Chemotherapy-induced neutropenia (CIN) is a common hematological adverse events and dose-limiting toxicities of chemotherapy. CIN may lead to dose reduction and delay of chemotherapeutic agents, febrile neutropenia and severe infection, which results in increased treatment cost, reduced efficacy of chemotherapy, and even life-threatening morbidities. Assessment of risk of CIN, early detection of FN and infection, and proper prevention and treatment play a crucial role in reducing the occurrence of CIN-related morbidities, improving patient treatment safety and anticancer efficacy. Based on evidence and expert opinion, the expert committee of Chinese Anti-Cancer Association issued "the consensus on diagnosis and treatment of chemotherapy-induced neutropenia in China (2023 edition)", which is an update version of the 2019 edition, aiming to provide reference for the diagnosis and treatment of CIN for Chinese oncologists.
Humans ; Granulocyte Colony-Stimulating Factor ; Consensus ; Neutropenia/prevention & control* ; Neoplasms/drug therapy* ; Antineoplastic Agents/adverse effects* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).
Humans ; Antineoplastic Agents/adverse effects* ; Maximum Tolerated Dose ; Neoplasms/drug therapy* ; Neutropenia/chemically induced* ; Prospective Studies

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia

OBJECTIVE: To explore the effect of age on the time of neutropenia after initial induction therapy for newly diagnosed acute myeloid leukemia (AML) patients. METHODS: Data of 18-65 years old AML patients treated in our hospital from Junuary 2015 to July 2020 were retrospectively analyzed. The clinical characteristics, time of neutropenia after initial induction treatment, early responses, and related influencing factors for the time of neutropenia were analyzed and compared between 18-40 years old group and 41-65 years old group. RESULTS: There were 112 patients enrolled in this study, including 66 (58.9%) males, and their median age was 46 years old. Compared with 18-40 years old group, the incidence of FLT3-ITD gene mutation increased (P=0.039) but core binding factor (CBF) decreased (P=0.003) significantly in 41-65 years old group. The incidence of neutropenia was 97.3%, and the average time was (18.70±1.192) days. The time of neutropenia was (21.43±1.736) days in 41-65 years old group, which was longer than (14.91±1.356) days in 18-40 years old group (P=0.006). The time of neutropenia in CBF positive group was shorter than that in negative group (P=0.012), as well as in patients with remission (CR+CRi) (≤ 2 courses) than those with non-remission (NR) (P=0.024), while in high-risk group was longer than that in low-risk group (P=0.040). Multivariate analysis showed that age, FLT3-ITD gene mutation positive, and non-remission (NR) after two courses of treatment were independent risk factors for the time of neutropenia. CONCLUSION In non-elderly patients with newly diagnosed AML, age is an influencing factor for the time of neutropenia. Key words　　;
Adolescent ; Adult ; Aged ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Male ; Middle Aged ; Mutation ; Neutropenia ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM. METHODS: A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT. RESULTS: The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%). CONCLUSIONS Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Cisplatin/therapeutic use* ; Humans ; Lung Neoplasms/drug therapy* ; Mesothelioma/drug therapy* ; Mesothelioma, Malignant ; Neutropenia ; Pemetrexed/therapeutic use* ; Platinum/therapeutic use* ; Pleural Neoplasms/drug therapy*

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Cytarabine/therapeutic use* ; Hematopoietic Stem Cell Transplantation ; Humans ; Idarubicin/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy* ; Neutropenia ; Prospective Studies ; Recurrence ; Retrospective Studies

