Cutaneous graft-versus-host disease (GVHD) is common in allogeneic haematopoietic stem cell transplantation. HLA mismatch is the most significant determinant of GVHD. Our study aimed to compare the incidence of cutaneous GVHD haploidentical (Haplo) and matched donors in an Asian population.Retrospective cohort study of the 2015-2019 bone marrow transplant registry was conducted in a transplant centre. We compared the incidence of cutaneous GVHD in Haplo with allogeneic matched unrelated donor (MUD) and matched-sibling donor (MSD) transplant recipients. Secondary objectives include acute and chronic GVHD incidence, dermatology referrals, and histological findings.One hundred and seventy-nine out of 203 cases were reviewed; 17 (9.5%) Haplo, 80 (44.7%) MUDs and 82 (45.8%) MSDs. The median follow-up for Haplo, MUD and MSD was 15.2, 34.2 and 35.7 months, respectively. Haplo had a higher cumulative incidence of cutaneous GVHD than MUD and MSD (p = 0.053). Chronic GVHD was only reported in MSD. The most common histology was vacuolar interface changes (13 [44.8%]) with a wide range of onset post-transplant (19-456 days).Haplo donors may have a higher GVHD incidence than MUD and MSD in our predominantly Asian cohort. This information may be helpful when counselling patients pre-transplant. Further prospective studies are required.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immunologically mediated, severe cutaneous adverse reactions involving cytotoxic T cells, natural killer cells and various mediators. In large studies, up to 15% of SJS/TEN occurred in patients with chronic corticosteroid use. It is unclear if this prior exposure to corticosteroids modified the disease course.To evaluate whether systemic corticosteroid usage prior to the onset of SJS/TEN modified the clinical course and outcome. If a disease-modifying effect is present, information from such an analysis may have implications on the therapeutic use of corticosteroids in SJS/TEN.This is a case-control study based on data collected in the EuroSCAR and RegiSCAR studies. Ninety-two cases of SJS/TEN with exposure to corticosteroids prior to the onset of disease, and 321 randomly selected SJS/TEN patients without prior exposure were included. Primary outcomes included progression of disease, disease severity and mortality. A secondary analysis of latency between the beginning of drug use and the onset of disease, based on exposure to a single high-risk drug, was also performed.On multivariate analysis, cases with prior exposure to corticosteroids had a longer progression of disease by 2·2 days [95% confidence interval (CI) 1·1-3·2]. The disease severity and mortality outcome were unaffected. In addition, there is evidence that corticosteroids delayed the onset of SJS/TEN in patients with exposure to high-risk drugs by 7·1 days (CI -0·2 to 14·5).The prior use of corticosteroids prolonged the period of disease progression without influencing the disease severity or mortality. In addition, when SJS/TEN is preceded by use of a single high-risk drug, the latency between the drug intake and the onset of SJS/TEN may also be increased. These findings suggest that corticosteroids have a mild impact on the course of SJS/TEN, and further studies are required to clarify any potential therapeutic effects.
Sodium hypochlorite is a clear yellowish solution with a characteristic odour of chlorine and is commonly used as a disinfectant and a bleaching agent. It is used in various healthcare settings for its fast-acting and broad-spectrum antimicrobial activity. It is a known irritant and there are some reports that it can also cause allergic contact dermatitis of type IV hypersensitivity. We report a case of work-related type I hypersensitivity to sodium hypochlorite, presenting with recurrent urticarial rash and a positive prick test reaction to this chemical. He was subsequently excused from further exposure with no further recurrences of the urticarial rash. To the best of our knowledge, this is the first such reported case due to work in the healthcare setting.
