Raza Azra, Qawi Huma, Andric Tanja, Dar Saleem, Lisak Laurie, Huang Ray-Win, Venugopal Parameswaran, Gezer Sefer, Gregory Stephanie A., Hsu Wei-Tong, Loew Jerome, Robin Erwin, Rifkin Shelby, Shah Rohit, Divgi Ajit, Taylor Robert, Grosset Alan
Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois.
Hematology. 2000;5(4):275-284. doi: 10.1080/10245332.2000.11746517.
Twenty-five patients with a diagnosis of myelodysplastic syndromes (MDS) were randomized to either begin therapy with pentoxifylline, ciprofloxacin and dexamethasone (PCD) immediately (10 patients) or after a 12 week observation period (control arm, 15 patients). PCD was administered with the goal of suppressing cytokine-induced excessive intramedullary apoptosis of hematopoietic cells. No marked fluctuations of blood counts were noted during the period of observation. Twenty-two patients completed at least 12 weeks of therapy: 18/22 showed some type of hematologic response, 9/18 showing an improvement in absolute neutrophil count only (p = < 0.001) and 9/18 showing multi-lineage responses. No unique category of MDS responded better, however 19/25 patients had refractory anemia (RA)/RA with ringed sideroblasts. The median time to response was 6 weeks and 3/18 responding patients maintained their responses beyond a year. We conclude that hematologic improvement in response to PCD therapy supports the validity of this unique anti-cytokine approach. Future trials should combine PCD therapy with established approaches (growth factors/chemotherapy) and also should focus on identifying more effective ways of suppressing the pro-apoptotic cytokines in MDS.
