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- Albin, Maria, et al.
(author)
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Acute myeloid leukemia and clonal chromosome aberrations in relation to past exposure to organic solvents
- 2000
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In: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 26:6, s. 482-491
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The effects of occupational and leisure-time exposures on the risk of acute myeloid leukemia (AML) were investigated with emphasis on clonal chromosome aberrations (CCA) and morphological subtypes. METHODS: Consecutively diagnosed cases of AML (N=333) and 1 population referent per case were retrospectively included in the study. Information on worktasks, companies, and leisure-time activities was obtained with telephone interviews. Exposure probability and intensity were assessed by occupational hygienists. Associations were evaluated with logistic regression. RESULTS: Exposure to organic solvents was associated with an increased risk of AML [low exposure: OR 1.5 (95% confidence interval (95% CI) 1.0-2.3, moderate-high exposure: OR 2.3 (95% CI 1.0-5.0)]. For exposure to solvents, but not to benzene, the OR was 1.2 (95% CI 0.69-2.0) for "low" and 2.7 (95% CI 1.0-7.3) for "moderate-high" exposure. The observed effects increased with intensity and duration of exposure. The estimated effects were higher for patients >60 years of age at the time of diagnosis. The effect of exposure to organic solvents was not differential with regard to morphology [except possibly erythroleukemia: OR 4.2, 95% CI 1.0-17 or the presence of CCA in general]. No increased risk for AML with complex CCA or with total or partial losses of chromosomes 5 or 7 were observed, but a higher risk was found for AML with trisomy 8 (OR 11, 95% CI 2.7-42) as the sole aberration. CONCLUSIONS: Exposure to organic solvents was associated with an increased risk of AML. This association was not due to benzene exposure alone and may be modified by age. Furthermore, specific associations with trisomy 8, and possibly also erythroleukemia, were suggested.
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- Andersson, Anna, et al.
(author)
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Paired multiplex reverse-transcriptase polymerase chain reaction (PMRT-PCR) analysis as a rapid and accurate diagnostic tool for the detection of MLL fusion genes in hematologic malignancies
- 2001
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In: Leukemia. - 1476-5551. ; 15:8, s. 1293-1293
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Journal article (peer-reviewed)abstract
- The MLL gene in chromosome band 11q23 is frequently rearranged in acute lymphoblastic and acute myeloid leukemias. To date, more than 50 different chromosomal regions are known to participate in translocations involving 11q23, many of which affect MLL. The pathogenetically important outcome of these rearrangements is most likely the creation of a fusion gene consisting of the 5' part of the MLL gene and the 3' end of the partner gene. Although abnormalities of the MLL gene as such are generally associated with poor survival, recent data suggest that the prognostic impact varies among the different fusion genes generated. Hence, detection of the specific chimeric gene produced is important for proper prognostication and clinical decision making. We have developed a paired multiplex reverse-transcriptase polymerase chain reaction analysis to facilitate a rapid and accurate detection of the most frequent MLL fusion genes in adult and childhood acute leukemias. To increase the specificity, two sets of primers were designed for each fusion gene, and these paired primer sets were run in parallel in two separate multiplex one-step PCR reactions. Using the described protocol, we were able to amplify successfully, in one single assay, the six clinically relevant fusion genes generated by the t(4;11)(q21;q23) [MLL/AF4], t(6;11)(q27;q23) [MLL/AF6], t(9;11)(p21-22;q23) [MLL/AF9], t(10;11)(p11-13;q23) [MLL/AF10], t(11;19)(q23;p13.1) [MLL/ELL], and t(11;19)(q23; p13.3) [MLL/ENL] in cell lines, as well as in patient material.
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3. |
- Billstrom, R., et al.
