrison CJ; Medical Research Council Adult Leukaemia Working Party ETV6/AML1 fusion by FISH in adult acute lymphoblastic leukemia.
SO - Leukemia 2002 Apr;16(4):669-74
AD - LRF/UKCCG Karyotype Database in ALL, Department of Haematology, The Royal Free and University College Medical School, London, UK.
Dual-color interphase fluorescence in situ hybridization (FISH) with ETV6 and AML1 probes was used for the first time on a series of 159 adult patients with acute lymphoblastic leukemia (ALL), for detection of the t(12;21)(p13;q22) translocation. Seven patients (4.4%) were found, with 50-100% of positive cells, of whom one of two tested, proved negative for the fusion product by RT-PCR. Two of them, aged 43 and 50 years, are the oldest patients so far confirmed to have the translocation. Three who relapsed at 10, 11 and 24 months, suggest that adults may not enjoy the good short-term prognosis reported for t(12;21)-positive children. Thirty-one-negative cases had signal numbers differing from the two expected for each gene. In 15 cases these results were consistent with the karyotype. In nine cases with uninformative cytogenetics, the numbers were consistent with those for centromeres and indicated a hidden aneuploidy. Loss of ETV6 genes in two cases and AML1 amplification in three others were not suspected from the cytogenetics. In conclusion, FISH proved to be reliable in defining ETV6/AML1 positivity in this group of patients as well as providing valuable insights into negative cases.
UI - 11960354
AU - Salonen MJ; Siimes MA; Salonen EM; Vaheri A; Koskiniemi M
TI - Antibody status to HHV-6 in children with leukaemia.
SO - Leukemia 2002 Apr;16(4):716-9
AD - Haartman Institute, Department of Virology, University of Helsinki, Helsinki, Finland.
Forty children with acute lymphoblastic (33) or myeloid leukaemia (seven) were studied for IgG and IgM antibodies and IgG avidity against human herpesvirus 6 (HHV-6) at the time of diagnosis, and compared with age-, sex- and season-matched children with various neurological diseases of suspected viral origin. Of the children with leukaemia, 97.5% had IgG antibodies and 40% IgM antibodies to HHV-6 compared with 92.3% and 7.7% of reference subjects (P = 0.005). A seronegative child with leukaemia seroconverted 3 weeks after the diagnosis. The avidity of IgG antibodies (based on the resistance to urea treatment) was high in all children with leukaemia. One reference child had HHV-6-specific IgG antibodies with low avidity, which together with his positive IgM indicated an acute infection. The presence of specific IgM antibodies in 40% of children with leukaemia and the high avidity of IgG suggest a reactivation or an inaproppriate primary response to HHV-6 infection. The results support the conclusion of the role of the HHV-6 infection at the onset of childhood leukaemia.
UI - 11960355
AU - Hrusak O; Trka J; Zuna J; Polouckova A; Kalina T; Stary J; Czech
TI - Pediatric Hematology Working Group Acute lymphoblastic leukemia incidence during socioeconomic transition: selective increase in children from 1 to 4 years.
SO - Leukemia 2002 Apr;16(4):720-5
AD - Institute of Immunology, 2nd Medical School, Charles University, Prague, Czech Republic.
Pre-school acute lymphoblastic leukemia (ALL) peak is consistent in developed but not in developing countries and its magnitude apparently correlates with the socioeconomic status. A population-based study describing ALL incidence during socioeconomic transition has been lacking. Central European post-communist countries (with very low foreign migration and centralized statistics) offer reliable data for the period before and during major socioeconomic changes. Population-based data on Czech ALL patients younger than 18 years were taken from two independent Czech national registries partially overlapping in time (1980-1998, n = 1236 and 1991-1999, n = 570). During the 1980s and 1990s, ALL incidence among children 1-4 years increased 1.5 times (P = 0.01). This increase was more prominent in females than in males (slopes 0.13 and 0.09, P values 0.03 and >0.05, respectively). No significant change was observed in other age groups (0, 5-9, 10-14, 15-17 years or all others combined). We discuss possible underlying socioeconomic factors including infant care and breast-feeding, hygiene, birth order, industry and pollution. Moreover, we try to pinpoint the immunophenotypic/molecular-genetic subsets of ALL that might be socioeconomically affected. Selective increase of ALL in children 1-4 years old provides epidemiological evidence that etiology and/or trigger mechanisms are different for a considerable proportion of these children and that these mechanisms are exogenous.
