Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Hepatic Insufficiency/etiology , Liver/physiopathology , Adult , Aged , Austria/epidemiology , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/physiopathology , Cohort Studies , Disease Susceptibility , Elasticity Imaging Techniques , Fibrosis , Graft vs Host Disease/epidemiology , Graft vs Host Disease/immunology , Graft vs Host Disease/pathology , Graft vs Host Disease/physiopathology , Hepatic Insufficiency/epidemiology , Hepatic Insufficiency/pathology , Hepatic Insufficiency/physiopathology , Hepatic Veno-Occlusive Disease/epidemiology , Hepatic Veno-Occlusive Disease/etiology , Hepatic Veno-Occlusive Disease/pathology , Hepatic Veno-Occlusive Disease/physiopathology , Humans , Liver/drug effects , Liver/pathology , Liver/radiation effects , Middle Aged , Myeloablative Agonists/adverse effects , Risk , Transplantation Conditioning/adverse effects , Whole-Body Irradiation/adverse effects , Young AdultABSTRACT
HLA class I molecules participate in natural killer cell regulation by acting as ligands for inhibitory killer cell Ig-like receptors (KIRs). One individual may express one or more inhibitory KIR lacking the corresponding HLA ligand. The role of this 'missing KIR ligand' constellation in hematopoietic SCT (HSCT) remains controversial and depends on incompletely defined transplant variables. We have retrospectively analyzed the effects of missing HLA-C group 1/2 and Bw4 KIR ligands in the recipients on the outcome in 382 HSCT, comparing 118 BMT to 264 PBSC transplants (PBSCT). In the multivariate Cox analysis of PBSCT, poor PFS was observed in homozygous HLA-C group 2 (C2/2) recipients (risk ratio (RR), 1.59; P=0.026). In contrast, C2 homozygosity was not unfavorable after BMT (RR, 0.68; P=0.16). C2 homozygous recipients (n=68) had better PFS after BMT than after PBSCT (RR, 0.17; P=0.001), due to fewer relapses (RR, 0.27; P=0.018). Missing Bw4 favorably influenced PFS after BMT (RR, 0.56; P=0.04), but not after PBSCT. These data suggest opposite effects of missing KIR ligands in BMT vs PBSCT. Larger studies are required to reassess whether BMT should be preferred to PBSCT as an option for C2/C2 recipients.
Subject(s)
Bone Marrow Transplantation , Bone Marrow , HLA-C Antigens , Receptors, KIR , Adolescent , Adult , Aged , Child , Female , Humans , Ligands , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation , Retrospective Studies , Transplantation, HomologousABSTRACT
A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ≥7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P>0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections.
Subject(s)
Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Aspergillosis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Aspergillosis/mortality , Austria/epidemiology , Female , Humans , Immunocompromised Host , Incidence , Male , Middle Aged , Prospective Studies , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
Fresh frozen bone marrow biopsies were evaluated immunohistochemically, applying monoclonal antibodies against CD31, CD34, VEGFR-2 and CD133, a novel marker identifying human endothelial progenitor cells (EPCs). Specimens of 51 patients diagnosed with MDS were compared with 16 AML and 18 controls. The percentage of CD34 expressing cells was increased and CD31 expression was decreased in advanced stages of MDS compared with normal BM. VEGFR-2 expression was also raised in MDS. Here we show for the first time that increased numbers of CD133 positive cells are present in the majority of MDS patients. Additionally, those cells occasionally seem to contribute to capillary forming units in bone marrow.
