Significant improvements have occurred for adolescent and young adult (AYA) B-cell acute lymphoblastic leukemia (B-ALL) patients following the widespread adoption of “pediatric-inspired” treatment regimens for AYA patients cared for in adult oncology settings. However, for AYA patients, aged 15 to 39, an outcomes gap remains in B-ALL, necessitating the incorporation of novel therapies into up-front treatment regimens. As a result, clinical trial enrollment remains the current standard of care for AYA B-ALL across disease subtypes when available and accessible. Currently, several up-front trials are looking to incorporate the use of inotuzumab, blinatumomab, and chimeric antigen receptor T-cell therapy into existing chemotherapy backbones for AYA patients, as well as tyrosine kinase inhibitors for both Philadelphia-positive (Ph+) and Ph-like B-ALL. In addition to ongoing attempts to improve up-front treatments by incorporating immunotherapy and targeted approaches, the increased use of next generation sequencing for measurable residual disease evaluation has led to superior risk-stratification and a decreased need to pursue consolidative hematopoietic stem cell transplantation during the first complete remission for many patients.

1.
Toksvang
LN
,
Lee
SHR
,
Yang
JJ
,
Schmiegelow
K.
Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations
.
Leukemia
.
2022
;
36
(
7
):
1749
-
1758
.
doi:10.1038/s41375-022-01591-4
.
2.
Carobolante
F
,
Chiaretti
S
,
Skert
C
,
Bassan
R.
Practical guidance for the management of acute lymphoblastic leukemia in the adolescent and young adult population
.
Ther Adv Hematol
.
2020
;
11
(
3 February
):
204062072090353
.
doi:10.1177/2040620720903531
.
3.
Muffly
L
,
Alvarez
E
,
Lichtensztajn
D
,
Abrahao
R
,
Gomez
SL
,
Keegan
T.
Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukemia: a population-based study
.
Blood Adv
.
2018
;
2
(
8
):
895
-
903
.
doi:10.1182/bloodadvances.2017014944
.
4.
Stock
W
,
La
M
,
Sanford
B
, et al.
What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children's Cancer Group and Cancer and Leukemia Group B studies
.
Blood
.
2008
;
112
(
5
):
1646
-
1654
.
doi:10.1182/blood-2008-01-130237
.
5.
Stock
W
,
Luger
SM
,
Advani
AS
, et al.
A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403
.
Blood
.
2019
;
133
(
14
):
1548
-
1559
.
doi:10.1182/blood-2018-10-881961
.
6.
Siegel
SE
,
Stock
W
,
Johnson
RH
, et al.
Pediatric-inspired treatment regimens for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: a review
.
JAMA Oncol
.
2018
;
4
(
5
):
725
-
734
.
doi:10.1001/jamaoncol.2017.5305
.
7.
Rytting
ME
,
Jabbour
EJ
,
Jorgensen
JL
, et al.
Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Munster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen
.
Am J Hematol
.
2016
;
91
(
8
):
819
-
823
.
doi:10.1002/ajh.24419
.
8.
Siegel
SE
,
Coccia
PF
,
Barr
R
,
Hayes-Lattin
B
,
Bleyer
A.
RE: a reappraisal of sex-specific cancer survival trends among adolescents and young adults in the United States
.
JNCI: J Natl Cancer Inst
.
2019
;
111
(
6
):
633
-
634
.
doi:10.1093/jnci/djz019
.
9.
Almanza-Huante
E
,
Espinosa-Bautista
K
,
Rangel-Patiño
J
,
Demichelis- Gómez
R.
Comparison of two pediatric-inspired regimens to Hyper-CVAD in Hispanic adolescents and young adults with acute lymphoblastic leukemia
.
Clin Lymphoma Myeloma Leuk
.
2021
;
21
(
1
):
55
-
62.e2
.
doi:10.1016/j.clml.2020.07.017
.
10.