UI - 11960364
AU - van der Burg M; Smit B; Brinkhof B; Barendregt BH; Verschuren MC; Dib M;
TI - Beverloo HB; van Dongen JJ; Langerak AW A single split-signal FISH probe set allows detection of TAL1 translocations as well as SIL-TAL1 fusion genes in a single test.
SO - Leukemia 2002 Apr;16(4):755-61
AD - Dept of Immunology, Erasmus University Rotterdam/University Hospital Rotterdam, The Netherlands.
About 30% of T cell acute lymphoblastic leukemias (T-ALL) carry TAL1 gene aberrations. In the majority of cases (approximately 25%), this concerns a submicroscopic deletion of approximately 90 kb in chromosome region 1p32, which deletes the coding regions of the SIL gene and the untranslated region of the TAL1 gene, thereby placing the TAL1 gene under control of the SIL promoter region. Translocation (1;14)(p32;q11) involving the TAL1 gene occurs at a much lower frequency (3%), whereas some other rare variant translocations have been described as well. In this study we developed a set of TAL1 FISH probes based on the split-signal FISH principle that enables detection of both types of TAL1 gene aberrations in single test. For this purpose, one probe was designed downstream of the TAL1 gene (TAL1-D) and the second probe in the region upstream of the TAL1 gene, partly covering the SIL gene (SIL-U). We show that this split-signal FISH probe set allows reliable detection of the unaffected SIL-TAL1 gene region with a fusion signal, SIL-TAL1 fusion genes with loss of the SIL-U signal, and TAL1 gene translocations with a split-signal, independent of the involved partner gene.
UI - 11960365
AU - Guidal C; Vilmer E; Grandchamp B; Cave H
TI - A competitive PCR-based method using TCRD, TCRG and IGH rearrangements for rapid detection of patients with high levels of minimal residual disease in acute lymphoblastic leukemia.
SO - Leukemia 2002 Apr;16(4):762-4
UI - 11960366
AU - Taub JW; Matherly LH; Ravindranath Y; Kaspers GJ; Rots MG; Zantwijk CH
TI - Polymorphisms in methylenetetrahydrofolate reductase and methotrexate sensitivity in childhood acute lymphoblastic leukemia.
SO - Leukemia 2002 Apr;16(4):764-5
UI - 11902549
AU - Pui C H; Campana D; Evans W E
TI - Childhood acute lymphoblastic leukaemia--current status and future perspectives.
SO - Lancet Oncol 2001 Oct;2(10):597-607
AD - Leukaemia/Lymphoma Division, Fahad Nassar Al-Rashid Chair of Leukaemia Research at St Jude Children's Research Hospital, Memphis, TN 38105, USA. email@example.com
The current cure rate of 80% in childhood acute lymphoblastic leukaemia attests to the effectiveness of risk-directed therapy developed through well-designed clinical trials. In the past decade there have been remarkable advances in the definition of the molecular abnormalities involved in leukaemogenesis and drug resistance. These advances have led to the development of promising new therapeutic strategies, including agents targeted to the molecular lesions that cause leukaemia. The importance of host pharmacogenetics has also been recognised. Thus, genetic polymorphisms of certain enzymes have been linked with host susceptibility to the development of de novo leukaemia or therapy-related second cancers. Furthermore, recognition of inherited differences in the metabolism of antileukaemic agents has provided rational selection criteria for optimal drug dosages and scheduling. Treatment response assessed by measurements of submicroscopic leukaemia (minimal residual disease) has emerged as a powerful and independent prognostic indicator for gauging the intensity of therapy. Ultimately, treatment based on biological features of leukaemic cells, host genetics, and the amount of residual disease should improve cure rates further.
UI - 11699206
AU - Betts DR; Riesch M; Grotzer MA; Niggli FK
TI - The investigation of karyotypic instability in the high-hyperdiploidy subgroup of acute lymphoblastic leukemia.
