Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932

被引：73

作者：

Angiolillo, Anne L. ^{[1
,2
]}

Schore, Reuven J. ^{[1
,2
]}

Kairalla, John A. ^{[3
,4
]}

Devidas, Meenakshi ^{[5
]}

Rabin, Karen R. ^{[6
]}

Zweidler-McKay, Patrick ^{[7
]}

Borowitz, Michael J. ^{[8
]}

Wood, Brent ^{[9
]}

Carroll, Andrew J. ^{[10
]}

Heerema, Nyla A. ^{[11
]}

Relling, Mary V. ^{[12
]}

Hitzler, Johann ^{[13
]}

Lane, Ashley R. ^{[1
]}

Maloney, Kelly W. ^{[14
,15
]}

Wang, Cindy

Bassal, Mylene ^{[16
]}

Carroll, William L. ^{[17
,18
]}

Winick, Naomi J. ^{[19
]}

Raetz, Elizabeth A. ^{[17
,18
]}

Loh, Mignon L. ^{[20
,21
]}

Hunger, Stephen P. ^{[22
,23
,24
]}

机构：

[1] Childrens Natl Med Ctr, Washington, DC 20010 USA

[2] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA

[3] Univ Florida, Coll Med, Dept Biostat, Gainesville, FL 32610 USA

[4] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Biostat, Gainesville, FL 32610 USA

[5] St Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA

[6] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA

[7] ImmunoGen Inc, Boston, MA USA

[8] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA

[9] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA

[10] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA

[11] Ohio State Univ, Wexner Med Ctr, Dept Pathol, Columbus, OH 43210 USA

[12] St Jude Childrens Res Hosp, Memphis, TN USA

[13] Hosp Sick Children, Toronto, ON, Canada

[14] Univ Colorado, Sch Med, Childrens Hosp Colorado, Aurora, CO USA

[15] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA

[16] Childrens Hosp Eastern Ontario, Div Pediat Hematol Oncol, Ottawa, ON, Canada

[17] NYU, Langone Med Ctr, Dept Pediat, New York, NY USA

[18] NYU, Langone Med Ctr, Perlmutter Canc Ctr, New York, NY USA

[19] Univ Texas Southwestern Med Ctr, Dallas, TX USA

[20] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA

[21] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Inst, San Francisco, CA 94143 USA

[22] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA

[23] Univ Penn, Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA

[24] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2021年 / 39卷 / 13期

关键词：

EVENT-FREE SURVIVAL; MAINTENANCE THERAPY; ORAL METHOTREXATE; CONTINUATION THERAPY; SYSTEMIC EXPOSURE; RELAPSE; CANCER; MERCAPTOPURINE; CHEMOTHERAPY; PHARMACOKINETICS;

D O I：

10.1200/JCO.20.00494

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose:AALL0932 evaluated two randomized maintenance interventions to optimize disease-free survival (DFS) while reducing the burden of therapy in children with newly diagnosed NCI standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL).Methods:AALL0932 enrolled 9,229 patients with B-ALL; 2,364 average-risk (AR) patients were randomly assigned (2 x 2 factorial design) at the start of maintenance therapy to vincristine/dexamethasone pulses every 4 (VCR/DEX4) or every 12 (VCR/DEX12) weeks, and a starting dose of weekly oral methotrexate of 20 mg/m(2) (MTX20) or 40 mg/m(2) (MTX40).Results:Five-year event-free survival and overall survival (OS) from enrollment (with 95% CIs), for all eligible and evaluable SR B-ALL patients (n = 9,226), were 92.0% (91.1% and 92.8%) and 96.8% (96.2% and 97.3%), respectively. The 5-year DFS and OS from the start of maintenance for randomly assigned AR patients were 94.6% (93.3% and 95.9%) and 98.5% (97.7% and 99.2%), respectively. The 5-year DFS and OS for patients randomly assigned to receive VCR/DEX4 (n = 1,186) versus VCR/DEX12 (n = 1,178) were 94.1% (92.2% and 96.0%) and 98.3% (97.2% and 99.4%) v 95.1% (93.3% and 96.9%) and 98.6% (97.7% and 99.6%), respectively (P = .86 and .69). The 5-year DFS and OS for AR patients randomly assigned to receive MTX20 versus MTX40 were 95.1% (93.3% and 96.8%) and 98.8% (97.9% and 99.7%) v 94.2% (92.2% and 96.1%) and 98.1% (97.0% and 99.2%), respectively (P = .92 and .89).Conclusions:The 0NCI-SR AR B-ALL who received VCR/DEX12 had outstanding outcomes despite receiving one third of the vincristine/dexamethasone pulses previously used as standard of care on Children's Oncology Group (COG) trials. The higher starting dose of MTX of 40 mg/m(2)/week did not improve outcomes when compared with 20 mg/m(2)/week. The decreased frequency of vincristine/dexamethasone pulses has been incorporated into frontline COG B-ALL trials to decrease the burden of therapy for patients and their families.

引用

页码：1437 / +

页数：18

共 46 条

[31] Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital [J].

Pui, CH ;

Sandlund, JT ;

Pei, DQ ;

Campana, D ;

Rivera, GK ;

Ribeiro, RC ;

Rubnitz, JE ;

Razzouk, BI ;

Howard, SC ;

Hudson, MM ;

Cheng, C ;

Kun, LE ;

Raimondi, SC ;

Behm, FG ;

Downing, JR ;

Relling, MV ;

Evans, WE .

BLOOD, 2004, 104 (09) :2690-2696

[32] Treating Childhood Acute Lymphoblastic Leukemia without Cranial Irradiation [J].

Pui, Ching-Hon ;

Campana, Dario ;

Pei, Deqing ;

Bowman, W. Paul ;

Sandlund, John T. ;

Kaste, Sue C. ;

Ribeiro, Raul C. ;

Rubnitz, Jeffrey E. ;

Raimondi, Susana C. ;

Onciu, Mihaela ;

Coustan-Smith, Elaine ;

Kun, Larry E. ;

Jeha, Sima ;

Cheng, Cheng ;

Howard, Scott C. ;

Simmons, Vickey ;

Bayles, Amy ;

Metzger, Monika L. ;

Boyett, James M. ;

Leung, Wing ;

Handgretinger, Rupert ;

Downing, James R. ;

Evans, William E. ;

Relling, Mary V. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (26) :2730-2741

[33]

Relling MV, 1999, BLOOD, V93, P2817

[34]

Reynolds C. R., 2015, Behavior Assessment System for Children Manual, V3rd ed.

[35] A note on quantifying follow-up in studies of failure time [J].

Schemper, M ;

Smith, TL .

CONTROLLED CLINICAL TRIALS, 1996, 17 (04) :343-346

[36] The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse [J].

Schmiegelow, K. ;

Heyman, M. ;

Gustafsson, G. ;

Lausen, B. ;

Wesenberg, F. ;

Kristinsson, J. ;

Vettenranta, K. ;

Schroeder, H. ;

Forestier, E. ;

Rosthoej, S. .

LEUKEMIA, 2010, 24 (04) :715-720

[37] RISK OF RELAPSE IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA IS RELATED TO RBC METHOTREXATE AND MERCAPTOPURINE METABOLITES DURING MAINTENANCE CHEMOTHERAPY [J].

SCHMIEGELOW, K ;

SCHRODER, H ;

GUSTAFSSON, G ;

KRISTINSSON, J ;

GLOMSTEIN, A ;

SALMI, T ;

WRANNE, L .

JOURNAL OF CLINICAL ONCOLOGY, 1995, 13 (02) :345-351

[38] Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia: Clinical Facts and Fiction [J].

Schmiegelow, Kjeld ;

Nielsen, Stine N. ;

Frandsen, Thomas L. ;

Nersting, Jacob .

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 2014, 36 (07) :503-517

[39] Central and peripheral nervous system toxicity of common chemotherapeutic agents [J].

Sioka, Chrissa ;

Kyritsis, Athanassios P. .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2009, 63 (05) :761-767

[40] Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia [J].

Smith, M ;

Arthur, D ;

Camitta, B ;

Carroll, AJ ;

Crist, W ;

Gaynon, P ;

Gelber, R ;

Heerema, N ;

Korn, EL ;

Link, M ;

Murphy, S ;

Pui, CH ;

Pullen, J ;

Reaman, G ;

Sallan, SE ;

Sather, H ;

Shuster, J ;

Simon, R ;

Trigg, M ;

Tubergen, D ;

Uckun, F ;

Ungerleider, R .

JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (01) :18-24

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