Sasaki
K
,
Jabbour
E
,
Short
NJ
, et al.
Acute lymphoblastic leukemia: a population-based study of outcome in the United States based on the surveillance, epidemiology, and end results (SEER) database, 1980-2017
.
Am J Hematol
.
2021
;
96
(
6
):
650
-
658
.
doi:10.1002/ajh.26156
.
11.
Gupta
S
,
Dai
Y
,
Chen
Z
, et al.
Racial and ethnic disparities in childhood and young adult acute lymphocytic leukaemia: secondary analyses of eight Children's Oncology Group cohort trials
.
Lancet Haematol
.
2023
;
10
(
2
):
e129
-
e141
.
doi:10.1016/S2352-3026(22)00371-4
.
12.
Boissel
N.
New developments in ALL in AYA
.
Hematology Am Soc Hematol Educ Program
.
2022
;
2022
(
1
):
190
-
196
.
doi:10.1182/hematology.2022000336
.
13.
Maury
S
,
Chevret
S
,
Thomas
X
, et al.
Rituximab in B-lineage adult acute lymphoblastic leukemia
.
N Engl J Med
.
2016
;
375
(
11
):
1044
-
1053
.
doi:10.1056/NEJMoa1605085
.
14.
Hoshitsuki
K
,
Zhou
Y
,
Miller
AM
, et al.
Rituximab administration in pediatric patients with newly diagnosed acute lymphoblastic leukemia
.
Leukemia
.
2023
;
37
(
9
):
1782
-
1791
.
doi:10.1038/s41375-023-01992-z
.
15.
Aldoss
I
,
Shah
BD
,
Park
JH
, et al.
Sequencing antigen-targeting antibodies and cellular therapies in adults with relapsed/refractory B-cell acute lymphoblastic leukemia
.
Am J Hematol
.
2023
;
98
(
4
):
666
-
680
.
doi:10.1002/ajh.26853
.
16.
Kantarjian
HM
,
DeAngelo
DJ
,
Stelljes
M
, et al.
Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study
.
Cancer
.
2019
;
125
(
14
):
2474
-
2487
.
doi:10.1002/cncr.32116
.
17.
O'Brien
MM
,
Ji
L
,
Shah
NN
, et al.
Phase II trial of inotuzumab ozogamicin in children and adolescents with relapsed or refractory B-cell acute lymphoblastic leukemia: Children's Oncology Group Protocol AALL1621
.
J Clin Oncol
.
2022
;
40
(
9
):
956
-
967
.
doi:10.1200/JCO.21.01693
.
18.
McNeer
JL
,
Rheingold
SR
,
Devidas
M
, et al.
A phase 3 trial of inotuzumab ozogamicin for high-risk B-ALL: second safety phase results from Children's Oncology Group AALL1732
.
J Clin Oncol
.
2023
;
41
(
suppl 16
):
10016
.
doi:10.1200/JCO.2023.41.16_suppl.10016
.
19.
Kantarjian
H
,
Stein
A
,
Gokbuget
N
, et al.
Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia
.
N Engl J Med
.
2017
;
376
(
9
):
836
-
847
.
doi:10.1056/NEJMoa1609783
.
20.
Gokbuget
N
,
Dombret
H
,
Bonifacio
M
, et al.
Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia
.
Blood
.
2018
;
131
(
14
):
1522
-
1531
.
doi:10.1182/blood-2017-08-798322
.
21.
Brown
PA
,
Ji
L
,
Xu
X
, et al.
Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial
.
JAMA
.
2021
;
325
(
9
):
833
-
842
.
doi:10.1001/jama.2021.0669
.
22.
Locatelli
F
,
Zugmaier
G
,
Rizzari
C
, et al.
Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial
.
JAMA
.
2021
;
325
(
9
):
843
-
854
.
doi:10.1001/jama.2021.0987
.
23.
