Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with chronic myeloid leukaemia treated with busulphan for 4-5 years, developed signs of busulphan toxicity and portal hypertension with ascites, oesophageal varices and jaundice. At post-mortem there was minimal leukaemic infiltration but there were alterations in the liver architecture sufficient to explain the portal hypertension. The pathogenesis of the liver changes and their possible relationship to splenomegaly and busulphan toxicity are considered.
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PMID:Portal hypertension in a patient with chronic myeloid leukaemia. 26 81

Forty-three operative procedures were performed on a population of 250 patients with myeloproliferative disorders, including polycythemia vera, myeloid metaplasia (MM) and chronic myelogenous leukemia (CML). The overall operative mortality was approximately 7% and the incidence of excessive bleeding which could be related to coagulopathy was 5%. Twenty-one patients with MM or CML underwent splenectomy for palliation of symptoms related to the enlarged spleen or hematologic problems. Eighty-four percent of the latter group were improved. Adverse hematologic effects which could be attributed to splenectomy in these patients were confined to two patients who developed marked thrombocytosis. Among the 23 patients with MM, 9 had portal hypertension. Three underwent portacaval shunt and one a splenorenal shunt for bleeding varices. One of the patients died of hepatic necrosis. Estimated hepatic blood flow determinations (EHBF) in 4 patients with portal hypertension demonstrated a marked absolute increase and an increase in the ratio of EHBF/Cardiac Index. Absence of any evidence of intrahepatic or extrahepatic obstruction in these patients and the demonstration that splenectomy relieved portal hypertension defined at surgery in 4 patients, suggests that augmented adhepatic flow contributes to portal hypertension in some cases. The review leads to the conclusions that: 1) Operative procedures in prepared patients with myeloproliferative disorders are not associated with prohibitive mortality and morbidity rates. 2) Splenectomy is indicated for patients with increasing transfusion requirements and symptomatic splenomegaly or hypersplenism and should be performed early in the course of disease. 3) When associated portal hypertension and bleeding varices are present, hemodynamic studies should be carried out to define if splenectomy alone, or a portal systemic decompressive procedure is indicated.
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PMID:Myeloproliferative disorders. 105 48

Portal haemodynamic studies were carried out in 11 subjects, seven with chronic myeloid leukaemia and four with chronic lymphatic leukaemia, and results compared with those obtained in five patients with 'idiopathic' splenomegaly and with control subjects. All 11 patients with chronic leukaemia had intrasplenic pressures above 11 mmHg and of these four had pressures above 20 mmHg. Portosystemic collaterals were seen on splenovenography in four of these patients. Hepatic vein wedge pressure was above 7 mmHg in nine patients and these high levels were a result of increased free hepatic vein pressure. The corrected sinusoidal pressure and post sinusoidal resistance were essentially normal in all patients. Evidence of increased pre-sinusoidal resistance was seen in six patients. Estimated hepatic blood flow above 1500 ml/min was seen in six patients and all had evidence of histological portal or sinusoidal infilatration. Patients with 'idiopathic' splenomegaly regardless of increased liver blood flow did not have a significant increase in intrasplenic pressure and no alteration in other haemodynamic parameters. It appears that increased liver blood flow alone in a normal liver can only minimally elevate intrasplenic pressure but can play a significant part in the pathogenesis of portal hypertension when liver structure is altered.
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PMID:Portal hypertension in chronic leukaemia. 105 78

Portal hypertension with varices developed in 18/675 patients with chronic myeloid leukaemia (CML) in a randomized trial comparing busulphan with busulphan and thioguanine. All 18 had received the drug combination and none busulphan alone (P less than 0.0001). Ascites was also seen significantly more often in the combination arm (P less than 0.05). These results strongly suggest that the addition of thioguanine was responsible for the development of portal hypertension. The histological features were predominantly those of non-cirrhotic portal hypertension--either idiopathic portal hypertension with minimal morphological abnormalities, nodular regenerative hyperplasia or in two cases leukaemic infiltration only was noted. Cirrhosis was present in 3/16 cases studied. Both treatment groups developed abnormal liver function tests during the chronic phase, but particularly with progression of the disease. During chronic phase abnormalities were significantly more frequent in those receiving busulphan and thioguanine-alkaline phosphatase (P less than 0.02), transaminases (P less than 0.04), bilirubin (P less than 0.05), multiple abnormalities (P less than 0.01). The development of portal hypertension was often associated with abnormalities of these tests; however, lack of specificity precludes their use as a predictor of subsequent clinical problems. Thioguanine confers no survival advantage in this disease. In view of its hepatotoxicity it should not be used routinely for maintenance of control in chronic phase CML.
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PMID:Thioguanine used in maintenance therapy of chronic myeloid leukaemia causes non-cirrhotic portal hypertension. Results from MRC CML. II. Trial comparing busulphan with busulphan and thioguanine. 195 75

Four patients developed clinically important portal hypertension with histological features of idiopathic portal hypertension while they were receiving cytotoxic drugs for chronic myeloid leukaemia and Hodgkin's disease. Mild sclerosis of some small portal triads was the only abnormality seen at light microscopical examination in three of the four cases. In the remaining case light microscopical findings seemed to be normal. Two cases examined by electron microscopy showed perisinusoidal fibrosis; in one case this was the only abnormality detected. There is an association between idiopathic portal hypertension and the use of chemotherapeutic agents, particularly thioguanine. Adequate histological examination of liver tissue, including electron microscopic studies, is recommended for patients who develop hepatic problems while receiving cytotoxic treatment to elucidate this problem.
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PMID:Idiopathic portal hypertension associated with cytotoxic drugs. 233 18

Of 501 patients with chronic myeloproliferative diseases (c-MPD) 18 developed thrombosis of major abdominal vessels including 6 with hepatic vein thrombosis (Budd-Chiari syndrome). The complication was seen in 14 of 140 (10%) patients with polycythemia vera (PV), 3 of 23 (13%) patients with essential thrombocythemia (ET), 1 of 106 (1%) patients with idiopathic myelofibrosis (IMF), and none of 232 patients with chronic myelogenous leukemia (CML). Leading symptoms and signs were abdominal pain, progressive splenomegaly, widening abdominal girth, ascites, venous collaterals, and nausea and vomiting. The diagnostic modalities with highest specificity were angiography and explorative laparotomy. A causal relationship between the thrombotic event and hematocrit, thrombocyte count, or hemostatic abnormalities at the time of diagnosis could not be established. Detailed laboratory tests of platelet function and coagulation and fibrinolytic parameters of 5 surviving patients did not show any specific defect. Despite medical and surgical intervention, 39% of the patients died within 2 months after diagnosis of the thrombosis. The majority of the survivors developed further complications like liver cirrhosis with portal hypertension and esophageal varices or the short bowel syndrome after extensive bowel resection for mesenterial infarction.
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PMID:Budd-Chiari syndrome and thrombosis of other abdominal vessels in the chronic myeloproliferative diseases. 279 52

5 patients receiving continuous busulphan and 6-thioguanine for chronic myeloid leukaemia (CML) were found to have oesophageal varices associated with abnormal liver function tests. 3 of these cases presented with gastrointestinal haemorrhage and 1 patient died. The 2 other cases had varices discovered at endoscopy. Nodular regenerative hyperplasia (NRH) of the liver was identified as the cause of portal hypertension in the 4 patients on whom liver biopsies were done. The administration of busulphan and thioguanine in combination is likely to be associated with the development of NRH, with portal hypertension and oesophageal varices occurring in a substantial proportion of cases.
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PMID:Oesophageal varices associated with busulphan-thioguanine combination therapy for chronic myeloid leukaemia. 288 64

Myelofibrosis with myeloid metaplasia (MMM) is a collective term that describes the related disorders AMM, PPMM, and PTMM. The chronic myeloid disorders include chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, and agnogenic myeloid metaplasia (myelofibrosis). These disorders display varying propensities for pathologic enlargement of the spleen which can lead to mechanical discomfort, hypercatabolic symptoms, anemia, thrombocytopenia, and portal hypertension. Splenectomy has been found to be of little benefit in the early stages of chronic myeloid leukemia. Similarly, the benefit of splenectomy in advanced cases is limited to symptomatic palliation and treatment of delayed engraftment after allogeneic bone marrow transplantation. Although polycythemia vera and essential thrombocythemia are also characterized by splenomegaly, splenectomy is not considered a therapeutic option in the absence of transformation of the disease into myelofibrosis with myeloid metaplasia. Splenectomy has been studied most in myelofibrosis with myeloid metaplasia. Although there is no clear survival advantage to splenectomy in this disorder, the surgical procedure can result in substantial palliation of mechanical discomfort, hypercatabolic symptoms, portal hypertension, and anemia. However, the procedure is associated with an approximately 9% mortality rate, and the postsplenectomy occurrence of extreme thrombocytosis, hepatomegaly, and leukemic transformation is of major concern.
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PMID:Splenectomy in chronic myeloid leukemia and myelofibrosis with myeloid metaplasia. 1098 48

The case of a 65 year old woman referred for further evaluation of back pain and with abnormalities at ultrasound including increase in portal vein diameter and splenomegaly is presented. Other tests, including bone marrow biopsy and Doppler ultrasound, led to a diagnosis of portal vein thrombosis secondary to chronic myeloid leukemia. After prompt cytoreductive therapy with leukapheresis and hydroxyurea, resolution of portal vein thrombosis and portal hypertension was achieved within a in one-month period. An abnormal increase of cells in circulating blood may lead to portal vein thrombosis in patients with myeloproliferative disorders such as chronic myeloid leukemia. Chronic myeloid leukemia is an unusual cause of portal vein thrombosis and portal hypertension. Early administration of cytoreductive therapy may lead to the resolution of portal vein thrombosis. In this report, etiopathogenetic factors of portal vein thrombosis and the role of cytoreductive therapy in the dissolution of thrombosis are discussed.
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PMID:Rapid resolution of portal vein thrombosis and noncirrhotic portal hypertension following cyto-reductive therapy in a patient with chronic myeloid leukemia. 1461 43

Gamna Gandy bodies are usually seen in spleen in cases of chronic venous congestion. We present a case of CML showing gamna gandy bodies. These may have occurred as a part of evolving portal hypertension which maybe due to antileukemic therapy or CML per se or due to a combination of both factors.
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PMID:Gamna Gandy bodies of spleen seen in CML: a causal association--a case report. 1547 Nov 30


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