A cohort study of vincristine-induced peripheral neuropathy in children / 中国当代儿科杂志

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.

Vincristine sulfate treatment influence on kidney function of female dogs with transmissible venereal tumor / Influência do tratamento com sulfato de vincristina na função renal de cadela com tumor transmissível venéreo

Chemotherapy agents have some undesirable and non-selective cytostatic effects. Considering that kidneys are vulnerable to drug-induced toxicity, this study evaluated renal injury caused by vincristine sulfate (VS) in 12 female dogs diagnosed with transmissible venereal tumor (TVT). The animals were treated with VS (0.025 mg/kg IV) every 7 days for 4 weeks. During treatment, the animals were subjected to clinical examination, blood count, serum measurement of symmetric dimethylarginine (SDMA), blood urea nitrogen (BUN), creatinine, alanine aminotransferase, and alkaline phosphatase. In addition, urinalysis and urinary gamma-glutamyl transferase (GGT) measurements were performed. All parameters were determined three times: before beginning the treatment (T0), after 14 days (T1), and after 28 days (T2). During the study period, there were no changes in serum urea or creatinine levels, urine specific gravity, or persistent proteinuria. Furthermore, urinary GGT measurement did not indicate tubular lesions, and consistent elevation of SDMA was found in only one patient above the reference range. The results showed that weekly therapy with VS as a single agent for 28 days does not induce renal injury in most cases.(AU)

Os agentes quimioterápicos possuem efeitos citostáticos indesejáveis e não seletivos. Considerando a vulnerabilidade renal à toxicidade induzida por drogas, este estudo avaliou a lesão renal causada pelo sulfato de vincristina (VS) em 12 cadelas com diagnóstico de tumor venéreo transmissível (TVT). Os animais foram tratados com VS (0,025 mg / kg IV) a cada sete dias, durante quatro semanas. No transcurso do tratamento, os animais foram submetidos a exame clínico, hemograma, dosagem sérica de dimetilarginina simétrica (SDMA), nitrogênio ureico sanguíneo (BUN), creatinina, alanina aminotransferase e fosfatase alcalina. Além disso, foram realizadas análises de urina e medições de gama-glutamil transferase (GGT) urinária. Todos os parâmetros foram mensurados em três tempos, antes do início do tratamento (T0), aos 14 dias (T1) e aos 28 dias (T2). Durante o período do estudo, não houve alterações nas concentrações de ureia ou creatinina séricas, na gravidade específica da urina ou proteinúria persistente. Além disso, a medição de GGT urinária não indicou lesões tubulares, e elevação consistente de SDMA foi encontrada em apenas um paciente acima do intervalo de referência. Os resultados mostraram que a terapia semanal com VS como agente único por 28 dias não induz lesão renal na maioria dos casos.(AU)

Efeitos de sulfato de vincristine sobre os testículos de ratos albinos, tratados na fase pré-púbere / Effects of vincristine sulphate on albino rat testis treated in the prepuberal phase

Este trabalho visou avaliar os efeitos de sulfato de vincristine sobre os testículos de ratos tratados na fase pré púbere, sobretudo quanto às alterações das células de Sertoli e das células germinativas. Foram utilizados 30 animais controles e 30 tratados com sulfato de vincristine. As aplicações da droga ocorreram aos 15 dias de vida, e a eutanásia aos 40, 64 e 127 dias de vida para possibilitar a avaliação em diferentes estágios de desenvolvimento reprodutivo. Foram realizadas medidas biométricas (pesos corpóreos e testiculares), medidas morfométricas testiculares, (eixos testiculares maiores e menores, diâmetros testiculares de túbulo e lúmen seminíferos, e altura do epitélio seminífero) e estereológicas (volumes testiculares e as densidades de volume do tecido tubular e do tecido intersticial testicular). As medidas biométricas foram feitas em todos os animais do experimento, e as avaliações morfométricas e estereológicas foram realizadas em 200 túbulos seminíferos. Os resultados demonstraram que sulfato de vincristine reduz parâmetros biométricos como peso corpóreo, peso testicular e volume testicular total. Variáveis morfométricas e estereológicas como diâmetro dos túbulos seminíferos, altura do epitélio seminífero e volume dos túbulos seminíferos também foram reduzidos. Os tipos celulares mais atingidos foram as espermatogônias, espermátides tardias e células de Sertoli.(AU)

