| 1. |
- Modvig, S, et al.
(author)
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Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting.
- 2021
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35, s. 1894-1906
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Journal article (peer-reviewed)abstract
- PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p<0.0001), 29 (HzR 2.7, p<0.0001), and 79 (HzR 3.5, p<0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4×10-2 versus 5.2×10-3, p<0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y=3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD>10-4 associated with a CIR5y=22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.
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| 2. |
- Quist-Paulsen, P., et al.
(author)
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T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol
- 2020
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:2, s. 347-357
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Journal article (peer-reviewed)abstract
- The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
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| 3. |
- Danielsson, M., et al.
(author)
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Prevalence, duration of exposure and predicting factors for snus use among young Finnish men: a cross-sectional study
- 2021
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In: Bmj Open. - : BMJ. - 2044-6055. ; 11:9
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Journal article (peer-reviewed)abstract
- Objective The health hazards of tobacco products depend on the level of exposure, but little is known about the characteristics of snus use. The aim of this study was to investigate the duration of daily exposure to snus among occasional and daily users and its associated predictive factors among young Finnish men. Design Cross-sectional questionnaire study. Setting Three out of 16 Finnish Defence Forces units. Participants 1280 young Finnish male conscripts starting their military service in 2016 chosen by simple random sampling. Primary and secondary measures The prevalence, duration of use and the amount of daily usage of snus and cigarettes were investigated. The attitudes towards perceived harmfulness of snus and the predictive factors affecting the total time of snus consumption were examined. Results Almost a fifth (19.5%) of the conscripts reported daily snus use, and a further 16% reported occasional use. Daily snus use was associated with an earlier starting age, longer duration of use and higher daily exposure time compared with occasional use. On average, daily snus users consumed 10 portions and occasional users three portions per day (p<0.001). The daily total exposure time for daily users was 372 min (95% CI 344 to 401) and for occasional users 139 min (95% CI 106 to 171). Respondents with an upper secondary education had significantly less daily total exposure than those with basic comprehensive education (p=0.036). Perceptions of snus as a harmful substance resulted in a significantly lower duration of exposure. Conclusion Snus use was very common among young Finnish men. High snus exposure duration was associated with an earlier starting age, a longer history of use and a careless attitude to its health hazards. A higher education level was a protective factor for total exposure time. Studies of the long-term health effects and dependency profile of snus use are needed.
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| 4. |
- Hakkarainen, M, et al.
(author)
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The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia
- 2023
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:23, s. 2853-2866
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Journal article (peer-reviewed)abstract
- Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.
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| 5. |
- Hakkarainen, M, et al.
(author)
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The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia
- 2023
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:23, s. 2853-2866
-
Journal article (peer-reviewed)abstract
- Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.
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