Litzow
MR
,
Sun
Z
,
Paietta
E
, et al.
Consolidation therapy with blinatumomab improves overall survival in newly diagnosed adult patients with B-lineage acute lymphoblastic leukemia in measurable residual disease negative remission: results from the ECOG-ACRIN E1910 randomized phase III National Cooperative Clinical Trials Network Trial
.
Blood
.
2022
;
140
(
suppl 2
):
LBA-1
-
LBA-1
.
doi:10.1182/blood-2022-171751
.
24.
June
CH
,
Sadelain
M.
Chimeric antigen receptor therapy
.
N Engl J Med
.
2018
;
379
(
1
):
64
-
73
.
doi:10.1056/NEJMra1706169
.
25.
Myers
RM
,
Shah
NN
,
Pulsipher
MA.
How I use risk factors for success or failure of CD19 CAR T cells to guide management of children and AYA with B-cell ALL
.
Blood
.
2023
;
141
(
11
):
1251
-
1264
.
doi:10.1182/blood.2022016937
.
26.
Qayed
M
,
Bleakley
M
,
Shah
NN.
Role of chimeric antigen receptor T-cell therapy: bridge to transplantation or stand-alone therapy in pediatric acute lymphoblastic leukemia
.
Curr Opin Hematol
.
2021
;
28
(
6
):
373
-
379
.
doi:10.1097/moh.0000000000000685
.
27.
Maude
SL
,
Laetsch
TW
,
Buechner
J
, et al.
Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia
.
N Engl J Med
.
2018
;
378
(
5
):
439
-
448
.
doi:10.13039/100008272
.
28.
Shah
BD
,
Ghobadi
A
,
Oluwole
OO
, et al.
Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study
.
J Hematol Oncol
.
2022
;
15
(
1
):
170
.
doi:10.1186/s13045-022-01379-0
.
29.
Wieduwilt
MJ.
Ph+ ALL in 2022: is there an optimal approach?
Hematology
.
2022
;
2022
(
1
):
206
-
212
.
doi:10.1182/hematology.2022000338
.
30.
Pfeifer
H
,
Wassmann
B
,
Pavlova
A
, et al.
Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)
.
Blood
.
2007
;
110
(
2
):
727
-
734
.
doi:10.1182/blood-2006-11-052373
.
31.
Jabbour
E
,
Haddad
FG
,
Short
NJ
,
Kantarjian
H.
Treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia—from intensive chemotherapy combinations to chemotherapy-free regimens: a review
.
JAMA Oncol
.
2022
;
8
(
9
):
1340
-
1348
.
doi:10.1001/jamaoncol.2022.2398
.
32.
Alghandour
R
,
Sakr
DH
,
Shaaban
Y.
Philadelphia-like acute lymphoblastic leukemia: the journey from molecular background to the role of bone marrow transplant—review article
.
Ann Hematol
.
2023
;
102
(
6
):
1287
-
1300
.
doi:10.1007/s00277-023-05241-2
.
33.
Roberts
KG
,
Reshmi
SC
,
Harvey
RC
, et al.
Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the Children's Oncology Group
.
Blood
.
2018
;
132
(
8
):
815
-
824
.
doi:10.1182/blood-2018-04-841676
.
34.
Tran
TH
,
Hunger
SP.
The genomic landscape of pediatric acute lymphoblastic leukemia and precision medicine opportunities
.
Semin Cancer Biol
.
2022
;
84
(
28
):
144
-
152
.
doi:10.1016/j.semcancer.2020.10.013
.
35.
Aldoss
I
,
Yang
D
,
Tomasian
V
, et al.
Outcomes of allogeneic hematopoietic cell transplantation in adults with fusions associated with Ph-like ALL
.
Blood Adv
.
2022
;
6
(
17
):
4936
-
4948
.
doi:10.1182/bloodadvances.2022007597
.
36.
Pui
CH
,
Roberts
KG
,
Yang
JJ
,
Mullighan
CG.
