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  • 1
    In: European Journal of Haematology, Wiley, Vol. 83, No. 2 ( 2009-08), p. 99-107
    Abstract: In 1997–2003, a protocol for treatment of acute myeloid leukaemia (AML) (except promyelocytic leukaemia) was activated in four Swedish health care regions covering 50% of the national population. Based on cytogenetics and clinical findings, patients aged 18–60 yr were assigned to one of three risk groups. In this report we account for the long‐term clinical outcome of enrolled patients. Patients received idarubicin and cytarabine in standard doses as induction therapy and consolidation courses included high‐dose cytarabine. Allogeneic stem cell transplantation (allo‐SCT) from an human leucocyte antigen‐identical sibling was recommended in standard and poor‐risk patients, whereas unrelated donor transplant was reserved for poor‐risk patients. Autologous (auto‐SCT) was optional for standard or poor risk patients not eligible for allo‐SCT. Two hundred seventy‐nine patients with de novo or secondary (9%) AML, median age 51 (18–60) yr, corresponding to 77% of all patients in the population, were included. Twenty (7%) patients were assigned to the good risk group, whereas 150 (54%) and 109 patients (39%) were assigned to standard‐ and poor‐risk groups, respectively. Induction failures accounted for 55 patients; 16 early deaths eight of whom had white blood cell (WBC) 〉 100 at diagnosis, and 39 refractory disease. Thus, complete remission (CR) rate was 80%. At study closure, the median follow‐up time of living patients was 90 months. Median survival time from diagnosis in the whole group was 27 months and 4‐yr overall survival (OS) rate was 44%. In good, standard, and poor risk groups, 4‐yr OS rates were 60, 57 and 24%, respectively. Median relapse‐free survival (RFS) time in CR1 was 25 months and RFS at 4 yr was 44%. Four‐year RFS rates were significantly ( P   〈  0.001) different between the three risk groups; 64% in good risk, 51% in standard risk and 27% in poor risk patients. One hundred‐ten transplantations were performed in CR1; 74 allo‐SCT (50 sibling, 24 unrelated donor), and 36 auto‐SCT. Non‐relapse mortality was 16% for allo‐SCT patients. Outcome after relapse was poor with median time to death 163 d and 4‐yr survival rate 17%. Three conclusions were: (i) these data reflect treatment results in a minimally selected population‐based cohort of adult AML patients 〈 60 yr old; (ii) a risk‐adapted therapy aiming at early allogeneic SCT in patients with a high risk of relapse is hampered by induction deaths, refractory disease, and early relapses; and (iii) high WBC count at diagnosis is confirmed as a strong risk factor for early death but not for relapse.
    Type of Medium: Online Resource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2009
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  • 2
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4888-4888
    Abstract: The prevalence of survivors of adult AML has previously been calculated, but the prevalent population has not been characterized. We analysed all 6289 patients diagnosed with adult AML from 1997-2013 as reported in the Swedish AML registry, with a complete survival follow-up. We found 1148 patients, 563 males and 585 females, who were alive on January 1, 2014, constituting 18% of the total, and of them 204 (18%) were diagnosed during 2013. Patients who had their initial treatment at pediatric departments, and people diagnosed with AML before 1997 are not included. The mean age of survivors was 53.4 years at diagnosis and 59.3 years in 2014, and 303 (26%) were 70 years or older in 2014. The overall prevalence of patients diagnosed at age 20 or more was 15.2 per 100,000 (males 15.0 and females 15.4 per 100,000). There were 124 with prior acute promyelocytic leukemia (APL) (11%), 54 with inv(16) (5%), 44 with t(8;21) (4%), and 82 with NPM1 mut/FLT3 wt (7%), 75 with FLT3 -ITD (7%), and 82 with complex karyotype (7%). Karyotype results were not available in 10%, and molecular data only since 2007. Four hundred two (35%) had undergone allogeneic stem cell transplantation, out of which 32 (8%) had had complex karyotype, 43 (11%) FLT3-ITD, 136 (34%) normal karyortype, and 41 (10%) good risk but were transplanted after relapse. Among the 426 non-transplanted prevalent patients who had survived at least 3 years, 94 (22%) had prior APL, 25 (6%) t(8;21), 24 (6%) inv(16), 126 (30%) normal karyotype, and 11 (3%) complex karyotype, including eight monosomal karyotypes and two with del(7) and one del(5q). Among non-complex karyotypes there were four MLL abnormalities, two del(5q) and two monosomy 7. Although long-term survivors more often have pretreatment good-risk features, this patient group is still heterogeneous, and also contains older people and those with intermediate/high risk cyogenetics. Figure 1. Prevalence in January 1, 2014 of Swedish people with a previous diagnosis of AML by sex and current age per 100,000 inhabitants in 2014, and mean incidence 1997-2014 per 100,000 inhabitants in Sweden 2005. Figure 1. Prevalence in January 1, 2014 of Swedish people with a previous diagnosis of AML by sex and current age per 100,000 inhabitants in 2014, and mean incidence 1997-2014 per 100,000 inhabitants in Sweden 2005. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 3
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 281-281
