Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant-06 protocol: Results from an international phase III randomized study

Rob Pieters, Paola De Lorenzo, Philip Ancliffe, Luis Alberto Aversa, Benoit Brethon, Andrea Biondi, Myriam Campbell, Gabriele Escherich, Alina Ferster, Rebecca A. Gardner, Rishi Sury Kotecha, Birgitte Lausen, Chi Kong Li, Franco Locatelli, Andishe Attarbaschi, Christina Peters, Jeffrey E. Rubnitz, Lewis B. Silverman, Jan Stary, Tomasz Szczepanski & 3 others Ajay Vora, Martin Schrappe, Maria Grazia Valsecchi

Research output: Contribution to journalArticle

Abstract

PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stemcell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 3 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE1MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant- 06 did not improve compared with that in Interfant-99.

Original languageEnglish
Pages (from-to)2246-2256
Number of pages11
JournalJournal of Clinical Oncology
Volume37
Issue number25
DOIs
Publication statusPublished - 8 Jul 2019

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Transplantation
Etoposide
Prednisone
Consolidation Chemotherapy
6-Mercaptopurine
Mitoxantrone
Daunorubicin
Survival
Gene Rearrangement
Cytarabine
Cyclophosphamide
Survival Rate
Drug Therapy

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Pieters, Rob ; De Lorenzo, Paola ; Ancliffe, Philip ; Aversa, Luis Alberto ; Brethon, Benoit ; Biondi, Andrea ; Campbell, Myriam ; Escherich, Gabriele ; Ferster, Alina ; Gardner, Rebecca A. ; Kotecha, Rishi Sury ; Lausen, Birgitte ; Li, Chi Kong ; Locatelli, Franco ; Attarbaschi, Andishe ; Peters, Christina ; Rubnitz, Jeffrey E. ; Silverman, Lewis B. ; Stary, Jan ; Szczepanski, Tomasz ; Vora, Ajay ; Schrappe, Martin ; Valsecchi, Maria Grazia. / Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant-06 protocol : Results from an international phase III randomized study. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 25. pp. 2246-2256.
@article{35f910e6f3804494bb7c48f80c3e12f9,
title = "Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant-06 protocol: Results from an international phase III randomized study",
abstract = "PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stemcell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 3 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1{\%} (SE, 2.1) and 58.2{\%} (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4{\%} (SE, 2.5) and 62.1{\%} (SE, 2.4), which were 10{\%} to 12{\%} higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE1MAE 39.3{\%} [SE 4.0; n = 169] v IB 36.8{\%} [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9{\%} (SE, 3.4) with the intention to undergo SCT; only 46{\%} of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant- 06 did not improve compared with that in Interfant-99.",
author = "Rob Pieters and {De Lorenzo}, Paola and Philip Ancliffe and Aversa, {Luis Alberto} and Benoit Brethon and Andrea Biondi and Myriam Campbell and Gabriele Escherich and Alina Ferster and Gardner, {Rebecca A.} and Kotecha, {Rishi Sury} and Birgitte Lausen and Li, {Chi Kong} and Franco Locatelli and Andishe Attarbaschi and Christina Peters and Rubnitz, {Jeffrey E.} and Silverman, {Lewis B.} and Jan Stary and Tomasz Szczepanski and Ajay Vora and Martin Schrappe and Valsecchi, {Maria Grazia}",
year = "2019",
month = "7",
day = "8",
doi = "10.1200/JCO.19.00261",
language = "English",
volume = "37",
pages = "2246--2256",
journal = "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "25",

}

Pieters, R, De Lorenzo, P, Ancliffe, P, Aversa, LA, Brethon, B, Biondi, A, Campbell, M, Escherich, G, Ferster, A, Gardner, RA, Kotecha, RS, Lausen, B, Li, CK, Locatelli, F, Attarbaschi, A, Peters, C, Rubnitz, JE, Silverman, LB, Stary, J, Szczepanski, T, Vora, A, Schrappe, M & Valsecchi, MG 2019, 'Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant-06 protocol: Results from an international phase III randomized study' Journal of Clinical Oncology, vol. 37, no. 25, pp. 2246-2256. https://doi.org/10.1200/JCO.19.00261

Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant-06 protocol : Results from an international phase III randomized study. / Pieters, Rob; De Lorenzo, Paola; Ancliffe, Philip; Aversa, Luis Alberto; Brethon, Benoit; Biondi, Andrea; Campbell, Myriam; Escherich, Gabriele; Ferster, Alina; Gardner, Rebecca A.; Kotecha, Rishi Sury; Lausen, Birgitte; Li, Chi Kong; Locatelli, Franco; Attarbaschi, Andishe; Peters, Christina; Rubnitz, Jeffrey E.; Silverman, Lewis B.; Stary, Jan; Szczepanski, Tomasz; Vora, Ajay; Schrappe, Martin; Valsecchi, Maria Grazia.

In: Journal of Clinical Oncology, Vol. 37, No. 25, 08.07.2019, p. 2246-2256.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant-06 protocol

T2 - Results from an international phase III randomized study

AU - Pieters, Rob

AU - De Lorenzo, Paola

AU - Ancliffe, Philip

AU - Aversa, Luis Alberto

AU - Brethon, Benoit

AU - Biondi, Andrea

AU - Campbell, Myriam

AU - Escherich, Gabriele

AU - Ferster, Alina

AU - Gardner, Rebecca A.

AU - Kotecha, Rishi Sury

AU - Lausen, Birgitte

AU - Li, Chi Kong

AU - Locatelli, Franco

AU - Attarbaschi, Andishe

AU - Peters, Christina

AU - Rubnitz, Jeffrey E.

AU - Silverman, Lewis B.

AU - Stary, Jan

AU - Szczepanski, Tomasz

AU - Vora, Ajay

AU - Schrappe, Martin

AU - Valsecchi, Maria Grazia

PY - 2019/7/8

Y1 - 2019/7/8

N2 - PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stemcell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 3 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE1MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant- 06 did not improve compared with that in Interfant-99.

AB - PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stemcell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 3 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE1MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant- 06 did not improve compared with that in Interfant-99.

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U2 - 10.1200/JCO.19.00261

DO - 10.1200/JCO.19.00261

M3 - Article

VL - 37

SP - 2246

EP - 2256

JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

SN - 0732-183X

IS - 25

ER -