Background: For AML (excluding APL), there has until recently been no major changes in AML‐specific drug therapy, but improvements of supportive care and access to allogeneic transplantation (SCT). Aims: We aimed to analyze changes in survival from AML (non‐APL) over the period 1997–2016, and to identify and characterize patient subsets with greater improvement. Methods: Data from all Swedish AML‐patients, diagnosed from 1997 and reported in the Swedish AML Registry (n = 7708), including type of AML, diagnostic findings, therapy including allogeneic stem cell transplantation, and outcome, was analyzed. Survival up to September 2018, early death rate and CR rate by year of diagnosis, age, sex, performance status, type of AML, genetic risk, and therapy was calculated using Cox regression and Log rank analyses where date of diagnosis was grouped into four five‐year periods 1997‐2016. Results: Due to the early and large mortality amongst older patients the relative or cause‐specific survival were of no use, as confirmed by parallel relative survival analyses (data not shown). Cox regression (univariate and multivariate) identified strong correlation to survival with age, type of AML (de novo vs secAML), ECOG performance status, and year of diagnosis (all p < 0.001), and also sex in multivariate analysis (p = 0.015). Thus, survival improved by time (log rank, p < 0.00001). However, when different age cohorts were independently analysed (Figure), we found that the improved survival was restricted to ages 50–75 years (n = 3513, log rank, p < 0.00001), with no improvement in younger (<50 years, n = 825, p = 0.67) or older patients (>75 years, n = 2657, p = 0.50). Furthermore, males 50–75 years had improved survival over time (n = 1949, p < 0.00001), but not females (n = 1564, p = 0.69). Thus, in the first half of the study period males had poorer survival than females, but male survival improved to equal survival by sex in the latter part. Changes over time were seen for performance status, early death rate, complete remission rate, and transplantation rate, but with only minor differences between the sexes. Figure: Multivariate Cox regression with ECOG PS and AML type (de novo vs sec) as covariates. For each sex‐age group combination, the hazard was determined by a separate period dependent categorical variable with 1997–2001 as baseline. Summary/Conclusion: Despite no new chemotherapeutic drugs, survival has improved over the past twenty years, mainly in middle‐aged male patients. Females have since long time had a better survival than males in the overall population and among patients with other cancers, also including AML in past times. However, in the most recent decade, males 50–75‐year old with AML now survive as long as female same‐aged patients. The results were similar across risk groups, but most clear in patients with de novo AML, non‐high‐risk genetics and good performance status. Many factors may contribute to changes in outcome over time, such as transplant rates and general health. However, the sex difference remains unexplained. No improvement in survival was seen in younger and older patients. image

Prevalence and Characteristics of Survivors from Adult Acute Myeloid Leukemia (AML) in Sweden 2014

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 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 <80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both P<0.001), followed by sex (P=0.0135) and a karyotype including -7/del(7q) (P=0.048).

