Haploidentical Transplants with Post-Transplant Cyclophosphamide for Relapsed or Refractory Hodgkin Lymphoma: The Role of Comorbidity Index and Pretransplant Positron Emission Tomography

Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P?=?.03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P = .01; HR, 3.3; 95% CI, 1.2 to 9.0; P?=?.02; and HR, 4.2; 95% CI, 1.7 to 9.9; P?=?.001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P?=?.005, HR, 3.8; 95% CI, 1.5 to 9.7; P?=?.005; and 3.2; 95% CI, 1.3 to 7.9; P?=?.01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS.     

Catheter-Related Thrombosis in Patients with Lymphoma or Myeloma Undergoing Autologous Stem Cell Transplantation

Catheter-related thrombosis (CRT) occurs frequently during autologous hematopoietic cell transplantation (AHCT) and data regarding the incidence, risk factors, and management are understudied. We evaluated 789 consecutive patients with lymphoma and myeloma that underwent AHCT over 10 years (2006 to 2016) and detected the incidence of CRT was 6.3%; only 32% of CRT were symptomatic. The majority occurred within 100 days of AHCT (86%) and median time from tunneled line placement to CRT was 44 days (range, 11 to 89 days). Outcomes of these 50 patients with CRT were compared with age- and disease-matched AHCT control subjects to identify risk factors. History of prior venous thromboembolism (VTE) (20.9% versus 7.0%, P = .02) was the only significant risk factor. Treatment with low-molecular-weight heparin was tolerated with rare minor bleeding (4%), although CRT recurrence or extension (10%) and subsequent VTE (12%) were common. CRT did not impact on nonrelapse mortality or risk of relapse; 2-year progression-free survival was 55% in CRT cases versus 54% in control subjects (P = .42). CRT appears to be common in patients with lymphoma and myeloma undergoing AHCT and significantly contributes to morbidity. Further study to determine mitigating strategies and modify risk factors for CRT is warranted.     

Evolving issues in understanding and treating bacterial vaginosis

Bacterial vaginosis is a synergistic polymicrobial syndrome characterized by depletion of Lactobacillus spp., especially those that produce hydrogen peroxide, and an intense increase in the quantity of commensal vaginal anaerobic bacteria to 100- to 1000-fold above normal levels. While the bacterial spectrum of these organisms has long been known to include Gardnerella vaginalis, Prevotella spp., anaerobic Gram-positive cocci, Mobiluncus spp. and Mycoplasma hominis, innovative use of molecular diagnostics has identified novel species apparently associated with this syndrome, including Atopobium vaginalis. Effecting resolution of bacterial vaginosis is important, in particular for the 8 to 23% of women afflicted with symptomatic disease during their reproductive years. Bacterial vaginosis has been consistently associated with numerous adverse sequelae related to the upper genital tract, including pelvic inflammatory disease and postsurgical infection in the setting of invasive gynecologic procedures, and may increase women's risk of acquiring HIV infection. Pregnant women with bacterial vaginosis experience a higher rate of preterm delivery and low-birth-weight infants. While antibiotics with activity against anaerobes--typically, metronidazole and clindamycin applied vaginally or taken orally--are the mainstays of therapy, bacterial vaginosis frequently recurs. For these reasons, innovative approaches to therapy are urgently required.     

Food-related quality of life in patients with inflammatory bowel disease and irritable bowel syndrome

Quality of Life Research - Food-related quality of life (FRQoL) evaluates the impact of diet, eating behaviors, and food-related anxiety on a person’s quality of life. This is the first study...     

Polysomnographic diagnosis of idiopathic REM sleep behavior disorder

The presence of either excessive tonic chin EMG activity during REM sleep, or excessive phasic submental or limb EMG twitching is required to diagnose REM sleep behavior disorder (RBD). The aim was to identify cut‐off values and to assess the sensitivity and specificity of these values taken separately or combined to diagnose idiopathic RBD patients. Eighty patients presenting with a clinical diagnosis of idiopathic RBD and 80 age‐ and gender‐matched normal controls were studied in the sleep laboratory. Receiver operating characteristic curves were drawn to find optimal cut‐off values for three REM sleep EMG parameters. Tonic and phasic EMG activity were measured in the chin, but not in the limbs. Videos were examined during the recording but were not systematically reviewed by the authors. Total correct classification of 81.9% was found for tonic chin EMG density ≥30%; 83.8% for phasic chin EMG density ≥15% and 75.6% for ≥24 leg movements per hour of REM sleep. Five patients did not fulfill any of these three polysomnographic (PSG) criteria. Conversely, one subject of the control group met the PSG criteria for RBD. This study estimates the diagnostic value of a visual scoring method for the diagnosis of idiopathic RBD and establishes cut‐off values to be used in clinical and research set‐ups. For the five RBD patients who did not show chin EMG abnormalities, it cannot be excluded that they had increased phasic EMG activity in the upper limbs and presented visible motor activity. © 2010 Movement Disorder Society     

Importance of the cutoff ratio for detecting antibodies against hepatitis A virus in oral fluids by enzyme immunoassay

Multiple studies have examined the use of oral fluids in modified serum-based assays aiming to replace serum in antibody detection for hepatitis A. However, the reliable detection of HAV immunity in oral fluid requires an extremely sensitive assay; most immunoassays designed for serum antibody determination lack sufficient sensitivity for this purpose. Consequently, an “in-house” competitive enzyme immunoassay (EIA) designed specifically for use with oral samples collected using a ChemBio^® device was developed to detect total anti-HAV antibodies (IgG and IgM). This system was compared to an in-house competitive EIA and a commercial EIA considered to be the “gold standard” using corresponding serum samples (n = 225) to determine the accuracy of the assay and to evaluate the importance of the cutoff ratio for the detection of anti-HAV antibodies in oral fluids. When the median serum cutoff and the optimal oral fluid cutoff (ROC analysis) obtained from the in-house competitive EIA were compared, the oral fluid cutoff was found to be 28.8% higher than the serum cutoff. When different oral fluid cutoff values were compared, a reduction of about 17% was shown to be essential to increase test accuracy. At an oral fluid cutoff value of 0.351, sensitivity and specificity were higher, reaching 91.7% and 86.2% (p < 0.001, AUROC = 0.915), respectively. The convenience, accuracy and non-invasive nature of the developed method make it a useful alternative to serum-based assays for discriminating between HAV-immune and non-immune individuals.     

Extracellular DNA in biofilms

Extracellular DNA (eDNA) is an important biofilm component that was recently discovered. Its presence has been initially observed in biofilms of Pseudomonas aeruginosa, Streptococcus intermedius, Streptococcus mutans, then Enterococcus faecalis and staphylococci. Autolysis is the common mechanism by which eDNA is released. In P. aeruginosa eDNA is generated by lysis of a bacterial subpopulation, under control of quorum sensing system. In E. faecalis autolysis proceeds in a fratricide mode, resulting from a process similar to necrosis of eukaryotic cells. In Staphylococcus aureus autolysis originates by an altruistic suicide, i.e., a programmed cell death similar to apoptosis of eukaryotic cells. In S. aureus autolysis is mediated by murein hydrolase, while in S. epidermidis by the autolysin protein AtlE. In P. aeruginosa eDNA is located primarily in the stalks of mushroom-shaped multicellular structures. In S. aureus the crucial role of eDNA in stabilizing biofilm is highlighted by the disgregating effect of DNase I. eDNA represents an important mechanism for horizontal gene transfer in bacteria. eDNA and other microbial structural motifs are recognized by the innate immune system via the TLR family of pattern recognition receptors (PRRs).