This study evaluated the vincristine sulfate effect on rat testes treated in pre pubertal stage, especially regarding the changes of Sertoli cells and germ cells. Thirty control rats and 30 rats treated with vincristine sulfate were used. The drug application occurred at 15 days of life, and euthanasia at 40, 64 and 127 days of life to enable evaluation at different stages of reproductive development. Biometric measurements were performed (body and testicular weights), testicular morphometric measures (major and minor testicular axis and of seminiferous tubule and seminiferous lumen) and stereological (testicular volumes and volume densities of the tubular and testicular interstitial tissue). The biometric measurements were made on all rats in the experiment, and morphometric and stereological analysis was carried out in 200 seminiferous tubules. The results demonstrate that vincristine sulfate reduces biometric parameters such as body weight, testicular weight and the total testicular volume. Morphometric and stereological variables as diameter of the seminiferous tubules, height of the seminiferous epithelium and volume of the seminiferous tubules were also reduced. The most affected cell types were spermatogonia, late spermatids and Sertoli cells.(AU)

Interleukin-4 protects from chemotherapy-induced peripheral neuropathy in mice modal via the stimulation of IL-4/STAT6 signaling

Abstract Purpose: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Methods: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. Results: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1β and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. Conclusion: Anti-inflammatory cytokine IL-4 protects rodent model from vincristine-induced peripheral neuropathy via the stimulation of IL-4/STAT6 signaling and inhibition of the pro-inflammatory cytokines.

Single Nodular Opacity of Granulomatous Pneumocystis Jirovecii Pneumonia in an Asymptomatic Lymphoma Patient

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.

Preliminary evaluation of children treated with metronomic chemotherapy and valproic acid in a low-income country: Metro-Mali-02.

BACKGROUND: Metronomics is defined by the combination of metronomic chemotherapy and drug repositioning. Since off‑patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, metronomics appears to be an invaluable alternative to bring affordable targeted therapies in low‑income countries. OBJECTIVE: The aim of this study was to report on the preliminary efficacy and safety of a metronomic vincristine/cyclophosphamide/methotrexate/ valproic acid regimen given to children with refractory cancer of various tumor types or with a very advanced disease. MATERIALS AND METHODS: This prospective, single‑center study evaluated the use of a metronomics protocol, consisting of a first cycle of weekly vincristine 1.5 mg/m2 (days: 1, 8, 15 and 22), daily cyclophosphamide 25 mg/m2 (days: 1‑21), twice weekly methotrexate 15 mg/m² (days: 21‑42) and daily valproic acid (30 mg/kg/d) followed by a 1‑week break. For the following cycles, vincristine was administrated only at week 1 and 5 of the cycle. This treatment was proposed to children with refractory disease and patients who were not eligible for the protocols available in the hospital. Adverse events were determined through laboratory analyses and investigator observations. RESULTS: From January 2010 to January 2011, 7 children (mean age: 5.4 ± 3 years old) were treated. Most frequent diagnosis was retinoblastoma. Two partial responses were observed in patients with neuroblastoma and retinoblastoma. These two patients are alive with stable disease at last follow‑up (6 and 26 months, respectively) after stopping treatment. CONCLUSION: Metronomics allows treating patients with advanced or refractory or relapsing disease and the introduction of targeted treatments in low‑income countries. The potential of metronomics in children and young adults living in middle‑ and low‑income countries warrants further larger studies.

Frequency and severity of neutropenia in diffuse large beta-cell non Hodgkin's lymphoma after first cycle of chemotherapy comprising cyclophosphamide, doxorubicin, vincristine with prednisolone

Chemotherapy used for malignant diseases may produce severe neutropenia in first cycle which may compel for dose modification and early termination of therapy. This descriptive cross sectional study was planned to see the frequency and severity of neutropenia after first cycle of chemotherapy comprising cyclophosphamide, doxorubicin, vincristine with prednisolon in patients of diffuse large B-cell non Hodgkin's lymphoma presenting at Oncology Department Combined Military Hospital Rawalpindi from August 2009 to July 2010. Thirty patients of diffuse large B-cell non Hodgkin's lymphoma diagnosed on lymph node biopsy presenting for the first time at Oncology Department Combined Military Hospital Rawalpindi were included. They were admitted in the ward and evaluated with history, physical examination and staging investigations. Patients were then planned for first cycle of chemotherapy comprising cyclophosphamide, doxorubicin, and vincristine with prednisolon. After the first cycle of chemotherapy they were monitored for expected neutropenia in the ward. The neutrophil counts were repeated on days 7 and 10 following chemotherapy. Neutropenia was graded as defined in the operational definition and all the data was entered on a specially designed data card. As much as 3.3% of patients suffered from grade IV neutropenia [absolute neutrophil count of <0.5x10[9]/L], 3.3% had grade III neutropenia [absolute neutrophil count of 0.5x10[9]/L- 0.9x10[9]/L], 6.6% had Grade II neutropenia [absolute neutrophil count 1.0x10[9]/L-1.4x10[9]/L and 10% had Grade I neutropenia [absolute neutrophil count 1.5x10[9]/L-1.9x10[9]/L. Overall 23.2% suffered from neutropenia of all grades post 1st cycle of chemotherapy comprising cyclophosphamide, doxorubicin, vincristine with prednisolon in diffuse large B-cell non Hodgkin's lymphoma. Further studies are required to find the risk factors to predict this complication in our population