OBJECTIVE: To observe the clinical efficacy and safety of polymyxin B sulfate in febrile neutropenia patients with hematonosis. METHODS: Clinical data of 50 patients in the department of hematology, Fujian Medical University Union Hospital from October 2019 to September 2020 were collected. All the patients developed febrile neutropenia after chemotherapy or hematopoietic stem cell transplantation. According to the results of drug susceptible test, polymyxin B sulfate was administrated mainly when the empirical antimicrobial treatments was poor and the pathogenic microbes test was positive. RESULTS: A total of 85 times of infection occurred in 50 patients. The infection sites were lung, blood flow, intestinal tract, oral cavity, perianal, soft tissue and nasal cavity. Gram negative bacteria was the main pathogenic microbe. After administration of polymyxin B sulfate when the etiology was confirmed, the total effective rate was 68%, especially the effective rate increased significantly after more than 7 days of polymyxin B sulfate treatment. Also, 24% and 8% of the patients were discharged automatically and died respectively. The effective rate of patients receiving carbapenem antibiotics changed to polymyxin B sulfate within 14 or 7 days was 80% and 70.6%, respectively, while the effective rate of patients who changed after 2 weeks was only 33.3%. The effective rate of patients receiving tigecycline changed to polymyxin B sulfate within 14 or 7 days was 80% and 66.7%, respectively. The incidence of adverse reactions of polymyxin B sulfate was low, most of which were mild, and only one patient occurred rhabdomyolysis. CONCLUSION Polymyxin B sulfate has good clinical efficacy and safety in febrile neutropenia patients with hematonosis.
Anti-Bacterial Agents/therapeutic use* ; Carbapenems ; Febrile Neutropenia/drug therapy* ; Humans ; Polymyxin B/therapeutic use* ; Tigecycline

OBJECTIVE: To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL). METHODS: A prospective study was performed on children with ALL who cyclophosphamide, cytarabine, and 6-mercaptopurine were used for consolidation therapy. PEG-rhG-CSF (PEG-rhG-CSF group) or rhG-CSF (rhG-CSF group) was injected after chemotherapy. The plasma concentration of PEG-rhG-CSF was measured, and clinical outcome and safety were observed for both groups. RESULTS: A total of 17 children with ALL were enrolled, with 9 children in the PEG-rhG-CSF group and 8 children in the rhG-CSF group. In the PEG-rhG-CSF group, the peak concentration of PEG-rhG-CSF was 348.2 ng/mL (range 114.7-552.0 ng/mL), the time to peak was 48 hours (range 12-72 hours), and the half life was 14.1 hours (range 11.1-18.1 hours). The plasma concentration curve of PEG-rhG-CSF was consistent with the mechanism of neutrophil-mediated clearance. Compared with the rhG-CSF group, the PEG-rhG-CSF group had a significantly shorter median time to absolute neutrophil count (ANC) recovery (P<0.05). There were no significant differences between the two groups in ANC nadir, incidence rate of febrile neutropenia, duration of grade IV neutropenia, incidence rate of infection, and length of hospital stay. No bone pain or muscle soreness was observed in either group (P>0.05). CONCLUSIONS The pharmacokinetic characteristics of PEG-rhG-CSF in children with ALL receiving consolidation chemotherapy are consistent with the mechanism of neutrophil-mediated clearance, with a short half life and fast recovery of ANC, and there are no significant differences in safety between PEG-rhG-CSF and rhG-CSF.
Child ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Humans ; Neutropenia ; Polyethylene Glycols ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prospective Studies ; Recombinant Proteins

OBJECTIVE: To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.METHODS: A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.RESULTS: A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).CONCLUSION: There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.
Carboplatin ; Disease-Free Survival ; Drug Therapy ; Humans ; Neoadjuvant Therapy ; Neutropenia ; Ovarian Neoplasms ; Paclitaxel ; Proportional Hazards Models ; Retrospective Studies ; Treatment Outcome

neutropenia (41.67%), hemorrhage (37.5%), hypertension (33.33%), proteinuria (12.5%), fatigue (37.5%), and hand-foot syndrome (27.08%). Most of them were grade 1–2, and no drug-related death occurred.CONCLUSIONS: Apatinib can improve the disease control rate of recurrent and metastatic cervical cancer when chemotherapy has failed, and the treatment is well tolerated. This represents that apatinib may be a new treatment option for metastatic cervical cancer patients.]]>
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Fatigue ; Follow-Up Studies ; Hand-Foot Syndrome ; Hemorrhage ; Humans ; Hypertension ; Leukopenia ; Molecular Targeted Therapy ; Neutropenia ; Proteinuria ; Radiotherapy ; Retrospective Studies ; Uterine Cervical Neoplasms