Kai Gjerløff Schmidt

Cytogenetic findings in adult de novo acute myeloid leukaemia. A population-based study of 303/337 patients

Summary. During a 10‐year period (1992–2001) in the region of Southern Denmark, 337 patients aged 15 years or older (range 16–93 years, median 67 years) were diagnosed with acute myeloid leukaemia (AML). Cytogenetic analysis was carried out in 90%, of whom 53% had clonal chromosome aberrations. Some 24% and 31% had only numerical or structural abnormalities respectively. The remaining patients showed both types of abnormalities. Ploidy levels in decreasing order were: pseudodiploidy, 41%; hyperdiploidy, 32%; and hypodiploidy, 27%. Pseudodiploidy characterizes type M3 (70%) and hypodiploidy M6 (56%). Recurrent cytogenetic abnormalities – t(8;21), t(15;17) and inv(16) – were found in 3·3%, 3·3% and 2·0% of all patients respectively. Prognostically intermediate and adverse aberrations were found in 39% and 44%, respectively, of those with an abnormal karyotype. Rare recurrent aberrations were found in two patients in this material. A previously described non‐recurrent abnormality was found to be recurrent in one patient [der(20)t(11;20)(q13.2;p13)]. New, previously undescribed abnormalities were found in 41 patients. Statistically significant correlations were found between t(15;17) and young age (P < 0·001), inv(16) and young age (P < 0·006), −17 and M6 (P = 0·007), and M6 and complex karyotype with five or more unrelated aberrations (P = 0·004). We conclude that this truely population‐based cytogenetic study of adult AML showed distributions of chromosome abnormalities that differ from those described so far.

Chromosome Aberrations in Adult Hodgkin Disease in a Danish Population-Based Study

During a 6-year period, 31 patients with Hodgkin disease (HD) were analyzed for chromosome aberrations on lymphoid tissue. We obtained metaphases in 87% (27/31). The number of cells analyzed per case ranged from 17 to 31 (median 25), and the number of abnormal mitoses was between 1 and 17 (median 6). Chromosome aberrations were found in 59% (16/27). Numerical aberrations involved all chromosomes. The most frequently gained chromosomes were numbers 2 and 9, and the most frequently lost were numbers 10, 16, 21, 22, and X. Chromosomes most frequently involved in structural aberrations were numbers 1 and 6. The most frequent subgroups were nodular sclerosis (NS) (n = 16) and mixed cellularity (MC) (n = 10). Six NS patients and 8 patients with MC showed an abnormal clone. For the NS patients with an abnormal karyotype, 4 of 6 had a gain of chromosome 2, and all had structural aberrations of chromosome 1. Of the 6 MC patients, where a partial analysis was possible, 4 had a gain of chromosome 9, 2 had structural aberrations involving chromosome 6 and 2 of chromosome 14. In 1 case a translocation normally associated with non-Hodgkin lymphoma (NHL) was found (t[11;14]), whereas other translocations characteristic of NHL, such as t(8;14), t(14;18), and t(2;5) were not observed. A review of the literature on cytogenetic investigations in HD performed on lymphoid tissue showed that the most frequently gained or lost chromosomes were 1, 2, 5, 9, and 12 for NS and 2, 5, and 9 for MC. The most frequently affected chromosomes in structural aberrations were 1 and 6 for NS, and 1, 7, and 14 for MC. Involvement of chromosome 1, 6, and 14 in structural aberrations is characteristic of lymphoid neoplasms, as are the most frequently involved bands (1p36, 6q21-q26, 14q11, and 14q32) further supporting a B- or T-cell origin of the neoplastic cell in HD. The high hyperploidy seen in HD is not a frequent observation in NHL. Although certain chromosome aberrations seem to be characteristic of HD as opposed to NHL, specific nonrandom aberrations have yet to be identified. The rather low number of abnormal mitoses found in most HD cases underlies the importance of analyzing a large number of metaphases.

Infection-Induced Transient Remission of Idiopathic Thrombocytopenic Purpura

In 2 cases of idiopathic thrombocytopenic purpura a transient increase in platelet count was observed during and following infectious episodes. This association which is in contrast to the previously reported aggravating effect of infection on immune thrombocytopenia may be of rather frequent occurrence, being overlooked, however, because of lack of relevant clinical manifestations.