Use of pyridoxine and pyridostigmine in children with vincristine-induced neuropathy.

Four children with vincristine (VCR)-induced neuropathy are being reported. All cases were followed with the diagnosis of acute lymphoblastic leukemia. Two were boys aged between 2 and 13 year. Electromyographic examination consisted of sensoriomotor polyneuropathy with axonal involvement in three patients. In another patient, it consisted of motor axonal polyneuropathy. In all patients, pyridoxine and pyridostigmine were successfully used in the treatment of VCR-induced neuropathy. They recovered completely with this drug combination. Recovering period of symptoms was between 1-2 week.

Vincristine induced neurotoxicity in cancer patients.

Ten out of 20 children, treated with usual doses of vincristine for various types of childhood cancers, developed neurotoxicity during treatment. Peripheral neurotoxicity (mixed motor-sensory 4/10, pure motor 3/10, pure sensory 3/10) was seen in the form of weakness of lower limbs, areflexia, neuropathic pain, or sensory loss. Autonomic neuropathy presented as constipation and urinary retention in 2 children, while 2 children developed encephalopathy in form of seizures, confusion, aphasia, and transient blindness. In children with severe neuropathy, vincristine administration was withheld/dose reduced till clinical improvement started, which took about 2-3 weeks time. Nerve conduction velocity showed motor-sensory axonal polyneuropathy. Electrophysiological abnormalities were found to persist even six months after clinical recovery in children with neurotoxicity. We found a relatively higher incidence of vincristine induced neuropathy in Indian children, which was probably due to coexistence of severe malnutrition in them.

Simultaneous isolated bilateral facial palsy : A rare vincristine-associated toxicity.

We describe a case of a 15-year-old boy with vincristine-induced simultaneous isolated bilateral facial palsy. The boy presented with superior vena caval syndrome (SVC syndrome), right-sided pleural effusion and anterior mediastinal lymphadenopathy. Histopathological examination of left axillary lymph node was suggestive of lymphoblastic lymphoma. We started chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisolone. SVC syndrome disappeared completely after the 1st cycle, and he achieved remission after the 3rd cycle of chemotherapy. He noticed that he could not close his eyes. Neurological examination revealed bilateral lower motor neuron facial palsy. Findings from examination of other cranial nerves and peripheral nerves were normal. Results of MRI of brain and cerebrospinal fluid examination were normal. He received 6 mg vincristine before developing toxicity.

Bilateral vocal cord paralysis following treatment with vincristine.

The neurotoxicity of the vincristine is well known, however, cranial neuropathy is not widely recognized. We describe a child with acute lymphoblastic leukemia who developed vincristine-induced bilateral vocal cord paralysis. Vocal cord paralysis resolved spontaneously upon withdrawal of the vincristine. Vinca-alkaloid-induced vocal cord paralysis is a potentially dangerous but reversible condition.

Unilateral vocal cord palsy following chemotherapy for lymphoma

Unilateral vocal cord patsy is not uncommon. The common aetiologies include post neck operation particularly thyroid surgery, trauma to the neck, primary or metastatic neck node or bronchogenic carcinoma. We present a case of a 61 years old Malay gentleman who was diagnosed to have lymphoma and started on usual chemotherapy regime for lymphoma. Later on, he developed unilateral vocal cord palsy. Possible aetiologies were discussed

Rituximab-CHOP Induced Interstitial Pneumonitis in Patients with Disseminated Extranodal Marginal Zone B Cell Lymphoma

A 69-year-old male was diagnosed in February 2004 with stage IV extranodal marginal zone B cell lymphoma involving the mediastinal nodes, lung parenchyma and bone marrow with high LDH. Shortness of breath developed following the 5th course of Rituximab-CHOP chemotherapy (cyclophosphamide, Vincristine, Doxorubicin, Prednisolone). Bronchoscopy guided transbronchial lung biopsy revealed interstitial thickening and type II pneumocyte activation, compatible with interstitial pneumonitis. After treatment with prednisolone a complete resolution of the dyspnea was observed. The patient was well on routine follow-up at the outpatient clinic, with no progression of lymphoma or interstitial pneumonitis.