Abstract Background. Korean American women have one of the highest breast cancer mortality rates and lowest breast cancer screening rates among American women. In response to the need to enhance breast cancer screening, this study aims to develop and test a 7-day mobile phone application (app)-based Mammogram (mMammogram) intervention designed to promote breast cancer screening among Korean American women. To date, mobile app technology has not been used for mammogram promotion. Methods. Using FBM Model, we developed a mammogram intervention designed to increase knowledge of breast cancer screening, intent to receive mammogram, and the receipt of a mammogram. A series of focus groups were conducted to inform the development of the intervention. A randomized controlled trial was conducted with baseline, one week post-intervention, and 6-month follow-up testing among 120 Korean American women who were aged 40 and older and had not had mammograms within the last 2 years. The intervention group (60) received an individually and culturally tailored text messages via mobile app with health navigation services. The control group (60) received a brochure including information on breast cancer, screening guidelines, and a list of clinics that offer low-cost or free mammography without health navigation services. Results. At one week post-test, statistically significant between-group differences were found; intervention subjects reported higher scores of knowledge in breast cancer and screening guideline than subjects in control group (mean differences: 1.70, p < 0.05). No statistical between group differences identified in intention to receive screening. However, significant between-group difference was found in the receipt of mammogram at 6-month follow-up test; 40.0% (24/60) of the intervention group received mammograms whereas 25.0% (15/60) of the brochure group received mammograms after intervention (p < 0.05). 100% of the participants expressed satisfaction with the intervention and 98.3% reported that they would recommend the program to their friends. Conclusions. This study provides evidence of the effectiveness and feasibility of the mammogram intervention with health navigation services in promoting breast cancer screening. Mobile application-based intervention is a promising tool to increase both knowledge and receipt of mammograms. Given the widespread usage of mobile phone among minority populations, a mobile phone-based health intervention could be an effective method of reaching hard-to-recruit populations with high breast cancer burden, using individually tailored messages that cover broad content areas and overcome restrictions to place and time of delivery. Citation Format: Lee HY, Le C, Ghebre R, Yee D. Mobile phone multimedia messaging intervention for breast cancer screening. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-08-03.
Penicillin allergies are frequently reported, yet up to 90% of cases are not true allergies upon further evaluation [1]. Drug provocation testing (DPT) remains the gold standard for diagnosis. Prolonged DPT may enhance diagnostic sensitivity [2] and patient confidence in future penicillin usage [3], though concerns about unnecessary antibiotic exposure remain. The latest European Academy of Allergy & Clinical Immunology (EAACI) position paper calls for further evidence to clarify its role [4]. In this prospective study, we aimed to evaluate our centre's multidisciplinary penicillin allergy evaluation programme, focusing on the safety and utility of a 5-day prolonged DPT for patients with delayed onset or unknown reactions. From March 2019 to May 2023, adults referred to the Singapore General Hospital outpatient allergy centre for suspected penicillin allergy were recruited, excluding those with severe cutaneous adverse reactions. At the initial visit, detailed clinical histories and patient backgrounds were recorded. Reactions were classified as 'Immediate' (within 6 h of antibiotic consumption) or 'Delayed' (after 6 h). On challenge day, skin prick testing (SPT) and intra-dermal testing (IDT) were conducted, following European Network of Drug Allergy (ENDA) and EAACI guidelines [5, 6]. Negative skin tests were followed by graded in-clinic DPT, conducted with divided doses every 30 min until full therapeutic dose. Patients were then observed in clinic for an hour; if no objective reaction occurred, an immediate reaction was considered excluded. For patients with index reactions with delayed/unknown onset, and/or unknown clinical history, delayed IDT reading was performed, and if negative, a 5-day at-home prolonged DPT was then implemented. Patients were monitored through follow-up calls to ensure compliance and document reactions. Suspected positive reactors were encouraged to submit photographs or return for in-clinic evaluation. A total of 321 patients were included. The most commonly investigated drug was co-amoxiclav (87.2%), followed by amoxicillin (10.0%). The index reaction occurred within 6 h in 78 patients (24.3%), after 6 h in 81 (25.2%), while 162 (50.5%) were unable to recall their onset. The most common index reactions were rash (46.7%), angioedema (24.3%) and itch (15.0%). Of the 320 patients who completed evaluation (Figure 1a), 17 (5.3%) had positive skin tests. The remaining 303 underwent in-clinic DPT, with 33 (10.9%) having positive reactions. One patient had a positive delayed IDT. Among the 200 patients proceeding to prolonged DPT, 34 (17.0%) had positive reactions, mostly occurring after Day 3 (70.6%) (Figure 1b). The most frequent reactions included rash (23, 67.6%), itch (19, 55.9%) and/or angioedema (9, 26.5%). None exceeded the index reaction's severity; all were managed conservatively without corticosteroids or hospitalisation. Overall, 85 (26.6%) patients were confirmed to have true penicillin allergy, while 235 (73.4%) were safely de-labelled. Secondary analysis showed that patients with positive prolonged DPT or delayed IDT were less likely to report urticaria (11.3% vs. 30.0%, p = 0.043) as their index reaction. Additional information about study methods and findings is available in the following repository: https://doi.org/10.5281/zenodo.14690499. In our study, prolonged DPT identified 34 (17.0%) additional cases of true penicillin allergy, increasing diagnostic yield by 40.0% compared to single-day DPT alone. These findings are consistent with prior studies [2, 7], including a large systematic review by Kulalert et al., where prolonged DPT nearly doubled diagnostic yield (Risk ratio 1.94) [8]. The mechanism underlying delayed positive challenge reactions is presently unclear. It is generally accepted that prolonged DPT aims to identify delayed hypersensitivity reactions; in our cohort, patients with positive delayed challenges were less likely to present with urticaria (11.4% vs. 30.0%, p = 0.043). However, we hypothesise that prolonged DPT can also identify immediate reactors who were re-sensitised, which could explain why some reactions only manifest after Day 3. Identifying these reactions is critical, as they might otherwise be misdiagnosed as non-allergic following a single-day DPT. We acknowledge that it is challenging to determine whether delayed reactions during prolonged DPT stem from prolonged antibiotic intake, or would have occurred following the in-clinic DPT dose alone. One potential solution is the use of a washout period; however, this may reduce compliance. Moreover, Chiriac et al.'s 20-year study of single-day DPTs for suspected beta-lactam allergies found that only 1.1% of positive provocations occurred after 48 h [9]. In our cohort, most positive prolonged DPT reactions (70.6%) emerged only from Day 3 onwards, suggesting these are true allergies that would have likely been missed without prolonged DPT. We also cannot exclude that a proportion of positive prolonged DPT reactions were due to re-sensitisation or de novo sensitisation. However, it is arguable that these reactions might have occurred irrespective of prolonged DPT if the patient had been prescribed a full penicillin course during a subsequent illness, which would be inconvenient and unpleasant. Additionally, some delayed reactions were self-reported, potentially contributing to the higher rates of delayed positive reactions observed. While patients were encouraged to submit photographs or return for in-clinic evaluation, some were unable or declined. The absence of post-challenge follow-up to confirm future penicillin tolerance is another limitation. Further studies are required to address these gaps. In conclusion, our findings suggest that a 5-day prolonged DPT may enhance diagnostic yield for suspected penicillin allergy in adults, while remaining safe. Patients with delayed onset or unknown index reactions may benefit from prolonged DPT. Further research is needed to determine the optimal duration and assess the utility of a washout period. H.Y.L. and K.J.L.C. contributed to the conception of the study. A.J.S.A. and C.J.C. were involved in data collection and verification. A.J.S.A. and K.J.L.C. were involved in data analysis. All authors contributed to the writing and/or proofreading of the manuscript. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
8107 Background: Overcoming EGFR TKI resistance (R) is a major clinical challenge; reported mechanisms include EGFR T790M mutation (mt), MET amplification (amp) and PIK3CA mt. As the PI3K pathway is a central convergent signaling node, we hypothesized that addition of buparlisib (BKM) could overcome EGFR TKI-R. Methods: Patients (pt) resistant to EGFR TKI (Jackman JCO 2010) were enrolled to determine safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of BKM-gef. Using a “3+3” design, escalating doses of BKM were added to pt progressing on gef (Gp A). Pt not on gef preceding enrolment received a 2 wk run in (Gp B). Given the favorable CNS penetration of BKM, a CNS gp with brain metastases only was included. Pt had pretreatment biopsies and sequential PET-CT scans (baseline & d28). Results: 15 pt have been treated at 3 dose levels: BKM 80 mg/d (n=6), 100 mg/d (n=6), 80 mg 5d on 2d off (5/2, n=3), with gef 250 mg/d. Gp A (n=9, 1 CNS), B (n=6, 1 CNS), F:M (9:6), median age 63 (47-73) and majority >3 lines of therapy. DLT was G3 diarrhea observed in 2/6 pt at BKM100. Common adverse events (AE, all grades) include rash (80%), diarrhea (73%), fatigue (60%), anorexia (47%), mucositis (40%). Notably, 40% of pt had late (beyond DLT period) G3 toxicities such as rash and diarrhea. MTD is BKM 80/d and gef 250/d. To improve the overall safety profile, an intermittent schedule of BKM80 5/2 was also found to be feasible. In gp B, PET-CT done after 2 wk run-in of gef, 3/4 evaluable pt demonstrated reduction in SUV max of which 1 had PR. With addition of BKM, reduction in SUV max (>25%) was seen in 4/10 pt (gp A & B). Median PFS 2.8 m (95%CI 2.3 – 8.1), two pt in CNS gp had PFS of 2.8 and 10.7 m. Molecular analyses revealed 6/12 (50%) harbored T790M mt, 2/5 (40%) MET amp, 0/12 PI3KCA mt. In gp A, 4/9 pt (2 T790M; 1 MET amp) had clinical responses, including slight tumor shrinkage and reduced pleural effusion, but required dose reductions due to AE. PK profiles are being analyzed. Conclusions: MTD is gef 250-BKM 80/d. Antitumor activity has been observed with addition of BKM in EGFR TKI-R pt. In view of late toxicities and long t½ of BKM, exploring alternative schedules is warranted. A dose expansion cohort at MTD is currently ongoing. Clinical trial information: NCT01570296.
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