Reacción adversa a medicamento con signos cutáneos (erupción liquenoide) atribuibles a imatinib, y respuesta favorable al tratamiento con fototerapia UVB de banda angosta / Adverse drug reaction with skin signs (lichenoid rash) attributable to imatinib, and favorable response to treatment with narrowband UVB phototherapy

Resumen El imatinib es un agente antineoplásico que actúa como inhibidor de la tirosina-cinasa. Los efectos adversos cutáneos son, en general, leves y autolimitados. Dentro de estos, la erupción liquenoide es infrecuente y suele mejorar sólo con tratamiento tópico. Presentamos el caso de una paciente con erupción liquenoide por imatinib refractaria al tratamiento con corticoides tópicos, con respuesta favorable a terapia de luz ultravioleta B de banda estrecha. No existen casos publicados a la fecha en la literatura de erupción liquenoide por imatinib tratada con fototerapia.

Abstract Imatinib is an antineoplastic agent that acts as a tyrosine kinase inhibitor. Cutaneous adverse effects are generally mild and self-limited. The lichenoid eruption due to imatinib is rare. It usually improves just with topical treatment. We present the case of a patient with a lichenoid reaction due to imatinib, refractory to treatment with topical corticosteroids, with a favorable response to narrow-band ultraviolet B phototherapy. There are no published cases to date in the literature of lichenoid eruption due to imatinib treated with phototherapy.

Application of HRM Analysis in Detection of PDGFRA Exon 10 Polymorphism in CML Patients with Imatinib Resistance

@#Introduction: Imatinib mesylate has been widely used as a standard treatment for chronic myeloid leukemia (CML). It acts as a selective competitive inhibitor of the BCR-ABL tyrosine kinase. Despite the excellent efficacy on CML treatment, some patients developed resistance to the treatment. Mutation in the PDGFRA may be one of the factors involved in the mechanism of resistance that affects the response to imatinib. The mutational status of PDGFRA is highly relevant for prognosis and treatment prediction in CML patients. Thus, this study is intended to establish and validate a High Resolution Melting (HRM) analysis for PDGFRA exon 10 c.1432 T>C polymorphism in CML patients. Methods: High resolution melting (HRM) analysis was used to identify the c.1432 T > C polymorphism in PDGFRA exon 10 (n =86; response = 43; resistance = 43). The results from HRM analysis were compared and validated with Sanger sequencing. The association between the polymorphism and treatment response was assessed by statistical analysis using binomial logistic regression analysis. Results: HRM analyses showed two different melt curves. One curve followed the shape of the reference, homozygous wild type (TT) and the other curve showed a different melting profile than the reference with the TC genotype (heterozygous variant). The results revealed that heterozygous variant (TC) genotype showed a high risk of acquiring resistance with an OR of 3.795; 95% CI: 1.502-9.591, with a statistically significant association, p = 0.005. HRM analysis also showed 100% sensitivity and specificity in the detection of PDGFRA exon 10. Conclusion: The HRM analysis of PDGFRA exon 10 c.1432 T>C was successfully established. The exon 10 c.1432 T>C polymorphism shows a higher risk for the development of resistance toward imatinib treatment.

Gastrointestinal stromal tumor: outcomes of the past decade in a reference institution in southern brazil / Tumor estromal gastrointestinal (gist): resultados da última década em uma instituição de referência no sul do brasil

ABSTRACT - BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the digestive tract and has a wide variation in biological behavior; surgical resection remains the main form of treatment. AIM: This study aimed to analyze clinicopathological characteristics and survival of patients with GIST in a reference institution for oncological diseases. METHODS: An observational, longitudinal, and retrospective study of patients diagnosed with GIST from January 2011 to January 2020 was carried out by analyzing epidemiological and clinical variables, staging, surgical resection, recurrence, use of imatinib, and curves of overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 38 patients were included. The majority (58%) of patients were males and the median age was 62 years. The primary organs that were affected by this tumor were stomach (63%) and small intestine (17%). Notably, 24% of patients had metastatic disease at diagnosis; 76% of patients received surgical treatment and 13% received neoadjuvant treatment; and 47% of patients received imatinib as adjuvant or palliative therapy. Tumor recurrence was 13%, being more common in the liver. The 5-year OS was 72.5% and DFS was 47.1%. The operated ones had better OS (87.1% vs. 18.5%) and DFS (57.1% vs. 14.3%) in 5 years. Tumor size ≥5 cm had no difference in OS at 5 years, but DFS was 24.6%, when compared with 92.3% of smaller tumors. Patients who were undergoing neoadjuvant therapy and/or using imatinib did not show any significant differences. CONCLUSIONS: Surgical treatment with adequate margins allows the best gain in survival, and the use of imatinib in more advanced cases has prognostic equity with less advanced-stage tumors. Treatment of metastatic tumors seems promising, requiring further studies.