Function and Morphology of 111In-Labelled Platelets

111In-labelled human platelets were aggregated with ADP and subjected to ultrastructural morphometric analysis. In addition, the hemostatic function in vivo and the ultrastructural morphology ex vivo of rabbit platelets were examined. The platelet isolation and labelling procedures exerted no certain influence on the aggregation response, and platelet surface/volume calculations did not indicate that platelet activation had taken place. Bleeding time experiments in rabbits indicated that the hemostatic effectiveness of the labelled platelets was unimpaired. Transfused 111In-labelled platelets isolated from the recipient rabbits exhibited fewer electromicroscopic signs of platelet activation than the same platelets prior to transfusion. Our results indicate that the described procedure for isolation and 111In-labelling of platelets induces only insignificant damage to the platelets.

Incidence of idiopathic thrombocytopenic purpura among adults

It was with great interest that we read the paper by Neylon et al (2003), which claimed to present for the first time a population-based cohort of adult idiopathic thrombocytopenic purpura (ITP) patients. However, we reported population-based incidence estimates of adult ITP in 1999, in a paper that, to the best of our knowledge, was unprecedented (Frederiksen & Schmidt, 1999). We provided incidence estimates for different age groups, for both sexes at different platelet count cut-off points, and across three different time periods. Using the same platelet count cut-off point as Neylon et al (2003), this gave us an estimated incidence in Danish adults at 3Æ2/100 000/year, twice the figure reported by Neylon et al (2003). Our incidence rates in all age groups were higher than those reported by Neylon et al (2003) in their prospective study, despite the fact that the platelet concentration distribution, number of asymptomatic patients, and median age of the cohorts (56 years) were very similar or identical. The reason for this discrepancy is not entirely clear. Our collection of data was retrospective but, in general, a prospective study would increase the awareness of a disease which would lead to an increased incidence if the cases were to be recruited solely from specialized departments. It is, however, not clear to us how the cases were recruited by Neylon et al (2003). In Denmark, all persons have a unique and permanent identification number [the Central Population Register (CPR) number], which is the key to individual information in all registries. The CPR covers the entire Danish population (from 1968 onwards), and the CPR number is a prerequisite for obtaining any form of social benefit, health care, education or salary (Frank, 2000). Identification of our ITP cases was facilitated by this CPR system. The higher incidence estimate in our study may be due to the fact that it is based on all ITP patients diagnosed in any hospital, any outpatient clinic, by private practising physicians, or general practitioners in the study region. Neylon et al (2003) did refer to our study, which was cited in support of an incidence of fatal haemorrhage in ITP reaching 10Æ4%. This statement is disconcordant with the (published) fact that only two (old) patients died from haemorrhage in our cohort of 221 patients.

Acute Platelet Activation Induced by Smoking Cigarettes: In Vivo and Ex Vivo Studies in Humans

The epidemiological and pathological evidence for a relationship between cigarette smoking and atherosclerosis is considerable (1). In particular, a strong correlation between cigarette smoking and acute cardiac events in those with an already compromised coronary circulation is evident (2). As platelets seem to play a central role for the development of atherosclerosis and its thromboembolic complications (3), it is natural that a vivid interest has been taken in the effects of cigarette smoking on platelet function.

Improved Results of AML Treatment in Adults during a 12-Year Period. A Population-Based Study

In the period 01. 01. 1984–31. 12. 1995 a total of 317 adult AML patients were diagnosed in the counties of Funen and Ribe, corresponding to an annual incidence rate of 4.8/105. The median age of these patients was 68 years. Curative chemotherapy was administered to 203 patients (64%) with a median age of 62 years. The three consecutive 4-year periods were characterized by somewhat different principles of AML treatment. In the periods 1984–1987 and 1988–1991 most patients received daunorubicin-AraC, and aclarubicin-AraC, respectively, as induction therapy. In both periods three fourths of CR patients received high-dose AraC based post-remission therapy. In the period 1991–1995 almost all patients were treated with repeated courses of mitoxantrone and high-dose AraC. The CR rate increased from 43% to 77% in the study period. The duration of CR did not change over time, whereas a prolongation of survival was seen, indicating that around 20% of all patients with AML can now be cured.

Is 111In-Leucocyte Scintigraphy Useful in the Evaluation of Patients with Prolonged Fever of Unknown Origin?

A substantial proportion of the patients referred for 111In white blood cell scanning (111In WBCS) have been febrile for prolonged periods with no or only vague symptoms or signs to suggest the cause of the fever. The paucity of 111In WBCS-data in this clinical setting thus seems surprising.