ANZTCT consensus position statement on ruxolitinib in steroid-refractory acute and chronic graft-versus-host disease.

This position paper provides an overview of the assessment and management of both acute and chronic graft-versus-host disease (GvHD). There is a focus on the use of ruxolitinib, a selective inhibitor of Janus kinase (JAK)1 and JAK2, for the treatment of corticosteroid-refractory and corticosteroid-dependent GvHD.

Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis.

Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by inflammation, marrow fibrosis, and an inherent risk of blastic transformation. Hematopoietic allogeneic stem cell transplant is the only potentially curative therapy for this disease, however, survival gains observed for other transplant indications over the past two decades have not been realized for MF. The role of transplantation may also evolve with the use of novel targeted agents. The chronic inflammatory state associated with MF necessitates pretransplantation assessment of end-organ function. Applying the transplant methodology employed for other myeloid disorders to patients with MF fails to acknowledge differences in the underlying disease pathophysiology. Limited understanding of the causes of poor transplant outcomes in this cohort has prevented refinement of transplant eligibility criteria in MF. There is increasing evidence of heterogeneity in molecular disease grade, beyond the clinical manifestations which have traditionally guided transplant timing. Exploring the physiological consequences of disease chronicity unique to MF, acknowledging the heterogeneity in disease grade, and using advanced prognostic models, molecular diagnostics and other organ function diagnostic tools, we present an innovative review of strategies with the potential to improve transplant outcomes in this disease. Larger, prospective studies which consider the impact of molecular-based disease grade are needed for MF transplantation.

Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation.

fludarabine with intravenous busulfan at doses of 3.2 mg/kg (Flu/Bu1) or 6.4 mg/kg (Flu/Bu2). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication of hematopoietic stem cell transplantation (HCT) that is felt to be triggered, at least in part, by damage to the liver sinusoidal endothelium from cytotoxic conditioning regimens. Accordingly, the incidence of VOD/SOS after reduced-intensity conditioning (RIC) HCT is low compared with myeloablative transplantation, and the natural history, risk factors, and outcomes of VOD/SOS after RIC have not been well characterized. We retrospectively reviewed 1583 consecutive patients receiving RIC HCT at the Dana-Farber Cancer Institute between 2007 and 2017 and ascertained 26 cases of VOD/SOS. The median day of VOD/SOS onset was 26 days (range, 5 to 48) and the cumulative incidence at day 50 was 1.6% (95% confidence interval [CI], 1.1% to 2.4%). Day 100 nonrelapse mortality rate was 23% in the VOD/SOS cohort compared with 6.4% in patients without VOD/SOS (P = .006). Cumulative incidence of VOD/SOS at day 50 was 3.1% after RIC regimen with Flu/Bu2 ± ATG (fludarabine with two doses of busulfan, total dose 6.4 mg/kg, with or without anti-thymocyte globulin), compared with 0.15% after Flu/Bu1 ± ATG (fludarabine with single busulfan dose 3.2 mg/kg, with or without anti-thymocyte globulin) (P = .0002); the incidence rate was 2.1% after RIC HCT with sirolimus-containing graft-versus-host disease prophylaxis, compared with 0.8% for RIC without sirolimus (P = .06). Significant risk factors identified in multivariable analysis for the development of VOD/SOS were sirolimus use (hazard ratio [HR], 5.1; 95% CI, 1.8 to 14.2; P = .002) and RIC regimen with Flu/Bu2 ± ATG (HR, 34; 95% CI, 4.5 to 252; P < .001) or other (HR, 32; 95% CI, 3.9 to 257; P = .001) compared with Flu/Bu1 ± ATG. Rising serum tacrolimus or sirolimus levels, new acute kidney injury, and increasing platelet transfusion requirements were significant early predictors of onset in the week preceding prior VOD/SOS diagnosis. When compared with a previously published cohort of 76 patients with VOD/SOS who developed VOD/SOS after myeloablative HCT in the same time period, VOD/SOS after RIC occurred later and was associated with a lower peak bilirubin level and better overall survival. The variability in presenting features for RIC VOD/SOS highlights the importance of maintaining a high index of suspicion for this entity in RIC HCT.

Laboratory Monitoring of Oral Vitamin K Anticoagulation.

Vitamin K antagonists (VKA) have been used for many years as effective anticoagulant therapy. The laboratory plays a crucial role in measuring the prothrombin time (PT) and calculating the international normalized ratio (INR). Each component of the calculation has the potential to increase error in the final result. This article discusses the laboratory aspects of monitoring VKA including sample requirements, PT, determination of the INR, point of care (POC) testing, external quality assurance/proficiency testing, and reversal strategies for VKA therapy. The implementation of the PT/INR reporting standard was a significant improvement in laboratory medicine. However, further room for improvement exists in the management of PT/INR testing, to clarify the role of POC testing and continue the harmonization process to ensure reliability and reproducibility of INR results.

The association of socioeconomic deprivation with access and survival after hematopoietic stem cell transplantation in New Zealand.

BACKGROUND: Socioeconomic deprivation (SED) is a risk factor for reduced survival of hematopoietic stem cell transplant (HSCT) recipients. This study aimed to evaluate access and long-term survival of HSCT recipients. METHODS: This was a hospital HSCT Registry-based retrospective cohort study. Patients who underwent HSCT from January 2010 to June 2020 were identified. HSCT recipients younger than 16 years of age, patients who reported their residential address as a post office box or the Department of Corrections, and those who left the country after HSCT were excluded from the study. HSCT recipients with the 2018 New Zealand deprivation index (NZDep2018) deciles 8, 9, and 10 were assigned to the higher SED group and those with NZDep2018 deciles from 1 to 7 were allocated to the lower SED group. The total number of New Zealanders in the higher and lower SED strata was obtained from the 2018 Census. RESULTS: Eight hundred fifty-one HSCT recipients met the eligibility criteria. HSCT recipients from the higher and lower SED strata of the New Zealand population had similar access to HSCT (odds ratio = .9; 95% confidence interval (CI): .77-1.04; p = .155). Mortality in the higher and lower SED groups of HSCT recipients was 9.6/100 person-years (95% CI: 7.7-12/100 person-years) and 8.1/100 person-years (95% CI: 6.9-9.4/100 person-years), respectively. The mortality ratio was 1.2 (95% CI: .9-1.6), p = .098. Both groups had similar survival. CONCLUSION: New Zealand residents from the higher and lower SED strata have similar access to HSCT. SED is not associated with reduced survival in adult HSCT recipients.