RESUMO - RACIONAL: O Tumor estromal gastrointestinal (Gastrointestinal stromal tumor - GIST) é a neoplasia mesenquimal mais comum do trato digestivo, possui comportamento biológico variado e a principal forma de tratamento é a ressecção cirúrgica. OBJETIVO: analisar as características clínico-patológicas e a sobrevida de pacientes com GIST em uma instituição de referência para doenças oncológicas. MÉTODOS: Foi realizado um estudo observacional, longitudinal e retrospectivo de pacientes com diagnóstico de GIST de janeiro de 2011 a janeiro de 2020, analisando variáveis epidemiológicas e clínicas, estadiamento, ressecção cirúrgica, recidiva, uso de imatinibe e curvas de sobrevida global (SG) e sobrevida livre de doença (SLD). RESULTADOS: foram incluídos 38 pacientes, a maioria (58%) do sexo masculino, idade mediana de 62 anos. Os principais órgãos primários foram estômago (63%) e intestino delgado (17%). 24% tinham doença metastática ao diagnóstico. 76% receberam tratamento cirúrgico e 13% tratamento neoadjuvante. 47% dos pacientes receberam Imatinib como terapia adjuvante ou paliativa. A recorrência tumoral foi de 13%, mais comum no fígado. SG de 5 anos foi de 72,5% e SLD 47,1%. Os operados tiveram melhor SG (87,1% vs. 18,5%) e SLD (57,1% vs. 14,3%) em 5 anos. O tamanho do tumor igual ou maior que 5 cm não teve diferença na SG em 5 anos, mas SLD foi de 24,6%, em comparação com 92,3% dos tumores menores. Pacientes em terapia neoadjuvante e/ou em uso de imatinibe não apresentaram diferenças significativas. CONCLUSÕES: O tratamento cirúrgico com margens adequadas permite o melhor ganho de sobrevida, e o uso de Imatinibe em casos mais avançados tem equidade prognóstica com tumores em estágio menos avançado. O tratamento de tumores metastáticos parece promissor, necessitando de mais estudos.

Quimioterapia intensiva asociada a imatinib en leucemia linfoblástica aguda del adulto, Philadelphia positivo. Experiencia en un hospital público / Intensive chemotherapy with tyrosine kinase inhibitors in philadelphia-positive acute lymphoblastic leukemia

Background: Before the advent of tyrosine kinase inhibitors (TKIs), patients with Philadelphia-positive Acute Lymphoblastic Leukemia (Ph+ALL) had a poor prognosis. The association of TKIs to intensive chemotherapy (CT) improved outcome. Aim: To evaluate results of an intensive CT protocol including TKI in a public hospital in Santiago, Chile. Material and Methods: All patients with Ph+ALL diagnosed between January 2010 and February 2019, and who met inclusion criteria for intensive CT, received the Ph+ALL national protocol in association with imatinib and were included in this analysis. Results: Thirty-five patients aged 15 to 59 years received treatment. Complete response (CR) was obtained in 97%. Measurable residual disease (MRD) was negative in 61% (19/31 evaluable cases) during follow-up, and 55% (16/29) were MRD (-) before three months. Relapse was observed in 13 cases. Three patients underwent allogeneic hematopoietic stem cell transplant (HSCT), two in CR1. The overall survival (OS) and event-free survival (EFS) at three years were 52 and 34%, respectively. In patients who achieved MRD negativity before three months, no statistically significant differences in OS (64 and 42% respectively, p = 0.15) or EFS (35 and 32% respectively, p = 0.37) were observed. Conclusions: The prognosis of Ph+ALL improved with the association of imatinib to intensive CT. MRD-negative status before three months in this series was not significantly associated with better outcomes. Our series suggests that the Ph+ALL national protocol associated to TKI is a therapeutic alternative with high CR and aceptable MRD (-) rates.