    Abstract: Allogeneic stem cell transplantation (SCT) is widely used as post-remission treatment in younger patients with poor or intermediate risk AML. Transplant decisions are mainly based on cytogenetic and molecular risk group, age, comorbidity and on the availability of a suitable donor. Secondary AML, including therapy-related AML (t-AML) and AML after an antecedent hematological disorder (AHD-AML), constitutes more than one fourth of the AML cases and is a predictor of a poor outcome. However, the extent to which SCT improves outcome of this patient group is poorly studied. In this study, we set out to investigate the role of SCT for the survival of secondary AML patients within the population-based Swedish Adult Acute Leukemia Registry. In total, 5881 patients with AML diagnosed during the period 1997 – 2013 were included in the study. Of these, 4233 (72%) were de novo AML, 1098 (19%) AHD-AML and 550 (9%) t-AML. The median age at diagnosis was 70 in de novo AML, 73 in AHD-AML and 70 in t-AML. The gender distribution was equal in de novo AML (51% males). In AHD-AML, there was a male predominance of 57% whereas in t-AML, there was a female predominance of 56%. The proportion of patients who underwent SCT in first remission (CR1) was 10% in de novo AML, 5% in AHD-AML and 8% in t-AML (de novo vs AHD-AML p 〈 0.001, de novo vs t-AML p = 0.068, AHD-AML vs t-AML p = 0.081; Fisher's exact test). In patients aged 65 or below, the proportion of SCT in CR1 was 24%, 21% and 20%, respectively. The median age of SCT patients was 48 (range 17 – 71) in de novo AML, 57 (27 – 76) in AHD-AML and 49.5 (18 – 68) in t-AML. In de novo AML, the distribution of genetic risk groups among SCT patients was 3% low risk, 55% intermediate risk and 42% high risk. Corresponding figures for AHD-AML was 0%, 34% and 66% and for t-AML 5%, 45% and 50% respectively (de novo vs AHD-AML p = 0.004, de novo vs t-AML p = 0.299, AHD-AML vs t-AML p = 0.124; Fisher's exact test). The estimated median survival after the date of SCT in CR1 was 15 months in AHD-AML and 22 months in t-AML but not reached in de novo AML (95% lower confidence limit 107 months). Among patients 〈 65 years who had been in CR for 3 months (genetic low risk excluded), those with secondary AML had a greater benefit from consolidation with SCT than those with de novo AML (Figure 1). The projected 7-year survival in de novo AML was 60% with SCT and 44% with conventional post remission therapy (CPRT) as compared to 46% and 21%, respectively, in secondary AML. The survival hazard with SCT was 0.45 in secondary AML (95% CI 0.28-0.72) as compared to 0.66 in de novo AML (CI 0.53 – 0.82), by multivariable Cox regression adjusting for type of secondary AML, age, sex, and cytogenetic risk group. To refine the analysis correcting for major confounding factors, a matched pair analysis was performed in patients with CR longer than 3 months. Matching criteria were type of secondary AML (AHD or t-AML), cytogenetic risk group and age (+/- 3 years). Remission of the patient with CPRT was at least as long as the time between CR1 and transplantation for the matched patient undergoing SCT. The projected 7-year survival rate was 43% in the SCT and 8% in the CPRT group (p = 0.01; log-rank test, Figure 2) further indicating a benefit for SCT as post remission therapy in secondary AML. We conclude that SCT improves survival in patients with secondary AML. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 4
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 47, No. 9 ( 2006-01), p. 1768-1773
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2006
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  • 5
    In: Blood, American Society of Hematology, Vol. 113, No. 18 ( 2009-04-30), p. 4179-4187
    Abstract: Acute myeloid leukemia (AML) is most common in the elderly, and most elderly are thought to be unfit for intensive treatment because of the risk of fatal toxicity. The Swedish Acute Leukemia Registry covers 98% of all patients with AML (nonacute promyelocytic leukemia) diagnosed in 1997 to 2005 (n = 2767), with a median follow-up of 5 years, and reports eligibility for intensive therapy, performance status (PS), complete remission rates, and survival. Outcomes were strongly age and PS dependent. Early death rates were always lower with intensive therapy than with palliation only. Long-term survivors were found among elderly given intensive treatment despite poor initial PS. Total survival of elderly AML patients was better in the geographic regions where most of them were given standard intensive therapy. This analysis provides unique real world data from a large, complete, and unselected AML population, both treated and untreated, and gives background to treatment decisions for the elderly. Standard intensive treatment improves early death rates and long-term survival compared with palliation. Most AML patients up to 80 years of age should be considered fit for intensive therapy, and new therapies must be compared with standard induction.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 6
  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2269-2269
