T/myeloid mixed-phenotype acute leukemia treated with venetoclax and decitabine:A case report

BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for MPAL is yet to be established,owing to its rarity.CASE SUMMARY A 55-year-old male was diagnosed with T/myeloid MPAL.Vincristine,prednisolone,daunorubicin,and L-asparaginase were administered as induction chemotherapy.Septic shock occurred 10 days after induction,and bone marrow examination following recovery from sepsis revealed refractory disease.Venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk.There were no serious infections,including febrile neutropenia,at the end of the treatment.After receiving two additional cycles of venetoclax/decitabine,the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response(CR)to treatment.CONCLUSION CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.

Retrospective analysis of extra-gastrointestinal stromal tumors

AIM:To investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors(EGISTs)in South Korea.METHODS:A total of 51 patients with an EGIST were identified.The clinicopathologic features,including sex,age,location,tumor size,histology,mitotic rate,immunohistochemical features,genetic status and survival data,were analyzed.RESULTS:The median age was 55 years(range:29-80years),and male:female ratio was 1:1.04.The most common site was in the mesentery(n=15)followed by the retroperitoneum(n=13)and omentum(n=8).The median tumor size was 9.0 cm(range:2.6-30.0cm)and the median mitotic rate was 5.0/50HPF.(1/50-185/50).KIT was analyzed in 16,which revealed 10cases with wild-type KIT and 6 cases with an exon 11mutation.Among 51 patients,31 patients had undergone surgery,and 10 had unresectable disease and had taken palliative imatinib,which resulted in 22.7 mo of progression-free survival.Of the patients who had undergone surgery,18 did not take adjuvant imatinib,and 8 of these were categorized as"high risk"according to the risk criteria.However,the relapse-free survival was not different(P=0.157)between two groups.CONCLUSION:Because the biologic behaviors of GISTs differ according to the location of the tumor,a more stratified strategy is required for managing EGISTs including incorporation of molecular features.

Gastric leptomeningeal carcinomatosis: Multi-center retrospective analysis of 54 cases

AIM: To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis (LMC) of gastric cancer.METHODS: We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.RESULTS: The male-to-female ratio was 32:22, and the patients ranged in age from 28 to 78 years (median,48.5 years). The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients (70%).The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 (51%) of the patients were Bormann typeand 15 (33%) patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache (85%) and nausea/vomiting (58%) were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases (82%). Intrathecal (IT) chemotherapy was administered to 36 patients-primarily methotrexate alone (61%), but also in combi-nation with hydrocortisone/± Ara-C (39%). The median number of IT treatments was 7 (range, 1-18). Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients (46%) achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk (95% CI: 4.3-9.1 wk). In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration (P = 0.038, P = 0.010, and P = 0.002, respectively). However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration (3.6, 6.7 and 14.6 wk, P = 0.030, RR: 0.415, 95% CI: 0.188-0.918).CONCLUSION: Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.

减量FOLFIRINOX方案挽救性治疗吉西他滨抵抗的晚期胰腺癌:一项Ⅱ期研究

背景与目的奥沙利铂、伊立替康、氟尿嘧啶和亚叶酸的联合化疗方案(FOLFIRINOX)极大提高了晚期胰腺癌患者的生存期。然而,FOLFIRINOX方案作为吉西他滨失败后二线治疗的疗效尚未进行前瞻性的检测。我们研究了减量FOLFIRINOX方案治疗吉西他滨抵抗的晚期胰腺癌患者的可行性和安全性。方法在14家医院进行了这一多中心II期前瞻、开放标签的单臂研究。经组织学确诊为胰腺浸润性导管腺癌、有可测量或可评价的病灶、东部肿瘤协作组体能状况评分0或1分、器官功能良好、年龄19岁或以上的患者符合入组条件。减量FOLFIRINOX方案的组成:奥沙利铂65 mg/m2、伊立替康135 mg/m2和亚叶酸400 mg/m2,第1天静脉注射;5?氟尿嘧啶2000 mg/m2,第1–2天持续静脉输注46 h;每2周重复。主要终点为FOLIFLIOX治疗起始后的无进展生存期。次要终点为客观缓解率、疾病控制率、总生存期、安全性和耐受性。采用Kaplan?Meier法评估了总生存期和无进展生存期。结果我们招募了来自14个中心的39例患者。客观缓解率为10.3%,疾病控制率为64.1%。6个月和1年总生存率分别为59.0%和15.4%。中位无进展生存期和总生存期分别为3.8个月[95%置信区间(confidence interval,CI)=1.5–6.0个月]和8.5个月(95%CI=5.6–11.4个月)。3或4级不良事件为中性粒细胞减少(41%)、恶心(10.3%)、食欲减退(10.3%)、贫血(7.7%)、黏膜炎(7.7%)、肺炎/胸膜融合(5.1%)和乏力(5.1%)。发生1例由感染性休克引起的治疗相关死亡。结论减量FOLFIRINOX方案有望作为二线方案治疗吉西他滨抵抗的胰腺癌。

Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study

Background:Combination therapy with oxaliplatin,irinotecan,fluorouracil,and leucovorin(FOLFIRINOX)chemotherapy drastically improves survival of advanced pancreatic cancer patients.However,the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively.We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer.Methods:A multicenter phase II prospective open-label,single-arm study was conducted at 14 hospitals.Patients with histologically proven invasive ductal pancreatic adenocarcinoma,a measurable or evaluable lesion,Eastern Cooperative Oncology Group performance status 0 or 1,adequate organ function,and aged 19 years or older were eligible.Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2,irinotecan 135 mg/m2,and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2,repeated every 2 weeks.The primary endpoint was progression-free survival from the initiation of FOLFIRINOX.Secondary endpoints were the objective response rate,disease control rate,overall survival,safety,and tolerability.We estimated overall survival and progression-free survival using the Kaplan-Meier methods.Results:We enrolled 39 patients from 14 institutions.The objective response rate was 10.3%,while the disease control rate was 64.1%.The 6-month and 1-year overall survival rates were 59.0%and 15.4%,respectively.Median progression-free survival and overall survival were 3.8 months(95%confidence interval[CI]1.5-6.0 months)and 8.5 months(95%CI 5.6-11.4 months),respectively.Grade 3 or 4 adverse events were neutropenia(41.0%),nausea(10.3%),anorexia(10.3%),anemia(7.7%),mucositis(7.7%),pneumonia/pleural effusion(5.1%),and fatigue(5.1%).One treatment-related death attributable to septic shock occurred.Conclusion:Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancre-atic cancer.