Decision analysis for transplant candidates with primary myelofibrosis in the ruxolitinib era

The recent progress with ruxolitinib treatment might improve quality-of-life as well as overall survival in patients with primary myelofibrosis (PMF). Therefore, the optimal timing of allogeneic hematopoietic cell transplantation (HCT) remains to be elucidated in the ruxolitinib era. We constructed a Markov model to simulate the 5-year clinical course of transplant candidates with PMF, and compared outcomes between immediate HCT and delayed HCT after ruxolitinib failure. Since older age was associated with an increased risk of mortality, we analyzed patients aged < 60 and ≥ 60 separately in subgroup analyses. The expected life years was consistently longer in delayed HCT after ruxolitinib failure regardless of patient age. Regarding quality-adjusted life years (QALYs), a baseline analysis showed that immediate HCT was inferior to delayed HCT after ruxolitinib failure (2.19 versus 2.26). In patients aged < 60, immediate HCT was equivalent to delayed HCT after ruxolitinib failure (2.31 versus 2.31). On the other hand, in patients aged ≥ 60, immediate HCT was inferior to delayed HCT after ruxolitinib failure (1.98 versus 2.21). A one-way sensitivity analysis showed that the utility of being alive without chronic graft-versus-host disease after immediate HCT was the most influential parameter for QALYs, and that a value higher than 0.836 could reverse the superiority of delayed HCT after ruxolitinib failure. As a result, delayed HCT after ruxolitinib failure is expected to be superior to immediate HCT, especially in patients aged ≥ 60, and is also a promising strategy even in those aged < 60

Evaluation of the validity of preemptive therapy against cytomegalovirus disease based on antigenemia assay with a cutoff of 20 positive cells per two slides.

BACKGROUND: Preemptive therapy with ganciclovir (GCV) based on the results of a cytomegalovirus (CMV) antigenemia assay is a standard strategy for preventing CMV disease after allogeneic hematopoietic cell transplantation (HCT). However, the appropriate threshold of antigenemia-positive cells for deciding when to start GCV remains unclear. PATIENTS: This retrospective study included 80 recipients who received HCT from an alternative donor between 2007 and 2011. In 2009, we switched the threshold from 3 (3A group, n=24) to 20 (20A group, n=56) antigenemia-positive cells per two slides for preemptive therapy after HCT from an alternative donor. RESULTS: Early CMV disease within 100 days after HCT was observed in one patient in the 20A group. Antiviral agents including GCV, val-GCV, and foscarnet were given in 17 (71%) and 36 (64%) patients in the 3A and 20A groups, respectively (p=0.23). In 13 (23%) patients in the 20A group, the initiation of preemptive therapy was avoided because of the change in the cutoff value for CMV antigenemia. However, the total dose of GCV was not different between the two groups. The use of steroid was significantly associated with CMV antigenemia of at least 20 positive cells among patients with low-level antigenemia at the first detection. CONCLUSION: The increased threshold up to 20 positive cells for starting preemptive therapy was not associated with a significant increase in CMV disease, but the total dose of GCV was not reduced and there was one early CMV disease in the 20A group. We should explore how to identify patients who are at high risk for increased antigenemia among patients with low-level antigenemia, but at least, preemptive therapy should not be withheld in patients who are already receiving systemic steroid

Cumulative dose of ganciclovir (GCV) as preemptive therapy.

<p>Cumulative dose of ganciclovir (GCV) as preemptive therapy.</p