During the 17-year period 1972 through 1988, a total of seven cases of agranulocytosis associated with the use of dapsone for the treatment of dermatitis herpetiformis were reported in Sweden. The median age of the patients involved was 61 years; three of them were male. The median duration of dapsone treatment was 7 weeks and the daily prescribed dose was 100 mg. Based on sales and prescription data, the crude relative risk of agranulocytosis during dapsone treatment of dermatitis herpetiformis was 50, and the total risk was one case per 3000 patient years of exposure to dapsone. In relation to the number of new cases of dermatitis herpetiformis, agranulocytosis was estimated to develop in 1 of 240 to 425 patients receiving dapsone therapy. Patients should be instructed to seek medical care immediately in case of fever.

113 patients with acute myelogenous leukemia (AML), representing 82% of the total cohort of AML patients within the geographical area of northern Sweden, were recorded. The total complete remission (CR) rate was 47.8 %, and median survival was 4 months. The probability of long‐term survival for all patients without exclusions was only 5%. Thus, the results from this study differ strongly from data on patient outcome in most therapy studies in AML, where the influence of patient selection on the results is larger. The median age in our patients was 63 years, which is also higher than in most other studies. Elderly patients had a low CR rate (24% in patients >70 yr), but remission duration was similar in the different age groups. Patients treated according to “high‐dose” protocols had a CR rate of 64%, while only 14% of less aggressively treated patients achieved remission. A better response rate after more aggressive chemotherapy was evident also in elderly patients. CR rate was 81% in patients below 60 yr of age who had no antecedent blood disorder and who had had symptoms for less than 3 months. Other variables with prognostic implications were: cytogenetic subgroup, antecedent hematological disease, and level of serum ferritin. High serum ferritin was associated with short CR duration. Ferritin is produced by the leukemic cells and could be regarded as a marker for leukemic activity.

Gene transfer into human hematopoietic stem cells using Ad5 is inefficient due to lack of the primary receptor CAR and the secondary receptors alphavbeta3 integrin and alphavbeta5 integrin, and due to the high seroprevalence of Ad5 antibodies in most adults, resulting in diminished gene transduction. In the present study, we screened six species (species A-F) of adenovirus, displaying different tropisms for interaction with CD34+ cells, at the level of virus attachment and expression. Virus particles were biotinylated and their binding capacity was determined by FACS analysis using streptavidin-FITC. Ad11p, Ad35, and Ad3 (species B) showed high binding affinity, while Ad7, Ad11a (species B), and Ad37 (species D) displayed intermediate affinity. Virions of Ad4 (species E), Ad5 (species C), Ad31 (species A), and Ad41 (species F) hardly bound to hematopoietic progenitor cells. Using a double-labeling system, we demonstrated that adenoviruses bind to quiescent CD34+ cells. Ad11p virions showed the highest affinity among the adenoviruses detected. We further confirmed that virus fiber-specific receptors were present on the hematopoietic progenitor cell surface, because both recombinant fiber of Ad11p and specific antiserum against rfiber could block virus attachment. The ability of the adenoviruses to infect hematopoietic cells was studied by immunofluorescence staining. The adenoviruses from species B and Ad37 showed higher infectivity than Ad31, Ad5, Ad4, and Ad41. Among the studied species B adenoviruses, Ad11p manifested a superior infectivity. Thus, we have confirmed that these cells have high-affinity receptors for species B:2 human adenovirus, Ad11p, and this virus may be used as candidate vector to target therapeutic genes to hematopoietic stem cells.

Relapses after autologous transplantation are a serious clinical problem in patients with haematological diseases. The decision making for handling of such patients is difficult and the aim of this retrospective analysis of posttransplant relapses was 1) to obtain information of practical importance for the management of future relapses and 2) to evaluate the basis for clinical phase I-II trials of salvage therapy combined with biological modifiers. Included in the study were 283 patients with acute leukemia, multiple myeloma and malignant lymphoma who relapsed after autologous transplantations during a five year period from 1989 to 1994. Chemo- and radiotherapy was given to 229 patients after relapse or due to progressive disease and the response evaluated after 90 days. Fifty four patients (24%) obtained a complete remission and 44 patients (19%) partial responses. The overall median survival from relapse was 5 months. In the group given salvage treatment the median survival was 7 months and in the 54 patients who obtained remission the median survival was 15 months. So far 6 of 14 patients in continuous complete remission have a remission time after relapse longer than the time in remission after transplantation. Survival after relapse depended upon the time from transplantation to relapse, primary disease and if salvage therapy was given. In conclusion posttransplant relapses can be treated but the strategy has to be evaluated in future clinical trials.

A total of 44 adults aged 18-78 years were allocated to an open randomized study whose aim was to compare the efficacy and toxicity of mitoxantrone with those of daunorubicin in previously untreated patients presenting with acute myeloid leukemia. In one arm, induction treatment consisted of mitoxantrone plus cytarabine given on a 3- plus 7-day schedule. Post-induction treatment consisted of two courses of mitoxantrone plus cytarabine given on a 2- plus 5-day schedule. In the control arm, mitoxantrone was replaced by daunorubicin. In all, 14 of 21 eligible and evaluable patients in the mitoxantrone arm achieved a complete remission (CR). In the control arm, 14 of 20 subjects attained a CR. The median survival was 365 days for patients randomized to mitoxantrone-cytarabine and 401 days for those given daunorubicin-cytarabine. The efficacy and toxicity of mitoxantrone were similar to those of daunorubicin.