Use of simplified strategies to evaluate early treatment response in childhood acute lymphoblastic leukemia

Scrideli, Carlos Alberto; Queiroz, Rosane de Paula; Bernardes, José Eduardo; Defavery, Ricardo; Valera, Elvis Terci; Tone, Luíz Gonzaga

doi:10.1016/j.leukres.2005.11.021

Cited by 5 publications

(6 citation statements)

References 7 publications

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“…This pattern of stratification of patients was also observed for the group of intensively treated children ( Figure 3B). These data support previously published preliminary results concerning a small number of patients submitted to two different treatment protocols 17 and suggest that positive MRD detection by a simplified technique at the end of induction therapy may be the most important prognostic factor in children with ALL. As also observed in the present study, the detection of high MRD rates (10 -2 to 10 -3 ) on day 15 30,31 or day 19 15 and between weeks 4 and 12 [5][6][7][8][9][10][11][12][13][14] of induction therapy has been associated with an unfavorable prognosis.…”

Section: Discussionsupporting

confidence: 90%

“…The presence of two or more markers was detected in 88.4% of the cases investigated, showing that the simpli- fied technique can be used for the study of MRD in most children with ALL and confirming the preliminary data obtained with a similar methodology. 17 Although the present method is less sensitive, the results obtained were similar to those reported with the use of more complex techniques such as RQ-PCR and flow cytometry, mainly in the higher risk group. 2,[8][9][10][11][12][13][14][15] In addition, the frequency of detection of the rearrangements at diagnosis and the frequency of positivity for MRD during the phases analyzed were closely similar at the three treatment centers, showing good reproducibility of the technique used.…”

Section: Discussionsupporting

confidence: 84%

“…15,17 The objective of the present study was to determine the prognostic impact of the presence of MRD on days 14 and 28 of induction therapy in children with ALL treated according to the protocol of the Brazilian Group of Treatment of Childhood Acute Leukemia (GBTLI-99) using a simplified PCR methodology with consensus primers for the detection of rearrangements in the immunoglobulin (IG) and T-cell receptor (TCR) genes.…”

Section: Introductionmentioning

confidence: 99%

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A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Scrideli

Assumpção²,

Ganazza³

et al. 2009

Haematologica

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The online version of this article contains a supplementary appendix. BackgroundMinimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and MethodsWe analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. ResultsAt least one marker was detected by polymerase chain reaction in 96.4% of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor. ConclusionsThis simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Scrideli

Assumpção²,

Ganazza³

et al. 2009

Haematologica

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“…They reported that the 10-year incidence of relapse or remission failure was significantly higher for patients with 0.01% or more leukemic cells on day 1912). A simplified MRD PCR method with consensus primers for Ig and TCR gene rearrangements rather than standard PCR method using tailor-made reagents for each patient have been reported to have a significant value in discriminating between good and poor responders among children with ALL10, 11, 23). Our study provides supportive evidence for the feasibility of a simplified MRD assay using minimal immunophenotypic markers.…”

Section: Discussionmentioning

confidence: 99%

“…More simplified methods for MRD detection during the early period of treatment have been reported to help identify patients at a high risk of relapse10-12). The purpose of our study was to analyze the results of a simplified flow cytometric assay based on aberrant expression of myeloid antigens or expression of CD19/CD10/CD34, and to determine the prognostic significance of MRD detected by flow cytometry during induction chemotherapy in children with ALL.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of minimal residual disease detected by a simplified flow cytometric assay during remission induction chemotherapy in children with acute lymphoblastic leukemia

et al. 2010

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PurposeOur study attempted to determine the prognostic significance of minimal residual disease (MRD) detected by a simplified flow cytometric assay during induction chemotherapy in children with B-cell acute lymphoblastic leukemia (B-ALL).MethodsA total of 98 patients were newly diagnosed with precursor B-ALL from June 2004 to December 2008 at the Asan Medical Center (Seoul, Korea). Of those, 37 were eligible for flow cytometric MRD study analysis on day 14 of their induction treatment. The flow cytometric MRD assay was based on the expression intensity of CD19/CD10/CD34 or aberrant expression of myeloid antigens by bone marrow nucleated cells.ResultsThirty-five patients (94.6%) had CD19-positive leukemic cells that also expressed CD10 and/or CD34, and 18 (48.6%) had leukemic cells with aberrant expression of myeloid antigens. Seven patients with ≥1% leukemic cells on day 14 had a significantly lower relapse-free survival (RFS) compared to the 30 patients with lower levels (42.9% [18.7%] vs. 92.0% [5.4%], P=0.004). Stratification into 3 MRD groups (≥1%, 0.1-1%, and <0.1%) also showed a statistically significant difference in RFS (42.9% [18.7%] vs. 86.9% [8.7%] vs. 100%, P=0.013). However, the MRD status had no significant influence on overall survival. Multivariate analysis demonstrated that the MRD level on day 14 was an independent prognostic factor with borderline significance.ConclusionAn MRD assay using simplified flow cytometry during induction chemotherapy may help to identify patients with B-ALL who have an excellent outcome and patients who are at higher risk for relapse.

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Current Awareness in Hematological Oncology

2007

Hematological Oncology

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Reviews; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non‐Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Use of simplified strategies to evaluate early treatment response in childhood acute lymphoblastic leukemia

Cited by 5 publications

References 7 publications

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Prognostic significance of minimal residual disease detected by a simplified flow cytometric assay during remission induction chemotherapy in children with acute lymphoblastic leukemia

Current Awareness in Hematological Oncology

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