(author)
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Acute myeloid leukemia with inv(16)(p13q22) : Involvement of cervical lymph nodes and tonsils is common and may be a negative prognostic sign
- 2002
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In: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 71:1, s. 15-19
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) with inv(16)(p13q22) or the variant t(16,16)(p13,q22), is strongly associated with the FAB subtype M4Eo. A high incidence of CNS involvement was reported in the 1980s, but otherwise little is known about the pattern of extamedullary leukemia (EML) manifestations in this AML type. We have compiled clinical and cytogenetic data on 27 consecutive AML cases with inv(16)/t(16,16) from southern Sweden. In general, these AMLs displayed the clinical features that have previously been described as characteristic for this disease entity: low median age, hyperleukocytosis, M4Eo morphology, and a favorable prognosis. However, CNS leukemia was only seen in relapse in one patient diagnosed in 1980, whereas the most common EML manifestation in our series was lymphadenopathy (5/27, 19%), most often cervical with or without gross tonsillar enlargement. A review of previously published, clinically informative cases corroborates that lymphadenopathy, with preference for the cervical region, is the most common EML at diagnosis in inv(16)-positive AML (58/175, 33%). CNS leukemia, on the other hand, has been reported in only 17% of the cases, mostly in the relapse setting, with a diminishing frequency over time, possibly due to protective effects of high-dose cytarabine. Other reported EML sites include the scalp, ovaries, and the intestine. Cervicotonsillar EML was in our series associated with a shorter duration of first remission, (P< 0.05), and may hence prove to be an important clinical parameter when deciding treatment strategies in AML with inv(16)/t(16,16). © 2002 Wiley-Liss, Inc.
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4. |
- Billstrom, R, et al.
(author)
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Poor survival in t(8;21) (q22;q22)-associated acute myeloid leukaemia with leukocytosis
- 1997
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In: European Journal of Haematology. - 1600-0609. ; 59:1, s. 47-52
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Journal article (peer-reviewed)abstract
- Twenty-nine consecutive cases with a t(8;21)(q22;q22) in the bone marrow (BM) karyotype were retrospectively studied concerning clinical, morphological and cytogenetic data. All had been diagnosed as acute myeloid leukaemia (AML), 27 FAB subtype M2 and two M1, comprising 5% of all cytogenetically analysed AML during 18 yr. Auer rods were the most consistent t(8;21)-associated morphological finding and were demonstrated in 92% of the reviewed BM specimens, whereas BM eosinophilia was seen in only 24%. The median age was 53 yr, and 30% of the patients were > 60 yr old. Twenty-four patients had received induction chemotherapy; 22 of these (91%) entered a complete remission (CR). The median survival time in treated patients was 18 months. Leukocytosis at diagnosis (> or = 20 x 10(9)/1) was significantly (p = 0.01) associated with shorter survival time. All four children are still in first CR after 9-80 months. Seven cases (25%) developed granulocytic sarcomas, discovered either at diagnosis (n = 4) or at first relapse (n = 3). Secondary chromosome abnormalities were found in 62% of the cases, most often loss of a sex chromosome. The presence of such secondary aberrations did not correlate with any morphological or clinical characteristics, including survival. This first Scandinavian study of AML with t(8;21) corroborates the previous findings that these AMLs are characterized by distinct morphological features, a high frequency of CR and a striking tendency to develop extramedullary leukaemic manifestations. Leukocytosis at diagnosis indicates a less favourable prognosis.
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- Johansson, B, et al.
(author)
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Abberant cytogenetic evolution pattern of Philadelphia-positive chronic myeloid leukemia treated with interferon-alpha
- 1996
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In: Leukemia. - 1476-5551. ; 10:7, s. 1134-1138
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Journal article (peer-reviewed)abstract
- The cytogenetic evolution of 32 Philadelphia (Ph)-positive chronic myeloid leukemias (CML) receiving interferon-alpha (IFN-alpha) therapy was compared to the patterns in untreated CML and cases treated with busulfan (Bu), hydroxyurea (Hy), and allogeneic bone marrow transplantation (BMT). Half of the CML receiving IFN-alpha had at least one of the well-known major or minor route aberrations whereas 16 cases displayed unusual secondary abnormalities, of which only del(7p) and del(13q) were recurrent; a frequency significantly higher than in CML without therapy or after Bu and Hy treatment (P < 0.001) but similar to the one found post-BMT. The incidence of cases with cytogenetically divergent subclones, ie cell populations with unrelated aberrations in addition to the t(9;22), was also higher in the IFN-alpha group compared to the untreated, Bu and Hy groups (P < 0.01) but similar to the post-BMT group. Finally, 14 of the 32 IFN-alpha-treated CML displayed cytogenetic evolution already during the chronic phase; again a higher incidence than in the untreated, Bu and Hy groups (P < 0.001) but not different from the post-BMT group. These findings strongly indicate that IFN-alpha, directly or indirectly, can induce clones with aberrant chromosomal evolution patterns to evolve and proliferate, but the mechanisms underlying these cytogenetic peculiarities remain to be elucidated.
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8. |
- Juliusson, Gunnar, et al.
(author)
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Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.