Renal tuberculosis in an imatinib-treated chronic myeloid leukemia / Tuberculose renal em paciente com leucemia mieloide crônica tratado com imatinibe

ABSTRACT Imatinib, which inhibits tyrosine kinase activity of Bcr-Abl protein, is a standard form of treatment for chronic myeloid leukemia (CML). Through its immunomodulatory effect it affects T cell function in a number of ways. It inhibits antigen-induced T cell activation and proliferation. Antigen-specific T-cells and macrophages are vital for protection against Mycobacterium tuberculosis. Here we present a case of renal tuberculosis associated with imatinib therapy in the maintenance phase of CML. With granulomatous interstitial nephritis and positive tubercular DNA on renal biopsy, the condition was successfully treated with anti-tubercular therapy. This case provides support to the hypothesis that imatinib therapy in CML increases the susceptibility to tuberculosis and strict vigilance is required to enable its early detection and treatment.

RESUMO O imatinibe, um inibidor da atividade da tirosina-quinase da proteína BCR-ABL, faz parte do padrão de tratamento para leucemia mieloide crônica (LMC). Por conta de seu efeito imunomodulador, o imatinibe afeta a função dos linfócitos T de várias maneiras ao inibir a sua ativação e proliferação induzidas por antígenos. Linfócitos T e macrófagos antígeno-específicos são vitais para a proteção contra o Mycobacterium tuberculosis. O presente artigo relata um caso de tuberculose renal associada a terapia com imatinibe na fase de manutenção da LMC. Com nefrite intersticial granulomatosa e positividade para DNA de M. tuberculosis na biópsia renal, o paciente foi tratado com sucesso com terapia antituberculínica. O presente caso corrobora a hipótese de que a terapia com imatinibe na LMC aumenta a suscetibilidade à tuberculose, exigindo vigilância rigorosa para permitir sua detecção e tratamento precoces.

Hipofosfatemia inducida por drogas: fierro carboximaltosa e imatinib. Casos clínicos / Hypophosphatemia induced by carboxymaltose iron and imatinib. Report of two cases

Hypophosphatemia is a relatively frequent and a potentially serious adverse drug effect. Clinically it is characterized by bone pain and muscle weakness. There are several mechanisms by which a drug can induce hypophosphatemia and they can be classified according to whether or not they are mediated by an excess of Fibroblast Growth Factor 23 (FGF23). We report two patients with the condition: (i) A 49-year-old woman with Chronic Myeloid Leukemia (CML) and gastric sleeve surgery at 46 years of age. After receiving intravenous carboxymaltose iron in one occasion due to refractory anemia, she developed symptomatic hypophosphatemia. Urinary phosphate losses associated with high FGF23 levels were confirmed. Plasma phosphate returned to normal values 90 days after the iron administration. (ii) A 40-year-old man with a history of CML in whom imatinib was started. He developed symptomatic hypophosphatemia due to non FGF23-mediated hyperphosphaturia. As treatment with imatinib could not be interrupted, hypophosphatemia and its symptoms resolved with oral phosphate intake. These cases illustrate the importance of recognizing and treating drug-induced hypophosphatemia in a timely manner, and thus avoid the morbidity associated with this entity.

Development and validation of highly selective method for the determination of imatinib mesylate and dexketoprofen trometamol combination in three different media

Imatinib mesylate is a small molecule used in cancer therapy as a thyrosine kinase inhibitor. Dexketoprofen trometamol is a non-steroidal anti-inflammatory drug that has seen use in cancer therapy in combination with an anticancer drug to minimize tumor size and to reduce pain in patients. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as potential model drugs to be used in combination. A new, simple and selective Ultra Performance Liquid Chromatography method was developed and validated to determine the drug substances in distilled water, in a pH 7.4 phosphate buffer and in Dulbecco's Modified Eagle Medium. The proposed method was developed using a BEH C-18 column with isocratic elution. A mixture of methanol:acetonitrile (80:20, v/v) and pH 9.5, 0.05 M ammonium acetate were (70:30, v/v) used as a mobile phase. Detection was carried out with a flow rate of 0.3 mL/min, a column temperature of 30°C and an injection volume of 20 µL. The method was validated considering linearity, accuracy, precision, specificity, robustness, detection limit and quantitation limit values, and was found to be linear in a range from 0.05 to 20.0 µg/mL for the three different media

Neuroprotective potential of imatinib in global ischemia-reperfusion-induced cerebral injury: possible role of Janus-activated kinase 2/signal transducer and activator of transcription 3 and connexin 43

The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusion-induced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.