SO - Leuk Lymphoma 2001 Jun;42(1-2):187-93
AD - Department of Oncology, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland. David.Betts@kispi.unizh.ch
Acute lymphoblastic leukemia (ALL) of childhood has been cytogenetically well characterized, and approximately 25% of cases will have a high-hyperdiploid (51-68) chromosome complement. In a 5 year period a consecutive series of 152 presentation ALL's were karyotyped. In all cases a result was obtained and 138 (91%) had a detectable abnormal clone of which 44 (29%) were high-hyperdiploid. Within the high-hyperdiploidy group karyotypic cell to cell variation was observed in many cases. To provide further evidence of this phenomenon a dual-color fluorescence in-situ hybridization (FISH) experiment was performed on stored fixed suspension from 14 ALL's with such a karyotype. In each case 4-6 probes were investigated, employing probes to centromeres of chromosomes X, 4, 6, 8, and 10 and a locus specific probe to chromosome 21q22. It was found that the FISH produced results that were generally in good agreement with the G-banding findings and supported the notion of karyotypic cell to cell variation. FISH further showed that most of cases would have two extra copies of chromosome 21 in the majority of leukemic cells and a single extra copy in the minority. A further finding was that fewer cells contained extra copies of chromosomes 6, 8 and 10 than was expected based on the comparison of the signal number of the other probes investigated. In contrast chromosomes X, 4, and 21 seldom displayed this feature. We have demonstrated that karyotypic instability as defined by karyotypic cell to cell variation is a feature of the high-hyperdiploid subgroup in childhood ALL. It is questioned whether the underlying defect resulting in the observed karyotypic instability of this subgroup is one of the primary causative events in the formation of the leukemia.
UI - 11699220
AU - Uckun FM; Pallisgaard N; Hokland P; Navara C; Narla R; Gaynon PS; Sather
TI - H; Heerema N Expression of TEL-AML1 fusion transcripts and response to induction therapy in standard risk acute lymphoblastic leukemia.
SO - Leuk Lymphoma 2001 Jun;42(1-2):41-56
AD - Children's Cancer Group ALL Biology Reference Laboratory, Parker Hughes Institute, 2665 Long Lake Road, Suite 300, St. Paul, MN 55113, USA.
We prospectively examined the frequency of the t(12;21)TEL-AML1 fusion in 504 children with newly diagnosed standard risk ALL using RT-PCR assays. Cells from 95 patients (18.8%) were TEL-AML1+. There was a significantly higher frequency of pseudodiploidy among the TEL-AML1+ cases (39.4% versus 14.1%, P = 0.001), primarily because structural abnormalities involving 12p and del(6q) occurred more frequently in the TEL-AML1+ group. TEL-AML1+ ALL was more sensitive to the induction chemotherapy than TEL-AML1- ALL. The percentage of "rapid early responders", i.e., patients who achieved an M1 (< 5% blasts) or M2 (5-25% blasts) marrow status on day 7 of induction chemotherapy, was significantly higher among TEL-AML1+ cases. The quality of remission of RT-PCR positive cases was excellent, as evidenced by the very low to absent MRD burden of their end-of-induction bone marrow specimens. TEL-AML1+ patients also had an excellent early EFS outcome. The probability of EFS at 30 months from study entry were 98.9 +/- 1.0% for the TEL-AML1+ group and 92.1 +/- 1.5% for the TEL-AML1- group (P = 0.0001). This prospective study significantly expands the knowledge gained from previous studies regarding the prognostic significance of t(12;21)TEL-AML1 fusion in pediatric ALL.
UI - 11699224
AU - Firat H; Favier R; Adam M; Leverger G; Landman-Parker J; Cayre Y; Douay
TI - L Determination of myeloid antigen expression on childhood acute lymphoblastic leukaemia cells: discrepancies using different monoclonal antibody clones.
SO - Leuk Lymphoma 2001 Jun;42(1-2):75-82
AD - Service d'Hematologie Biologique, Hopital d'enfants Armand Trousseau, 26 Avenue du Docteur Arnold Netter, 75571 Paris, France.
