Granulocyte transfusions: efficacy in treating fungal infections in neutropenic patients following bone marrow transplantation

Background: A retrospective study was conducted to evaluate the efficacy of granulocyte transfusions in neutropenic patients with fungal infections following bone marrow transplantation. Study Design and Methods: Systemic fungal infection was detected in 87 patients during the first 100 days following bone marrow transplantation; 50 received granulocytes in addition to appropriate antifungal agents. The median age was 17 years in the transfused patients (range, 1.5–57) and 35 years in the nontransfused patients (range, 0.8–50). Granulocyte transfusions were given on a daily to twice-daily basis. To evaluate their responses, patients were categorized by infection type (candidal [n = 38] vs. noncandidal [n = 49]) and site (fungemia alone [n = 30] vs. invasive infection [n = 57]). Resolution of infection was defined as the resolution of signs and symptoms and negative cultures and/or histopathology. Results: No benefit of granulocyte transfusions could be shown in the resolution of infection in patients with either invasive noncandidal infection (29% in the transfused patients vs. 23% in the nontransfused patients, p > 0.1) or candidal sepsis (56% vs. 50%, p > 0.1). Among patients with delayed marrow recovery, no difference was seen in the resolution of infection in the transfused (25.9%) and nontransfused (50%) patients (p > 0.1); nor was any difference between the transfused and nontransfused patients evident in the duration of febrile episode associated with the fungal infection. Granulocyte transfusions were well tolerated, with the only complications being fever in 12 patients (24%), chills in 10 (20%), and respiratory distress in 2 (4%). Despite attempts to stratify by infection type, invasiveness, and marrow recovery, it was not possible to show any benefit of granulocyte transfusions in this group. Conclusions: It is likely that only through a prospective randomized trial can the question of the efficacy of granulocyte transfusions in treating fungal infections be conclusively answered.     

A DOUBLE-BLIND,COMPARATIVE STUDY OF DOTHIEPIN AND CLOMIPRAMINE IN THE TREATMENT OF MAJOR DEPRESSIVE ILLNESS

Dothiepin, a well-established antidepressant, has been compared with clomipramine in a single-blind study which demonstrated that dothiepin was better tolerated but there was no difference in efficacy. The present study was performed to recent European guidelines on good clinical practice using a randomised, double-blind, parallel-group methodology. One hundred and one patients suffering from major depressive disorder as defined by DSM-III-R were randomised to receive either clomipramine (25-150 mg daily) or dothiepin (75-150 mg daily) for up to six weeks. The clomipramine group comprised 51 patients, the dothiepin group 50 patients. At baseline, both groups had a mean age of 41-43 years and gave similar mean scores on the Hamilton Depression Rating Scale (23.5 for clomipramine, 23.6 for dothiepin). At endpoint it was reduced in both groups but there were no significant differences between the groups (mean change from baseline for the clomipramine and dothiepin groups was -14.6 and -14.1 respectively). Thirty-one clomipramine patients and 41 dothiepin patients completed six weeks' treatment. Withdrawal from treatment (20 patients for clomipramine, nine for dothiepin) was significantly different (p=0.0105). When reasons for withdrawal were analysed, 13 clomipramine patients and two dothiepin patients withdrew because of adverse events, this difference being significant (p=0.002). Thus both treatments were effective in treating patients suffering from major depressive disorder, but patients receiving dothiepin suffered fewer adverse events and were more likely to complete their treatment.     

Successful allogeneic cryopreserved marrow transplantation

Cryopreservation has been used extensively in autologous marrow transplantation (BMT), but there has been limited use in allogeneic BMT. We describe here 6 cases of successful engraftment following allogeneic BMT with cryopreserved marrow. Patients suffered from Wiscott-Aldrich syndrome, osteopetrosis, aplastic anemia, and acute lymphocytic, acute non-lymphocytic, and chronic myelogenous leukemia, and ranged in age from 5 mos to 35 yrs. Marrow was collected using standard techniques. In one case T-cells were removed to prevent graft-vs-host disease. Marrow was frozen for a variety of reasons. Buffy coat cells were frozen at controlled rate in 10% DMSO, and stored in liquid nitrogen for 6 to 49 d. Engraftment (WBC greater than 1000/uL x 3 d) occurred from 13 to 37 d post BMT. In 4 of 4 cases in which data are available, donor origin of engraftment was documented, 1 with cytogenetics, 2 with red cell typing, and 4 with restriction fragment length polymorphisms. 3 patients are alive and well 21, 21, and 42 months post BMT. These results suggest frozen marrow can be successfully used for allogeneic BMT.     

Comparison of two- and three-dimensional transvaginal ultrasound in the visualisation of intrauterine devices

The aims of the study were to evaluate whether three-dimensional transvaginal ultrasound (3D TV US) is superior to two-dimensional transvaginal ultrasound (2D TV US) at visualising intrauterine devices and determining their position. This prospective study included 52 participants with an intrauterine device fitted, who underwent 2D TV US and 3D TV US. 2D TV US and 3D-reconstructed coronal images were reviewed by two gynaecological radiologists to assess ease of visualisation and position of the intrauterine devices. Statistical analysis was performed using Wilcoxon signed-rank, McNemar and Chi-squared tests. The inter-observer agreement was measured using Cohen’s Kappa. Intrauterine device visualisation scores were significantly higher with 2D TV US compared with 3D TV US (Radiologist 1 p = <0.001, Radiologist 2 p = 0.007). A significant number of T-arms appeared to perforate into the adjacent myometrium on the 3D-reconstructed coronal image, but were normal on the 2D images (Radiologist 1 p = <0.001, Radiologist 2 p = 0.008). Radiologist 1 found 19 perforated T-arms on 3D TV US compared with four on 2D TV US. Radiologist 2 found 13 perforated T-arms on 3D TV US compared with five on 2D TV US. Both radiologists agreed on the positions of the intrauterine devices substantially with 3D TV US (Kappa = 0.69) and moderately with 2D TV US (Kappa = 0.55). The 3D TV US did not visualise an intrauterine device better than 2D TV US. The 3D-reconstructed coronal image of the uterus can reliably display cases of T-arm perforation into the adjacent myometrium, which could be missed on 2D TV US images. The 3D TV US should be used in addition to 2D TV US in all cases where an intrauterine device is under evaluation.