Preliminary Results of a Combined Score Based on sIL2-Rα and TIM-3 Levels Assayed Early After Hematopoietic Transplantation.

Assays of cytokines in the plasma at the onset of graft-vs. -host disease (GVHD) can predict disease severity and treatment-related mortality (TRM); however, the optimal time during which cytokines should be tested and the specific panel of cytokines with the highest predictive ability remain unknown. We chose a predefined time point, 18 days after hematopoietic stem cell transplantation (HSCT), to measure the levels of six cytokines in the plasma: soluble interleukin-2 receptor alpha (sIL2-Rα), T-cell immunoglobulin domain and mucin domain-3 (TIM-3), suppression of tumorigenicity-2 (ST-2), intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). The study included 95 patients, who underwent allogeneic hematopoietic transplantation at our institution. Plasma levels of sIL2-Rα and TIM-3, measured as continuous data, had predictive value for overall survival (sIL2-Rα, p = 0.002; TIM-3, p = 0.0007), while TRM could be predicted by sIL2-Rα (p = 0.0005), IFN-gamma (p = 0.01), and IL-6 (p = 0.0001). No cytokine was associated with the risk of relapse. Patients were categorized into groups, according to cytokine thresholds determined by receiver operating characteristic curve analysis (sIL2-Rα ≤ or > 8,100 pg/ml; TIM-3 ≤ or > 950 pg/ml) and multivariate analysis was conducted. High levels of both TIM-3 and sIL2-Rα were significant predictors of poor survival [TIM-3 > 950 pg/ml: hazard ratio (HR) = 6.214 (95% CI 1.939-19.910), p = 0.002 and sIL2-Rα > 8.100 pg/ml: HR = 2.644 (95% CI 1.308-5.347), p = 0.006]. Using these cutoff thresholds, we constructed a composite scoring system that could distinguish three different groups of patients with varying rates of TRM: high risk, 41.7%; intermediate risk, 10.8%; and low risk, 7.1% (Gray's test: p = 0.001). If confirmed in a validation cohort, this composite scoring system could be used to guide the modulation of post-transplant immune suppressive therapy.

Acute Chest Syndrome: the role of erythro-exchange in patients with sickle cell disease in Sicily.

Acute Chest Syndrome (ACS) describes a syndrome characterized by the presence of a new pulmonary infiltrate on a chest X-ray, fever, and respiratory symptoms and is the leading cause of death and hospitalization in sickle cell disease (SCD). We studied 21 patients affected by SCD (13 HbSbeta+, 4 HbS beta(o), 4 HbSS, mean age 38.2 years). Six out of the 21 patients developed one episode of ACS (two patients had positive blood cultures, for Mycoplasma pneumoniae and Haemophilus influenzae respectively). The aim of our study was to evaluate the therapeutic efficacy of red cell-exchange during ACS. This procedure decreases HbS levels. The patients who underwent erythro-exchange showed a dramatic clinical and radiographic improvement with stabilized HbS levels between 20% and 30%. During follow up (14-32 months), none of the 6 patients developed viral complications related to transfusion therapy, alloimmunization or recurrence of ACS. In conclusion, in regard to the pre- and post-red cell-exchange clinical and laboratory data, we can say that red cell-exchange provides a dramatic resolution of the episode of ACS, minimizes the development of iron overload, and rapidly decreases HbS and hematocrit levels. In light of our results, we hypothesize that ACS episodes are secondary to pulmonary damage and to a gradual worsening related to age, and that there is some evidence that individuals affected by SCD in the third to fourth decade of life are more susceptible to ACS and/or other severe disease-related complications, needing repeated and strict clinical follow up.