BACKGROUND: Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment, and the concomitant symptoms, including cytokine release syndrome (CRS) or immune-related adverse events (irAEs), are frequently reported. However, clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell (GPBMC) infusion in patients receiving microtransplant (MST) have not yet been well depicted. METHODS: We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison. Clinical symptoms and their correlation with clinical features, laboratory findings, and clinical response were explored. RESULTS: Fever (58.0% [51/88]) and chills (43.2% [38/88]) were the significant early-onset symptoms after GPBMC infusion. Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills (3 [2-5] loci vs. 5 [3-5] loci, P  = 0.043 and 66.7% [12/18] vs. 37.1% [26/70], P  = 0.024). On the other hand, those with decreased CD4 + /CD8 + T-cell ratio developed more fever (0.8 [0.7-1.2] vs. 1.4 [1.1-2.2], P  = 0.007). Multivariable analysis demonstrated that younger patients experienced more fever (odds ratio [OR] = 0.963, 95% confidence interval [CI]: 0.932-0.995, P  = 0.022), while patients with younger donors experienced more chills (OR = 0.915, 95% CI: 0.859-0.975, P  = 0.006). Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion, which indicated mild and transient inflammatory response. Although no predictive value of infusion-related syndrome to leukemia burden change was found, the proportion of host pre-treatment activated T cells was positively correlated with leukemia control. CONCLUSIONS Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes, which were associated with donor- or recipient-derived risk factors, with less safety and tolerance concerns than reported CRS or irAEs.
Humans ; Leukocytes, Mononuclear ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Unrelated Donors ; Granulocyte Colony-Stimulating Factor ; Graft vs Host Disease

Objective:To evaluate the efficacy and safety of continuous infusion of low-dose intravenous (Ⅳ) heparin during perioperative period of simultaneous pancreas-kidney (SPK) transplantation for donation after citizen death (DCD) donor to prevent pancreatic thrombosis post-transplantation.Methods:From January 2015 to August 2019, 46 DCD donors undergoing SPK were divided into retrospective cohort groups 1 ( n=27) and 2 ( n=19). Group 1 received aspirin enteric-coated tablets only at Day 1 post-SPK. In Group 2, 5-7 days of continuous infusion of heparin 260 IU per hour at Day 1 post-SPK was followed by a daily intake of aspirin enteric-coated tablets of 100 mg. Incidence of thrombus, recovery of graft function and adverse reactions of anticoagulant therapy were observed. Results:Thrombosis occurred in (5.3%, 1/19 vs 14.8%, 4/27) in heparin and non-heparin groups. Thrombosis and graft loss were significantly lower in heparin group than those in non-heparin group ( P<0.05). Conclusions:Continuous infusion of low-dose heparin vein is effective and safe in preventing thrombosis after SPK transplantation.

Objective To explore the clinical value of uncinate process resection combined with portalsuperior mesenteric vein resection and end-to-end anastomosis in distal pancreatectomy.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 11 patients who underwent distal pancreatectomy combined with portal-superior mesenteric vein resection and end-to-end anastomosis in the Peking University Cancer Hospital (8 patients) and Jilin Guowen Hospital (3 patients) between January 2014 to April 2018 were collected.During the vascular reconstruction,uncinate process of the pancreas was first resected for reducing anastomotic tension,and then end-to-end anastomosis was done after portal-superior mesenteric vein resection.Observation indicators:(1) intraoperative situations;(2) postoperative recovery situations;(3) postoperative pathological examination situations;(4) follow-up and survival situations.Follow-up using outpatient examination and imaging examination was performed to detect patients' postoperative survival,tumor recurrence and metastasis and postoperative venous anastomotic patency up to May 2018.Measurement data with normal distribution were represented as x±s.Measurement data with skewed distribution were described as M (range).The non-recurrence and non-metastasis survival curve,overall survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method.Results (1) Intraoperative situations:11 patients received uncinate process resection of the pancreas,and successfully underwent distal pancreatectomy combined with portal-superior mesenteric vein resection and end-to-end anastomosis.Eight patients underwent distal pancreatectomy + Appleby combined with celiac axis resection due to pancreatic tumor involving common hepatic artery,including 2 undergoing combined total gastrectomy due to gastric ischemia;2 patients underwent distal pancreatectomy;1 patient underwent distal pancreatectomy + distal gastrectomy due to blood supply obstacle of distal stomach.Operation time and volume of intraoperative blood loss of 11 patients were (5.8± 1.1) hours and 800 mL (range,200-2 500 mL).(2) Postoperative recovery situations:there was no grade C of pancreatic fistula of 11 patients.Four patients had grade B of pancreatic fistula,including 2 were cured by drainage-tube indwelling of pancreatic wound ＞ 3 weeks,1 was cured by continous washing due to pancreatic fistula combined with infection,and 1 was cured by the second abdominal puncture drainage due to pancreatic fistula with fever;1 of 4 patients was combined with grade C of delayed gastric emptying and cured by conservative treatment,and other 3 patients didn't occur postoperative complications.Of 5 patients diagnosed as biochemical fistula,1 had esophagus-jejunum anastomotic leakage,and 1 had changes of hepatic ischemia in S2,S3 and S4b segments by CT examination and recovered normal liver function at 2 weeks postoperatively,with long-term hepatatrophia in S2 and S3 segments.There was no postoperative death and reoperation in 11 patients.Duration of postoperative hospital stay of 11 patients was (22± 5) days.(3) Postoperative pathological examination results:tumors of 11 patients were located in neck and body of the pancreas,with a maximum diameter of (4.8± 1.7)cm.Among 11 patients,10 were confirmed with moderate-or low-differentiated ductal adenocarcinoma and 1 with anaplastic carcinoma.The length of portal-superior mesenteric vein resection of 11 patients was (2.6± 0.8) cm.Seven of 11 patients occurred different degrees of tumor infiltration in the portal-superior mesenteric vein,and other 4 patients occurred inflammatory adhesion,without tumor infiltration.(4) Follow-up and survival situations:11 patients were followed up for 3.0-37.6 months,with a median time of 15.7 months.During the follow-up,8 patients died of tumor recurrence and /or metastasis,and 3 survived;the non-recurrence and non-metastais survival time and overall survival time were respectively 9.0 months (range,3.0-37.6 months) and 24.6 months (range,3.0-37.6 months).One patient was complicated with anastomotic stenosis and surrounding varices of portal-superior mesenteric vein by postoperative half-year reexamination,anastomotic vein anomalies and venous thrombosis were not found in other patients before local tumor recurrence and / or death.Conclusion The combined uncinate process resection of the pancreas cannot increase the risk of postoperative pancreatic fistula,and it could effectively reduce the anastomotic tension in the distal pancreatectomy combined with portal-superior mesenteric vein resection and reconstruction,meanwhile,it can also achieve end-to-end anastomosis after longer vein resection.