Prospective clinical studies including large numbers of patients have led to the conclusion that co-expression of myeloid antigens in childhood acute lymphoblastic leukaemia (My+ ALL) does not have prognostic significance. However, reports of the frequency of My+ ALL in children vary widely across laboratories using different mAb clones and staining and analysing procedures. Taking two commonly accepted thresholds of positivity for myeloid antigens (20 and 30%), we analysed the immunoreactivity of the most widely employed mAb clones against CD13 (SJ1D1, L138 and My7) and CD33 (My9, P67.6 and D3HL60) and compared the proportions of My+ ALL detected by these clones in childhood ALL. The correlation between myeloid antigen expression and the presence of the t(12;21) translocation was analysed concomitantly in the same samples. The percentage of ALL cases positive for myeloid markers varied significantly depending on the mAb clone and the positive threshold. Among patients with B-ALL, the proportion of CD13+ ALL was significantly lower using SJ1D1 than using L138 or My7, while the proportion of CD33+ ALL was significantly higher for My9 than for P67.6 or D3HL60. Analysis of the co-expression of CD13 and CD33 on B-ALL cells using combinations of mAb clones showed that this frequency was either underestimated by the SJ1D1/D3HL60 or overestimated by the L138/P67.6 and My7/My9 combinations. A correlation between CD13/CD33 positivity and the t(12;21) translocation was uniformly observed in B-ALL patients for a positive threshold of 30%, whereas SJ1D1/D3HL60 detected no correlation between t(12;21) and CD13/CD33 positivity when the threshold was lowered to 20%. These data show that the mAb clones commonly used to detect the CD13 and CD33 surface antigens have variable immunoreactivity against childhood ALL cells, which may partly explain the conflicting reports concerning the prognostic significance of myeloid antigen expression in paediatric ALL and its association with different translocations. The present findings may also be of clinical importance for therapeutic choices.
UI - 11861265
AU - Gleissner B; Gokbuget N; Bartram CR; Janssen B; Rieder H; Janssen JW;
TI - Fonatsch C; Heyll A; Voliotis D; Beck J; Lipp T; Munzert G; Maurer J; Hoelzer D; Thiel E; German Multicenter Trials of Adult Acute Lymphoblastic Leukemia Study Group Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis.
SO - Blood 2002 Mar 1;99(5):1536-43
AD - Department of Hematology, Oncology, and Transfusion Medicine, University Hospital Benjamin Franklin, Free University of Berlin, Germany. firstname.lastname@example.org
The BCR-ABL fusion, the molecular equivalent of the Philadelphia translocation, gains importance for treatment stratification in adult acute lymphoblastic leukemia (ALL). In this prospective study, samples from 478 patients with CD10(+) B-cell precursor ALL (c-ALL and pre-B ALL) underwent BCR-ABL reverse transcription-polymerase chain reaction (RT-PCR) analysis with double testing of positive samples. Patients were stratified according to the PCR result and treated in 2 German Multicenter Trials of Adult ALL. The outcome was followed and the prognostic impact of BCR-ABL was compared to clinical risk features. Of the 478 samples, 432 had an evaluable BCR-ABL result. Thirty-seven percent of the c-ALL and pre-B ALL patients were BCR-ABL(+) (p190, 77%; p210, 20%; simultaneous p190/p210, 3%). BCR-ABL positivity was associated with the high-risk features of older age (45 years versus 30 years median age; P =.0001) and higher white blood cell counts (23 500/microL versus 11 550/microL; P =.0001). Univariate and multivariate analyses revealed BCR-ABL as the leading factor for a poor prognosis (P =.0001) in comparison to clinical risk criteria. Irrespective of the breakpoint, presence of any BCR-ABL transcript predicted a lower chance of initial treatment response (68.4% versus 84.6%; P =.001) and a lower probability of disease-free survival at 3 years (0.13 versus 0.47; P =.0001). This bad outcome was not influenced by postinduction high-dose treatment stratifications. The results show a high prevalence of BCR-ABL fusion transcripts with predominance of p190. BCR-ABL RT-PCR is confirmed as a sensitive, rapid method to diagnose t(9;22), and p190 and p210 are unequivocally demonstrated as the most important predictors of poor long-term survival despite intensified chemotherapy.
UI - 11916514
AU - Scrideli CA; Kashima S; Cipolloti R; Defavery R; Bernardes JE; Tone LG
TI - Minimal residual disease in Brazilian children with acute lymphoid leukemia: comparison of three detection methods by PCR.