Philadelphia chromosome-like acute lymphoblastic leukemia
.
Clin Lymphoma Myeloma Leuk
.
2017
;
17
(
8
):
464
-
470
.
doi:10.1016/j.clml.2017.03.299
.
37.
Schwab
C
,
Ryan
SL
,
Chilton
L
, et al.
EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications
.
Blood
.
2016
;
127
(
18
):
2214
-
2208
.
doi:10.1182/blood-2015-09-670166
.
38.
Tasian
SK
,
Assad
A
,
Hunter
DS
,
Du
Y
,
Loh
ML.
A phase 2 study of ruxolitinib with chemotherapy in children with Philadelphia chromosome-like acute lymphoblastic leukemia (INCB18424-269/AALL1521): dose-finding results from the part 1 safety phase
.
Blood
.
2018
;
132
(
suppl 1
):
555
.
doi:10.1182/blood-2018-99-110221
.
39.
Aldoss
I
,
Afkhami
M
,
Yang
D
, et al.
High response rates and transition to transplant after novel targeted and cellular therapies in adults with relapsed/refractory acute lymphoblastic leukemia with Philadelphia-like fusions
.
Am J Hematol
.
2023
;
98
(
6
):
848
-
856
.
doi:10.1002/ajh.26908
.
40.
Berry
DA
,
Zhou
S
,
Higley
H
, et al.
Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis
.
JAMA Oncol
.
2017
;
3
(
7
):
e170580
.
doi:10.1001/jamaoncol.2017.0580
.
41.
Della Starza
I
,
De Novi
LA
,
Elia
L
, et al.
Optimizing molecular minimal residual disease analysis in adult acute lymphoblastic leukemia
.
Cancers (Basel)
.
2023
;
15
(
2
):
374
.
doi:10.3390/cancers15020374
.
42.
Dhédin
N
,
Huynh
A
,
Maury
S
, et al.
Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia
.
Blood
.
2015
;
125
(
16
):
2486
-
2496
.
doi:10.1182/blood-2014-09-599894
.
43.
Rau
RE
,
Dai
Y
,
Devidas
M
, et al.
Prognostic impact of minimal residual disease at the end of consolidation in NCI standard-risk B-lymphoblastic leukemia: a report from the Children's Oncology Group
.
Pediatr Blood Cancer
.
2021
;
68
(
4
):
e28929
.
doi:10.1002/pbc.28929
.
44.
Short
NJ
,
Jabbour
E
,
Albitar
M
, et al.
Recommendations for the assessment and management of measurable residual disease in adults with acute lymphoblastic leukemia: a consensus of North American experts
.
Am J Hematol
.
2019
;
94
(
2
):
257
-
265
.
doi:10.1002/ajh.25338
.
45.
Short
NJ
,
Kantarjian
H
,
Ravandi
F
, et al.
High-sensitivity next-generation sequencing MRD assessment in ALL identifies patients at very low risk of relapse
.
Blood Adv
.
2022
;
6
(
13
):
4006
-
4014
.
doi:10.1182/bloodadvances.2022007378
.
46.
Short
NJ
,
Jabbour
E
,
Macaron
W
, et al.
Ultrasensitive NGS MRD assessment in Ph+ ALL: prognostic impact and correlation with RT-PCR for BCR::ABL1
.
Am J Hematol
.
2023
;
98
(
8
):
1196
-
1203
.
doi:10.1002/ajh.26949
.
47.
Liang
EC
,
Dekker
SE
,
Sabile
JMG
, et al.
Next-generation sequencing-based MRD in adults with ALL undergoing hematopoietic cell transplantation
.
Blood Adv
.
2023
;
7
(
14
):
3395
-
3402
.
doi:10.1182/bloodadvances.2023009856
.
48.
Truong
TH
,
Jinca
C
,
Mann
G
, et al.