Objective: To investigate the prognostic effect of neonatal morbidities on poor outcomes at 12 months corrected age in very low birth weight (VLBW) premature infants . Method: From November 2013 to October 2014, a multi-center retrospective study was conducted in 8 tertiary Maternal and Children′s hospitals in Guangdong, Hunan and Fujian. The premature infants survived to a postmenstrual age (PMA) of 36 weeks with birth weight less than 1 500 g and without congenital diseases were included, and divided into two groups according to poor outcomes. The birth weight, gestational age, morbidities and poor outcomes (death, cerebral palsy, cognitive delay, et al) were recorded. Data were analyzed with Chi-square test to investigate the relationship between morbidities and poor outcomes. And the predictive effect of the top three morbidities were analyzed by Logistic regression analysis. Result: Total of 834 VLBW premature infants (473 boys and 361 girls) finished the follow-up, whose average gestational age and birth weight were (30.6±1.8) weeks and (1 189±159)g. The incidences of BPD, severe ROP, NEC, brain injury and sepsis were 207 (24.8%), 119 (14.3%), 58 (7.0%), 281 (33.7%) and 124 (14.9%), respectively. There were significant differences between the two groups in the incidences of BPD, severe ROP, NEC, brain injury and sepsis(χ²=42.10, 47.20, 4.81, 44.28, 18.63, all P<0.01), which had significant correlation with poor outcomes at 12 months corrected age. The three top morbidities were severe ROP, BPD and brain injury(OR=3.82, 2.90, 2.80). Combined morbidities with BPD, severe ROP and brain injury correlated with higher risk of poor outcomes (one morbidity, OR=3.14, β=1.15; two morbidities, OR=7.31, β=1.99; three morbidities, OR=22.41, β=3.11; all P<0.01). Conclusion BPD, severe ROP, NEC, brain injury and sepsis were the risk factors of poor outcomes at 12 months corrected age in VLBW infants. And the more combined morbidities with severe ROP, BPD and brain injury, the higher risk of poor outcomes in this population. Trial registration Clinical Trails, NCT03104946.

BACKGROUNDThe management of Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is controversial due to the early recurrence after curative hepatectomy, and many variables were related to the prognosis. The purpose of this study was to predict the tumor recurrence in early postoperative period of the patients with BCLC stage B HCC.

METHODSFrom January 2004 to January 2012, 104 patients with BCLC stage B HCC underwent hepatectomy. Clinicopathological factors and follow-up data were statistically analyzed to establish a predicting scoring system.

RESULTSThe overall survival rates for one, three, and five years were 69.2%, 52.7%, and 42.3%, and the disease-free survival rates for one, three, and five years were 52.9%, 47.3%, and 37.5%, respectively. The multiple factors analysis showed that the micro-vessel invasion, lymph nodes metastasis, multiple lesions, and the high expression of HMGB1 were independent factors (P < 0.05). A scoring system was established to predict the early recurrence within one year after the surgery for BCLC stage B HCC, according to the analysis results with a specificity of 85.1% and a sensitivity of 80.3%.

CONCLUSIONVariant clinicopathological factors were associated with early postoperative recurrence for BCLC stage B HCC and recurrence early after hepatectomy was more likely in patients with a higher score of the scoring system.

Carcinoma, Hepatocellular ; metabolism ; pathology ; surgery ; Disease-Free Survival ; Female ; HMGA1a Protein ; metabolism ; Hepatectomy ; Humans ; Liver Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Treatment Outcome

Background The management of Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is controversial due to the early recurrence after curative hepatectomy,and many variables were related to the prognosis.The purpose of this study was to predict the tumor recurrence in early postoperative period of the patients with BCLC stage B HCC.Methods From January 2004 to January 2012,104 patients with BCLC stage B HCC underwent hepatectomy.Clinicopathological factors and follow-up data were statistically analyzed to establish a predicting scoring system.Results The overall survival rates for one,three,and five years were 69.2％,52.7％,and 42.3％,and the disease-free survival rates for one,three,and five years were 52.9％,47.3％,and 37.5％,respectively.The multiple factors analysis showed that the micro-vessel invasion,lymph nodes metastasis,multiple lesions,and the high expression of HMGB1 were independent factors (P ＜0.05).A scoring system was established to predict the early recurrence within one year after the surgery for BCLC stage B HCC,according to the analysis results with a specificity of 85.1％ and a sensitivity of 80.3％.Conclusion Variant clinicopathological factors were associated with early postoperative recurrence for BCLC stage B HCC and recurrence early after hepatectomy was more likely in patients with a higher score of the scoring system.

To explore the risk factors of graft rejection in non-myeloablative transplantation between HLA-identical siblings and to evaluate methods to increase donor cell engraftment, 8 patients with graft rejection were studied . The results showed that the usage of immunosup-pressive agents, low early engraft rate, and the kind of disease being CML were closely related with graft rejectioa For patients with graft rejection, second non-myeloablative transplantation is a useful way.

Objective To compare the results of mobilization of peripheral stem cells of two different G-CSF dosage schedules in 30 healthy donors. Methods In one group 15 healthy subjects received 5?g/kg filgrastim once daily subcutaneously (SC), while in the other group another 15 individuals received 2.5?g/kg of filgrastim twice daily SC. Peripheral blood stem cells were collected after five days of filgrastim administration, and flow cytometric immunophenotyping was performed for the first harvest. Results The MNC count was 2.93?10 8/kg donor body weight in the 5?g/kg Qd group compared with 4.42?10 8/kg in the 2.5?g/kg bid group (P0.05). Conclusion Administration of filgrastim twice a day at 2.5?g/kg instead of once a day at 5?g/kg is more efficient in mobilizing stem cells without obvious side effect.

Objective To explore the clinical effects of second non-myeloablative stem cell transplantation (NAST). Methods Six cases of malignant hematological diseases receiving second NAST were retrospectively analyzed. Of them, 3 were suffered from transplant rejection after 1st NAST and the remaining 3 were stable mixed chimerism. Results Five of the patients achieved complete donor's chimerism and have been in disease-free-survival for 6～27 months. 1 GVHD occurred in only one of the 6 patients, and no transplant-related death happened. Conclusion Second NAST is effective for the treatment of patients with transplant rejection,and is also rational choice for those patients with refractory or relapse malignant hematological diseases.

Objective To investigate the significance of HLA haploidentical peripheral blood stem cell transplantation for the treatment of intestinal form of acute radiation sickness. Methods Patient “A” from Shandong province suffered from a 60 Co radiation accident with a dose of 20-25Gy, and was diagnosed as intestinal form of acute radiation sickness. On the 3rd day after irradiation, total environmental protection (TEP), antibiotics treatment and emergency HLA zygosity with his elder sister were done, and HLA haploidentical peripheral blood stem cell transplantation was performed with a preconditioning regimen of “CTX+ATG+Flu”. The regimen for protecting from GVHD was “CsA/FK506+MMF+CD25+MSC”. Results WBC began to increase on the 17th day after treatment, and WBC recovered to 5.1?109/L on the 19th day, platelet to over 30?109/L, and RCT to normal. Bone marrow image showed hematopoietic recovery of the three cell lineages. Continuously detection of the implantation ratio of donor's cells by STR-PCR, sexual chromosome analysis and HLA zygosity showed stable complete donor-derived chimera. No GVHD was observed. On the 19th days after treatment, chest X-ray films and CT suggested that a mixed bacterial and fungous infection existed in the patient's lungs. The severest skin damage occurred on the 25th day which occupied 14% of whole body surface. The functions of lung, kidney and heart were damaged sequentially. The patient died of multiple organ failure (MOF) 33 days after admission. Conclusion It is the first time to report a successful HLA haploidentical peripheral blood stem cell transplantation for the treatment of intestinal form of acute radiation sickness in China. A successful transplantation might be a key for prolonging the survival period of such a patient.