Neutropenic enterocolitis.

We report a case of neutropenic enterocolitis diagnosed on computerized tomography abdomen in a 56-year-old man having high-grade non-Hodgkin's lymphoma. After appropriate management, the patient recovered completely.

Resultados a largo plazo del tratamiento con quimioterapia y radioterapia en linfoma no Hodgking localizado, de grados intermedio y alto / Long term results for intermediate and high grade localized non Hodgkin lymphoma, treated with chemotherapy and radiotherapy

Background: Treatment of intermediate and high grade non-Hodgkin lymphoma (NHL) includes chemotherapy with or without radiotherapy, depending on the clinical stage. The standard treatment for advanced NHL is 8 cycles of combined chemotherapy, cyclophosphamide, adriamicin, vincristine and prednisone (CHOP). Patients presenting with localized disease are treated with fewer chemotherapy cycles and involved field radiotherapy, with good results. Aim: To evaluate the treatment results including overall survival (OS) and event-free survival (EFS) in localized aggressive NHL patients treated at the Pontificia Universidad Católica de Chile, Clinical Hospital. Patients and Methods: Retrospective analysis of all patients with Ann Arbor stages I and II referred to the hematology and radiotherapy clinic between 1998 and 2003. OS and EFS analysis was made according to the Kaplan and Meier method. Log-rank and Cox methods were used for univariate and multivariate analyses, respectively. Chemotherapy and radiotherapy toxicities were scored according to World Health Organization (WHO) and Radiation Therapy Oncology Group (RTOG) scales, respectively. Results: 39 patients (20 men), aged between 20 to 85 years, were the source for this study. The average follow-up was 51 months (range 6-115). The 5 years OS and EFS were 72,4 percent and 63,3 percent, respectively. On univariate analysis, age over 60 was the only variable that affected negatively OS and EFS. Acute toxicity caused by chemotherapy and radiotherapy was uncommon. Conclusions: Age over 60 was the only independent variable associated with poor prognosis. The number of chemotherapy cycles and the drug combination did not influence the results. These results support the usefullness of a shortened chemotherapy regimen plus involved field radiotherapy.

Vincristine induced cranial polyneuropathy.

We describe a 5-year-old girl showed recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received chemotherapy according to the previously described modified St. Jude total therapy studies XIII. Five days after the fourth dose of vincristine, she presented with bilateral ptosis. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. She received 3.8 mg cumulative dose of vincristin before development of ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks. The both agents were given for 3 weeks and were well tolerated without any side effects. During the follow up period we did not observe residue or recurrence of the ptosis.

Acute respiratory distress syndrome due to Strongyloides stercoralis in non-Hodgkin's lymphoma.

Strongyloides stercoralis is a nematode endemic in tropical and subtropical regions. In immunocompetent subjects, pulmonary disease caused by the parasite is unremarkable but the same can be life threatening in immunocompromised subjects. Though described in literature it is rarely seen in Indian subjects. We report a patient with ARDS due to Strongyloides stercoralis complicating non-Hodgkin's lymphoma with neutropenia.

Chemotherapy-induced palmer planter erythrodysesthesia.

We report a case of palmar plantar erythrodysesthesia (PPE) in a case of acute lymphoblastic leukemia treated with VALP regime. The treating physician must be aware of this uncommon complication of chemotherapeutic agents to avoid unnecessary investigations.

Quimioterapia neoadyuvante en cáncer de cuello uterino localmente avanzado / Neoadjuvant chemotherapy in advanced cervical cancer

Se presentan los resultados de una serie clínica de 15 pacientes portadoras de cáncer escamoso de cuello uterino localmente avanzado, estadios clínico I B2-II B, a quienes se les administró una quimioterapia neoadyuvante con cisplatino, vincristina y bleomicina durante 3 ciclos y luego fueron evaluadas para cirugía radical. Se logró una respuesta parcial o completa que permitió realizar la cirugía en 14 de las 15 pacientes tratadas. Cuando los márgenes o los ganglios estuvieron positivos para tumor se agregó raditerapia pelviana