How I monitor residual disease in chronic myeloid leukemia

Radich, Jerald P.

doi:10.1182/blood-2009-02-163485

Cited by 46 publications

(33 citation statements)

References 32 publications

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“…Even though quantitative PCR transcripts may show some variability, especially at very low absolute levels, a rise of 5-to 10-fold is considered worrisome and may prompt change in therapy. 72 If there is less than a 5-fold increase in transcript levels, it is reasonable to repeat quantitative PCR in 1 to 3 months without altering therapy. 72 Finally, compliance on TKI therapy is critical for patients of all age groups.…”

Section: Laboratory Monitoringmentioning

confidence: 99%

“…72 If there is less than a 5-fold increase in transcript levels, it is reasonable to repeat quantitative PCR in 1 to 3 months without altering therapy. 72 Finally, compliance on TKI therapy is critical for patients of all age groups. Marin et al followed 87 patients with CCyR and found that medication adherence was strongly associated with the ability to obtain molecular responses.…”

Section: Laboratory Monitoringmentioning

confidence: 99%

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How I treat childhood CML

Andolina

Neudorf

Corey

2012

Blood

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Chronic myeloid leukemia (CML) is composed of 3% of pediatric leukemias, making evidence-based recommendations difficult. Imatinib has revolutionized the treatment for adult CML by eliminating allogeneic stem cell transplantation for almost all patients in chronic phase. Shown effective in pediatric CML, imatinib and successive tyrosine kinase inhibitors (TKI) have provided more therapeutic options. Because stem cell transplantation has been better tolerated in children and adolescents, the decision to treat by either TKI or transplantation is controversial. We present a recent case of a 12-month-old boy diagnosed with BCR-ABL ؉ CML to highlight the controversies in treatment recommendations. We review the pediatric stem cell transplantation outcomes as well as the pediatric experience with imatinib and other TKIs. Finally, we compare the side effects as well as costs associated with allogeneic stem cell transplantation versus TKI therapy. We recommend that frontline therapy for pediatric CML in chronic phase is TKI therapy without transplantation. Patients in accelerated or blast crisis or who fail to reach landmarks on TKIs either because of intolerance or resistance should pursue stem cell transplantation. Although we recommend adopting adult clinical experience to guide therapeutic decision making, the issues of infant CML, drug formulation, pharmacokinetics, and adolescent compliance merit clinical investigation.

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Section: Laboratory Monitoringmentioning

confidence: 99%

Section: Laboratory Monitoringmentioning

confidence: 99%

How I treat childhood CML

Andolina

Neudorf

Corey

2012

Blood

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“…24 A practical approach to monitoring patients with CML has recently been proposed. 44 Despite the relatively small sample size and retrospective nature of this single center analysis, the presence of ACA significantly affected overall survival and to a lesser degree response to nilotinib. However, BCR-ABL kinase domain mutations conferred resistance to nilotinib, as evidenced by fewer cytogenetic remissions, but did not affect survival.…”

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confidence: 99%

Impact of additional chromosomal aberrations and BCR-ABL kinase domain mutations on the response to nilotinib in Philadelphia chromosome-positive chronic myeloid leukemia

Kim

Türkmen²,

Schwarz³

et al. 2009

Haematologica

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BackgroundAdditional chromosomal aberrations in Philadelphia chromosome-positive chronic myeloid leukemia are non-random and strongly associated with disease progression, but their prognostic impact and effect on treatment response is not clear. Point mutations in the BCR-ABL kinase domain are probably the most common mechanisms of imatinib resistance. Design and MethodsWe assessed the influence of additional chromosomal aberrations and BCR-ABL kinase domain mutations on the response to the second-generation tyrosine kinase inhibitor nilotinib after imatinib-failure. Standard cytogenetic analysis of metaphases was performed to detect additional chromosomal aberrations and the BCR-ABL kinase domain was sequenced to detect point mutations. ResultsAmong 53 patients with a median follow-up of 16 months, of whom 38, 5 and 10 were in chronic phase, accelerated phase and blast crisis, respectively, 19 (36%) had additional chromosomal aberrations and 20 (38%) had BCR-ABL kinase domain mutations. The 2-year overall survival rate of all patients without additional chromosomal aberrations (89%) was higher than that of patients with such aberrations (54%) (P=0.0025). Among patients with chronic phase disease, overall survival at 2 years was 100% and 62% for patients without or with additional chromosomal aberrations, respectively (P=0.0024). BCR-ABL kinase domain mutations were associated with lower remission rates in response to nilotinib, with 9 of 20 (45%) of these patients achieving a major cytogenetic remission as compared to 26 of 33 (79%) patients without mutations (P<0.05). However, overall survival was not affected by BCR-ABL kinase domain mutations. ConclusionsWhereas BCR-ABL kinase domain mutations may confer more specific resistance to nilotinib, which will predominantly affect response rates, the presence of additional chromosomal aberrations may reflect genetic instability and, therefore, intrinsic aggressiveness of the disease which will be less amenable to subsequent alternative treatments and thus negatively affect overall survival. Conventional cytogenetic analyses remain mandatory during follow-up of patients with chronic myeloid leukemia under tyrosine kinase inhibitor therapy.Key words: chronic myeloid leukemia, nilotinib, additionl chromosomal aberrations.Citation: Kim TD, Türkmen S, Schwarz M, Koca G, Nogai H, Bommer C, Dörken B, Daniel P, and le Coutre P. Impact of additional chromosomal aberrations and BCR-ABL kinase domain mutations on the response to nilotinib in Philadelphia chromosome-positive chronic myeloid leukemia. Haematologica. 2010;95:582-588. doi:10.3324/haematol.2009 This is an open-access paper. © F e r r a t a S t o r t i F o u n d a t i o n Impact of additional chromosomal aberrations and BCR-ABL

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“…[2,5,16] BCR-ABL1 RQ-PCR allows for a 2-to 3-log higher level of analytic sensitivity than that of cytogenetic and/or fluorescence in situ hybridization assessments, which, along with morphologic hematologic assessments, are also used to measure response to TKI treatment. [17] With optimized methodology, RQ-PCR can detect a single cell expressing BCR-ABL1 in a background of 100,000 normal cells. [18] However, BCR-ABL1 RQ-PCR is a nonautomated, multistep process [ Figure 1] subject to many sources of variation, including the handling and processing of the blood samples, the RQ-PCR reaction and its components, and the normalization and reporting of results.…”

Section: Rationale For Development Of the International Scalementioning

confidence: 99%