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Peritransplantation Ruxolitinib Prevents Acute Graft-versus-Host Disease in Patients with Myelofibrosis Undergoing Allogenic Stem Cell Transplantation

Kröger N, Shahnaz Syed Abd Kadir S, Zabelina T, Badbaran A, Christopeit M, Ayuk F, et al.

Biol. Blood Marrow Transplant., 2018 10;24(10):2152-2156.
PMID: 29800615 DOI: 10.1016/j.bbmt.2018.05.023

JAK inhibition by ruxolitinib is approved for treating myelofibrosis and also has shown efficacy in treating steroid-resistant acute and chronic graft-versus-host disease (GVHD). In 12 patients with myelofibrosis (median age, 63 years; range, 43 to 71 years) who were treated with ruxolitinib and underwent allogeneic stem cell transplantation (ASCT), ruxolitinib was continued (2 × 5 mg daily) until stable engraftment. No graft failure was observed, and leukocyte engraftment was achieved after a median of 12 days (range, 11 to 18 days). One patient developed fever of unknown origin after discontinuation of ruxolitinib; otherwise, no withdrawal syndrome was observed. Overall, only 1 patient each experienced acute GVHD grade I or II, resulting in an 8% incidence of acute GVHD grade II-IV at day +100, with no nonrelapse mortality. Complete chimerism was achieved in 11 patients after a median of 40 days, and molecular clearance of the underlying driver mutation was noted in 10 patients after a median of 32 days. Cytomegalovirus (CMV) reactivation occurred in 5 patients (41%), 1 of whom had CMV colitis as well, but all resolved after ganciclovir treatment. In 2 patients, ruxolitinib had to be discontinued on day 17 and day 18 after ASCT due to cytopenia after engraftment. Levels of inflammatory cytokines IL-8, IL-10, IL-6, TNFR2, INF-α, and INF-β were reduced after ruxolitinib treatment. After day +100, 4 patients developed acute GVHD (1 with grade I, 2 with grade II, and 1 with grade III) after tapering of cyclosporine, and all patients were alive at a median follow-up of 17 months (range, 12 to 18 months).
Epidemiology and clinical profiles of cutaneous graft versus host disease in allogeneic peripheral blood stem cell transplantation

Kamal Rodin NS, Ismail NA, Abdul Wahid SF, Jamil A, Syed Zakaria SZ, Syed Abd Kadir SS, et al.

Malays J Pathol, 2021 Dec;43(3):361-373.
PMID: 34958057

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.
Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis

Shahnaz Syed Abd Kadir S, Christopeit M, Wulf G, Wagner E, Bornhauser M, Schroeder T, et al.

Eur J Haematol, 2018 Sep;101(3):305-317.
PMID: 29791053 DOI: 10.1111/ejh.13099

INTRODUCTION: Ruxolitinib is the first approved drug for treatment of myelofibrosis, but its impact of outcome after allogeneic stem cell transplantation (ASCT) is unknown.
PATIENTS AND METHODS: We reported on 159 myelofibrosis patients (pts) with a median age of 59 years (r: 28-74) who received reduced intensity ASCT between 2000 and 2015 in eight German centers from related (n = 23), matched (n = 86) or mismatched (n = 50) unrelated donors. Forty-six (29%) patients received ruxolitinib at any time point prior to ASCT. The median daily dose of ruxolitinib was 30 mg (range 10-40 mg) and the median duration of treatment was 4.9 months (range 0.4-39.1 months).
RESULTS: Primary graft failure was seen in 2 pts (4%) in the ruxolitinib and 3 (2%) in the non-ruxolitinib group. Engraftment and incidence of acute GVHD grade II to IV and III/IV did not differ between groups (37% vs 39% and 19% vs 28%, respectively), nor did the non-relapse mortality at 2 years (23% vs 23%). A trend for lower risk of relapse was seen in the ruxolitinib group (9% vs 17%, P = .2), resulting in a similar 2 year DFS and OS (68% vs 60% and 73% vs 70%, respectively). No difference in any outcome variable could be seen between ruxolitinib responders and those who failed or lost response to ruxolitinib.
CONCLUSIONS: These results suggest that ruxolitinib pretreatment in myelofibrosis patient does not negatively influence outcome after allogeneic stem cell transplantation.
Study site: 8 health clinics in Germany
The satisfaction and perception of Provisionally Registered Pharmacists (PRP) towards their internship training in the Ministry of Health, Malaysia facilities: A national survey

Syed M Haq AH, Md Yusof FA, Chan PL, Chok MCF, Phua GSY, Teoh CJ, et al.

Curr Pharm Teach Learn, 2018 07;10(7):854-874.
PMID: 30236423 DOI: 10.1016/j.cptl.2018.04.005

BACKGROUND: The pharmacy internship program is designed to provide comprehensive training for interns to perform various roles in pharmacy practice. In Malaysia, the current internship program has been in place since 2004 in public health facilities, but has never been extensively evaluated.
AIM: To assess the level of job satisfaction and perception of Provisionally Registered Pharmacists (PRP) towards the internship training provided.
METHODS: A cross-sectional nationwide survey was conducted amongst all PRPs undergoing training between December 2015 and February 2016 to assess their level of job satisfaction and perception towards the training requirements stipulated by the Pharmacy Board of Malaysia.
RESULTS: A total of 733 PRPs participated in the survey and the response rate was 95.8%. On the basis of the response received, 92.5% (n = 678) felt that the one year training period was 'just nice', 30.5% (n = 223) felt that the logbooks were 'too complicated', and 33.2% (n = 241) said the targets set by the Pharmacy Board of Malaysia were 'too high'. On a scale of 1 to 5, respondents rated 3.32 (SD 0.54) for mean score of job satisfaction. Significant factors influencing mean score of job satisfaction were: perceived fairness at the work place; perceived self-competence after one year of training; preceptors' competence; and pharmacy as a chosen career pathway.
CONCLUSION: Intern pharmacists were fairly satisfied with the internship training in government facilities in the Ministry of Health, Malaysia. A review of the internship logbooks and the practicality of targets set by the Pharmacy Board warrant further improvement.