Allogeneic hematopoietic stem cell transplantation for children with acute lymphoblastic leukemia: shifting indications in the era of immunotherapy
.
Front Pediatr
.
2021
;
9
(
December
):
782785
.
doi:10.3389/fped.2021.782785
.
49.
Goldstone
AH
,
Richards
SM
,
Lazarus
HM
, et al.
In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first CR, and an autologous transplantation is less effective than conventional consolidation/ maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993)
.
Blood
.
2008
;
111
(
4
):
1827
-
1833
.
doi:10.1182/blood-2007-10-116582
.
50.
Wieduwilt
MJ
,
Stock
W
,
Advani
A
, et al.
Superior survival with pediatric-style chemotherapy compared to myeloablative allogeneic hematopoietic cell transplantation in older adolescents and young adults with Ph-negative acute lymphoblastic leukemia in first complete remission: analysis from CALGB 10403 and the CIBMTR
.
Leukemia
.
2021
;
35
(
7
):
2076
-
2085
.
doi:10.1038/s41375-021-01213-5
.
51.
Seftel
MD
,
Neuberg
D
,
Zhang
MJ
, et al.
Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission
.
Am J Hematol
.
2016
;
91
(
3
):
322
-
329
.
doi:10.1002/ajh.24285
.
52.
Schultz
KR
,
Carroll
A
,
Heerema
NA
, et al.
Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031
.
Leukemia
.
2014
;
28
(
7
):
1467
-
1471
.
doi:10.1038/leu.2014.30
.
53.
Brown
PA
,
Shah
B
,
Advani
A
, et al.
Acute lymphoblastic leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
.
J Natl Compr Canc Netw
.
2021
;
19
(
9
):
1079
-
1109
.
doi:10.6004/jnccn.2021.0042
.
54.
Parsons
SK
,
Keegan
THM
,
Kirchhoff
AC
,
Parsons
HM
,
Yabroff
KR
,
Davies
SJ.
Cost of cancer in adolescents and young adults in the United States: results of the 2021 report by Deloitte Access Economics, commissioned by Teen Cancer America
.
J Clin Oncol
.
2023
;
41
(
17
):
3260
-
3268
.
doi:10.1200/JCO.22.01985
.
55.
Muffly
L
,
Maguire
FB
,
Li
Q
,
Kennedy
V
,
Keegan
TH.
Late effects in survivors of adolescent and young adult acute lymphoblastic leukemia
.
JNCI Cancer Spectr
.
2020
;
4
(
4
):
pkaa025
.
doi:10.1093/jncics/pkaa025
.
56.
Williams
AM
,
Liu
Q
,
Bhakta
N
, et al.
Rethinking success in pediatric oncology: beyond 5-year survival
.
J Clin Oncol
.
2021
;
39
(
20
):
2227
-
2231
.
doi:10.1200/JCO.20.03681
.
57.
Berkman
AM
,
Andersen
CR
,
Cuglievan
B
, et al.
Long-term outcomes among adolescent and young adult survivors of acute leukemia: a surveillance, epidemiology, and end results analysis
.
Cancer Epidemiol Biomarkers Prev
.
2022
;
31
(
6
):
1176
-
1184
.
doi:10.1158/1055-9965.EPI-21-1388
.
58.
Mittal
N
,
Saha
A
,
Avutu
V
,
Monga
V
,
Freyer
DR
,
Roth
M.
Shared barriers and facilitators to enrollment of adolescents and young adults on cancer clinical trials
.
Sci Rep
.
2022
;
12
(
1
):
3875
.
doi:10.1038/s41598-022-07703-5
.
59.
Jin
Z
,
Griffith
MA
,
Rosenthal
AC.
Identifying and meeting the needs of adolescents and young adults with cancer
.
Curr Oncol Rep
.
2021
;
23
(
2
):
17
.
doi:10.1007/s11912-020-01011-9
.
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