- 2006
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 20:1, s. 42-47
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Journal article (peer-reviewed)abstract
- Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention ( RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region ( range 36-76%) and the two-year overall survival, with no censored observations (6-21%) ( v 2 for trend = 11.3, P < 0.001; r(2) = 0.86, P < 0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates ( P = 0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.
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10. |
- Lazarevic, Vladimir, et al.
(author)
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Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience
- 2014
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In: Blood Cancer Journal. - London, United Kingdom : Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group. - 2044-5385. ; 4:e188
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Journal article (peer-reviewed)abstract
- The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8; 21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with greater than= 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients less than80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both Pless than0.001), followed by sex (P = 0.0135) and a karyotype including - 7/del(7q) (P = 0.048).
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11. |
- Mauritzson, Nils, et al.
(author)
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A single-center population-based consecutive series of 1500 cytogenetically investigated adult hematological malignancies: karyotypic features in relation to morphology, age and gender
- 1999
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In: European Journal of Haematology. - 1600-0609. ; 62:2, s. 95-102
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Journal article (peer-reviewed)abstract
- During the 18-yr period 1976-93, a population-based series of 1586 adults with suspected or confirmed hematological malignancies were successfully cytogenetically investigated at a single center. Eighty-six cases were excluded due to unretrievable medical records or if analyzed only in remission or at relapse. The remaining 1500 medical records were reviewed regarding morphology and clinical parameters in order to investigate possible associations between karyotypic pattern (normal, 1, 2 or complex anomalies; specific abnormalities) and gender, age and morphological subgroups. The impact of time-period, i.e. 1976-87 vs. 1988-93, and referring center on cytogenetic findings was also studied. A total of 372 acute myeloid leukemias (AML), 389 myelodysplastic syndromes (MDS), 64 acute lymphoblastic leukemias (ALL) and 262 chronic myeloid leukemias (CML) were identified, altogether 1087 cases. Patients with other (n=261) or no hematological malignancies (n = 152) were excluded from the present analysis. Cytogenetic abnormalities were detected in 52% AML, 51 % MDS, 68% ALL and 97% CML, frequencies that did not differ significantly between the 2 time periods or referring centers. No significant age- or gender-related differences in karyotypic patterns were discerned in AML, MDS, ALL or CML, whereas the karyotypic patterns varied among the FAB groups in both AML (p= 0.001) and MDS (p < 0.001). The specific abnormalities t(8;21), t(15;17) and inv(16) were more common (p < 0.001) in younger AML patients and 5q- was more frequent in females with MDS (p<0.001). These findings indicate, in contrast to previous series, that neoplasia-associated karyotypic aberrations are not more common among older patients or in males.
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12. |
- Mauritzson, Nils, et al.
(author)
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Survival time in a population-based consecutive series of adult acute myeloid leukemia--the prognostic impact of karyotype during the time period 1976-1993
- 2000
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In: Leukemia. - 1476-5551. ; 14:6, s. 1039-1043
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Journal article (peer-reviewed)abstract
- A consecutive population-based series of 372 adult acute myeloid leukemias, successfully cytogenetically investigated at a single center between 1976 and 1993, is reported. All medical records were reviewed in order to ascertain the prognostic impact of karyotype, divided into three groups; favorable (t(8;21), t(15;17), and inv(16) irrespective of karyotypic complexity; n = 40), poor (der(1;7), inv(3), -5, del(5q), -7, t(9;22), and complex karyotypes including whole or partial losses of chromosomes 5 and/or 7; n = 56), and intermediate (other abnormalities or normal karyotype; n = 276). The possible modification by age, gender, time period, morphologic subtype, and bone marrow transplantation (BMT) on this prognostic impact was also determined. The chemotherapy regimens used were heterogeneous over time but principally the same at any given point in time. The majority of the patients were treated with combinations including an anthracycline and cytarabine with curative intent. Gender, morphology, and BMT did not significantly modify the effect of cytogenetic patterns on survival time, whereas age and time period did. The hazard ratios for the subgroups favorable, intermediate, and poor were 1.0, 1.2 and 1.9 at age 20-49; 1.0, 2.5 and 4.5 at age 50-64; 1.0, 4.1 and 11.4 at age 65-74; 1.0, 1.4 and 2.2 for the time period 1976-1987 and 1.0, 2.0 and 6.7 for 1988-1993. The salient feature of the Kaplan-Meier curves was the improved survival during the later time period for patients with favorable and intermediate cytogenetic abnormalities. The present findings thus suggest that it is mainly these patient groups that have benefited from advances in therapy, including supportive care.
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