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Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy
Tomá? Pavlík, Eva Janou?ová, Zdeněk Pospí?il, Jan Mu?ík, Daniela ?á?ková, Zdeněk Rá?il, Hana Klamová, Petr Cetkovsky, Marek Trněny, Ji?í Mayer, Ladislav Du?ek
BMC Medical Research Methodology , 2011, DOI: 10.1186/1471-2288-11-140
Abstract: Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data.The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively) at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter.Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in this paper. Both quantities reliably illustrate a patient's disease status in time because they account for the proportion of patients in the second and subsequent disease remissions. Moreover, the model is also applicable in the future, regardless of what the progress in the CML treatment will be and how many treatment options will be available, respectively.Treatment guidelines and recommendations for patients treated for chronic myeloid leukaemia (CML) have changed dramatically over the last decade, as a BCR-ABL tyrosine kinase inhibitor (TKI), imatinib, was introduced in 1998 [1,2]. Since th
Neurological Complications Of Chronic Myeloid Leukaemia: Any Cure?
JD Emmanuel, MA Durosinmi
Nigerian Journal of Clinical Practice , 2008,
Abstract: Objective: To attempt to explain the non-reversal, contrary to the widely held view, of the neurological deficits complicating chronic myeloid leukaemia. Method: Using patients\' case folders and haematological malignancy register all cases of chronic myeloid leukaemia seen in Jos University Teaching Hospital between July 1995 and June 2005 were retrospectively studied. All the available literature on the subject was also reviewed. Results: Thirty-three cases of chronic myeloid leukaemia were seen within the study period. Five (15.15%) of them had one or more sensori-neural defects. Of the five, two (40%) patients presented with bilateral hearing impairment, each beginning with the left ear; one (20%) presented with left ear hearing loss; one (20%) came with severe left ear tinnitus; one (20%) presented with complete bilateral hearing and bilateral visual losses. Fundoscopy showed leukaemic deposits on the retina. Other causes of blindness and deafness, e.g. trauma and foreign body in the ear respectively, were excluded. Conclusion: While the complications due to hyperleucocytosis-induced stasis recover following the conventional treatment, those due to other pathogenetic mechanisms such as leukaemic deposits do not return to their pre-morbid states following disease control despite the use of the currently available treatment protocols. For future research, more still needs to be done to elicit other uncommon pathogenetic mechanisms underlying these complications with a view to finding specific treatment measures for worrisome chronic myeloid leukaemia-related sensori-neural deficits.
Leukaemia in childhood
M Kruger
Continuing Medical Education , 2010,
Abstract: Leukaemia means white blood. It is a disease of the white blood cells and was first described by Virchow in 1845.1 Leukaemia can present as an acute disease, occurring more often in the younger age groups, or as a chronic disease, usually in the older age group. Acute leukaemia is rare, but about 1 in 2 000 people will develop the disease.2 The two acute forms in children are acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). The chronic form is chronic myeloid leukaemia (CML).2,3
New drugs in the treatment of chronic myeloid leukaemia
Cilloni, Daniela;Rotolo, Antonia;Nicoli, Paolo;Bosa, Marco;Saglio, Giuseppe;
Revista Brasileira de Hematologia e Hemoterapia , 2008, DOI: 10.1590/S1516-84842008000800007
Abstract: the introduction of the bcr-abl kinase inhibitor, imatinib mesylate (gleevec?, novartis) led to significant changes in the treatment of chronic myeloid leukaemia (cml) patients. however, despite the impressive percentage of responding patients, some cml cases, particularly those in advanced phases of the disease, show primary resistance or relapse after the initial response. the second-generation bcr-abl inhibitors nilotinib (tasigna?, novartis) and dasatinib (sprycel?, bristol-myers squibb) have shown significant activity in clinical trials in patients who failed imatinib therapy, but these agents are still incapable of inhibiting the t315i mutant of bcr-abl and present partial activity in advanced phases of cml. the acquired biological notions of the mechanisms of tyrosine kinase inhibitor (tki) resistance has led to the development of new compounds, some of which have shown encouraging preliminary results in clinical trials, even against t315i mutants. in this paper we discuss the new emerging therapies which may overcome tki resistance in cml patients.
Stevens - Johnson Syndrome in Chronic Myeloid Leukemia  [cached]
Gupta P,Puri U,Maharajan B
Indian Journal of Dermatology, Venereology and Leprology , 2000,
Abstract: A case of Stevens - Johnson syndrome in a 48-year old woman not responding to conventional corticosteroid therapy which on subsequent investigations was found to be having chronic myeloid leukaemia. Patient improved with concomitant administration of busulphan therapy. Stevens - Johnson syndrome presentation in chronic myeloid leukaemia is rare.
Fibrin Degradation Products in Hyperleucocytic Chronic Myeloid Leukaemia  [PDF]
S.G. Ahmed,U.A. Ibrahim
Pakistan Journal of Biological Sciences , 2006,
Abstract: This study is aimed at finding out whether or not activation of the coagulation system and fibrin deposition occurs in Chronic Myeloid Leukaemia (CML) patients with Hyperleucocytic Syndromes (HLS). A total of 14 CML patients with HLS were evaluated with respect to white cell count, presence of symptoms and signs of HLS and plasma D-dimer levels. Equal number of sex and age matched CML patients without HLS were similarly evaluated. Patients with HLS had a significantly (p<0.05) higher mean white cell count of 510x109 L-1 as compared to their counterparts who did not present with HLS and had a mean white cell count of 120x109 L-1. All CML patients without HLS had normal levels of D-dimer with a mean value of 87 ng mL-1. However, among the CML patients with HLS, 78.6% had elevated D-dimer levels with a mean value of 325 ng m L-1, while the remaining 21.4% had normal D-dimer levels with a mean value of 95 ng m L-1. This data was interpreted to indicate that in the majority of cases of CML with HLS, microvascular endothelial damage and fibrin deposition occur and contribute to the microvascular blockade initiated by leucostasis. There is therefore, the need to investigate a possible beneficial role of low dose anticoagulation in mitigating secondary fibrin deposition and minimizing tissue infarction and sensory organ damage in such patients.
Extramedullary Myeloid Cell Tumour Presenting As Leukaemia Cutis
Thappa Devinder Mohan,Basu Debdatta,Rao K Ramachandra,Karthikeyan Kaliaperumal
Indian Journal of Dermatology , 2002,
Abstract: We herewith report a case of extramedullary myeloid cell tumour presenting as leukaemia cutis for its rarity. It occurred in a 50 year old male patient who presented to us with a 40 days history of painless raised solid skin swellings over the trunk. Histopathological examination of the skin biopsy and bone marrow biopsy showed features suggestive of non-Hodgkina€ s lymphoma. Immunophenotyping on skin biopsy specimens and bone marrow biopsy found tumour cells expressing CD43 and Tdt but were negative for CD3 and CD20. These features were consistent with extramedullary myeloid cell tumour involving skin and subcutis (cutaneous manifestation of acute myeloid leukaemia.
Rheumatoid Arthritis Patients with Acute Myeloid Leukaemia  [PDF]
Medhat Haroun
Journal of Medical Sciences , 2004,
Abstract: The aim of this study was to examine the difference in serum immunoglobulin concentrations in the sera of rheumatoid arthritis (RA) patients, RA patients with acute myeloid leukaemia (AML) and to compare with those found in normal subjects. This study was performed in 43 of normal adult individuals (group 1), 40 RA patients (group 2) and 37 RA individuals with AML (group 3) were used for analysis of immunoglobulin levels by SDS polyacrylamide gel electrophoresis and ELISA. Measurements were made before treatment in the group with AML as well as when patients were both on and off chemotherapy. It was found that group 1 had a mean IgA level of 3.0 mg mL-1 and IgM level of 1.82 mg mL-1. Group 2 had a mean IgA level of 5.5 mg mL-1 and IgM level of 1.91 mg mL-1, while group 3 had a mean IgA level of 1.2 mg mL-1 and IgM level of 0.95 mg mL-1. Significant increases in IgA level in group 2 (p<0.00001) while the levels of both IgA and IgM in group 3 were significantly decreased (p<0.00001). This decrease was significant during induction and maintenance treatment, with restoration to normal once the patient was off therapy. There was no significant difference in IgG level in both groups 2 and 3 compared to group 1 (p<0.53). The finding of normal IgG level at diagnosis suggests that the leukaemia process itself did not initiate the fall. In addition, the influence course of treatment on rheumatoid arthritis patients with AML has a direct relation to the level of IgA and IgM due to complex interactions of chemotherapy.
The translocation of AgNORs in large nucleoli of early granulocyte progenitors in patients suffering from chronic phase of chronic myeloid leukaemia
Karel Smetana,Ilona Jiraskova,Dana Mikulenkova,Hana Klamova
Journal of Applied Biomedicine , 2009,
Abstract: The present study was undertaken to provide more information of the translocation of AgNORs to thenucleolar periphery in human early granulocyte progenitors such as myeloblasts and promyelocytes. The bonemarrow smears of patients untreated or treated with the cytostatic therapy appeared to be a convenient modelfor such study because they possessed a satisfactory number of these cells. The translocation of AgNORs tothe nucleolar periphery in early granulocytic progenitors was observed in all studied patients but with differentincidence. Since the translocation of AgNORs to the nucleolar periphery was induced in experimental studiesin vitro by the cell ageing, it seems to be likely that even some granulocyte progenitors in patients sufferingfrom chronic myeloid leukaemia might age without a further differentiation. In addition, the incidence of suchcells was markedly and significantly increased by the targeted cytostatic therapy with imatinib. At thisoccasion it should be noted that these patients were also characterised by a significantly decreasedgranulopoiesis.
New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22)(q34;p11;q11)
Abdeljabar El Andaloussi,Chrystele Bilhou-Nabera
Journal of Biomedicine and Biotechnology , 2007, DOI: 10.1155/2007/92385
Abstract: A Chronic myeloid leukaemia (CML) case with a new complex t(9;18;22)(q34;p11;q11) of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH). In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importance of combined cytogenetic analysis for diagnosis and guidance of treatment in clinical diagnosis of CML.
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