Skin biopsies in acute myeloid leukemia patients undergoing intensive chemotherapy are safe and effect patient management

Abstract There is paucity of data regarding the diagnostic yield and safety of skin biopsies in patients with acute myeloid leukemia (AML), though skin eruptions are common in these patients. We evaluated 216 patients treated in our hemato-oncology unit at a tertiary medical center between 2007 and 2018 and identified 35 patients who underwent 37 skin biopsies. The majority of biopsies were performed during induction treatment for AML (n = 26, 70%), whereas the remainder of biopsies were done prior to induction initiation (n = 8, 22%) or during consolidation chemotherapy (n = 3, 8%). Pathology findings were inconclusive in 13 cases (35%), while diagnostic biopsies were positive for drug eruptions (24%), leukemia cutis (16%), infections (11%), reactive processes (8%) and Sweet syndrome (5.5%). In almost half of cases (16/37) tissue cultures were performed. Of those, only a quarter (4/16) were positive. Histopathology and tissue culture results altered immediate patient care in 3 cases (8%), yet information obtained from biopsies had potential to affect long term patient care in 8 additional cases (21.6%). Although most skin biopsies were performed while patients had severe thrombocytopenia and neutropenia, only one patient had a complication due to the biopsy (fever and local bleeding). With the limitation of a retrospective analysis, our study suggests that skin biopsies in patients treated for AML are relatively safe. Although biopsy results infrequently alter immediate patient management, long term effect on patient care expand the potential diagnostic yield of skin biopsies

Vascular Endothelial Growth Factor Augments Arginine Transport and Nitric Oxide Generation via a KDR Receptor Signaling Pathway

Background/Aims: Vascular endothelial growth factor (VEGF) is an endothelium-specific peptide that stimulates angiogenesis via two receptor tyrosine kinases, Flt-1 and KDR. Endothelial nitric oxide synthase (eNOS) plays a major role in VEGF signaling. Delivery of arginine to membrane bound eNOS by the cationic amino acid transporter-1 (CAT-1) has been shown to modulate eNOS activity. The current studies were designed to test the hypothesis that VEGF enhances eNOS activity via modulation of arginine transport by CAT-1. Methods: Using radio-labeled arginine, {[3H] L-arginine} uptake was determined in human umbilical vein endothelial cells (HUVEC) following incubation with VEGF with and without silencing the VEGF receptors Flt-1 or KDR. Subsequently, western blotting for CAT-1, PKCα, ERK 1/2, JNK, and their phosphorylated forms were performed. NO generation was measured by the Griess reaction. Results: VEGF (50 and 100 ng/ml) significantly augmented endothelial arginine transport in a time dependent manner, an effect which was prevented by Sunitinib (2 µM), a multi targeted receptor tyrosine kinase inhibitor. The increase in arginine transport velocities by VEGF was not affected by silencing Flt-1 while silencing KDR abrogated VEGF effect. Furthermore, incubating cells with 50 and 100 ng of VEGF for 30 minutes significantly augmented CAT-1 abundance. The expression of PKC-α, JNK, and ERK1/2 and their phosphorylated forms were unchanged following incubation of HUVEC with VEGF. The concentration of NO2/NO3 following incubation with VEGF was significantly higher than from untreated cells. This increase was significantly attenuated by silencing KDR. Conclusions: VEGF increases arginine transport via modulation of CAT-1 in endothelial cells. This effect is exclusively dependent on KDR rather than Flt-1

Infection prevention practices among EBMT hematopoietic cell transplant centers: the EBMT Infectious Disease Working Party survey

We aimed to describe the current status of infection prevention practices among EBMT centers. Questionnaires were distributed to all 553 EBMT transplant centers to capture clinical practices regarding antimicrobial prophylaxis, protective measures, isolation procedures and growth-factor support of patients undergoing hematopoietic cell transplantation. Responses from 127 centers in 32 countries were obtained. Most centers housed patients in single rooms (autologous-82%; allogeneic-98%), with high-efficiency particulate air (HEPA)-filters (autologous-73%; allogeneic-100%) and positive pressure (autologous-61%; allogeneic-88%). Pre-engraftment G-CSF was utilized by 77 and 31% of centers after autologous and allogeneic transplantation, respectively (P < 0.00001). Antibacterial prophylaxis was provided by 57 and 69% (P = 0.086) of centers and antifungal prophylaxis by 65 and 84% (P = 0.0008) of centers, to patients undergoing autologous and allogeneic transplantation, respectively. Yet, 16 and 3% of centers provided neither antibacterial nor antifungal prophylaxis to patients undergoing autologous and allogeneic transplantation, respectively. Considerable variation existed between centers and across countries in antimicrobial prophylaxis practices, medications employed and duration of preventive therapy. There were considerable discordances between guidelines and daily practices. JACIE accredited and non-accredited centers did not differ significantly in their antimicrobial prophylaxis practices. Whether these differences between transplant centers translated into differences in infectious morbidity, mortality and financial costs, warrants further research

Characteristics and outcomes of children, adolescents and young adults with relapsed/refractory non-hodgkin lymphoma undergoing autologous stem cell transplant

Abstract Background There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). Methods Patients aged 0–39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed. Results Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6–39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P  25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0–196.6) months after ASCT, and SPM was the cause of death in five (50%) of them. Conclusions CAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS