We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

Objective:To investigate the influence of perioperative probiotics supplement on short-term clinical outcomes in gastric cancer patients receiving neoadjuvant chemotherapy combined with radical gastrectomy.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 80 patients who underwent neoadjuvant chemotherapy combined with radical gastrectomy in the Affiliated Hospital of Qingdao University from July 2020 to September 2021 were selected. Based on random number table, patients were allocated into two groups. Patients undergoing perioperative probiotics supplement were allocated into the experiment group, and patients undergoing perioperative conventional treatment were allocated into the control group, respectively. Observation indicators: (1) grouping situations of the enrolled patients; (2) intraoperative situations; (3) follow-up and postoperative situations; (4) inflammation related hematological indexes. Follow-up was conducted using telephone interview and outpatient examina-tion to detect postoperative complications and startup of adjuvant chemotherapy up to October 31,2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was performed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the Mann-Whitney U test. Repeated measurement data were analyzed by the repeated ANOVA or generalized estimating equation. Results:(1) Grouping situations of the enrolled patients. A total of 80 patients were selected for eligibility. There were 51 males and 29 females, aged 64(42-80)years. Of the 80 patients, there were 40 patients in the experiment group and 40 patients in the control group, respectively. (2) Intraoperative situations. All patients in the experiment group and the control group underwent radical gastrectomy successfully. Cases with yield pathologic TNM (ypTNM) stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲ after neoadjuvant chemotherapy, cases undergoing laparoscopic radical gastrectomy or Da Vinci robotic radical gastrectomy, the operation time, the volume of intraoperative blood loss, cases undergoing digestive tract recons-truction as Billroth Ⅱ anastomosis or Roux-en-Y anastomosis were 2, 7, 15, 13, 19, 21,205(180-240)minutes, 50(30-60)mL, 6, 34 in the experiment group, versus 4, 6, 12, 16, 23, 17, 218(190-251)minutes, 50(43-60)mL, 11, 29 in the control group, showing no significant difference in the above indicators between the two groups ( U=683.00, χ2=0.80, U=668.00, 681.00, χ2=1.87, P>0.05). (3) Follow-up and postoperative situations. All the 80 patients were followed up for 1 month after surgery. Cases with postoperative infectious complications were 6 in the experiment group, versus 15 in the control group, showing a significant difference between the two groups ( χ2=5.23, P<0.05). The application of antimicrobial agent, time to postoperative first flatus, time to postoperative first defecation, time to tolerance of solid food, duration of postoperative hospital stay, time to postopera-tive startup of adjuvant chemotherapy were 3(3-6)doses, 53(49-66)hours, 72(62-82)hours, (72±18)hours, 6.0(5.5-7.0)days, 26.0(25.0-28.0)days in the experiment group, versus 6(3-10)doses, 66(60-88)hours, 94(82-112)hours, (107±23)hours, 7.0(6.4-8.3)days, 30.0(28.0-33.0)days in the control group, showing significant differences in the above indicators between the two groups ( U=471.50, 432.00, 343.50, t=-7.62, U=411.50, 319.50, P<0.05). (4) Inflam-mation related hematological indexes. ① The white blood cell counts before surgery and at postoperative day 1, 3, 5 were (5.6±1.4)×10 9/L, (9.9±3.2)×10 9/L, (7.7±2.6)×10 9/L, (6.8±1.8)×10 9/L in the experiment group, versus (6.1±1.9)×10 9/L, (12.3±2.9)×10 9/L, (9.7±3.6)×10 9/L, (7.8±2.7)×10 9/L in the control group, meeting the mauchly′s test of sphericity ( χ2=4.17, P>0.05). Results of intrasubject effect test showed that there were significant differences in the time effect, intervention effect and interaction effect of white blood cell counts between the two groups ( F=106.61, 10.45, 4.56, P<0.05). ② The neutrophilic granulocyte percentages before surgery and at postoperative day 1, 3, 5 were 55%±10%, 76%±11%, 73%±9%, 69%±9% in the experiment group, versus 56%±9%, 84%±5%, 79%±8%, 74%±9% in the control group, not meeting the mauchly′s test of sphericity ( χ2=16.63, P<0.05). Results of multi-variate test showed that there were significant differences in the time effect, intervention effect and interaction effect of neutrophilic granulocyte percentages between the two groups ( F=92.42, 11.46, 5.55, P<0.05). ③ The levels of C-reactive protein before surgery and at postoperative day 1, 3, 5 were 1.35(1.15-1.97)mg/L, 14.94(8.24-21.22)mg/L, 33.39(13.02-66.02)mg/L, 18.36(8.27-60.43)mg/L in the experiment group, versus 1.62(0.97-2.27)mg/L, 24.03(10.42-36.52)mg/L, 81.66(31.20-116.76)mg/L, 46.84(28.30-80.26)mg/L in the control group, not meeting the normal distribution. Results of generalized estimation equation test showed that there were significant differences in the time effect, intervention effect and interaction effect of levels of C-reactive protein between the two groups ( Waldχ2=145.74, 9.48, 9.90, P<0.05). ④ The levels of procalcitonin before surgery and at postoperative day 1, 3, 5 were 0.02(0.02-0.04)μg/L, 0.08(0.06-0.12)μg/L, 0.12(0.07-0.21)μg/L, 0.09(0.06-0.15)μg/L in the experiment group, versus 0.02(0.02-0.04)μg/L, 0.14(0.07-0.71)μg/L, 0.35(0.14-0.71)μg/L, 0.24(0.10-0.48)μg/L in the control group, not meeting the normal distribution. Results of generalized estimation equation test showed that there were signifi-cant differences in the time effect, intervention effect and interaction effect of levels of procalcitonin between the two groups ( Waldχ2=62.88, 14.71, 18.33, P<0.05). Conclusion:Perioperative supple-ment of probiotics can reduce the incidence of postoperative infectious com-plications and the application of antimicrobial agent, promote recovery of gastrointestinal function, reduce the level of inflammation related indexes, shorten the duration of postoperative hospital stay and the time to postoperative startup of chemotherapy in patients undergoing neoadjuvant chemotherapy combined with radical gastrectomy.

Objective:To explore the feasibility and efficacy of umbilical cord blood transplantation (UCBT) in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).Methods:From May 2014 to December 2019, clinical data were retrospectively reviewed for 7 PNH patients undergoing UCBT. The grades were severe ( n=6) and extremely severe ( n=1). The causes were primary PNH ( n=4) and PNH-aplastic anemia (AA) syndrome ( n=3). There were 5 males and 2 females with a median age of 29 (20-47) years, a median weight of 60(50-71) kg and a median time from diagnosis to transplantation of 62.5(7.7-171) months. All of them were accompanied by transfusion dependence. Myeloablative ( n=6) and reduced-intensity ( n=1) pretreatment was offered. The regimen of preventing GVHD was cyclosporine A plus short-term mycophenolate mofetil without ATG. The median number of input nucleated cells was 2.4(1.71-4.28)×10 7/kg and the median number of CD34+ cells 1.58(0.88-3.02)×10 5/kg. Results:Neutrophil and erythroid engraftment was obtained with a median neutrophil engraftment time of 17(15-21) days and a median erythroid engraftment time of 27. Engraftment time of 37(25-101) days for platelets >20×10 9/L and 62(27-157) days for platelets >50×10 9/L. The incidence of 100-day acute GVHD was 28.6%(95%CI 0-55.3%). The severity of GVHD was grade Ⅱ° acute ( n=2) and mild ( n=1). The median follow-up period was 13.5(3-71.4) months. Six patients survived while another with PNH-AA syndrome with iron overload died of gastrointestinal hemorrhage. The 2-year overall survival rate was 83.3%(95%CI 27.3-97.5%). Conclusions:With excellent engraftment and survival in the treatment of PNH, UCBT is indicated for patients without HLA full-match donor. PNH-AA syndrome with iron overload may be one of the important prognostic factors.

Objective:To explore the differences of immune reconstitution between peripheral blood stem cell transplantation and umbilical cord blood transplantation.Methods:A total of 300 patients (aged 18 (8, 33), 163 males and 137 females) with malignant hematological diseases who received allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of University of Science and Technology of China from January 2018 to March 2020 were enrolled in this study, including 255 cases of umbilical cord blood transplantation and 45 cases of peripheral blood stem cell transplantation. Multicolor flow cytometry was applied to analyze lymphocyte subsets of the percentages and absolute counts in the two donor types and peripheral blood of patients after receiving hematopoietic stem cell transplantation. The differences between the two grafts were compared, and the lymphocyte subsets results were evaluated at 1, 2, 3, 4, 6, 9, 12, and 18 months after transplantation. 18-month disease-free survival (DFS) within the 300 patients under the two transplantation types were retrospectively analyzed.Results:1. The proportion of NKT cells in peripheral blood group was significantly higher than that in cord blood group (2.79% vs 0.24%, P<0.001). 2. The proportion of helper T cells in the UCBT group was higher than that in the PBSCT group, as well as the counts 6 months after transplantation ( P<0.05). 3. The proportion of NK1 cells (3 rd to 9 th month) and count (4 th to 12 th month) in UCBT group were significantly higher than those in PBSCT group ( P<0.05). 4. NKT cells in the UCBT group were lower than those in the PBSCT group (proportion and count) throughout the monitoring process ( P≤0.001). 5. The proportion of DNT cells (within 1 year) and count (within 6 months) in the UCBT group were significantly lower than those in the PBSCT group ( P<0.05). Conclusions:Compared with the peripheral blood stem cell transplantation group, the umbilical cord blood transplantation patients had a faster rate of lymphocyte reconstitution, and patients received umbilical cord blood transplantation had a stronger ability of immune reconstitution and could achieve long-term hematopoiesis.

Objective:To explore the clinical characteristics, diagnosis and treatment of acute leukemia patients during pregnancy.Methods:The clinical data of 16 cases with acute leukemia during pregnancy from January 2009 to December 2018 in the First Affiliated Hospital of USTC were retrospectively analyzed. The diagnosis and treatment regimens, pregnancy outcome, the early fetus and survival status of patients were also analyzed.Results:All 16 leukemia cases were confirmedly diagnosed and classified by bone marrow puncture, including 13 cases of acute myeloid leukemia (5 cases of non-acute promyelocytic leukemia and 8 cases of acute promyelocytic leukemia) and 3 cases of acute lymphoblastic leukemia. At the time of confirmed diagnosis, 6 patients were in first trimester, 6 cases in second trimester and 4 cases in late trimester. As for pregnancy outcome, 1 patient had natural birthing, 5 patients underwent cesarean operation, 9 patients underwent artificial abortion and 1 patient had spontaneous abortion. Chemotherapy was performed in 15 patients during pregnancy, 11 patients received chemotherapy for treatment of primary disease after pregnancy, 3 patients died during the treatment. During the follow-up of 13 cases, 8 patients survived and 5 patients lost follow-up.Conclusions:Early diagnosis of acute leukemia during pregnancy is very important. Bone marrow puncture should be performed timely to make clear diagnosis when blood routine result is abnormal during antenatal care. Multidisciplinary consultation should be initiated in time, and the best treatment plan should be worked out to guard against serious complications during pregnancy.

Objective:To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) .Methods:Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) .Results:The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95% CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95% CI 20.0%-35.0%) and 22.4% (95% CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95% CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95% CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95% CI 62.7%-77.8%) and 72.2% (95% CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95% CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% ( P=0.001) , and the 5-year OS rates were 79.9% (95% CI 70.3%-86.7%) , 71.1% (95% CI 50.4%-84.4%) and 52.9% (95% CI 33.0%-69.3%) ( χ2=7.552, P=0.020) , respectively. Conclusions:For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.

Objective To evaluate the effect of pretransplant iron overload on the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA). Methods Clinical data of 80 SAA recipients who underwent allo-HSCT for the first time were retrospectively analyzed. According to the incidence of iron overload, all recipients were divided into the iron overload group (n=20) and non-iron overload group (n=60). The engraftment rate, incidence of postoperative complications and clinical prognosis of the recipients afterallo-HSCT were statistically compared between two groups. The influencing factors of 2-year overall survival (OS) and 180 d transplantation related mortality (TRM) were analyzed by Cox proportional hazards regression model. Results The engraftment rate of neutrophils in the non-iron overload group was 98% (59/60), significantly higher than 75% (15/20) in the iron overload group (P < 0.05). The engraftment rate of platelet in the non-iron overload group was 90% (54/60), significantly higher than 65% (13/20) in the iron overload group (P < 0.05). The incidence rate of bloodstream infection in the non-iron overload group was 23% (14/60), remarkably lower than 40% (8/20) in the iron overload group (P < 0.05). The 180 d TRM of the recipients in the non-iron overload group was 17%, significantly lower than 45% in the iron overload group (P < 0.05). The 1- and 2-year OS of the recipients in the non-iron overload group were 82% and 80%, significantly higher than 50% and 44% in the iron overload group (both P < 0.05). Iron overload or not was an independent risk factor of the OS and TRM of the recipients (both P < 0.05). Conclusions Iron overload can affect the OS and TRM of SAA patients after allo-HSCT.

Objective:This study aimed to examine the safety and efficacy of CD19 chimeric antigen receptor T cell (CD19 CAR-T) therapy in relapsed/refractory Philadelphia chromosome-positive acute B-precursor lymphoblastic leukemia (R/R Ph + B-ALL) . Methods:The clinical data of 14 patients with R/R Ph + B-ALL treated with CD19 CAR-T cell therapy from November 2016 to April 2019 were retrospectively analyzed. Results:Among the 14 patients in this study, 7 were male and 7 were female, with a median age of 33 (7-66) years old. The efficacy was evaluated on the 28th day following CAR-T cells infusion; the overall response rate was 100.0% (14/14) , the complete response (CR) rate was 92.9% (13/14) , and the partial response (PR) rate was 7.1% (1/14) . After CAR-T cells infusion,12 cases (85.7%) developed cytokine release syndrome (CRS) : 1 case of grade 1 CRS, 4 cases of grade 2 CRS, 6 cases of grade 3 CRS, and 1 case of grade 4 CRS. Moreover, one case developed CAR T-cell-related encephalopathy syndrome (CRES) ; 14 cases had Ⅲ-Ⅳ hematological toxicity; and 13 CR cases had B cell dysplasia. These adverse reactions were all controllable. The median follow-up time was 441 (182-923) d. The median overall survival (OS) and progression-free survival (PFS) were 515 [95% confidence interval ( CI) 287-743] days and 207 (95% CI 123-301) days, respectively. Conclusion:CD19 CAR-T cell therapy is safe and effective for R/R Ph + B-ALL treatment. However, the long-term efficacy needs to be further improved.

Objective:To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

Objective: To compare the clinical efficacy of umbilical cord blood transplantation (UCBT) and hematopoietic stem cell transplantation from HLA-matched sibling donors (MSD-HSCT) in the treatment of myelodysplastic syndrome-EB (MDS-EB) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) . Methods: A cohort of 64 patients (including 38 cases of MDS-EB and 26 cases of AML-MRC) who received UCBT/MSD-HSCT from February 2011 to December 2017 were retrospectively analyzed. Results: ①Compared with MSD-HSCT group, UCBT group had a higher proportion of AML-MRC patients [52.8% (19/36) vs 25.0% (7/28) , P=0.025], and a lower median age [13 (1.5-52) years vs 32 (10-57) years, P=0.001]. ②The engraftment of neutrophils both in UCBT and MSD-HSCT groups on +42 d was 100%, and the median engraftment time was 17.5 (11-31) d and 11.5 (10-20) d, respectively. The engraftment of platelet at +100 d in UCBT group was 91.4%, the median engraftment time was 40 (15-96) d; The engraftment of platelet at +100 d in MSD-HSCT group was 100%, and the median engraftment time was 15 (11-43) d. ③There were no statistically significant differences in terms of the cumulative incidence of Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD of 100 d and transplant related mortality (TRM) of 180 d, relapse rate, overall survival (OS) , disease-free survival (DFS) between UCBT and MSD-HSCT groups (P>0.05) . ④The 3-year cumulative incidence of chronic GVHD (cGVHD) and severe chronic GVHD in UCBT group were lower than of MSD-HSCT group [28.3% (95%CI 13.4%-45.3%) vs 67.9% (95%CI 46.1%-82.4%) , P=0.002; 10.3% (95%CI 2.5%-24.8%) vs 50.0% (95%CI 30.0%-67.1%) , respectively, P<0.001]. The cumulative 3-year incidence of GVHD-free and relapse-free survival (GRFS) of UCBT group was significantly higher than of MSD-HSCT group [55.0% (95%CI 36.0%-70.6%) vs 28.6% (95%CI 13.5%-45.6%) , P=0.038]. Conclusion UCBT could obtain better quality of life after transplantation than MSD-HSCT in treatment of MDS-EB/AML-MRC.