Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol
Standard
Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol. / Stutterheim, Janine; van der Sluis, Inge M; de Lorenzo, Paola; Alten, Julia; Ancliffe, Philip; Attarbaschi, Andishe; Brethon, Benoit; Biondi, Andrea; Campbell, Myriam; Cazzaniga, Giovanni; Escherich, Gabriele; Ferster, Alina; Kotecha, Rishi S; Lausen, Birgitte; Li, Chi Kong; Lo Nigro, Luca; Locatelli, Franco; Marschalek, Rolf; Meyer, Claus; Schrappe, Martin; Stary, Jan; Vora, Ajay; Zuna, Jan; van der Velden, Vincent H J; Szczepanski, Tomasz; Valsecchi, Maria Grazia; Pieters, Rob.
In: J CLIN ONCOL, Vol. 39, No. 6, 20.02.2021, p. 652-662.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol
AU - Stutterheim, Janine
AU - van der Sluis, Inge M
AU - de Lorenzo, Paola
AU - Alten, Julia
AU - Ancliffe, Philip
AU - Attarbaschi, Andishe
AU - Brethon, Benoit
AU - Biondi, Andrea
AU - Campbell, Myriam
AU - Cazzaniga, Giovanni
AU - Escherich, Gabriele
AU - Ferster, Alina
AU - Kotecha, Rishi S
AU - Lausen, Birgitte
AU - Li, Chi Kong
AU - Lo Nigro, Luca
AU - Locatelli, Franco
AU - Marschalek, Rolf
AU - Meyer, Claus
AU - Schrappe, Martin
AU - Stary, Jan
AU - Vora, Ajay
AU - Zuna, Jan
AU - van der Velden, Vincent H J
AU - Szczepanski, Tomasz
AU - Valsecchi, Maria Grazia
AU - Pieters, Rob
PY - 2021/2/20
Y1 - 2021/2/20
N2 - PURPOSE: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide).MATERIALS AND METHODS: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10-4), and high (≥ 5 × 10-4).RESULTS: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively (P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively (P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively (P < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9).CONCLUSION: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may benefit from ALL-like consolidation (DFS 78.2% v 45.0%). Patients with positive EOC MRD had dismal outcomes. These findings will be used for treatment interventions in the next Interfant protocol.
AB - PURPOSE: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide).MATERIALS AND METHODS: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10-4), and high (≥ 5 × 10-4).RESULTS: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively (P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively (P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively (P < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9).CONCLUSION: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may benefit from ALL-like consolidation (DFS 78.2% v 45.0%). Patients with positive EOC MRD had dismal outcomes. These findings will be used for treatment interventions in the next Interfant protocol.
U2 - 10.1200/JCO.20.02333
DO - 10.1200/JCO.20.02333
M3 - SCORING: Journal article
C2 - 33405950
VL - 39
SP - 652
EP - 662
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 6
ER -