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

Chronic Myelogenous Leukemia (CML) is an oncohematological disease characterized by a clonal proliferation concerning the primitive hematopoietic cell. A typical cytogenetic alteration known as Philadelphia Chromosome (Ph1), a 9:22 chromosomic translocation which produces a hybrid gene BCR/ABL, is present in 95% of the patients. Nineteen CML patients (9 female and 10 male) underwent Bone Marrow Transplantation (BMT). Median age was 32 years (range 9 to 47); 15 of them were in chronic phase (CP), and 4 in accelerated phase (AP). At diagnosis, all patients were Ph1+, BCR/ABL+. The conditioning regimen consisted of busulphan and cyclophosphamide while patients in AP received etoposide as well. Seventeen patients received cyclosporine A, methotrexate and methylprednisone as prophylaxis for Graft Versus Host Disease (GVHD) while 2 patients received only the first two drugs. The 9.22 translocation was determined by means of RT-PCT technique using the primers NB1+, Abl3, B2A, CA3 and A2. The sensitivity of the method was 1 x 10(-6). Among the 19 patients who entered the protocol, 14 are alive and in clinical, hematological and cytogenetic remission (Ph1-) and 3 patients died due to acute GVHD, 1 due to graft failure and 1 due to Hemolytic Uremic Syndrome. Of the 4 transplanted patients in AP, 3 are alive and in complete remission. The patients had a 74% survival, with a median follow-up of 655 days. Complete hematopoietic chimerism was demonstrated in 16 patients, with the study of 3 loci, D1S80, APO B and D17S30. No relationship was found between post BMT hybrid BCR/ABL (RT.PCR) persistence and disease relapse; the presence of acute and/or chronic GVHD did not influence the BCR/ABL positivity. In our experience, BMT has proved to be the only therapeutic alternative for CML with complete clinical, hematological and cytogenetic remission and a mean survival of 74%, comparable to the international experience.
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PMID:[Bone marrow transplantation in chronic myeloid leukemia]. 1034 11

This case report describes 2 patients with chronic myeloid leukemia in whom hemolytic uremic syndrome developed while being treated with interferon-alpha and hydroxycarbamide. Hemolytic uremic syndrome was recognized by progressive renal dysfunction, thrombocytopenia, microangiopathic hemolytic anemia, and histologic features of thrombotic microangiopathy in the kidney. Although renal dysfunction progressed to dialysis-dependent renal failure in one patient despite treatment with prednisolone and plasmapheresis but not in other, withdrawal of the treatment resulted in a prompt resolution of thrombocytopenia and microangiopathic hemolytic anemia in both patients.
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PMID:Withdrawal of interferon-alpha results in prompt resolution of thrombocytopenia and hemolysis but not renal failure in hemolytic uremic syndrome caused by interferon-alpha. 1261 3

Alpha Interferon (IFN) is a biological agent used for the therapy of an increasing number of diseases, either as an established effective therapeutic tool or in the context of clinical trials. The use of IFN may be complicated by serious adverse reactions. We describe here the clinical course of a variety of vasculopathic complications in association with IFN-therapy in 12 patients with the diagnosis of chronic myeloid leukemia and 1 patient with malignant melanoma treated at our institute. Vascular manifestations in these patients include Raynaud's phenomena, digital ulcerations and gangrene, pulmonary vasculitis, pulmonary hypertension and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). These reactions occurred after 3 months to 3 years of 3-10 million units (MU) daily IFN therapy. Concomitant administration of hydroxyurea (HU) was noted in 5 patients. Discontinuation of IFN and initiation of immunosuppressive therapy brought about a complete resolution or arrested progression of these reactions. IFN-therapy may be complicated by severe vasculopathic/vasospastic complications that usually improve after its discontinuation. Possible underlying mechanisms for these complications are discussed. The early diagnosis of these complications may be vital and IFN should be immediately discontinued when early signs of these complications become evident.
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PMID:Vascular events associated with alpha interferon therapy. 1268 17

We report on a 61-year-old woman with chronic myeloid leukemia (CML) who developed a hemolytic uremic syndrome (HUS)-like episode following nonmyeloablative allogeneic hematopoietic stem cell transplantation. Macrohematuria, hypertension, hemolytic anemia with red cell fragmentation, thrombocytopenia, and progressive renal insufficiency were observed after thawed peripheral blood stem cell (PBSC) infusion. Although transient systemic hemolysis is known to occur during dimethylsulfoxide (DMSO)-cryopreserved stem cell infusion, HUS caused by DMSO has not been described in the literature. We speculate that one of the triggers of the HUS-like episode could have been renal microangiopathy caused by the long-term administration of interferon-alpha before the stem cell transplantation.
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PMID:[Hemolytic uremic syndrome-like episode following nonmyeloablative hematopoietic stem cell transplantation in a patient with chronic myeloid leukemia]. 1288 18

Various drugs have been associated with the development of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Among the biologic agents, alpha-interferon therapy, used for treatment of hepatitis B and chronic myelogenous leukemia, has been associated with TTP in a few recent reports. The authors report the first case of TTP/HUS occurring in a metastatic melanoma patient receiving treatment with high-dose interleukin-2 (IL-2). A 57-year-old patient with malignant melanoma presented with seizures 3 days after completing the first week of high-dose IL-2, and the characteristic hematologic picture revealed TTP/HUS. This occurrence is unlikely to be explained by the association with malignant melanoma, which was not presenting with widespread visceral disease at the time of the occurrence, or by the use of other medications. Similar cytokine release profiles are encountered in TTP, HUS caused by Shiga toxin-1, HUS caused by E. coli O157, after IL-2 or IL-2-containing biochemotherapy, as well as in TTP caused by interferon-alpha. This cytokine profile could reflect a common cause, or just the presence of similar pathways involved.
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PMID:Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome associated with high-dose interleukin-2 for the treatment of metastatic melanoma. 1572 58

Drug-mediated thrombotic microangiopathy may cause life-threatening medical emergencies. Novel targeted therapies have dramatically changed the prognosis of a number of oncological diseases. Tyrosine kinase inhibitors of the Breakpoint Cluster Region-Abelson (BCR-ABL) oncoprotein are used in patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Imatinib mesylate, which was the first anti-BCR-ABL tyrosine kinase inhibitor, has demonstrated a high tolerance profile and efficacy in these patients for many years. Good results have also been observed in patients with gastrointestinal stromal tumors. In this study, we describe two patients with Philadelphia chromosome-positive hematological malignancies who presented with secondary thrombotic microangiopathy that was most likely linked to the use of imatinib. Other potential causes of thrombotic microangiopathy were discarded, and the predisposing role of some comorbidities and potential short or long-term drug-drug interactions was assessed. The clinical and biological data were more indicative of atypical secondary hemolytic uremic syndrome in one of the cases and of secondary thrombotic microangiopathy with renal and cardiac impairment in the other, which is also categorized as secondary hemolytic uremic syndrome. The outcome was favorable after imatinib discontinuation and the treatment of severe cardiac and renal failures.
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PMID:Secondary thrombotic microangiopathy in two patients with Philadelphia-positive hematological malignancies treated with imatinib mesylate. 2559 69

Interferon (IFN) has been associated with development of thrombotic microangiopathy including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We reviewed literature from the earliest reported association in 1993, to July 2016 and found 68 cases. Analysis of this data shows: (1) Mean age at diagnosis was 47 years (95% CI, 44-50). (2) Majority of cases were seen where IFN was used for the treatment of chronic myelogenous leukemia (CML), multiple sclerosis (MS), chronic hepatitis C virus infection (HCV) and one case each for hairy cell leukemia (HCL) and Sezary syndrome. (3) There were no cases reported for polycythemia vera (PV) or lymphoma. (4) Sex distribution was nearly equivalent with the exception in patients with multiple sclerosis where there was female predominance (12 of 16 with reported data). (5) For pooled analysis, the average duration of treatment with IFN before TMA was diagnosed was 40.4 months. (6) Comparative analysis showed that patients with MS required the highest cumulative dose exposure before developing TMA (MS 68.6 months, CML 35.5 months, HCV 30.4 months). (7) Cases of confirmed TTP (where A disintegrin and Metalloprotease with thrombospondin type 1 motif 13: ADAMTS 13 level was measured) showed presence of an inhibitor. (8) In all cases of confirmed TTP, moderate to severe thrombocytopenia was a striking clinical feature at presentation while this was not a consistent finding in all other cases of TMA. (9) Outcome analysis revealed complete remission in 27 (40%), persistent chronic kidney disease (CKD) in 28 (42%) and fatality in 12 patients (18%). (10) Treatment with corticosteroids, plasma exchange and rituximab resulted in durable responses.
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PMID:Interferon induced thrombotic microangiopathy (TMA): Analysis and concise review. 2832 51

Most commonly seen side effects with Tyrosine kinase inhibitors (TKI's) are hematologic toxicities. Besides, with dasatinib autoimmune side effects can be seen. Thrombotic thrombocytopenic purpura (TTP) is a life- threatening disease that can be related to various causes mainly autoimmune disorders or antineoplastic drugs. Few cases of TKI associated secondary thrombotic microangiopathies (TMA) have been reported in literature. Most of cases were diagnosed as hemolytic uremic syndrome (HUS) rather than TTP. Herein, we describe a 37-year-old CML patient who was diagnosed as immune-mediated TTP related to dasatinib.
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PMID:Dasatinib-induced immune mediated-thrombotic thrombocytopenic purpura. 2947 47