It is well established that persons with cancer commit suicide more frequently than those without [1.Hem E. Loge J.H. Haldorsen T. Ekeberg O. Suicide risk in cancer patients from 1960 to 1999.J Clin Oncol. 2004; 22: 4209-4216Crossref PubMed Scopus (170) Google Scholar]. Males generally commit suicide more frequently than females. Head and neck and lung cancer have been associated with a higher risk of suicide. Based on personal clinical experience and the chronic and often devastating character of the disease we postulated that among patients with hematological malignancies, patients diagnosed with multiple myeloma (MM) carried an increased relative risk. Using the Swedish Cancer Registry we identified a total of 24 489 patients with MM and acute myeloid leukemia (AML) diagnosed in Sweden between 1 January 1973 and 31 December 2003 (16 666 with MM and 7 823 with AML). The male-female ratio was 1.17 and 1.02 and the median age 72 and 69 years for MM and AML patients, respectively. Among these patients, 43 suicides were reported to the Swedish Cause of Death Registry. The incidences per 10 000 person years were 6.1 and 8.9 for MM and AML patients, respectively, yielding a standardized mortality ratio (SMR) of 2.35 in MM and 4.58 in AML using the general population as reference. There were more suicides among men (n = 32) than among women (n = 11), but since this is observed also in the general population, the SMR:s for men and women were almost identical (2.69 and 2.62, respectively). The suicide incidence was higher during the first two calendar periods (1973-89; n = 31), with a minor but constant decline in incidence over the study period (Table 1). The suicide SMR was highest during the first two years following diagnosis, but the SMR remained increased even five years after diagnosis. The incidence rate differed little between the age groups. Except for the higher suicide SMR in AML patients, the features described above did not differ between MM and AML (Table 1). Thus, our postulated hypothesis of a higher suicidal rate in MM as compared to the chosen control group of AML patients was not verified. It was consequently of great interest to read in the Journal the recently published article by Kendal [2.Kendal W.S. Suicide and cancer: a gender-comparative study. Ann Oncol. 2007; 18: 381-387Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar]. This author analyzed >1.3 million cancer cases in Ontario, Canada diagnosed 1973-2001 from a gender-comparative perspective. In that study a 4.8 times excess in the overall number of male suicides over females was reported. Among females a hematological malignancy (Hodgkin, non-Hodgkin lymphoma, leukemia or MM) was not associated with a relative increased or decreased suicidal rate. However, males with MM showed an increased rate while a decreased relative suicidal rate was observed in male patients with leukemia. AML was not specifically investigated among the leukemias.Table 1Suicides among patients with AML and MM in relation to sex, age, year and time since diagnosis and calendar periodAML Person time (years)Number of suicidesIncidence/10 000 person yearsRelative risk (95% CI)Multiple Myeloma Person time (years)Number of suicidesIncidence/10 000person yearsRelative risk (95% CI)Sex male5777813.83.02 (0.80–11.37)27 325248.82.74 (1.23–6.09) female653734.6Reference = 1.0024 93383.2Reference = 1.00Year of diagnosis 73–791573319.111.89 (1.24–114.27)10 65087.51.56 (0.63–3.88) 80–894506715.59.69 (1.19–78.72)18 781136.91.44 (0.64–3.21) 90–03623411.6Reference = 1.0022 827114.8Reference = 1.00Years since diagnosis <13833513.01.82 (0.49–6.77)12 913129.32.58 (1.05–6.31) 1–2290526.90.96 (0.18–5.24)17 132127.01.94 (0.8–4.76) 3+557647.2Reference = 1.0022 21383.6Reference = 1.00Age <50492636.10.97 (0.16–5.82)25 1528.01.24 (0.26–5.85) 50–64319426.3Reference = 1.0012 48586.4Reference = 1.00 65+4194614.32.28 (0.46–11.32)37 258225.90.92 (0.41–2.07) Open table in a new tab The outcome of patients with MM has improved significantly since 1973, most prominent in patients below the age of 60 years [3.Kristinsson S. Landgren O. Dickman P.W. Rangert-Derolf Å BjÖRkholm M Patterns of survival in multiple myeloma: A population-based study of patients diagnosed in Sweden from 1973 to 2003.J Clin Oncol. 2007; (; 25: 1993–1999. Epub 2007 Apr 9)Crossref PubMed Scopus (256) Google Scholar]. High-dose melphalan with subsequent autologous stem cell support, thalidomide and a continuous improvement in supportive care probably contribute to this finding [3.Kristinsson S. Landgren O. Dickman P.W. Rangert-Derolf Å BjÖRkholm M Patterns of survival in multiple myeloma: A population-based study of patients diagnosed in Sweden from 1973 to 2003.J Clin Oncol. 2007; (; 25: 1993–1999. Epub 2007 Apr 9)Crossref PubMed Scopus (256) Google Scholar, 4.Durie B.G. New approaches to treatment for multiple myeloma: durable remission and quality of life as primary goals.Clin Lymphoma Myeloma. 2005; 6: 181-190Abstract Full Text PDF PubMed Scopus (31) Google Scholar], which may explain in part the decreasing suicidal rate seen during later calendar periods [1.Hem E. Loge J.H. Haldorsen T. Ekeberg O. Suicide risk in cancer patients from 1960 to 1999.J Clin Oncol. 2004; 22: 4209-4216Crossref PubMed Scopus (170) Google Scholar]. The prognosis for patients with AML has however not improved to the same extent, particularly not in patients >60 years [5.Derolf ÅR Landgren O Dickman P. Kristinsson S.Y. Björkholm M. Prognosis in acute myeloid leukemia: A population-based study on 5809 patients diagnosed in Sweden 1973-2001. Abstract 1845. Georgia, American Society of Hematology Atlanta2005Google Scholar]. Hopefully, we will be able to improve our understanding of this medical problem among patients with malignant hematological disorders and also better define associated risk factors. Such information is important for hematologists, oncologists and allied health professionals.

