OBJECTIVES: To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN. METHODS: The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups. RESULTS: A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05). CONCLUSIONS There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.
Child ; Humans ; Antineoplastic Agents, Phytogenic/adverse effects* ; Cohort Studies ; Peripheral Nervous System Diseases/diagnosis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Vincristine/adverse effects* ; Infant ; Child, Preschool ; Adolescent

Objective: To identify the risk factors and clinical features associated with the interstitial pneumonia in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) or rituximab, cyclophosphamide, liposomal doxorubicin, vincristine and prednisone (RCDOP) regimens. Methods: A retrospective study was conducted in 836 patients with DLBCL admitted to the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 114 patients were treated with RCDOP regimen. Using the method of propensity score matching according to age, gender, IPI score of patients, 114 patients treated with RCHOP regimen were selected as controls. Clinical data, including comorbidities, gender, age, B symptoms, international prognostic index (IPI) score, disease stage, serum lactic dehydrogenase (LDH) and β(2) microglobulin (β(2)-MG) level were collected and the risk factors of interstitial pneumonia were further analyzed. Results: The interstitial pneumonia developed more frequently in RCDOP group than RCHOP group (28.95% vs 2.60%, P<0.01) . As the dose of liposomal doxorubicin elevated from 25-30 mg/m(2) to 35-40 mg/m(2), the incidence of interstitial pneumonia accordingly increased from 17.30% to 38.71% (P<0.05) . By multivariate analysis, disease stage was an independent factor of interstitial pneumonitis. Conclusions: Front line regimens containing liposomal doxorubicin in DLBCL patients link to a higher incidence of dose-dependent interstitial pneumonia. Prevention and surveillance should be emphasized in future studies.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Cyclophosphamide ; Doxorubicin ; Humans ; Lung Diseases, Interstitial/chemically induced* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisone ; Retrospective Studies ; Rituximab ; Vincristine

The radiologic findings of a single nodule from Pneumocystis jirovecii pneumonia (PJP) have been rarely reported. We described a case of granulomatous PJP manifesting as a solitary pulmonary nodule with a halo sign in a 69-year-old woman with diffuse large B cell lymphoma during chemotherapy. The radiologic appearance of the patient suggested an infectious lesion such as angioinvasive pulmonary aspergillosis or lymphoma involvement of the lung; however, clinical manifestations were not compatible with the diseases. The nodule was confirmed as granulomatous PJP by video-assisted thoracoscopic surgery biopsy.
Aged ; Antibodies, Monoclonal, Murine-Derived/adverse effects/therapeutic use ; Antineoplastic Agents/adverse effects/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biopsy/methods ; Cyclophosphamide/adverse effects/therapeutic use ; Doxorubicin/adverse effects/therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy/microbiology ; Pneumocystis jirovecii/pathogenicity ; Pneumonia, Pneumocystis/*diagnosis/*radiography ; Positron-Emission Tomography ; Prednisone/adverse effects/therapeutic use ; Solitary Pulmonary Nodule/*microbiology ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; Vincristine/adverse effects/therapeutic use

Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Humans ; Male ; Neuroblastoma ; drug therapy ; Topotecan ; administration & dosage ; Vincristine ; administration & dosage

BACKGROUND/AIMS: This study investigated the expression of nuclear factor kappaB (NF-kappaB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. METHODS: Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-kappaB (IkappaB kinase alpha, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study. The expression was divided into two groups according to the intensity score (negative, 0 or 1+; positive, 2+ or 3+). RESULTS: The median age of the patients was 66 years (range, 17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their International Prognostic Indexs (IPIs). The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF-kappaB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-kappaB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-kappaB or CXCR4 was not associated with overall survival and EFS. On multivariate analysis that included age, gender, performance status, stage, and the IPI, no significant association between the grade of NF-kappaB or CXCR4 expression and survival was observed. CONCLUSIONS: The current study suggests that the tissue expression of NF-kappaB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chi-Square Distribution ; Cyclophosphamide/administration & dosage ; Disease Progression ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse/chemistry/*drug therapy/mortality/pathology ; Male ; Middle Aged ; Multivariate Analysis ; NF-kappa B/*analysis ; Neoplasm Staging ; Predictive Value of Tests ; Prednisone/administration & dosage ; Proportional Hazards Models ; Receptors, CXCR4/*analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Markers, Biological/*analysis ; Vincristine/administration & dosage ; Young Adult

Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age > or =65 yr, comorbidities, bone marrow involvement, and baseline serum albumin < or =3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.
Adolescent ; Adult ; Age Factors ; Aged ; Antibodies, Monoclonal, Murine-Derived/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chemotherapy-Induced Febrile Neutropenia/*etiology ; Cyclophosphamide/administration & dosage/adverse effects/therapeutic use ; Demography ; Doxorubicin/administration & dosage/adverse effects/therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/*drug therapy ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia/etiology/pathology ; Prednisone/administration & dosage/adverse effects/therapeutic use ; Retrospective Studies ; Risk Factors ; Sex Factors ; Vincristine/administration & dosage/adverse effects/therapeutic use ; Young Adult

To investigate vincristine-induced dopaminergic neurons toxicity and mechanism, and explore the molecular target to reduce the toxicity, zebrafish was chosen as a model animal, based on RT-PCR, Western blotting, whole mount in situ immunofluorescence and other technical means. The results showed that the transcription levels of tyrosine hydroxylase gene and dopamine transporter protein gene were inhibited. Furthermore, the number of dopaminergic neurons was decreased by vincristine. Autophagy was suppressed and beclin1 gene expression was inhibited in a dose-dependent manner by vincristine in larval zebrafish. Up-regulated beclin1 partly reduced vincristine-induced neurotoxicity, and down-regulated beclin1 increased toxicity. Beclin1 plays an important role in vincristine-induced dopaminergic neurons toxicity.
Animals ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; Dopaminergic Neurons ; drug effects ; pathology ; Dose-Response Relationship, Drug ; Down-Regulation ; Gene Expression Regulation ; drug effects ; Larva ; drug effects ; Tyrosine 3-Monooxygenase ; metabolism ; Vincristine ; adverse effects ; Zebrafish ; Zebrafish Proteins ; metabolism

OBJECTIVETo evaluate the efficacy, safety and prognostic impact of rituximab plus CHOP (R-CHOP) regimen on patients with diffuse large B-cell lymphoma (DLBCL), to access the impact of R-CHOP on patients' prognosis and to compare that with CHOP regimen.

METHODSFive hundred and seven newly diagnosed DLBCL patients were enrolled from Jan. 1, 2000 to May 1, 2010. Patients were administered with 6 cycles of CHOP or at least 4 cycles of R-CHOP treatments. Rituximab was administered intravenously on day 1 at a dose of 375 mg/m(2). The typical CHOP regimen include cyclophosphamide (750 mg/m(2), IV), doxorubicin (50 mg/m(2), IV) and vincristine (1.4 mg/m(2), IV, maximum 2 mg) and prednisone (60 - 100 mg, oral, day 3 - 7). The complete response (CR) rates, overall response (OR) rates, and side events of these 2 groups were compared.

RESULTSOf the 411 analyzable patients, 224 received CHOP regimen and 187 received R-CHOP regimen. CR rate for R-CHOP group and CHOP group was 77.01% and 71.43%, respectively. OR rate in R-CHOP group was higher than that in the CHOP group (95.19% vs 87.95%, P = 0.007). The median follow-up time of R-CHOP group was 28.1 months vs that of 35.2 months in CHOP group. There was significant difference in progression free survival (PFS) and overall survival (OS) between 2 groups (P = 0.018 and 0.034, respectively). At the end of follow-up, the estimated median PFS in R-CHOP group had not been reached, while that was 84.8 months in CHOP group. The median OS in both groups had not yet been reached. The adverse events in R-CHOP group were similar with that in CHOP group.

CONCLUSIONSR-CHOP is a safe and effective regimen for management of newly diagnosed DLBCL, with a better remission rate, PFS and OS.

