Congenital leukaemia: the Dutch experience and review of the literature

Bresters, Dorine; Reus, Angelino C. W.; Veerman, A. J. P.; Wering, E.R. van; Berg, Anna; Kaspers, Gertjan J. L.

doi:10.1046/j.1365-2141.2002.03459.x

Cited by 145 publications

(201 citation statements)

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“…This was important when immunophenotypic shifts occurred during treatment (20,26,27). The phenomenon of immunophenotypic switch is a relatively rare but significant problem in using the LAPs as a strategy for MRD detection (20,26). The analysis of LAPs by five-color MFC should help in addressing this problem as we detected more than 1 LAP in 78% of cases, which increases the probability of detection for MRD analysis.…”

Section: Discussionmentioning

confidence: 99%

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The use of receiver operating characteristic analysis for detection of minimal residual disease using five‐color multiparameter flow cytometry in acute myeloid leukemia identifies patients with high risk of relapse

Al-Mawali

Gillis

Lewis

2008

Cytometry Part B Clinical

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Background: Multiparameter flow cytometry (MFC) has been shown to be a useful approach for detection of minimal residual disease (MRD). The aim of the study was to determine the optimal threshold that can separate patients into two groups in terms of leukemic residual cells and relapse status after induction and consolidation chemotherapy.Methods: Five-color MFC and receiver operating characteristics (ROC) analysis were used to determine the optimal threshold. This study analyzed 54 acute myeloid leukemia (AML) patients.Results: LAPs were detected in 51/54 (94%) patients. MRD was evaluated in the bone marrow (BM) in morphologic complete remission from 25 and 22 patients after induction and consolidation, respectively. The threshold discriminating MRD 2 from MRD 1 cases was set at 0.15% residual leukemic cells, a level that allowed optimal sensitivity and specificity for prediction of relapse, both at postinduction (P 5 0.05) and postconsolidation (P 5 0.009) time points using ROC analysis. MRD level postinduction not only influenced relapse-free survival (RFS) (P 5 0.004) but also overall survival (OS) (P 5 0.003). Multivariate analysis showed that MRD level postinduction was a powerful independent prognostic factor for both RFS (P 5 0.037) and OS (P 5 0.026).Conclusions: Using the ROC analysis, the threshold of 0.15% was defined as the optimal value in discriminating risk categories in AML, and postinduction MRD assessment is able to better predict disease outcome than consolidation. Therefore, MRD analysis by MFC could be used for refining the selection of therapeutic strategies and improving clinical outcome in individual patients. q

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Section: Discussionmentioning

confidence: 99%

“…Moreover, in 78% of cases, leukemic cells simultaneously displayed more than one LAP. This was important when immunophenotypic shifts occurred during treatment (20,26,27). The phenomenon of immunophenotypic switch is a relatively rare but significant problem in using the LAPs as a strategy for MRD detection (20,26).…”

Section: Discussionmentioning

confidence: 99%

The use of receiver operating characteristic analysis for detection of minimal residual disease using five‐color multiparameter flow cytometry in acute myeloid leukemia identifies patients with high risk of relapse

Al-Mawali

Gillis

Lewis

2008

Cytometry Part B Clinical

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“…The definition is based on previous literature (eg, Bresters et al 15 ), although the type of MLL rearrangement shifts as infants are diagnosed later. A total of 91% of infants younger than 6 months had MLL rearrangements compared with 66% of infants 6 to 12 months of age.…”

Section: Org Frommentioning

confidence: 99%

“…Although it is assumed to be inevitably fatal and the toxicity of the chemotherapeutic agents in these very young infants is unclear, to the best of our knowledge, no series have been published on congenital ALL except for case reports. Bresters et al 15 reviewed 24 patients with congenital ALL diagnosed over 25 years who were described in case reports: all patients died.…”

Section: Introductionmentioning

confidence: 99%

Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol

Linden

Valsecchi

Lorenzo

et al. 2009

Blood

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Acute lymphoblastic leukemia (ALL) diagnosed in the first month of life (congenital ALL) is very rare. Although congenital ALL is often assumed to be fatal, no studies have been published on outcome except for case reports. The present study reports the outcome of 30 patients with congenital ALL treated with the uniform Interfant-99 protocol, a hybrid regimen combining ALL treatment with elements designed for treatment of acute myeloid leukemia. Congenital ALL was characterized by a higher white blood cell count and a strong trend for higher incidence of MLL rearrangements and CD10-negative B-lineage ALL compared with older infants. Induction failure rate was 13% and not significantly different from that in older infants (7%, P ‫؍‬ .14), but relapse rate was significantly higher in congenital ALL patients (2-year cumulative incidence [ IntroductionAcute lymphoblastic leukemia (ALL) in infants (up to 1 year of age) is known to be biologically different from ALL in older children diagnosed with ALL. ALL in infants is more often associated with a higher tumor load at diagnosis, 1,2 a rearrangement in the mixed lineage leukemia (MLL) gene, and very immature B-cell phenotype (pro-B ALL) without CD10 expression. 1-3 Infant ALL cells are more resistant to several standard chemotherapeutic agents, 3,4 and the disease is also characterized by a poorer prognosis compared with older children. [5][6][7][8][9][10][11][12][13][14] Congenital ALL is diagnosed at birth or within the first month of life and is very rare. Although it is assumed to be inevitably fatal and the toxicity of the chemotherapeutic agents in these very young infants is unclear, to the best of our knowledge, no series have been published on congenital ALL except for case reports. Bresters et al 15 reviewed 24 patients with congenital ALL diagnosed over 25 years who were described in case reports: all patients died.We recently reported the results of a large international collaborative trial, Interfant-99, in infants younger than 1 year with ALL. 14 Here, we detail the outcome and characteristics of 30 patients with congenital ALL who received uniform therapy with curative intent. Methods PatientsThe Interfant-99 trial design, the inclusion criteria, and recruitment methods have been published earlier. 14 Individual study groups obtained ethics approval from all participating institutions, and patient informed consent was obtained in accordance with the Declaration of Helsinki. Of the 518 infants diagnosed with ALL, which account for approximately 3% of the ALL population, 35 patients were younger than 1 month, confirming the rarity of congenital ALL (ϳ 2 children per every 1000 with ALL). The present study reports on 30 cases that were treated with Interfant-99 (Figure 1). ProceduresEnrolled patients were stratified into standard-risk and high-risk groups on the basis of their response to 1 week of daily systemic prednisone (at a dose of 60 mg/m 2 ) and 1 intrathecal dose of methotrexate. Patients were classified as standard risk if their peripheral bloo...

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“…Infants with AML are treated with BFM protocol. Prognosis of CL is very poor and carries a high mortality rate even with recent chemotherapeutic regimes [14]. Large number of chemotherapeutic agents have been used for treatment of CL with limited success.…”

Section: Discussionmentioning

confidence: 99%