Myelodysplastic syndromes and acute leukemia developing after imatinib mesylate therapy for chronic myeloid leukemia

Kovitz, Craig A.; Kantarjian, Hagop M.; Garcia‐Manero, Guillermo; Abruzzo, Lynne V.; Cortes, Jorge

doi:10.1182/blood-2006-04-017400

Cited by 138 publications

(104 citation statements)

References 23 publications

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“…Quantitative real-time PCR was found reliable to monitor the response to these interventions in several studies. 16,17,124,125 Both real-time PCR and nested PCR allow comparable sensitivities of 10 À4 -10 À6 , 8,126 to evaluate the response to imatinib 127 or donor lymphocytes 11 in relapse after SCT. However, the kinetics of disease can only be monitored by quantitative real-time PCR whereas nested PCR is able to confirm the achievement of complete molecular remission.…”

Section: CMLmentioning

confidence: 99%

“…4,12,13 This selection of adverse-risk cases is a specific challenge for diagnostics after SCT, and new elements such as molecular screening for TKI resistance-conferring mutations has been included in diagnostics in the post transplantation period. 14,15 Finally, cases of TKI-associated MDS or AML due to Ph-negative clonal evolution 16,17 are new indications for allo-SCT and require diligent follow-up after SCT.…”

Section: Introductionmentioning

confidence: 99%

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Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Bacher

Zander

Haferlach

et al. 2008

Bone Marrow Transplant

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Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by realtime PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.

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Section: CMLmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Bacher

Zander

Haferlach

et al. 2008

Bone Marrow Transplant

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“…These abnormalities, involving mostly chromosomes Y, 8 and 7, resemble chromosomal alterations typically present in myelodysplastic syndrome. 28 Their clinical consequence is unclear, as in most cases they are transient and appear to be less frequent in younger patients. 29 In an analysis including more than 500 patients, the overall prognosis for patients who had clonal aberrations and a Ph-negative status was good and was driven by the CML response to IMA.…”

Section: Adverse Effects Of Imamentioning

confidence: 99%

Innovative approaches of targeted therapy for CML of childhood in combination with paediatric haematopoietic SCT

Suttorp

2008

Bone Marrow Transplant

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Allogeneic haematopoietic SCT (HSCT) induces CRs in most patients with CML. With the excellent short-term treatment results induced by imatinib (IMA), attitudes have changed and only a minority of children are now transplanted upfront. This review addresses the role of IMA in children with CML, focusing on the starting dose of IMA, possible adverse effects, timing of HSCT in children, duration of IMA treatment and monitoring of treatment efficacy to unravel failure of early treatment of IMA as well as treatment of CML relapse after HSCT. As the paediatric experience with IMA is still very limited, many answers and algorithms are adapted from CML in adults. Basically, HSCT should be postponed to achieve an optimal tumour cell reduction by IMA treatment. Children with a low-risk EBMT score should undergo HSCT within 2 years after diagnosis to avoid prolonged exposure and unknown late effects of IMA. Without a perfectly HLA-matched donor, HSCT may be postponed until CML becomes refractory to IMA. As realized in the presently activated international trial CML-paed II, this approach represents a risk-adapted therapy with the benefit of being tailored to the needs and profile of an individual patient.

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“…With primary imatinib therapy, most effective at suppressing Ph(+) hematopoiesis, one might expect to unmask such abnormalities to a greater degree if present; to date, however, reports of this finding in primary imatinib-treated patients are less common. 2,5 While associated with isolated reported cases of secondary hematopoietic disorders including MDS and Ph(-) acute leukemias, 6 this phenomenon is usually benign in course and simply requires careful observation in most cases.…”

Section: Imatinib Resistance Past and Presentmentioning

confidence: 99%

Defining and Managing Imatinib Resistance

Mauro¹

2006

Hematology

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While imatinib is highly effective therapy, with improving prospects over time for sustained remission and potential to severely limit or eliminate disease progression and transformation, a minority of patients either fail or respond suboptimally to imatinib; as well, disease eradication may not be possible with imatinib. Distinct patterns of resistance have evolved with the use of imatinib, and Abl kinase mutations, which alter imatinib binding or favor kinase conformations inaccessible to imatinib, are a common finding associated with clinical resistance. Dasatinib and nilotinib, alternate Abl kinase inhibitors, restore hematologic and cytogenetic remission in the majority of patients with primary failure or acquired resistance in chronic phase disease; in advanced disease and Philadelphia chromosome (Ph)+ ALL, responses are more limited and relapse is common. Future studies with these agents will focus on further optimizing imatinib response, reduction of minimal residual disease, and prevention of resistance. Still newer inhibitors active against T315I mutant BCR-ABL may overcome primary and secondary resistance to dasatinib and nilotinib.

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Myelodysplastic syndromes and acute leukemia developing after imatinib mesylate therapy for chronic myeloid leukemia

Cited by 138 publications

References 23 publications

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Innovative approaches of targeted therapy for CML of childhood in combination with paediatric haematopoietic SCT

Defining and Managing Imatinib Resistance

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