acyclovir and Primary-Myelofibrosis

Alternaria species have been reported as a rare cause of fungal infection in organ and stem cell transplant recipients, but to date, no reports have been published of infection in humans caused by Alternaria rosae. Here, we report cutaneous A. rosae infection in a 66-year-old farmer with a history of primary myelofibrosis who had undergone allogeneic unrelated donor hematopoietic stem cell transplantation. Forty-nine days post transplant, he presented with a nodule on the thumb with no findings suggestive of disseminated infection. Pathology, culture, and molecular speciation showed the nodule was caused by cutaneous A. rosae. He had been on voriconazole as antifungal prophylaxis, but was found to have a subtherapeutic voriconazole level. He was switched to posaconazole based on published in vitro data showing its superior efficacy in Alternaria treatment. Susceptibility testing showed that the A. rosae isolate was indeed susceptible to posaconazole. His cutaneous lesion remained stable, but he died from respiratory failure secondary to lobar pneumonia. At lung autopsy, A. rosae was not identified in the lungs. We believe this to be the first published report, to our knowledge, of A. rosae infection in humans.

Topics: Acute Kidney Injury; Acyclovir; Aged; Alternaria; Alternariosis; Antibiotic Prophylaxis; Antifungal Agents; Drug Therapy, Combination; Fatal Outcome; Graft vs Host Disease; Hand; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Levofloxacin; Magnetic Resonance Imaging; Male; Microbial Sensitivity Tests; Paranasal Sinuses; Phaeohyphomycosis; Pneumonia; Prednisone; Primary Myelofibrosis; Respiratory Insufficiency; Spores, Fungal; Transplantation, Homologous; Triazoles; Voriconazole

The conditioning regimen preceding hematopoietic stem cell transplantation (HSCT) causes a rapid decrease in the platelet count and signs of disseminated intravascular coagulation, possibly indicating platelet activation. As impacts during the conditioning regimen may predict later transplantation-associated complications, we investigated changes in platelet membrane glycoproteins (GP) and the liberation of microparticles. Platelet receptors and granules of 49 patients undergoing HSCT were evaluated by flow cytometric analysis before and after the different phases of the conditioning regimen [chemotherapy, total body irradiation (TBI), therapy with antithymocyte globulin (ATG)] and final transplantation. Following chemotherapy a high surface expression of CD62P, a low mepacrine staining, and a reduced surface expression of CD42b (part of the GP Ib/V/IX complex) were found, indicating an irreversible activation of platelets. In addition, elevated levels of circulating microparticles were observed, which may reinforce the thrombosis risk in these patients. Treatment with ATG leads to an elevated surface expression of PAC-1 epitopes, which are neoepitopes appearing after activation of GP IIb/IIIa. However, a significant degranulation was not detectable, which may be the consequence of inhibitory influences on platelets during ATG-induced cytokine release syndrome. TBI and transplantation itself had no influence on platelets. This study was able to demonstrate activating effects on platelets by certain phases of the conditioning regimen in patients receiving HSCT. Chemotherapy, in particular, leads to a strong and irreversible platelet activation and a generation of microparticles, which may cause an increased thrombosis risk. Our findings underline the impact of platelets on the pathogenesis of hemostatic complications during HSCT.

Topics: Acyclovir; Adult; Aged; Anemia, Aplastic; Antigens, CD; Antiviral Agents; Blood Platelets; Female; Flow Cytometry; Hematopoietic Stem Cell Mobilization; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Middle Aged; Myelodysplastic Syndromes; Platelet Count; Platelet Membrane Glycoproteins; Primary Myelofibrosis; Ranitidine; Receptors, Cell Surface; Stem Cell Transplantation; Transplantation, Homologous