Two Cases of Veno-occlusive Disease/Sinusoidal Obstruction Syndrome After Thioguanine Treatment for Acute Lymphoblastic Leukemia.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation conditioning or high-dose chemotherapy. The underlying pathogenesis involves toxic injury to hepatocytes and sinusoidal endothelial cells. Presenting symptoms include ascites, weight gain, hepatomegaly, and hyperbilirubinemia. Severe VOD/SOS with multiorgan failure has a mortality rate of >80% if left untreated. Thioguanine, a chemotherapy drug used to treat acute lymphoblastic leukemia, has been shown to cause VOD/SOS. Here, we describe cases of 2 patients who developed very severe VOD/SOS after starting thioguanine for acute lymphoblastic leukemia; both achieved complete remission with defibrotide and experienced no defibrotide-related adverse events.

Extended Treatment With Mesenchymal Stromal Cells-Frankfurt am Main in a Pediatric Patient With Steroid-refractory Acute Gastrointestinal Graft-Versus-Host Disease: Case Report and Review of the Literature.

In acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation, there are various options available after the failure of initial steroid therapy. Since the publication of the first study in 2008, mesenchymal stromal cells (MSCs) have also been used with increasing frequency, including in pediatric patients with steroid-refractory aGVHD, and the manufacturing process has undergone further development. MSC-Frankfurt am Main (MSC-FFM, Obnitix), which is manufactured from pooled mononuclear bone marrow cells from 8 donors using a standardized process, resulted in a response rate of 84% in children with steroid-refractory aGVHD. We report on a 13-year-old female patient with acute myeloid leukemia who received Obnitix as a third-line treatment for gastrointestinal (GI) aGVHD in a life-threatening situation. The patient was initially given a total of 4 Obnitix infusions as per the regulatory approval, with her symptoms improving from day 9 after the first infusion. The second cycle of 4 Obnitix infusions followed due to persistent severe protein-losing enteropathy and resulted in complete remission. A systematic review of the literature on MSC in pediatric patients with steroid-refractory aGVHD confirms that MSC treatment beyond 4 weeks is employed in accordance with treatment protocols or on a case-by-case basis. To summarize, aGVHD activity can be checked endoscopically in patients with persistent GI symptoms and a second Obnitix cycle can then be administered if appropriate, with the goal of achieving complete remission. Future studies should also investigate the potential influence of tissue repair properties as an element in MSCs' efficacy in GI aGVHD.

A Retrospective Analysis of the Association Between Male Facial Hair and the Incidence of Peri-Prosthetic Infections.

Background: The wearing of male facial hair has been undergoing something of a renaissance for a number of years, with medical colleagues in the surgical disciplines being no exception. Meanwhile, there are a few reports in the literature that beards might have an increased bacterial colonization. This study aims to determine if wearing a beard leads to an increased rate of infection in total hip or knee arthroplasty. Patients and Methods: A retrospective analysis was performed on 20,394 primary hip and knee replacements that were implanted at a single university hospital. The rate of infections that occurred within one year after surgery and the surgeons performing the surgery were recorded. The surgeons were classified into clean-shaven and beard wearers. The beard wearers were further classified by individual facial hair styles, namely a moustache, chin beard, round beard, or full beard. Results: The overall rate of surgical site infections 365 days after surgery is 0.75%. There was no statistically significant association between surgical site infection and the presence of facial hair (p = 0.774) or specific beard types (p = 0.298). Conclusions: The results presented in this study show no differences in infection rates across different facial hair styles of male surgeons.

Analysis of risk factors for hepatic sinusoidal obstruction syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients.

PURPOSE: Hepatic sinusoidal obstruction syndrome (SOS) represents a serious complication following hematopoietic stem cell transplantation (HSCT). Our study aimed to investigate important risk factors of SOS in a pediatric population. METHODS: This retrospective study analyzed 105 children, adolescents and young adults who underwent allogeneic HSCT at our pediatric HSCT center in Jena. The observation period was 12 years and SOS was defined by the pediatric criteria of the European Society for Blood and Marrow Transplantation (EBMT). RESULTS: 15 out of all 105 patients developed SOS (14.3%). The median time from HSCT to SOS diagnosis was 12 days. The mortality rate of SOS was 20.0%. In univariate analyses, we identified the significant risk factors of patient age < 1 year [odds ratio (OR) = 7.25, p = 0.037], prior treatment with gemtuzumab ozogamicin (OR = 11.00, p = 0.020), high pretransplant ferritin levels above 1500 ng/mL (OR = 4.00, p = 0.033), 2000 ng/mL (OR = 4.69, p = 0.016), and 2400 ng/mL (OR = 5.29, p = 0.005) as well as international normalized ratio (INR) ≥ 1.3 (OR = 5.91, p = 0.009). The following risk factors could be confirmed in multivariate analysis: treatment with gemtuzumab ozogamicin (OR = 9.24, p = 0.048), ferritin > 2400 ng/mL (OR = 5.74, p = 0.023), and INR ≥ 1.3 (OR = 8.02, p = 0.007). CONCLUSION: Our study confirms several risk factors from the current literature. Additionally, this is the first report on the risk factor of high pretransplant INR.

Glutathione-S-transferases and Chemotherapy Resistance of Hodgkin's Lymphoma Cell Lines.

BACKGROUND: Glutathione-S-transferases (GSTs) are associated with multidrug resistance of tumor cells and are involved in drug detoxification and control of apoptosis. We analyzed the impact of GSTs on apoptosis of Hodgkin's lymphoma (HL) cells. MATERIALS AND METHODS: Expression of GST isoforms in HL cell lines was assessed by analysis of DNA microarray data and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The impact of the GST inhibitor ethacrynic acid (EA) on HL cell survival was analyzed in vitro. RESULTS: DNA microarray analysis and qRT-PCR analysis demonstrated higher expression of GST isoforms in chemoresistant HL cells. Therefore, GSTs may contribute to chemoresistance of HL cells. Incubation of GST-expressing chemoresistant L-1236 HL cells with EA significantly enhanced the activity of cisplatin against these cells. CONCLUSION: Our data suggest that the combined treatment with chemotherapy and GST inhibitors such as EA might be an interesting option for patients with chemoresistant HL.