SO - Leuk Res 2002 May;26(5):431-8
AD - Departamento de Pediatria and Puericultura, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
The minimal residual disease (MRD) detection by the polymerase chain reaction (PCR) in children with acute lymphoblastic leukemia has been pointed to be an adverse prognostic factor. Detection methods based on this technique using clone-specific primers are cumbersome and time consuming. The detection of monoclonal gene rearrangements of gamma T-cell receptors (TCRgamma) is a simpler although less sensitive method. In the present study, we analyzed the presence of MRD during four different phases of treatment (week 4; 3-6, 12-24 months, and end of treatment) in 34 Brazilian children with lymphoid leukemia by three detection methods based on the PCR technique: (1) using consensus primers for the detection of a clonal population for TCRgamma; (2) clone-specific primers for the junctional region of TCRgamma; and (3) a semi-nested reaction with an initial cycle with consensus primers followed by a second cycle with clone-specific primers. MRD presence was associated with a shorter event-free survival and was the major independent prognostic factor in most of the phases analyzed. The use of consensus primers for the detection of TCRgamma clonality, although less sensitive, proved to be a simpler, faster and less costly method whose positivity was associated with more than 90% relapse rates during all phases analyzed.
UI - 11846198
AU - Myoken Y; Sugata T; Kyo T; Fujihara M; Mikami Y
TI - Itraconazole prophylaxis for invasive gingival aspergillosis in neutropenic patients with acute leukemia.
SO - J Periodontol 2002 Jan;73(1):33-8
AD - Department of Oral Surgery, Hiroshima Red Cross and Atomic Bomb Survivors Hospital, Japan. email@example.com
BACKGROUND: Due to an increasing number of leukemic patients with invasive gingival aspergillosis during neutropenia (neutrophils <500 cells/microl for >10 days), we evaluated the efficacy of oral itraconazole prophylaxis for preventing this invasive infection at our hospital. METHODS: This was a retrospective, non-randomized study to analyze the onset of identified invasive gingival aspergillosis among 536 patients with acute leukemia at risk due to the presence of neutropenia from 1991 to 1998. Patients received itraconazole capsules levels at day 10 were measured in some patients. RESULTS: In the 39 invasive gingival aspergillosis were detected in 192 high risk patients with 469 episodes of neutropenia (7.8% of the high risk patients). 100 mg/day, there was a dramatic decrease in the infections resulting in 3 of 198 high risk patients with 511 episodes of neutropenia (1.5% of 1998, using itraconazole prophylaxis at 200 mg/day, no cases of the infection were observed in the 146 high risk patients with 380 episodes of neutropenia. The incidence of invasive gingival aspergillosis was significantly lower among patients administered itraconazole than among those without itraconazole (100 mg/day; P = 0.006 and 200 mg/day; P = 0.001). The mean itraconazole serum level in 20 patients receiving 100 mg/day was 71.78 ng/mL and in 16 patients receiving 200 mg/day was 202.67 ng/ml. CONCLUSIONS: These findings suggest that oral itraconazole could be effective for preventing invasive gingival aspergillosis in neutropenic patients with acute leukemia and warrants further randomized investigation.
UI - 11808713
AU - Perrillat F; Clavel J; Jaussent I; Baruchel A; Leverger G; Nelken B;
TI - Philippe N; Schaison G; Sommelet D; Vilmer E; Bonaiti-Pellie C; Hemon D Family cancer history and risk of childhood acute leukemia (France).
SO - Cancer Causes Control 2001 Dec;12(10):935-41
AD - Institut National de la Sante et de la Recherche Medicale, INSERM U170, Villejuif, France.
OBJECTIVE: A case-control study was carried out to investigate the role of a family history of solid tumor or hematologic neoplasm in the etiology of childhood acute leukemia. METHODS: Family cancer history in first- and second-degree relatives was compared in 279 incident cases (242 cases of acute lymphocytic leukemia and 37 of acute myeloid leukemia) and 285 controls. Recruitment was stratified by age, gender, hospital, area of residence, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. RESULTS: A significant association between childhood acute leukemia and a family history of hematologic neoplasm (OR = 2.7, confidence interval (CI) = 1.1-6.9) was found. This association was particularly clear-cut when the cases were restricted to acute myeloid leukemia (OR = 13.3, CI = 2.5-70.9). Childhood acute leukemia was associated with a family history of solid tumor (OR = 1.5, CI = 1.0-2.2), and elevated odds ratios were observed for family history of gastrointestinal cancer and melanoma. Those results are most unlikely to be explained by socioeconomic status and familial structure, which were very similar for the cases and controls. Differential misclassification is also unlikely for the first-degree relatives, even though it is difficult to rule it out for the second-degree relatives' history. CONCLUSION: The present study supports the hypothesis that a family history of cancer may be a risk factor for childhood acute leukemia.
