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：67

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
BALIS, FM
MURPHY, RF
LESTER, CM
POPLACK, DG
[J]. 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
Balis, FM
Holcenberg, JS
Poplack, DG
Ge, J
Sather, HN
Murphy, RF
Ames, MM
Waskerwitz, MJ
Tubergen, DG
Zimm, S
Gilchrist, GS
Bleyer, WA
[J]. 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
BALIS, FM
LESTER, CM
CHROUSOS, GP
HEIDEMAN, RL
POPLACK, DG
[J]. 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
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.
[J]. 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
BLEYER, WA
SATHER, HN
NICKERSON, HJ
COCCIA, PF
FINKLESTEIN, JZ
MILLER, DR
LITTMAN, PS
LUKENS, JN
SIEGEL, SE
HAMMOND, GD
[J]. 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
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.
[J]. 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
Bostrom, BC
Sensel, MR
Sather, HN
Gaynon, PS
La, MK
Johnston, K
Erdmann, GR
Gold, S
Heerema, NA
Hutchinson, RJ
Provisor, AJ
Trigg, ME
[J]. BLOOD, 2003, 101 (10) : 3809 - 3817

← 1 2 3 4 5 →