Imatinib mesylate in combination with chemotherapy in four children with de novo and advanced stage Philadelphia chromosome-positive acute lymphoblastic leukemia

Fuster, José Luís; Bermúdez, Mar; Galera, Ana; Llinares, María Esther; Calle, Doris; Ortuño, Francisco José

doi:10.3324/haematol.11525

Cited by 16 publications

(9 citation statements)

References 9 publications

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“…Although this compound became a crucial component of CML treatment, publications analysing its role in the management of childhood ALL are so far extremely rare. 39 The correlation of the two analysed MRD methods is very similar in the 'imatinib' vs 'non-imatinib' BM samples and our data do not demonstrate any tendency to lower BCR/ABL expression in Ig/TCR-positive cells during the imatinib treatment. Prospective studies with imatinib in childhood ALL are in progress worldwide; these studies will definitely show whether imatinib has a specific effect on BCR/ABL expression and the correlation of the DNA vs mRNA-based MRD approach.…”

Section: Discussionsupporting

confidence: 51%

Quantification of fusion transcript reveals a subgroup with distinct biological properties and predicts relapse in BCR/ABL-positive ALL: implications for residual disease monitoring

et al. 2009

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Minimal residual disease (MRD) monitoring is an essential tool for risk group stratification in current treatment protocols for childhood acute lymphoblastic leukaemia (ALL). Although quantitative detection of clonal immunoglobulin (Ig) and T-cell receptor (TCR ) gene rearrangements is currently considered to be the standard method, leukaemia fusion genes provide other possible targets for MRD follow-up, as already demonstrated in TEL/AML1-positive ALLs. We analysed and compared MRD levels quantified by BCR/ABL transcript detection and by the standard Ig/TCR-based method in 218 bone marrow specimens from 17 children with BCR/ABL-positive ALL. We found only a limited overall correlation of MRD levels as assessed by the two methods (correlation coefficient R 2 ¼ 0.64). The correlation varied among patients from excellent (R 2 ¼ 0.99) to very poor (R 2 ¼ 0.17). Despite identical sensitivity of the approaches, 20% of the samples were negative by the Ig/TCR approach whereas positive by the BCR/ABL method. We show that multilineage involvement is at least partly responsible for the discrepancy. Moreover, our data demonstrate that BCR/ABL monitoring enables better and earlier prediction of relapse compared to the standard Ig/TCR methodology. We conclude that BCR/ABLbased MRD monitoring of childhood ALL is a clinically relevant tool and should be performed in parallel with the standard Ig/ TCR follow-up.

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Section: Discussionsupporting

confidence: 51%

Quantification of fusion transcript reveals a subgroup with distinct biological properties and predicts relapse in BCR/ABL-positive ALL: implications for residual disease monitoring

et al. 2009

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“…Ph-positive B-ALL is an aggressive disease with a frequent resistance to chemotherapy treatment and a short survival rate (7)(8)(9)(10)(11). Introduction of specific inhibitors of the BCR/ABL1 tyrosine kinase, such as STI-571 (imatinib mesylate), has dramatically improved the prognosis of Ph-positive ALL patients (12,13). Therefore, treatment decisions making in newly diagnosed ALL patients are considerably affected by the presence or absence of t (9;22) translocation.…”

Section: Introductionmentioning

confidence: 99%

Role of flow‐cytometric immunophenotyping in prediction of BCR/ABL1 gene rearrangement in adult B‐cell acute lymphoblastic leukemia

Corrente

Bellesi

Metafuni

et al. 2017

Cytometry Part B Clinical

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We performed a retrospective analysis of 88 adult patients with B-ALL diagnosed in our center by a flow-cytometric assessment. Immunophenotypic expression of leukemic cells was explored by simultaneous evaluation of positivity, percentage of expressing cells and median fluorescence intensity (MFI). BCR/ABL1 fusion transcripts were assessed by RT-PCR analysis and were identified in 36 patients (40.9%). CD10 and CD34 were positive in the totality of BCR/ABL1-positive cases. Patients with gene rearrangement had a greater frequency of CD66c, CD13 and CD33 positivity compared with BCR/ABL1-negative cases. Moreover, BCR/ABL1-positive cases exhibited a greater median percentage and MFI values of CD13, CD33, CD66c, CD10, CD34 and CD25 expressions, but a lower median percentage and MFI values of CD38 and CD22 expressions than patients without gene rearrangement. Multivariate logistic regression analysis showed that CD10, CD38 and CD13 expressions were independent predictors for the presence of BCR/ABL1 rearrangement. Predictive probabilities of molecular occurrence based on these markers are proposed. © 2017 International Clinical Cytometry Society.

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“…New therapeutic agents such as tyrosine kinase inhibitors (imatinib and dasatinib) have been developed and yield good results in adults with Ph1-ALL [10-12]. Little information on the use of these drugs in children has been reported; the identification of predictors of responsiveness to early conventional treatment may thus be beneficial for the accurate stratification of children and for improving outcome [13,14]. …”

Section: Introductionmentioning

confidence: 99%

Impact of age, leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era: results of the FRALLE 93 study

Gandemer¹,

Auclerc

Pérel³

et al. 2009

BMC Cancer

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BackgroundWe explored the heterogeneity of philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL) in a study of the effect of early features on prognosis in children. Here we report the long-term results of the FRALLE 93 study conducted in the era before the use of tyrosine kinase inhibitors.MethodsBetween 1993 and 1999, 36 children with Ph1-ALL were enrolled into the FRALLE 93 protocol. After conventional four-drug induction, children were stratified by availability of an HLA-matched sibling.ResultsComplete remission (CR) was observed in 26 children (72%), of which 13 underwent allogeneic bone marrow transplantation (BMT). Thirty-one children were good responders to prednisone, defined on day 8, and 21 were good responders to chemotherapy, defined by day-21 bone marrow (M1). Overall five-year disease-free survival (DFS) was 42 ± 9.7%. Based on multivariate analysis, two groups showed marked differences in five-year outcome: children with age<10, leukocyte count <100,000/mm3 and day-21 M1 marrow had a more favorable prognosis (14 pts: 100% CR, event free survival [EFS]: 57%, overall survival [OS]: 79%), than the high-risk group (22 patients: 55% CR, EFS: 18%, OS: 27%) (p < 0.005). We also observed a non statistically significant difference (p = 0.14) in outcome between these groups for transplanted patients (5-year DFS: 83 ± 14% and 33 ± 15%, respectively).ConclusionAge, leukocyte count and early response to treatment defined by the D21 bone marrow response provide an accurate model for outcome prediction. The combination of available tools such as minimal residual disease assessment with determination of these simple factors could be useful for refining indications for BMT in the current era of tyrosine-kinase inhibitor-based therapy.

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Imatinib mesylate in combination with chemotherapy in four children with de novo and advanced stage Philadelphia chromosome-positive acute lymphoblastic leukemia

Cited by 16 publications

References 9 publications

Quantification of fusion transcript reveals a subgroup with distinct biological properties and predicts relapse in BCR/ABL-positive ALL: implications for residual disease monitoring

Quantification of fusion transcript reveals a subgroup with distinct biological properties and predicts relapse in BCR/ABL-positive ALL: implications for residual disease monitoring

Role of flow‐cytometric immunophenotyping in prediction of BCR/ABL1 gene rearrangement in adult B‐cell acute lymphoblastic leukemia

Impact of age, leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era: results of the FRALLE 93 study

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