UI - 11877265
AU - Dworzak MN; Froschl G; Printz D; Mann G; Potschger U; Muhlegger N;
TI - Fritsch G; Gadner H; Austrian Berlin-Frankfurt-Munster Study Group Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia.
SO - Blood 2002 Mar 15;99(6):1952-8
AD - Children's Cancer Research Institute, St Anna Kinderspital, Kinderspitalgasse 6, A-1090 Vienna, Austria. firstname.lastname@example.org
Detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) predicts outcome. Previous studies were invariably based on relative quantification and did not investigate sample-inherent parameters that influence test accuracy, which makes comparisons and clinical conclusions cumbersome. Hence, we conducted a prospective, population-based MRD study in 108 sequentially recruited children with ALL uniformly treated with the ALL-Berlin-Frankfurt-Munster (ALL-BFM) 95 protocol in Austria (median follow-up of 40 months). Using sensitive, limited antibody panel flow cytometry applicable to 97% of patients, we investigated 329 bone marrow samples from 4 treatment time points. MRD was quantified by blast percentages among nucleated cells (NCs) and by absolute counts (per microliter). Covariables such as NC count, normal B cells, and an estimate of the test sensitivity were also recorded. Presence and distinct levels of MRD correlated with a high probability of early relapse at each of the time points studied. Sequential monitoring at day 33 and week 12 was most useful for predicting outcome independently from clinical risk groups: patients with persistent disease (> or =1 blast/microL) had a 100% probability of relapse, compared to 6% in all others. Absolute MRD quantification was more appropriate than relative, due to considerable variations in total NC counts between samples. Regeneration of normal immature B cells after periods of rest from treatment limited the test sensitivity. In conclusion, MRD detection by flow cytometry is a strong and independent outcome indicator in childhood ALL. Standardization regarding absolute quantification on the basis of NCs and assessment during periods of continuous treatment promise to increase the accuracy, simplicity, and cost efficiency of the approach.
UI - 11902139
AU - Reid AG; Huntly BJ; Hennig E; Niederwieser D; Campbell LJ; Bown N;
TI - Telford N; Walker H; Grace CD; Deininger MW; Green AR; Nacheva EP Deletions of the derivative chromosome 9 do not account for the poor prognosis associated with Philadelphia-positive acute lymphoblastic leukemia.
SO - Blood 2002 Mar 15;99(6):2274-5
UI - 11964928
AU - Infante-Rivard C; Krajinovic M; Labuda D; Sinnett D
TI - Childhood acute lymphoblastic leukemia associated with parental alcohol consumption and polymorphisms of carcinogen-metabolizing genes.
SO - Epidemiology 2002 May;13(3):277-81
AD - Joint Department of Epidemiology and Biostatistics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. email@example.com
BACKGROUND: Limited information is available on the association of parental consumption of alcohol prior to and during pregnancy with the risk of childhood leukemia, as well as for the potentially modifying role of genetic polymorphisms. METHODS: We conducted a population-based, case-control study of 491 incident cases of acute lymphoblastic leukemia age 0-9 years and matched on age and sex to 491 healthy controls. Cases were identified at tertiary care centers in the Province of Quebec between 1980 and 1993. Each parent was interviewed separately about alcohol consumption habits. We also used a case-only design with 186 cases to estimate interaction odds ratios between prenatal exposure and child DNA variants in the GSTM1 and CYP2E1 genes. RESULTS: The adjusted odds ratio for any maternal consumption during pregnancy was 0.7 (95% confidence interval = 0.5-0.9). The interaction odds ratios for the GSTM1 null genotype during third pregnancy trimester was 2.4 (95% confidence interval = 1.1-5.4); the interaction odds ratio for CYP2E1 variant G-1295C (or allele *5) during the nursing period was 4.9 (95% confidence interval = 1.5-16.7). CONCLUSIONS: The observed association with maternal alcohol consumption during pregnancy could be due to the potential chemopreventive effects of flavonoids found in wine and beer. These possible effects of alcohol may be at least partially genetically determined, although data are preliminary.