6686 Background: Acute myeloid leukemias (AML) with near-tetraploidy (NT: 80–104 chromosomes, without aberrant near-diploid metaphases) were described in about 35 patients. The aim of the study was to collect laboratory and clinical data of patients with these rare types of AML. Methods: We describe 29 cases with NT-AML collected by the EGIL in a retrospective multicenter study from 8 European countries diagnosed between 1984 and 2003. Results: Three NT-AML cases were misdiagnosed as lymphoblastic malignancies. Imunophenotyping and liquid cultures of blasts with a phorbol TPA was essential for diagnosis in 13 and 2 cases, respectively. Twenty-three cases with M0-M5 AML (12 M0, 3 M1, 2 M2, 2 M4, 3 M5, 1 NOS), 19–83 (median 64) years old, exhibited erythroid and/or megakaryocytic (EM) dysplasia, CD34+ and other similarities and may represent a category of multi-lineage NT-AML M0-M5. Multi-lineage involvement was also found in 3 M6 and 1 M7 cases. Ten females, 36–83 (median 70.5) years old, were significantly older (p=0.031) than 17 males, 19–83 (median 59) years old. In 10 cases older than 60 years we diagnosed a secondary NT-AML that developed after chemo-and/or radiotherapy or after 2–7 months of a myelodysplasia. Complete remission (CR) was reached in 6 of 9 cases with M0-M5 AML younger than 60 years treated with intensive cytosine arabinoside and an anthracycline based therapy. Their median survival was 25.3 months with 3 cases having been at their 1st continuous CR after autologous stem cell transplantation (ASCT) for 21–54 months demonstrating the efficacy of this treatment modality. Only 3 of 7 cases older than 60 years with de novo M0-M5 AML reached CR and survived 15–32 months. None of cases with secondary M0-M5 AML reached CR. Their survival was short as that of M6 and M7 cases. Another category may represent a 67-year old patient with AML M0 without EM-dysplasia (single-lineage AML) who survived 80 months after standard dose chemotherapy. Conclusions: Among NT-AML patients the worst prognosis exhibit those with secondary multi-lineage M0-M5, M6, M7; a somewhat better prognosis cases with de novo multi-lineage M0-M5, especially after ASCT at the 1st CR. The best prognosis may exhibit patients with single-lineage NT-AML. No significant financial relationships to disclose.

Background: Over the last decades there have been advances in the treatment of patients with multiple myeloma (MM) and prognosis has improved with the introduction of new treatment strategies. However, few studies have addressed the issue which patients benefit most from these therapeutic changes over the years. Aims: To evaluate relative survival in all diagnosed MM patients in Sweden 1973–2001 and relate the changes to age, sex and type of hospital where diagnosis was made. Methods: All patients with MM notified to the Swedish Cancer Register in 1973–2001 were followed up by record linkage to the nationwide Cause of Death Register. Survival analyses were performed by obtaining relative survival (RS) defined as the ratio of observed versus expected survival. The study period was divided arbitrarily to four calendar periods: 1973–1979, 1980–1986, 1987–1993, and 1994–2002. Patients were grouped according to age at diagnosis (0–40, 41–50, 51–60, 61–70, 71–80, and 80+), sex, and hospital category. RS was estimated using SAS (Cary, NC, USA) and excess mortality modelled using Poisson regression. Results: A total of 13,376 patients (7,114 males and 6,262 females, mean age 69.8 years, and 32% diagnosed at a university hospital) were diagnosed with MM in Sweden between January 1st 1973 and December 31st 2001. The overall one-year RS estimates were 73%, 78%, 80%, and 81%, respectively, for the four calendar periods. The overall five-year RS was 31%, 32%, 34%, and 36% and the ten-year RS remained stable at 12%, 11% 13% in the first three periods; ten-year RS could not be calculated for the last calendar period. The increase in one-year RS was observed in all age categories over the four calendar periods, while the increase in five-year RS was restricted to patients <70 years. Younger age at onset was associated with a superior survival in all calendar periods. Differences in survival by age at diagnosis and calendar period were highly statistically significant (p<0.0001). Females had a superior 1- (p=0.002), 5- (p=0.024), and 10-year RS (p=0.019) compared to males, after adjusting for age and period. Patients diagnosed at university hospitals had superior 5- and 10-year RS (p=0.007) but not 1-year RS. Summary/conclusions: The present study shows an improved prognosis over time in a population-based study including > 13,000 MM patients diagnosed during a 29-year period. Of interest is that even one-year RS has improved in all age groups over the whole study period. Increase in five-year RS was only observed in patients aged <70 years. The ten-year RS did not improve over the first 20 years and could not be estimated for patients diagnosed in the last period. Younger age at diagnosis was associated with superior one-, five- and ten-year RS in all calendar periods. Females had a significantly better survival than males. A significant difference in survival was seen according to type of hospital, with patients diagnosed at a university hospital surviving longer. In conclusion, the results show that survival of MM patients has improved during the study period. However, long-term survival has not improved significantly. Males, elderly patients and patients diagnosed during early calendar periods experienced higher excess mortality.