Granulocytes (PMN) play an important role in antibacterial host defence. The modulation of PMN-function by different antibiotics has been shown previously. Therefore, we investigated the possible ...immuno-modulatory effects of four new quinolone antibiotics: ciprofloxacin, norfloxacin, pefloxacin, ofloxacin. Pure PMN-preparations were obtained from healthy volunteers and incubated for 30 min at 37 degrees C with the different quinolones at different concentrations (0.1-1-5-10 mg/l). A complete PMN-functional profile was assayed. At all concentrations tested no significant differences were seen for myeloperoxidase content, superoxide production and chemiluminescence. A significant stimulation of phagocytosis and killing occurred at 10 mg/l of norfloxacin and at 10 mg/l of pefloxacin. An increase of chemotaxis towards formyl-methionyl-leucyl-phenylalanine was noted at 10 mg/l of ofloxacin, while stimulation of hexose monophosphate shunt was seen at 1 mg/l of ciprofloxacin and 10 mg/l of ofloxacin. The mechanism whereby both subinhibitory and inhibitory concentrations of quinolones moderately influence PMN-responsiveness is not yet known. Further studies are needed to elucidate the nature of this quinolone-effect and to assess its relevance in vivo.
Lymphoproliferative diseases may occur as a complication of severe immunosuppression. In our own center two out of 46 heart transplant recipients, receiving a cyclosporin A containing ...immunosuppressive regimen, presented with this complication and are reported here. Hepatic involvement and an occult small bowel localisation, which only became evident after a chemotherapy-induced small bowel perforation, illustrate the predilection of posttransplant lymphoproliferations for extranodal sites. Both cases represent the extremes of a spectrum of post-transplant lymphoproliferations ranging from polyclonal benign lesions to monoclonal malignant lymphomas. Their B-cell origin was pathologically established, but in none of the two reported cases the previously postulated role of Epstein-Barr virus in the pathogenesis could be confirmed by serological tests. Severe immunosuppression played a major role in the pathogenesis of these disorders, as suggested by concomitant opportunistic infections occurring in both cases. The lymphoproliferation diagnosed in the polyclonal stage was reversible after reduction of the immunosuppressive therapy, without subsequent graft rejection. This observation underscores the importance of early recognition of lympho-proliferative disorders in organ transplant patients, allowing a prompt and successful reduction of the immunosuppressive therapy. Overwhelming opportunistic infections, occurring in the patient treated with cytotoxic drugs, illustrate the inherent risks of such an approach in an already severely immunosuppressed population.
Whether or not peripheral stem cells have an unlimited capacity for self renewal is debated. However, everyday haematopoietic requirements are met by progenitors; and it seems that few ‘real’ stem ...cells are needed. Although we may not yet have identified these ‘true’ stem cells, for practical purposes the long term culture-initiating cells (LTC-ICs) are a close approximation. To date, experience in peripheral blood progenitor cell (PBPC) transplantation is largely con fined to non-ablative regimens. It is therefore difficult to determine the number of PBPCs needed to effect long-term reconstitution. The number of tumour cells present among mobilised PBPCs can be reduced using the CD34 affinity colunm and by positive purging methods. The ex vivo expansion of CD34 cells also has the effect of diluting tumour cell concentration. In clinical use, PBPC transplantation has a proven role in support of high dose chemotherapy in certain haematological and oncological malignancies but the concept of dose intensification is not universally accepted. With the exception of leukaemia, lymphoma, myeloma or relapsed testicular cancer and possibly some subgroups of breast cancer, high dose chemotherapy does not demonstrate a survival benefit. For patients with CMT., autografting with Ph- cells appears to become a useful alternative to allogeneic BMT. Allogeneic PBPC transplantation may have potential, though work is preliminary. Cord blood transplantation between matched siblings is viable, but it is not yet clear whether this source will increase the donor pool for adults needing allogeneic transplantation. For gene therapy using haematopoietic cells to be effective, a greatly increased rate of transduction will be needed. Meeting in Paris in September 1996, a European School of Oncology Task Force considered a number of important questions relating to peripheral blood progenitor cell (PBPC) physiology and transplantation. This review is a brief account of their conclusions.
Acute graft-versus-host disease (aGVHD) has been classified according to the Seattle criteria as grades 0, I, II, III, and IV for 20 years. The predictive value of such detailed grading is a matter ...of debate; publications usually report GVHD as present or absent or as absent, moderate, or severe. The Working Party Chronic Leukemia of the European Group for Bone Marrow Transplantation analyzed data of 1,294 patients transplanted from an allogeneic donor for chronic myelogenous leukemia (CML) in first chronic phase and tested the predictive value of aGVHD grading for the following end-points: day 100 mortality (D100M), transplant-related mortality (TRM), relapse incidence (RI), leukemia-free survival (LFS), and survival (SURV). aGVHD was absent in 462 patients (35.7%), grade I occurred in 335 (25.8%), grade II in 264 (20.5%), grade III in 110 (8.5%), and grade IV in 123 patients (9.5%). A total of 297 patients (23%) died within 100 days, 495 patients (38%) died of any TRM, and 100 patients (8%) died of relapse. D100M according to grades 0, I, II, III, and IV was 17%, 13%, 19%, 38%, and 70%, respectively, with significant difference between 0-II versus III-IV. TRM was 28%, 27%, 43%, 68%, and 92%, respectively, with a distinct separation between 0-I versus II-IV. RI showed a continuous decrease of 37%, 30%, 23%, 18%, and 8%, respectively, with increasing aGVHD. LFS was 45%, 51%, 44%, 26%, and 7%, respectively, and was best for patients with grade I aGVHD. This finding was also reflected in a better overall survival (60%, 64%, 53%, 30%, and 8%, respectively). The better LFS for grade I aGVHD patients compared with patients with grade 0 or II aGVHD was confirmed (P = .05) in a multivariate analysis. These data document the value of the present 5-point grading of aGVHD, ie, different outcome is observed depending on endpoint analyzed. Restricting information about aGVHD to presence or absence is not warranted.
PDF
