• Identification of a miRNA panel as a biomarker for the diagnosis, prognosis, and prediction of acute graft-versus-host disease.Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Approximately 35% to 50% of HCT recipients develop aGVHD; however, there are no validated diagnostic and predictive blood biomarkers for aGVHD in clinical use. Here, we show that plasma samples from aGVHD patients have a distinct microRNA (miRNA) expression profile. We found that 6 miRNAs (miR-423, miR-199a-3p, miR-93*, miR-377, miR-155, and miR-30a) were significantly upregulated in the plasma of aGVHD patients (n 5 116) when compared with non-GVHD patients (n 5 52) in training and validation phases. We have developed a model including 4 miRNAs (miR-423, miR-199a-3p, miR-93*, and miR-377) that can predict the probability of aGVHD with an area under the curve of 0.80. Moreover, these elevated miRNAs were detected before the onset of aGVHD (median 5 16 days before diagnosis). In addition, the levels of these miRNAs were positively associated with aGVHD severity, and high expression of the miRNA panel was associated with poor overall survival. Furthermore, the miRNA signature for aGVHD was not detected in the plasma of lung transplant or nontransplant sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as an independent biomarker for the prediction, diagnosis, and prognosis of aGVHD. (Blood. 2013;122(19):3365-3375)

Background. Respiratory viral infections (RVIs) are frequent complications of hematopoietic stem cell transplant (HSCT). Surgical masks are a simple and inexpensive intervention that may reduce nosocomial spread.Methods. In this prospective single-center study, we instituted a universal surgical mask policy requiring all individuals with direct contact with HSCT patients to wear a surgical mask, regardless of symptoms or season. The primary endpoint was the incidence of RVIs in the mask period (2010-2014) compared with the premask period (2003)(2004)(2005)(2006)(2007)(2008)(2009).Results. RVIs decreased from 10.3% (95/920 patients) in the premask period to 4.4% (40/911) in the mask period (P < .001). Significant decreases occurred after both allogeneic (64/378 [16.9%] to 24/289 [8.3%], P = .001) and autologous (31/542 [5.7%] to 16/622 [2.6%], P = .007) transplants. After adjusting for multiple covariates including season and year in a segmented longitudinal analysis, the decrease in RVIs remained significant, with risk of RVI of 0.4 in patients in the mask group compared with the premask group (0.19-0.85, P = .02). In contrast, no decrease was observed during this same period in an adjacent hematologic malignancy unit, which followed the same infection control practices except for the mask policy. The majority of this decrease was in parainfluenza virus 3 (PIV3) (8.3% to 2.2%, P < .001).Conclusions. Requiring all individuals with direct patient contact to wear a surgical mask is associated with a reduction in RVIs, particularly PIV3, during the most vulnerable period following HSCT.

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High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy’s impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 106 CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P <0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P <0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57–1.25] and 0.96 for overall survival [95% CI 0.61–1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy’s benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared to historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared to 86 standard UCB recipients at our institution. Median time to neutrophil engraftment was shorter in NiCord than in standard UCB recipients (12.5 days vs. 26 days, p<0.001). Compared to standard UCB transplantation, NiCord recipients had significantly reduced risk for total infection (RR 0.69, p=0.01), grade 2–3 (moderate to severe) infection (RR 0.36, p<0.001), bacterial infection (RR 0.39, p=0.003), and grade 2–3 bacterial infection (RR 0.21, p=0.003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II–IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days compared to standard UCB recipients after adjustment for age and KPS (69.9 days vs. 49.7 days, p=0.005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, reduced total and bacterial infections, and shorter hospitalization in the first 100 days compared to standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit.