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)

Imatinib mesylate (Gleevec), an inhibitor of the BCR-ABL tyrosine kinase, was introduced recently into the therapy of chronic myeloid leukemia (CML). Several cases of emergence of clonal chromosomal abnormalities after therapy with imatinib have been reported, but their incidence, etiology and prognosis remain to be clarified. We report here a large series of 34 CML patients treated with imatinib who developed Philadelphia (Ph)-negative clones. Among 1001 patients with Ph-positive CML treated with imatinib, 34 (3.4%) developed clonal chromosomal abnormalities in Ph-negative cells. Three patients were treated with imatinib up-front. The most common cytogenetic abnormalities were trisomy 8 and monosomy 7 in twelve and seven patients, respectively. In 15 patients, fluorescent in situ hybridization with specific probes was performed in materials archived before the initiation of imatinib. The Ph-negative clone was related to previous therapy in three patients, and represented a minor pre-existing clone that expanded after the eradication of Ph-positive cells with imatinib in two others. However, in 11 patients, the new clonal chromosomal abnormalities were not detected and imatinib may have had a direct effect. No myelodysplasia was found in our cohort. With a median follow-up of 24 months, one patient showed CML acceleration and two relapsed.
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PMID:Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia. 1562 54

Targeted therapy with imatinib selectively suppresses Philadelphia-positive cells in chronic myeloid leukemia cells, with reappearance of apparently normal hemopoiesis in a considerable number of patients. Recently, clonal abnormalities have been observed in Philadelphia-negative cells during imatinib therapy, the biologic and prognostic significance of which is actually unknown. A case of trisomy 8 occurring in Philadelphia-negative cells, which was treated by bone marrow transplantation, is reported. Chromosomal abnormalities in Philadelphia-negative cells do not seem to herald disease transformation, but the long-term prognosis may be influenced by an increased incidence of myelodysplasia in younger patients.
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PMID:Trisomy 8 in Philadelphia-negative cells during imatinib therapy. 1530 14

To investigate the relationship of chromosomal aberrations at blastic crisis (BC) in chronic myelogenous leukemia (CML), with previous therapies and with atomic bomb (AB) exposure, we studied 114 CML patients who developed BC, including 23 AB survivors in Hiroshima. In total, only 45.6% showed major-route abnormalities, which figure was far lower than those previously reported, implying possibility of geographical difference. Occurrence of major-route abnormality was not associated with either duration of chronic phase or survival time after BC. Patients treated with interferon-alpha (IFNalpha) showed lower frequency of major-route abnormalities and lower number of abnormal chromosomes than did patients treated with busulfan (Bu). The frequency of trisomy 8 was lower and monosomy 7 was higher in IFNalpha-treated than in Bu-treated patients. The frequency of unusual abnormalities at BC in IFNalpha-treated patients was indistinguishable from those in Bu-treated patients and, notably, a more common (40%) feature in IFNalpha-treated patients was no change in the cytogenetic picture. Thus, we conclude that IFNalpha action on chromosome aberration is basically quite neutral and that IFNalpha does not induce any specific aberrations, including unusual ones at BC, with an exception of deletion of chromosome 7. Atomic bomb exposure status did not make any difference in secondary abnormalities at BC.
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PMID:Effect of interferon-alpha on chromosome abnormalities in treated chronic myelogenous leukemia patients. 1535 Mar 3

Recent data suggest that STI571 (Imatinib) induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT). However, little is known about molecular responses to STI571 and the duration of leukemia-free survival in these patients. We report on a 43 year old female patient who presented with a relapse from Ph+ CML in December 2000. Five years earlier she had received an SCT from an unrelated male donor in accelerated phase. At the time of relapse, she presented with marked leukocytosis (89,000 microl) and 10% blasts. In December 2000, therapy with Imatinib was started. After 3 months, the karyotype showed an XY, with trisomy 8 in about 50% of all metaphases, but without evidence of residual Ph+ cells. Moreover, in response to Imatinib, BCR/ABL transcripts decreased and were no longer detectable after 6 months. After a total observation period of 36 months, the patient is still in complete cytogenetic and molecular remission without signs of occurrence of a donor-type hematopoietic neoplasm or CML relapse. These data suggest that Imatinib is a useful agent for long term treatment of relapsed CML after allogeneic SCT.
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PMID:Detection of trisomy 8 in donor-derived Ph- cells in a patient with Ph+ chronic myeloid leukemia successfully treated with Imatinib (STI571) in relapse after allogeneic transplantation. 1535 47

An increase in the presence of the Ph-negative, trisomy 8 clone has been reported in chronic myelogenous leukemia (CML) under imatinib therapy, but any impact of the clone on patient prognosis remains uncertain. We report here on a 42-year-old male with CML who received imatinib after failure of interferon-alpha therapy. A chromosomal analysis revealed 18/20 trisomy 8 in bone marrow at 10 months of imatinib administration. Continuing imatinib at 300 mg daily resulted in a decrease in the number of trisomy 8 clones as well as the disappearance of Ph clone. Furthermore, the patient's pancytopenia was gradually improved. Imatinib therapy could be continued even with the emergence of trisomy 8.
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PMID:[Emergence and decrement of Ph-negative clone with trisomy 8 in CML during imatinib therapy]. 1551 Aug 36

After stem cell transplantation (SCT) close follow-up of chimerism and/or clonal disease markers is essential for early treatment of graft failure or relapse. We wanted to assess the sensitivity, clinical reliability and practicability of inter-phase FISH on untreated, native smears of BM or PB for this purpose. We investigated 23 children after SCT with sex mismatch (MM) and/or clone specific markers (monosomy 7, trisomy 8, MLL rearrangement, bcr-abl, TEL-AML-1). Diagnoses were ALL (8), AML (6), MDS (2), CML (2), large cell anaplastic lymphoma (1) and SAA (4). Eighteen children were transplanted from sex-mismatched donors, seven among them had shown a clonal marker at diagnosis. The remaining five patients with sex matched donors also had a clonal marker. For FISH, we used commercial probes on fresh or stored unmanipulated smears of PB or BM. Cut-off levels for clonal markers were established on control probands without hematologic disease, for host sex on probands of the opposite sex, respectively (mean +3 SD). The presence of host cells and/or clonal markers established at diagnosis by conventional karyotyping was followed up after SCT at regular intervals by FISH. Nineteen of the 23 patients studied achieved and maintained complete continuous hematologic remission with corresponding absence of host and/or disease markers. In one of them, a fatal extramedullary relapse occurred. The associated mixed chimerism was confirmed by FISH. In all four cases with hematological relapse, the respective marker (MLL, bcr-abl, Mo 7) reappeared and was successfully monitored during DLI and repeat SCT in two as well as parallelled by simultaneous demonstration of host cells in the two sex mismatched cases among them. We demonstrate the usefulness of FISH on native smears for clinical routine follow-up of SCT patients. FISH allowed identification of cell origin in non-hematologic material (spinal fluid, pericardial effusion). Chimerism analysis in BM was slightly more sensitive than in PB. FISH was feasible on frozen stored smears as well.
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PMID:FISH analysis of native smears from bone marrow and blood for the monitoring of chimerism and clonal markers after stem cell transplantation in children. 1564 46

We describe a 58-year-old male diagnosed with chronic myeloid leukaemia (CML) who failed to have a cytogenetic response to interferon-alpha and hydroxyurea. On subsequent therapy with imatinib mesylate he failed to have any cytogenetic response but also developed a complex clonal evolution with an additional Philadelphia (Ph) chromosome and trisomy 8 respectively in two Ph-positive subclones. The addition of cytosine arabinoside to imatinib resulted in reversion to single Ph-chromosome positivity with the disappearance of the previous additional clonal abnormalities. The case demonstrates the efficacy of combined treatment with imatinib and cytarabine in the management of CML resistant to single agent imatinib.
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PMID:CML clonal evolution with resistance to single agent imatinib therapy. 1617 20

There are increasing reports of Philadelphia-negative (Ph-negative) clonal hematopoiesis developing among patients with chronic myeloid leukemia (CML) treated with imatinib mesylate (IM). To establish the incidence and significance of these chromosomal abnormalities, we analyzed data on 141 consecutive patients with CML treated with IM at the British Columbia Cancer Agency and Vancouver General Hospital from 1999 to 2004. The cumulative incidence of developing a Ph-negative clone three years from the start of IM was 8.7% at a median of 13.3 months. The Ph-negative clonal abnormalities included monosomy 7 and/or trisomy 8 (seven patients), monosomy for chromosomes X and 22 (one patient), and a (12;16) translocation (one patient). Two of the patients presented with the same chromosomal abnormality in both Ph-negative and Ph-positive cells. None of the Ph-negative clonal abnormalities was associated with myelodysplasia. In a multivariate analysis, an interval from diagnosis to initiation of IM of 1 year or less was associated with an increased risk of developing a Ph-negative clone (relative risk = 20.2; P = 0.025). There was no difference, however, in event-free survival between patients who did and did not develop Ph-negative clones. Therefore, while the development of Ph-negative clonal hematopoiesis in patients with CML treated with IM is uncommon, it appears to be more frequent than that previously seen with IFN, but it does not seem to confer a worse prognosis.
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PMID:Philadelphia-negative clonal hematopoiesis following imatinib therapy in patients with chronic myeloid leukemia: a report of nine cases and analysis of predictive factors. 1696 50

Chromosomal abnormalities in Ph-negative metaphases from patients with chronic myeloid leukemia (CML) treated with imatinib have been described in some cases. Trisomy 8 is the most frequent, but monosomy 7 has also been described. However, the association of these chromosomal alterations with myelodysplasia has been scarcely reported. We report the appearance of monosomy 7 in Ph-negative cells, associated with severe dysplasia, in two patients with CML treated with imatinib, with a different outcome: one with a transient evolution and the other evolving to acute myeloid leukemia.
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PMID:Monosomy 7 with severe myelodysplasia developing during imatinib treatment of Philadelphia-positive chronic myeloid leukemia: two cases with a different outcome. 1756 75

We investigated chronic myelogenous leukemia (CML) patients who developed trisomy 8 abnormalities in Philadelphia-negative (Ph-) cells during imatinib mesylate treatment to evaluate the clinical outcome and laboratory features. Of the 470 CML patients, 1.5% (n = 7) developed trisomy 8 chromosomal abnormalities in Ph- cells. The median interval of the first trisomy 8 observation was 12 months. Our follow-up cytogenetic evaluations revealed that six of the patients demonstrated a complete or partial cytogenetic response and that all of the six patients revealed no dysplastic changes following a bone marrow examination. Moreover, the percentage of trisomy 8 in metaphase karyotyping has decreased in five of the seven subjects. In conclusion, these results suggest that the emergence of trisomy 8 in Ph- cells is transient and not related to therapy-related myelodysplasia or acute leukemia.
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PMID:Transient trisomy 8 abnormality in Philadelphia-negative cells during imatinib mesylate treatment of chronic myelogenous leukemia. 1898 2


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