This treatment protocol was effective in improving ALL survival among patients at the authors' institute compared with previous trials, although the outcome remains lower than that in more industrialized countries. Prognostic factors defined in this study were similar to those identified by other cooperative groups.
Summary:Our objective was to evaluate, probably for the first time, the impact of CD34 subsets on engraftment kinetics in allogeneic PBSC transplantation (PBSCT). PBSC graft components were analyzed in 62 cases for the absolute count/kg of total CD34 þ and the following subsets: DRÀ and þ , CD71 þ /À, CD38þ /À, CD33þ /À and CD61 þ /À. Time to ANC 40.5 and 41 Â 10 9 /l and platelets 420 and 450 Â 10 9 /l was reported. The median value for each parameter was used to discriminate rapid from slow engraftment. Four parameters showed significant predictive power of early neutrophil engraftment, namely CD34 þ / DRÀ (P ¼ 0.002), CD34 þ /38À (P ¼ 0.02), CD34 þ / CD61À (P ¼ 0.04) and total CD34 þ cell dose (P ¼ 0.04). Four parameters showed significant predictive power of early platelet engraftment, namely CD34 þ /CD61 þ (P ¼ 0.02), CD34 þ /CD38À and total CD34 þ cell dose (P ¼ 0.04) and CD34 þ /CD71À (P ¼ 0.05). Comparing patients who received 4to those who received o the threshold dose(s), only CD34 þ /CD38À lost its significance for neutrophil engraftment; and only CD34 þ /CD61 þ retained its significance for platelet engraftment (P ¼ 0.03); furthermore, the former group required significantly fewer platelet transfusions (P ¼ 0.018). We concluded that in allogeneic PBSCT, the best predictor of early neutrophil engraftment is the absolute CD34 þ /DRÀ and for early platelet engraftment is the absolute CD34 þ /CD61 þ cell dose.
Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1–35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10–11). Non-survivors’ HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 μM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ2=12.1, p=4.9×10−4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.
A great variety of patient- and product-related factors influence the outcome of platelet transfusions. Our study assessed the predictive value of a flow cytometric platelet cross match test for the outcome of HLA matched and unmatched platelet transfusions in patients with acute leukemia. Thirty nine patients (26 adults and 13 children) received 60 ABO compatible apheresis platelet unites ranging from 1 to 4 per patient (mean = 1.54; median = 2). We performed flowcytometric platelet cross-matching, HLA Class I typing by sequence-specific primer (SSP) for patients and complement-dependent cytotoxicity (CDC) for donors and screening of HLA Class I antibodies by ELISA. Effectiveness of platelet transfusion was evaluated using the corrected count increment which was calculated at 60 min and 18- to 24-h posttransfusion. Multivariate analysis was performed to detect which variable can predict transfusion response more than others. Cross-matched platelet transfusions associated with good response in 51.4% of transfusion events in adults and 73.3% in children. The noncrossmatched platelet transfusions associated with poor response in 83.3% in adults and 100% in children (P-values 0.143, 0.041, respectively). In the presence of clinical factors or HLA alloimmunization in adults, cross-matched platelets were associated with good response in 29.6 and 22.2% respectively. In children this occurred in 81.8 and 66.7%, respectively. In presence or absence of HLA matching, flow cytometry platelet cross-matching was the most predictor for transfusion response (P = 0.05). Because of the difficulties to find frequent HLA matched donors for acute leukemia patients; flow cytometric platelet cross-matching may provide the most useful way for selecting donors. It is useful even in the presence of alloimunization in children.
The level of different adhesion molecules expression in CLL is apparently reflected on the potential migratory behavior of the leukemic cells to different organs.
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