UI - 11954028
AU - Dahmoush L; Hijazi Y; Barnes E; Stetler-Stevenson M; Abati A
TI - Adult T-cell leukemia/lymphoma: a cytopathologic, immunocytochemical, and flow cytometric study.
SO - Cancer 2002 Apr 25;96(2):110-6
AD - National Institutes of Health/National Cancer Institute, Section of Cytopathology, Bethesda, Maryland 20892, USA.
BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a postthymic lymphoproliferative neoplasm of T cells caused by human T-cell lymphotropic virus (HTLV-1). Most cases are found in Japan, the Caribbean basin, and West Africa. DESIGN: To identify diagnostic parameters for cytology in this neoplasm, the authors undertook a retrospective review of all ATLL samples from 1990 to 2000. RESULTS: One hundred fourteen samples from 34 patients with the diagnosis of ATLL were reviewed: 80 cerebrospinal fluids, 7 pleural effusions, 4 bronchoalveolar lavages, 2 peritoneal effusions as well as fine-needle aspirations of 15 lymph nodes, 4 subcutaneous lesions, and 2 breast nodules. Twenty-one patients were women and 13 were men, with an age range of 30 to 71 years. Morphologically, all specimens were characterized by the presence of a polymorphous population of lymphocytes ranging from small bland-appearing lymphocytes to large atypical ones with bizarre, multilobulated nuclei (flower-like or clover leaf cells) with coarse chromatin and prominent nucleoli. The cytoplasm was deeply basophilic with occasional vacuoles. Immunocytochemistry was performed on 17 specimens from 14 patients. In all cases tested, tumor cells were immunoreactive for CD3, CD4, CD5, and CD25 and were nonimmunoreactive for CD7 and CD8. Flow cytometry was performed on 12 specimens from 9 patients. The tumor cells in all cases tested were positive for CD2, CD3, CD4, CD5, and CD25 and were negative for CD7. CONCLUSIONS: Despite the polymorphous nature of ATLL, diagnosis can be established by close attention to nuclear cytologic features in conjunction with ancillary studies such as immunocytochemistry and/or flow cytometry. Copyright 2002 American Cancer Society.
UI - 11952819
AU - Nordgren A; Heyman M; Sahlen S; Schoumans J; Soderhall S; Nordenskjold
TI - M; Blennow E Spectral karyotyping and interphase FISH reveal abnormalities not detected by conventional G-banding. Implications for treatment stratification of childhood acute lymphoblastic leukaemia: detailed analysis of 70 cases.
SO - Eur J Haematol 2002 Jan;68(1):31-41
AD - Department of Molecular Medicine, Karolinska Institutet, L8-02 Karolinska Hospital, SE-17176 Stockholm, Sweden. firstname.lastname@example.org
Seventy uniformly treated children with acute lymphoblastic leukemia were analysed for chromosomal abnormalities with conventional G-banding, spectral karyotyping (SKY) and interphase fluorescent in situ hybridisation (FISH) using probes to detect MLL, BCR/ABL, TEL/AML1 rearrangements and INK4 locus deletions. Numerical and/or structural changes could be identified in 80% of the patients by the use of molecular cytogenetic techniques, whereas abnormalities could be detected in 60% of the patients using G-banding alone. Altogether, 106 structural aberrations were defined by FISH compared to 34 using G-banding. Seventy-four percent of the patients had numerical aberrations, 54% structural aberrations and 20% had no identified aberrations. Twelve cases had prognostically unfavourable chromosomal aberrations that had not been detected in the G-banded analysis. We identified three novel TEL partner breakpoints on 1q41, 8q24 and 21p12, and a recurrent translocation t(1;12)(p32;p13) was found. In addition, two cases displayed amplification (7-15 copies) of AML1. Our results demonstrate the usefulness of SKY and interphase FISH for the identification of novel chromosome aberrations and cytogenetic abnormalities that provide prognostically important information in childhood ALL.
UI - 11878571
AU - Pui CH
TI - Risk assessment in acute lymphoblastic leukemia: beyond leukemia cell characteristics.
SO - J Pediatr Hematol Oncol 2001 Oct;23(7):405-8
AD - St. Jude Children's Research Hospital, and University of Tennessee, Memphis, USA.
UI - 11878574
AU - Gump J; McGavran L; Wei Q; Hunger SP
TI - Analysis of TP53 mutations in relapsed childhood acute lymphoblastic leukemia.
