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

[1] THE INFLUENCE OF ROUTE OF ADMINISTRATION ON THE HEPATIC-UPTAKE OF METHOTREXATE [J].

BALIS, FM ;

MURPHY, RF ;

LESTER, CM ;

POPLACK, DG .

CANCER DRUG DELIVERY, 1986, 3 (04) :239-242

[2] Pharmacokinetics and pharmacodynamics of oral methotrexate and mercaptopurine in children with lower risk acute lymphoblastic leukemia: A joint Children's Cancer Group and Pediatric Oncology Branch Study [J].

Balis, FM ;

Holcenberg, JS ;

Poplack, DG ;

Ge, J ;

Sather, HN ;

Murphy, RF ;

Ames, MM ;

Waskerwitz, MJ ;

Tubergen, DG ;

Zimm, S ;

Gilchrist, GS ;

Bleyer, WA .

BLOOD, 1998, 92 (10) :3569-3577

[3]

BALIS FM, 1983, CANCER RES, V43, P2342

[4] DIFFERENCES IN CEREBROSPINAL-FLUID PENETRATION OF CORTICOSTEROIDS - POSSIBLE RELATIONSHIP TO THE PREVENTION OF MENINGEAL LEUKEMIA [J].

BALIS, FM ;

LESTER, CM ;

CHROUSOS, GP ;

HEIDEMAN, RL ;

POPLACK, DG .

JOURNAL OF CLINICAL ONCOLOGY, 1987, 5 (02) :202-207

[5] Systemic Exposure to Thiopurines and Risk of Relapse in Children With Acute Lymphoblastic Leukemia A Children's Oncology Group Study [J].

Bhatia, Smita ;

Landier, Wendy ;

Hageman, Lindsey ;

Chen, Yanjun ;

Kim, Heeyoung ;

Sun, Can-Lan ;

Kornegay, Nancy ;

Evans, William E. ;

Angiolillo, Anne L. ;

Bostrom, Bruce ;

Casillas, Jacqueline ;

Lew, Glen ;

Maloney, Kelly W. ;

Mascarenhas, Leo ;

Ritchey, A. Kim ;

Termuhlen, Amanda M. ;

Carroll, William L. ;

Wong, F. Lennie ;

Relling, Mary V. .

JAMA ONCOLOGY, 2015, 1 (03) :287-295

[6] MONTHLY PULSES OF VINCRISTINE AND PREDNISONE PREVENT BONE-MARROW AND TESTICULAR RELAPSE IN LOW-RISK CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - A REPORT OF THE CCG-161 STUDY BY THE CHILDRENS-CANCER-STUDY-GROUP [J].

BLEYER, WA ;

SATHER, HN ;

NICKERSON, HJ ;

COCCIA, PF ;

FINKLESTEIN, JZ ;

MILLER, DR ;

LITTMAN, PS ;

LUKENS, JN ;

SIEGEL, SE ;

HAMMOND, GD .

JOURNAL OF CLINICAL ONCOLOGY, 1991, 9 (06) :1012-1021

[7]

BLEYER WA, 1978, CANCER-AM CANCER SOC, V41, P36, DOI 10.1002/1097-0142(197801)41:1<36::AID-CNCR2820410108>3.0.CO

[8]

2-I

[9] Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study [J].

Borowitz, Michael J. ;

Devidas, Meenakshi ;

Hunger, Stephen P. ;

Bowman, W. Paul ;

Carroll, Andrew J. ;

Carroll, William L. ;

Linda, Stephen ;

Martin, Paul L. ;

Pullen, D. Jeanette ;

Viswanatha, David ;

Willman, Cheryl L. ;

Winick, Naomi ;

Camitta, Bruce M. .

BLOOD, 2008, 111 (12) :5477-5485

[10] Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group [J].

Bostrom, BC ;

Sensel, MR ;

Sather, HN ;

Gaynon, PS ;

La, MK ;

Johnston, K ;

Erdmann, GR ;

Gold, S ;

Heerema, NA ;

Hutchinson, RJ ;

Provisor, AJ ;

Trigg, ME .

BLOOD, 2003, 101 (10) :3809-3817

← 1 2 3 4 5 →