Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: Results of the AIEOP-BFM-ALL 2000 study

Martin Schrappe, Maria Grazia Valsecchi, Claus R. Bartram, André Schrauder, Renate Panzer-Grümayer, Anja Möricke, Rosanna Parasole, Martin Zimmermann, Michael Dworzak, Barbara Buldini, Alfred Reiter, Giuseppe Basso, Thomas Klingebiel, Chiara Messina, Richard Ratei, Giovanni Cazzaniga, Rolf Koehler, Franco Locatelli, Beat W. Schäfer, Maurizio AricòKarl Welte, Jacques J M Van Dongen, Helmut Gadner, Andrea Biondi, Valentino Conter

Research output: Contribution to journalArticle

Abstract

The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers;MRDintermediate risk (MRDIR) if positive either at day 33 or 78 and <10+3 at day 78; and MRD high risk (MRD-HR) if ≥ 10-3 at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7-year event-free-survival (SE)was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P <.001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients).MRD≥ 10+3 at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials. gov; "Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia," protocol identification#NCT00430118 for BFM and #NCT00613457 for AIEOP.

Original languageEnglish
Pages (from-to)2077-2084
Number of pages8
JournalBlood
Volume118
Issue number8
DOIs
Publication statusPublished - Aug 25 2011

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
T-cells
Set theory
Recurrence
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoglobulin Genes
Chemotherapy
Gene Rearrangement
Polymerase chain reaction
Combination Drug Therapy
Disease-Free Survival
Immunoglobulins
Genes
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Schrappe, M., Valsecchi, M. G., Bartram, C. R., Schrauder, A., Panzer-Grümayer, R., Möricke, A., ... Conter, V. (2011). Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: Results of the AIEOP-BFM-ALL 2000 study. Blood, 118(8), 2077-2084. https://doi.org/10.1182/blood-2011-03-338707

Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL : Results of the AIEOP-BFM-ALL 2000 study. / Schrappe, Martin; Valsecchi, Maria Grazia; Bartram, Claus R.; Schrauder, André; Panzer-Grümayer, Renate; Möricke, Anja; Parasole, Rosanna; Zimmermann, Martin; Dworzak, Michael; Buldini, Barbara; Reiter, Alfred; Basso, Giuseppe; Klingebiel, Thomas; Messina, Chiara; Ratei, Richard; Cazzaniga, Giovanni; Koehler, Rolf; Locatelli, Franco; Schäfer, Beat W.; Aricò, Maurizio; Welte, Karl; Van Dongen, Jacques J M; Gadner, Helmut; Biondi, Andrea; Conter, Valentino.

In: Blood, Vol. 118, No. 8, 25.08.2011, p. 2077-2084.

Research output: Contribution to journalArticle

Schrappe, M, Valsecchi, MG, Bartram, CR, Schrauder, A, Panzer-Grümayer, R, Möricke, A, Parasole, R, Zimmermann, M, Dworzak, M, Buldini, B, Reiter, A, Basso, G, Klingebiel, T, Messina, C, Ratei, R, Cazzaniga, G, Koehler, R, Locatelli, F, Schäfer, BW, Aricò, M, Welte, K, Van Dongen, JJM, Gadner, H, Biondi, A & Conter, V 2011, 'Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: Results of the AIEOP-BFM-ALL 2000 study', Blood, vol. 118, no. 8, pp. 2077-2084. https://doi.org/10.1182/blood-2011-03-338707
Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grümayer R, Möricke A et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: Results of the AIEOP-BFM-ALL 2000 study. Blood. 2011 Aug 25;118(8):2077-2084. https://doi.org/10.1182/blood-2011-03-338707
Schrappe, Martin ; Valsecchi, Maria Grazia ; Bartram, Claus R. ; Schrauder, André ; Panzer-Grümayer, Renate ; Möricke, Anja ; Parasole, Rosanna ; Zimmermann, Martin ; Dworzak, Michael ; Buldini, Barbara ; Reiter, Alfred ; Basso, Giuseppe ; Klingebiel, Thomas ; Messina, Chiara ; Ratei, Richard ; Cazzaniga, Giovanni ; Koehler, Rolf ; Locatelli, Franco ; Schäfer, Beat W. ; Aricò, Maurizio ; Welte, Karl ; Van Dongen, Jacques J M ; Gadner, Helmut ; Biondi, Andrea ; Conter, Valentino. / Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL : Results of the AIEOP-BFM-ALL 2000 study. In: Blood. 2011 ; Vol. 118, No. 8. pp. 2077-2084.
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abstract = "The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers;MRDintermediate risk (MRDIR) if positive either at day 33 or 78 and <10+3 at day 78; and MRD high risk (MRD-HR) if ≥ 10-3 at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16{\%} of them were MRD-SR, 63{\%} MRD-IR, and 21{\%} MRD-HR. Their 7-year event-free-survival (SE)was 91.1{\%} (3.5{\%}), 80.6{\%} (2.3{\%}), and 49.8{\%} (5.1{\%}) (P <.001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32{\%} of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48{\%} of all patients).MRD≥ 10+3 at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials. gov; {"}Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia,{"} protocol identification#NCT00430118 for BFM and #NCT00613457 for AIEOP.",
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T1 - Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL

T2 - Results of the AIEOP-BFM-ALL 2000 study

AU - Schrappe, Martin

AU - Valsecchi, Maria Grazia

AU - Bartram, Claus R.

AU - Schrauder, André

AU - Panzer-Grümayer, Renate

AU - Möricke, Anja

AU - Parasole, Rosanna

AU - Zimmermann, Martin

AU - Dworzak, Michael

AU - Buldini, Barbara

AU - Reiter, Alfred

AU - Basso, Giuseppe

AU - Klingebiel, Thomas

AU - Messina, Chiara

AU - Ratei, Richard

AU - Cazzaniga, Giovanni

AU - Koehler, Rolf

AU - Locatelli, Franco

AU - Schäfer, Beat W.

AU - Aricò, Maurizio

AU - Welte, Karl

AU - Van Dongen, Jacques J M

AU - Gadner, Helmut

AU - Biondi, Andrea

AU - Conter, Valentino

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N2 - The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers;MRDintermediate risk (MRDIR) if positive either at day 33 or 78 and <10+3 at day 78; and MRD high risk (MRD-HR) if ≥ 10-3 at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7-year event-free-survival (SE)was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P <.001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients).MRD≥ 10+3 at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials. gov; "Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia," protocol identification#NCT00430118 for BFM and #NCT00613457 for AIEOP.

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