Epidemiology and clinical profiles of cutaneous graft versus host disease in allogeneic peripheral blood stem cell transplantation.

INTRODUCTION: The epidemiology of cutaneous graft versus host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT) in Malaysia has not been described. MATERIALS AND METHODS: We retrospectively analysed 691 allogeneic PBSCT patients between 2010-2017 in two centers. RESULTS: The prevalence of cutaneous GVHD was 31.4% (217/691). No associations were detected with race, age or gender of donor and recipients. Cutaneous GVHD was associated with host cytomegalovirus (CMV) seropositivity (p<0.01), conditioning (p<0.01), GVHD prophylaxis (p=0.046) and survival (p<0.01). Majority developed the acute form (58.1%;126/217). Biopsies in 20.7% (45/217) showed 55.6% positivity for GVHD. Overall, involvement was non-severe. A majority demonstrated complete response (CR) to first-line corticosteroids (70.0%;152/217). Secondline therapies (extracorporeal phototherapy (ECP), psolaren ultraviolet A (PUVA), mycophenolate, tumour necrosis factor (TNF) inhibitors, interleukins inhibitors, or CD20 monoclonal antibodies) were required in 65/217, with 38.5% CR. Second-line therapy was associated with gender (p=0.042), extra-cutaneous GVHD (p=0.021), treatment outcomes (p=0.026) and survival (p=0.048). Mortality in cutaneous GVHD was 24.0% with severe sepsis being the leading cause at Day 100 (7.8%) and 5-years (7.8%), and relapsed disease at 2-years (32.7%). In steroid refractoriness, severe GVHD caused 30.8% mortality. In cutaneous GVHD, survival at Day 100 was 95.4%; 80.2% at 2-years and 73.1% at 5-years. The median survival in cutaneous GVHD was significantly shorter at 55 months, compared to those without GVHD at 69 months (p=0.001). CONCLUSION: Cutaneous involvement is the commonest clinical manifestation of GVHD. A larger national study is warranted to further analyse severity and outcome of multiorgan GVHD, and factors associated with steroid refractoriness.

Antiulcer activity of methanol extract of Melastoma malabathricum leaves in rats.

OBJECTIVE: To determine the potential antiulcer activity of methanol extract of Melastoma malabathricum leaves (MEMM) using various established rat models. MATERIALS AND METHODS: Ten groups of rats were used and orally administered 10% DMSO (negative control), 100 mg/kg ranitidine (positive control) or MEMM (50, 250 and 500 mg/kg) followed by gastric ulcer induction either using ethanol or indomethacin. The stomachs were collected and subjected to macroscopic and microscopic analyses. RESULTS: MEMM exhibited significant (p < 0.05) antiulcer activity in the ethanol, but not in the indomethacin-induced gastric ulcer model. The percentage of antiulcer activity for 50-500 mg/kg MEMM ranged between 3 and 75%, respectively. The gross observations were supported by histological findings. MEMM also aggravated the indomethacin-induced gastric ulcer, leading to an increase in ulcer area formation and ulcer score. CONCLUSION: The M. malabathricum leaves showed antiulcer activity, which could be attributed to their antioxidant and anti-inflammatory activities. This requires further in-depth studies.

Evaluation of the GenoType® MTBDRsl assay for susceptibility testing of second-line anti-tuberculosis drugs.

BACKGROUND: The GenoType® MTBDRsl assay is a new rapid assay for the detection of resistance to second-line anti-tuberculosis drugs. OBJECTIVE: To evaluate the MTBDRsl assay on 342 multidrug-resistant tuberculosis isolates for resistance to ofloxacin (OFX), kanamycin (KM), capreomycin (CPM) and ethambutol (EMB), to compare the results to the agar proportion method, and to test discrepant results using DNA sequencing. RESULT: The sensitivity and specificity of the MTBDRsl assay were respectively 70.3% and 97.7% for OFX, 25.0% and 98.7% for KM, 21.2% and 98.7% for CPM and 56.3% and 56.0% for EMB. DNA sequencing identified mutations that were not detected by the MTBDRsl assay. The 8/11 phenotypically OFX-resistant isolates had mutations in gyrA (2/8 had an additional mutation in the gyrB gene), 1/11 had mutations only in the gyrB gene, 6/21 phenotypically KM-resistant isolates had mutations in the rrs gene, and 7/26 and 20/26 phenotypically CPM-resistant isolates had mutations in the rrs and tlyA genes. CONCLUSION: The MTBDRsl assay showed lower sensitivity than previous studies. The assay performed favourably for OFX; however, it was less sensitive in the detection of KM/CPM resistance and demonstrated low sensitivity and specificity for EMB resistance. It is recommended that the MTBDRsl assay include additional genes to achieve better sensitivity for all the drugs tested.