What happens to intolerant, relapsed or refractory chronic myeloid leukemia patients without access to clinical trials?

ABSTRACT Objective: To assess clinical outcomes of intolerant, relapsed or refractory patients who could not be treated with new tyrosine kinase inhibitors or experimental therapies. Methods: A retrospective cohort of 90 chronic myeloid leukemia patients in all phases of the disease treated with imatinib mesylate as their first TKI therapy, and with dasatinib or nilotinib as the next line of therapy. We evaluated clinical outcomes of these patients, with special focus on the group that needed more than two therapy lines. Results: Thirty-nine percent of patients were refractory or intolerant to imatinib. An 8-year overall survival rate of the patients who went through three or more lines of treatment was significantly lower, compared to those who were able to maintain imatinib as their first-line therapy (83% and 22%, respectively p < 0.01). Decreased overall survival was associated with advanced-phase disease (p < 0.01), failure to achieve major molecular response in first-line treatment (p < 0.01) and interruption of first-line treatment due to any reason (p = 0.023). Failure in achieving complete cytogenetic response and major molecular response and treatment interruption were associated with the progression to the third-line treatment. Conclusion: The critical outcome observed in relapsed, intolerant or refractory chronic phase CML patients reflects the unmet need for this group of patients without an alternative therapy, such as new drugs or experimental therapies in clinical trials. Broader access to newer treatment possibilities is a crucial asset to improve survival among CML patients, especially those refractory or intolerant to first-line therapies.

Tumores del estroma gastrointestinal / Gastrointestinal stromal tumors

Los tumores del estroma gastrointestinal (GIST) son neoplasias mesenquimales originadas en el tracto gastrointestinal. Su localización más frecuente es en estómago e intestino delgado. Pueden originarse a cualquier edad, pero más del 80% de los casos son mayores de 50 años sin predilección de sexo, aunque puede observarse en pacientes más jóvenes asociados a síndromes que predisponen el desarrollo de estos tumores. Presentan sintomatología inespecífica. La tomografía axial computarizada está recomendada para realizar el estudio de extensión y seguimiento de estos pacientes. Los marcadores inmunohistoquímicos más sensibles y específicos son el KIT y DOG1. El tratamiento en caso de lesiones primarias localizadas es la resección quirúrgica, con o sin terapia adyuvante con imatinib durante 3 años en dependencia del riesgo de recidiva. En los casos avanzados o metastásicos se recomienda terapia neoadyuvante con imatinib por tiempo indefinido; el tratamiento en casos de progresión o intolerancia a imatinib es el sunitinib.

Gastrointestinal stromal tumors (GIST) are mesenchymal neoplasms that arise in the gastrointestinal tract, usually in the stomach or the small intestine. GISTs can arise at any age, but more than 80% are reported in individuals older than 50 years men and women are affected at a roughly similar frequency. The few patients are who younger frequently have GIST associated with a syndrome. The clinical manifestations are non-specifics. The computer-tomography is recommended for staging and follow-up. The KIT and DOG1 are the most sensitive and specific immunohistochemistry markers. The standard treatment of localized GIST is complete surgical excision of the lesion, with or without adjuvant imatinib in dependence with the relapse risk. Neoadjuvant imatinib is the standard treatment for locally advanced and metastatic disease. In locally advanced and metastatic disease the imatinib treatment should be continued indefinitely. Following confirmed progression, or intolerance, to imatinib the standard second-line treatment is sunitinib.

Pay Attention to Diagnosis and Treatment of Gastrointestinal Stromal Tumors / 胃肠病学

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. The receptor tyrosine kinase inhibitor imatinib mesylate is used for the standard treatment of GIST and has achieved remarkable results. Thus, GIST has become the most successful model for targeted therapy of solid tumors. GIST is quite different from other gastrointestinal tumors in pathological diagnosis, endoscopic and imaging diagnosis, surgical principles and drug treatment. Multidisciplinary collaborative model plays an important role in the diagnosis and treatment of GIST. Contemporary medicine has entered a new era of standardized, individualized and precise diagnosis and treatment at molecular level. Clinicians, especially those engaged in gastrointestinal tumors, should pay attention to and standardize the diagnosis and treatment of GIST, and apply the experience gained from GIST to the clinical practice of precision medicine.

Research advances in the secondary resistance mechanism of imatinib in gastrointestinal stromal tumors / 中华胃肠外科杂志

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Though surgical resection is the only radical treatment, postoperative recurrence and metastasis often occur. The first-line therapy for the treatment of recurrent, metastatic and unresectable GIST is imatinib. More than 80% of patients can benefit from imatinib treatment, but half of patients will still have recurrence or metastasis within 2 years after treatment initiation, and secondary drug resistance is a major cause of disease progression. Therefore, adeep understanding of the mechanisms of secondary drug resistance will guide us to develop personalized therapeutic schedule in the future. This article describes the mechanism of IM secondary resistance from the aspects of gene alteration, abnormal activation of signal transduction pathway, autophagy, apoptosis and drug concentration. It is found that single drug therapy has certain limitations in patients with secondary resistance to IM. Using IM combined with downstream signaling molecule inhibitors, autophagy inhibitors, insulin-like growth factor 1 receptor (IGF-1R) inhibitors, heat shock protein 90 (HSP90) inhibitors, cytotoxic T lymphocyte - associated antigen - 4 (CTLA - 4) antibodies and mitochondrial inhibitors provide us new therapeutic ideas. However, these combination treatments are still in the research phase, and further trials are needed to confirm the safety and efficacy. With the gradual deepening of research on drug resistance mechanisms, it will provide more solutions to the current serious drug resistance problem.

Similarities and differences in diagnosis and treatment of gastrointestinal stromal tumors between China, Japan and Korea: from expert consensus to cooperation prospect / 中华胃肠外科杂志

The great success of tyrosine kinase receptor inhibitor (TKI) in gastrointestinal stromal tumors(GIST) has promoted it to become a classic model of targeted cancer therapy in the era of precision medicine. Multidisciplinary diagnosis and treatment and whole-process scientific management are the key to clinical diagnosis and treatment of GIST. There are many expert consensuses or guidelines on diagnosis and treatment of GIST in the world. The English version of expert consensuses on diagnosis and treatment of GIST has been issued by the East Asian countries represented by Japan, Korea and China, respectively, in combination with their own clinical practice. In 2016, the first edition of the Asian Expert Consensus on Diagnosis and Treatment of GIST was formulated jointly by the above - mentioned countries. This paper aims to explore the similarities and differences between Chinese and Asian Consensus on the diagnosis and treatment of GIST, to improve the understanding of GIST, and to bridge the gap and explore clues for future cooperation among these countries. The overall framework of both consensuses includes the pathological diagnosis, surgery and drug treatment of GIST. The differences include the following three aspects: (1) The different focus of pathological diagnosis of GIST. The Chinese Consensus has highlighted the requirements for the management of pathological specimens of GIST and the pathological evaluation after targeted therapy. The Chinese Consensus has also tried to clarify the algorithm of diagnosis of wild-type GIST, while wild-type GIST is introduced in very few words in the Asian Consensus. (2) The difference of surgical treatment of GIST focuses on the field of minimally invasive techniques, especially the application of endoscopy in the treatment of GIST. The Asian Consensus is cautious about laparoscopic surgery and has no comments on endoscopic resection at all. At present, the Chinese Consensus does not recommend routine endoscopic treatment in GIST, but the indications have been expanded to a certain extent, reflecting the clinical needs and development trends of endoscopic therapy in China. (3) The recommendation degree of medication for GIST varies. The difference includes the indication of adjuvant therapy, the recommendation after failure of first-line treatment, and discontinuation of TKIs preoperatively, and duration of postoperative adjuvant therapy. The difference between the Chinese Consensus and the Asian Consensus reflects the gap in the practice and clinical research of GIST between China and other Asian countries (e.g. Japan and Korea). Cooperation is the main theme in the field of medical science in the 21st century. China, Japan and South Korea are all located in East Asia and have certain shared features in terms of genetic and biological background, living habits and social environment, medical system and scientific research mode. It is a good entry point to carry out international cooperation research in the field of GIST. In view of some pending problems in the diagnosis and treatment of GIST, the cooperative research between China, Japan and Korea may focus on the following aspects: (1) The value of surgery in the treatment of advanced GIST. (2) The detection of imatinib blood concentration in East Asian population and optimized rational use of targeted drugs in the oriental population. (3) Chinese researchers should optimize the strategy of endoscopic treatment of GIST, design rigorous domestic multi-center clinical trials, and provide convincing data, so as to obtain international recognition. (4) Other related studies may include the diagnosis and treatment of wild-type GIST, the value of Ki-67 in the pathological evaluation of GIST, laparoscopic surgery for gastric GIST, and the optimal duration of imatinib adjuvant therapy. Researchers in China should attach importance to the value of clinical trials, especially cooperative clinical research. Starting with improving data quality, we should welcome cooperation with an open and confident attitude and strive to promote the clinical practice and research of GIST to a new height.

Long-term effect of neoadjuvant imatinib for locally advanced gastrointestinal stromal tumor / 中华普通外科杂志

Objective To explore the safety and long-term results of preoperative imatinib mesylate administration (IM) in patients with locally advanced gastrointestinal stromal tumors (GIST).Methods From Sep 2009 to Nov 2016,locally advanced GIST patients treated in Fujian Medical University Cancer Hospital were analysed retrospectively.Result 34 patients were included.Preoperative median IM treatment was 27 weeks(range 12-71 weeks).65％ patients had a partial response to IM,35％ showed stable disease.All patients underwent surgical R0 resection.The complication rate was 9％ and no death occurred within 30 days post operation.The median follow-up time was 62.2 months (range of 13-89 months).20 patients continued to take imatinib orally,14 patients did not.The 3 year survival rate of patients undergoing surgery was 67％.Univariate analysis showed that tumor location,preoperative imatinib effect,pathology,targeted therapy after surgery were factors affecting prognosis.Multivariate analysis show that the independent risk factors affecting prognosis were tumor location,pathology,targeted therapy after surgery.Conclusion In locally advanced GISTs,preoperative IM is useful and safe that can effectively decrease tumor size,facilitating resection.

Imatinib-induced hepatitis treated by corticosteroids in a patient with metastatic gastrointestinal stromal tumor / 영남의대학술지

Imatinib mesylate is currently used as the first-line treatment for metastatic gastrointestinal stromal tumors (GISTs). Imatinib-induced hepatotoxicity in patients with GIST is very rare. Its features vary from subclinical elevation of serum aminotransferase to clinically apparent acute hepatitis, which is associated with immunologic reactions. Imatinib-induced hepatotoxicity with autoimmune-like features can be treated by the discontinuation of imatinib mesylate and the administration of oral steroids. Here, we report a case of late-onset imatinib-induced hepatitis with autoimmune-like features in a patient with metastatic GIST, which was improved by oral corticosteroids.

Tratamiento neoadyuvante con imatinib de un tumor gigante del estroma gastrointestinal rectal / Neoadjuvant treatment with imatinib for a giant tumor of the rectal gastrointestinal stroma

Alrededor de 5 % de los tumores del estroma gastrointestinal (GIST) se localizan en el recto. Cuando se encuentran localmente avanzados, el tratamiento neoadyuvante con imatinib ha demostrado buenos resultados para reducir el volumen de este tipo de tumores. Se presenta el caso de un paciente con diagnóstico de GIST rectal gigante, al que se le administró neoadyuvancia con imatinib y, posteriormente, se sometió a resección anterior baja con anastomosis coloanal. Es imprescindible que la evaluación y el tratamiento sean multidisciplinarios en los GIST rectales, para tratar de obtener los mejores resultados ante esta entidad tan poco frecuente, poder evitar la comorbilidad asociada y practicar cirugías menos agresivas tras una buena reacción terapéutica al imatinib

Less than 5% of gastrointestinal stromal tumors (GIST) are located at the rectum. When these tumors are locally advanced, neoadjuvant therapy with imatinib has shown good results, reducing its volume. We present the case of a patient with a giant rectal GIST tumor, who underwent neoadjuvant imatinib therapy, and posterior low anterior resection with coloanal anastomosis. In rectal GIST tumors it is essential the multidisciplinary evaluation and treatment, in order to obtain the best possible results in this rare entity. After a good response to the treatment with imatinib, aggressive surgeries can be avoided, along with the associated morbidity that comes with it

Postoperative Cure for Metastatic Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor derived from Cajal cells originating from the myotonic plexus. The expression of tyrosine kinase (KIT) membrane receptors that are active on KIT is inhibited by the KIT inhibitor imatinib mesylate. GISTs are resistant to conventional chemotherapy, and radiation therapy is not significantly beneficial for GISTs. With the development of imatinib mesylate, approximately 81.6% of patients with advanced and metastatic GIST exhibit an effect above the stabilization response, thereby increasing the survival time. However, imatinib mesylate alone is unlikely to cure metastatic GISTs. Even with a partial or stable response, imatinib mesylate may be used for a longer time period. However, resection of grossly visible lesions should be considered for patients with a stable response during surgical treatment. In this study, we present a case of GIST with liver metastasis after imatinib mesylate treatment, which was followed up without recurrence after partial resection.

Loeffler endocarditis in chronic eosinophilic leukemia with FIP1L1/PDGFRA rearrangement: full recovery with low dose imatinib

No abstract available.

Two different KIT mutations may lead to different responses to imatinib in metastatic gastrointestinal stromal tumor

No abstract available.

Study of correlation between imatinib mesylate plasma levels and hematological profile of patients undergoing treatment for chronic myeloid leukemia / Estudo da correlação entre os níveis plasmáticos de mesilato de imatinibe e o perfil hematológico de pacientes com leucemia mieloide crônica em tratamento

ABSTRACT Introdution: Chronic myeloid leukemia (CML) is a genetic disorder of hematopoietic stem cells, resulting in a myeloproliferative expansion of blood cells. CML is associated with the presence of the Philadelphia chromosome (Ph), generating an oncogene (BCR-ABL). The current treatment of choice is imatinib mesylate (IM). Objective: To correlate serum levels of MI with hematological parameters in patients with CML. Method: A retrospective cross-sectional study in patients treated for CML. Serum level of IM was determined by a high-performance liquid chromatography with diode array detector (HPLC-DAD), and statistical analysis was performed using SPSS version 20.0 software. Results: We studied 55 CML patients - 24 men (43.6%) and 31 women (56.4 %) - with a mean age of 54 years, who used IM. Among these, 45 patients were in the chronic phase (81.6 %); seven, in the accelerated phase (13.1%); and three, in the blast crisis (5.2%). Patients received a mean IM dose of 434 mg/day. Serum levels of the patients presented an average of 1,092 ± 617 ng/ml, and, in all, 47 patients (85.4%) had hematologic response (HR). Conclusion: There was no correlation between the number of leukocytes, platelets and hemoglobin and the serum level of IM, although there is a trend with respect to hemoglobin (p = 0.062).

RESUMO Introdução: Leucemia mieloide crônica (LMC) é uma desordem genética de células-tronco hematopoiéticas, resultando em uma expansão mieloproliferativa das células sanguíneas. A LMC está associada à presença do cromossomo Philadelphia (Ph), o que gera um oncogene (BCR-ABL). Atualmente, o tratamento de primeira escolha é o mesilato de imatinibe (MI). Objetivo: Correlacionar os níveis séricos de MI com parâmetros hematológicos em pacientes com LMC. Método: Estudo transversal retrospectivo em pacientes com LMC em tratamento. O nível sérico de MI foi determinado por um sistema de cromatografia líquida de alta eficiência com detector de arranjo de diodos (CLAE-DAD), e a análise estatística foi realizada no programa SPSS versão 20.0. Resultados: Foram estudados 55 pacientes - 24 homens (43,6%) e 31 mulheres (56,4%) - com média de idade de 54 anos, portadores de LMC que utilizavam MI. Destes, 45 encontravam-se em fase crônica (81,6%); sete, em fase acelerada (13,1%) e três, em crise blástica (5,2%). Os pacientes em questão receberam uma média de dose do MI de 434 mg/dia. O nível sérico dos pacientes apresentou média de 1.092 ± 617 ng/ml e, ao todo, 47 pacientes (85,4%) apresentaram resposta hematológica (RH). Conclusão: Não houve correlação do número de leucócitos, plaquetas e hemoglobina com o nível sérico de MI, embora exista uma tendência observada com relação à hemoglobina (p = 0,062).