    Abstract: Despite improved diagnostics and better understanding of AML biology, the basic chemotherapy has remained unchanged for decades, with no progress in outcome. In Sweden, national guidelines for the comprehensive management of AML were implemented in 2006, containing primary therapy with daunorubicin 60 mg/sqm/8h d.1-3 and ara-C 1 g/sqm/2h b.i.d. d.1-5. This is repeated once, and followed by consolidation with slightly abbreviated DA to a total of 4 courses. Recommendations include full dose treatment to most patients up to 80 years, and allogeneic transplantation to fit patients with high- and intermediate-risk genetics. Guidelines are summarized in English at www.cancercentrum.se/sv/Vardprogram/AML (pdf file pp. 116-9). These guidelines replaced (multi)regional and local programs. We have now aimed to evaluate the impact of the guidelines through the Swedish national population-based AML registry, including 5561 adult AML non-APL patients (age median 71 yrs, mean 68 yrs), i.e., 98% of those diagnosed 1997-2013. Survival was updated in May 2014. Overall survival (OS) was analyzed by time period (1997-2001, 2002-2005, 2006-2009, and 2010-2013). OS for the whole AML population improved during this study period (log rank test, p=0.00027). The 3-year OS rate (%) is shown in the Figure. Survival improved in all age groups except in patients older than 80 years. Interestingly, the greatest improvement was seen in males and in patients with high-risk genetics and intensive treatment (n=846, OS by period p=0.006), whereas there was no significant improvement in low- and intermediate risk patients, nor in patients with secondary AML. More patients 〈 80 years (n=4272) received intensive treatment (72% pre vs 77% post-implementation, Chi-square 15.8, p=0.0001), similar in all genetic risk groups (low risk 90% to 97%, intermediate 83% to 87%, high risk 74% to 80%). However, fewer patients older than 80 years (n=1289) received intensive treatment (13% vs 9%, X2 4.5, p=0.03). The complete remission (CR) rate in patients 〈 80 yrs increased from 67% to 69% of treated (p=ns), i.e., from 50% to 54% of all (p=0.012). The CR rate improved the most among high-risk patients given intensive treatment (52% to 62%, p=0.003). Early death (ED) rate within 30 days from diagnosis decreased for intensively treated patients 〈 80 years (n=3181) from 8.5% to 6.3% (X2 5.8, p=0.016). With greater improvement of survival among males 〈 80 years the survival gap to females decreased. The improved survival following implementation of national guidelines may be the result of the guideline protocol itself, from improved adherence to a treatment schedule, from better supportive care, and/or better logistics and availability of treatment. The improved survival was likely in part due to that more patients were given intensive treatment with a decreased ED rate, but also due to better outcome with intensive treatment of high risk patients. Further analyzes in order to identify critical issues and improve guidelines are pending. Figure: Percentage 3-year overall survival of AML non-APL patients with or without treatment according to age and time period. Figure:. Percentage 3-year overall survival of AML non-APL patients with or without treatment according to age and time period. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 8
    In: American Journal of Hematology, Wiley, Vol. 90, No. 3 ( 2015-03), p. 208-214
    Abstract: Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population‐based studies are crucial for its accurate characterization. In this first large population‐based study on secondary AML, we studied AML with an antecedent hematological disease (AHD‐AML) or therapy‐related AML (t‐AML) in the population‐based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD‐AML, and 259 (7.7%) t‐AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD‐AML (HR 1.51; 95% CI 1.26–1.79) and t‐AML (1.72; 1.38–2.15) were independent risk factors for poor survival. The negative impact of AHD‐AML and t‐AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population‐based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients. Am. J. Hematol. 90:208–214, 2015. © 2014 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
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  • 9
    In: American Journal of Hematology, Wiley, Vol. 90, No. 9 ( 2015-09), p. 800-805
    Abstract: To ascertain the clinical implications of high hyperdiploid (HH; 49–65 chromosomes) and triploid/tetraploid (TT; 〉 65 chromosomes) adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. Of the 3,654 cytogenetically informative cases diagnosed between January 1997 and May 2014, 68 (1.9%) were HH ( n  = 50)/TT ( n  = 18). Patients with HH/TT were older than those with intermediate risk (IR) AML (median 71 years vs. 67 years; P  = 0.042) and less often had de novo AML (63% vs. 79%; P  = 0.004); no such differences were observed between HH/TT and complex karyotype (CK) AML. The overall survival (OS) was similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P  = 0.082), whereas OS was significantly longer (median 1.6 years; P  = 0.028) for IR AML. The OS was shorter for cases with HH than with TT (median 0.6 years vs. 1.4 years; P  = 0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs. 1.1 years; P  = 0.044). In conclusion, HH/TT AML is associated with a poor outcome, but chromosome numbers 〉 65 and absence of adverse aberrations seem to translate into a more favorable prognosis. Thus, HH/TT AMLs are clinically heterogeneous and should not automatically be grouped as high risk.Am. J. Hematol. 90:800–805, 2015. © 2015 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 1492749-4
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  • 10
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 25, No. 9 ( 2019-09), p. 1770-1778
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
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    detail.hit.zdb_id: 2057605-5
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