Allogeneic Hematopoietic Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A CIBMTR Analysis

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes

Uncommon cause of recurrent infections

We descibe the case of a girl of Indian origin who presented with recurrent infections. The only abnormality detected in the armoury of the immune system was consistent neutropenia. Mutation analysis revealed ELA2 (neutrophil elastase) gene mutation that has been associated with severe congenital neutropenia phenotype. Patient was treated with the granulocyte-colony stimulating factor (G-CSF) as prevention of infectious manifestations along with appropriate measure to curb secondary complications. She showed poor response to the G-CSF during stringent surveillance. After being on treatment for 1 year, she developed acute myelogenous leukemia as inherit complication of this disease

Safety of 2-hour IIVs of tacrolimus in the HSCT unit

Pharmacy residents have the opportunity to complete a research project during their residency training, which provides them with skills on how to conduct and manage a research project. Projects often represent an area of interest and need that has been recognized by the host institution’s pharmacy department. Projects are presented as a poster at an annual CSHP Ontario Branch Residency Research Night, and many eventually go on to be published in a peer-reviewed journal.Background: Administering intravenous (IV) tacrolimus by 24-hour continuous IV infusion (CIV), as recommended by the product monograph, poses significant logistical challenges in the allogeneic hematopoietic stem cell transplantation (HSCT) unit because it requires a dedicated central venous catheter lumen. Consequently, at our institution, tacrolimus has been administered via two-hour intermittent IV infusions (IIV) every twelve hours in the HSCT unit. Administration by IIV is not the standard of practice and shorter infusion times are cautioned due to higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions (IRRs), although there is a paucity of data to support this claim. The primary objective of this retrospective study was to evaluate the safety of a two-hour IIV of tacrolimus in an adult HSCT population. Efficacy was evaluated as a secondary endpoint. Methods and Patients: We performed a retrospective chart review of all patients who received IV tacrolimus at our institution from January 2002 – January 2016. We reviewed 104 patients who received 118 tacrolimus treatment courses by IIV (TTC) [median number of doses per TTC=22, range 1 – 158, interquartile range (IQR) = 28]. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and IRRs that occurred during TTC. The incidence of acute graft-versus-host disease (aGVHD) and disease relapse within 180 days of transplant were collected to evaluate efficacy. Results and Discussion: There were sixteen incidences (13.6%) of nephrotoxicity, defined as a doubling of serum creatinine from baseline. Nephrotoxicity resolved in all but six (5.1%) cases. Precipitating factor for nephrotoxicity unrelated to tacrolimus were identified by the physician in all six cases. There were 40 incidences (34.5%) of neurotoxicity [seizure, posterior reversible encephalopathy syndrome (PRES), tremor, paresthesia, visual disturbance], of which, eight (6.8%) were considered serious (seizure and/or PRES). All neurotoxicity reverted to baseline or resolved completely. One grade 2 infusion reaction occurred and resolved without discontinuation of tacrolimus. In the subset of patients who received tacrolimus for the prevention of aGVHD (n=41), seven patients (17.1%) developed grade II – IV aGVHD. Nine patients (8.7%) experienced relapse of their disease. Conclusions: We propose that a two-hour IIV of tacrolimus is a safe method of administration in the adult HSCT setting. Additional safety and efficacy data from other institutions will provide external validity to this conclusion

Clinical value of next‐generation sequencing compared to cytogenetics in patients with suspected myelodysplastic syndrome

Summary Next‐generation sequencing (NGS) increasingly influences diagnosis, prognosis and management of myelodysplastic syndrome (MDS). In addition to marrow morphology and flow cytometry, our institution performs cytogenetics (CG) and NGS‐based testing routinely in patients with suspected MDS. We evaluated the relative value of NGS in the assessment of patients with suspected MDS. We initially compared the diagnostic and prognostic information derived from CG and NGS in 134 patients. NGS enhanced the diagnostic yield compared to CG for clonal myeloid disorders (sensitivity 77% vs. 42·2%; specificity 90·2% vs. 78%; positive predictive value 92·8% vs. 76%; and negative predictive value 70·8% vs. 45·5%). The identification of poor prognosis mutations by NGS altered risk category in 27/39 (69·2%) patients with MDS with good/intermediate risk CG. Subsequently, we prospectively evaluated 70 patients with suspected MDS using an ‘NGS‐first approach’ with CG restricted to samples with morphological abnormalities. We rarely identified mutations or CG abnormalities in patients without dysplastic features. NGS has a superior diagnostic performance compared to CG in patients with suspected MDS. We estimate that by using an ‘NGS‐first approach’ we could reduce karyotyping by approximately 30%

Cell Therapy Transplant Canada (CTTC) Consensus-Based Guideline 2024 for Management and Treatment of Chronic Graft-Versus-Host Disease and Future Directions for Development

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD. This document will provide comprehensive and practical guidance that can be applied across Canada by healthcare professionals caring for patients with cGvHD. Hopefully, this guideline, based on input from GvHD treaters across the country, will aid in standardizing cGvHD care and facilitate access to much-needed novel therapies. This consensus paper aims to discuss the optimal approach to the initial assessment of cGvHD, review the severity scoring and global grading system, discuss systemic and topical treatments, as well as supportive therapies, and propose a therapeutic algorithm for frontline and subsequent lines of cGvHD treatment in adults and pediatric patients. Finally, we will make suggestions about the future direction of cGvHD treatment development such as (1) a mode-of-action-based cGvHD drug selection, according to the pathogenesis of cGvHD, (2) a combination strategy with the introduction of newer targeted drugs, (3) a steroid-free regimen, particularly for front line therapy for cGvHD treatment, and (4) a pre-emptive approach which can prevent the progression of cGvHD in high-risk patients destined to develop severe and highly morbid forms of cGvHD.Other UBCNon UBCReviewedFacultyResearche