SO - J Pediatr Hematol Oncol 2001 Oct;23(7):416-9
AD - Department of Pediatrics, University of Colorado School of Medicine, Denver, USA.
TP53 is the most commonly mutated gene in human cancer, but TP53 mutations are present in less than 5% of children with acute lymphoblastic leukemia (ALL) at initial presentation. Mutations are detected more frequently in children with relapsed T-cell ALL, but the potential role of TP53 mutations in relapsed B-lineage childhood ALL is not understood as well. The authors determined the nucleotide sequence of amplified DNA from exons 5 to 8 of the TP53 gene in leukemic cells obtained from 17 children with ALL at the time of first bone marrow relapse. All 17 contained only germline TP53 sequences. Review of the published literature disclosed that TP53 mutations have been found in 22% of cases of relapsed ALL. To understand the role of p53 abnormalities in this clinical setting, it will be important for future studies to analyze cases of relapsed ALL with assays capable of interrogating the functional integrity of the p53 pathway.
UI - 11918540
AU - Lee S; Kim DW; Kim YJ; Park YH; Min CK; Lee JW; Min WS; Kim CC
TI - Influence of karyotype on outcome of allogeneic bone marrow transplantation for adults with precursor B-lineage acute lymphoblastic leukaemia in first or second remission.
SO - Br J Haematol 2002 Apr;117(1):109-18
AD - Catholic Hemopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
The prognostic relevance of karyotype has been established in adult acute lymphoblastic leukaemia (ALL) patients treated with chemotherapy but not definitively evaluated in an allogeneic bone marrow transplantation (BMT) setting. To determine the factors affecting the outcome of allogeneic BMT for adults with precursor B-lineage ALL in first or second complete remission (CR), a total of 41 consecutive patients with a successful karyotype were enrolled in this study. There were 21 men and 20 women with a median age of 27 (15-43) years. The distribution of French-American-British (FAB) subtypes was as follows: L1 (n = 26), L2 (n = 15). Unfavourable karyotypes (n = 12) were defined as Ph+ or t(4;11). Disease status at the time of transplant was first CR (n = 35) or second CR (n = 6). With a median follow-up of 36 months, the 3-year probabilities of relapse and disease-free survival (DFS) were 36.3 +/- 8.4% and 57.3 +/- 8.4% respectively. Potential variables predicting worse relapse and DFS were FAB subtype (L2), extramedullary involvement, pre-BMT status (second CR), unfavourable karyotype and type of graft-versus-host disease (GVHD). Further multivariate analysis showed that karyotype and pre-BMT status were independently associated with relapse and DFS. In addition, chronic GVHD was found to be significantly associated with a lower relapse rate.
UI - 11996453
AU - Kulkarni AG
TI - Acute lymphoblastic leukemia presenting as breast mass.
SO - J Assoc Physicians India 2001 Dec;49():1213-4
UI - 12015077
AU - Wan S; Gong W; Sun X; Xu J; Tian D
TI - [Immunophenotyping of eighty six children with acute lymphoblastic leukemia by three-color flow cytometry]
SO - Zhonghua Xue Ye Xue Za Zhi 2002 Feb;23(2):83-6
AD - Department of Hematology, Xuanwu Hospital, CUMS, Beijing 100053, China.
OBJECTIVES: To evaluate the specificity of three-color flow cytometry in childhood acute lymphoblastic leukemia (ALL) immunophenotyping. METHODS: Immunophenotyping was performed by three-color flow cytometry analysis using CD(45)/SSC gating. RESULTS: The percentage of blasts was correlated better with leukemic cell count compared with that of FSC/SSC, and the false positive results were low. Among eighty six cases of ALL, 95.3% was B-ALL, in which common-ALL and Pro-B-ALL were 76.8% and 6.1%, respectively, and 2.3% was T-ALL. CD(34)(+) and myeloid-associated antigen expression were observed in 57.0% and 34.9% of the cases, respectively, among which Pro-B-ALL was the commonest. CD(33) was more commonly expressed than CD(13) in Pro-B-ALL cases, but no difference in the expression between these two antigens in other subtypes. CONCLUSION: Gating of CD(45)/SSC eliminated effection of normal cells to blasts in bone marrow, with which the immunophenotyping results were more reliable.
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