Aged ; Antibodies, Monoclonal ; administration & dosage ; adverse effects ; Antibodies, Monoclonal, Murine-Derived ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cyclophosphamide ; adverse effects ; therapeutic use ; Doxorubicin ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prednisone ; adverse effects ; therapeutic use ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Vincristine ; adverse effects ; therapeutic use

The study was aimed to evaluate the adverse effects of PAD (bortezomib + adriamycin + dexamethasone) and VAD (vincristine + adriamycin + dexamethasone) as chemotherapy regimens in multiple myeloma patients. 27 and 30 patients with multiple myeloma (MM) were enrolled in PAD and VAD groups respectively. MM patients accepted 3 - 5 cycles of VAD or PAD regimens. The type, degree and occurrence time of adverse reactions during the treatment were observed. The results showed that the rash was found in two patients only in PAD group, leucocytopenia, thrombocytopenia, peripheral neuropathy, infection, fatigue, nausea, constipation, and adverse effects of cortex hormone (hypertension, glycemia, hypokalemia, hyponatremia and acne) were found in the both two groups. The thrombosis was not observed in both two groups during treatment. Although statistical analysis indicated that only the incidence of thrombocytopenia was higher in PAD group than in VAD group with statistical difference but the incidence of leucocytopenia, peripheral neuropathy and infection in PAD group were higher than those in VAD group. Rash, constipation, peripheral neuropathy could be found in the first course of chemotherapy, while the others mostly emerged after 3 courses of treatment. The main reasons for the patients who's treatment was stopped include infection and intolerable peripheral neuropathy. Although peripheral neuropathy could be found in the two groups, but the chemotherapy was stopped only in 2 patients of PAD group after 3 cycles of treatment. It is concluded that compared with conventional VAD chemotherapy, PAD may improve therapeutic effect, but it may bring more severe toxicities to the patients with multiple myeloma.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Dexamethasone ; adverse effects ; therapeutic use ; Doxorubicin ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; Vincristine ; adverse effects ; therapeutic use

BACKGROUND/AIMS: The aim of our study was to determine the incidence and clinical features of severe pulmonary complications in patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) as the initial treatment for lymphoma. METHODS: A retrospective analysis of pulmonary infection and drug-induced interstitial pneumonitis (DIIP) was performed using lymphoma registry data. R-CHOP was administered in 71 patients and CHOP in 29 patients. RESULTS: The severe pulmonary adverse events tended to occur more frequently with R-CHOP (18.3%) than CHOP alone (13.8%), although the difference was not significant (p = 0.771). DIIP occurred in five patients in the R-CHOP arm (7%) and in one in the CHOP arm (3%). The continuous use of steroids for conditions other than lymphoma significantly increased the risk of pulmonary infection including Pneumocystis jiroveci pneumonia (p = 0.036) in the multivariate analysis. International prognostic index, tumor stage, smoking, previous tuberculosis, chronic obstructive pulmonary disease, and lymphoma involvement of lung parenchyma were not related to pulmonary adverse events. Patients who experienced severe pulmonary events showed shorter survival when compared to those without complications (p = 0.002). CONCLUSIONS: Our experiences with serial cases with DIIP during chemotherapy and the correlation of continuous steroid use with pulmonary infection suggest that the incidence of pulmonary complications might be high during lymphoma treatment, and careful monitoring should be performed.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/administration & dosage/*adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects ; Cyclophosphamide/administration & dosage/adverse effects ; Doxorubicin/administration & dosage/adverse effects ; Female ; Humans ; Incidence ; Lung Diseases, Interstitial/*chemically induced/mortality ; Lymphoma, Non-Hodgkin/*drug therapy/mortality ; Male ; Middle Aged ; Pneumocystis jirovecii ; Pneumonia, Bacterial/mortality ; Pneumonia, Pneumocystis/mortality ; Prednisone/administration & dosage/adverse effects ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Tuberculosis, Pulmonary/mortality ; Vincristine/administration & dosage/adverse effects ; Young Adult