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Leukemia in AYA
Chi-kong LI, MD
Department of Paediatrics
The Chinese University of Hong Kong,
Prince of Wales Hospital and Hong Kong Children’s Hospital
Improved overall survival of children with acute lymphoblastic leukaemia
treated on cooperative group trials
Hong Kong Ped Haem/Onc Study Group
US Children’s Oncology Group
DEFINITION OF AGE FOR AYA
• The United Kingdom (UK) defines teenagers and young adults as those aged 15–
24 years
• In the EUROCARE (a European multinational project to examine cancer survival)
study, AYA was defined as those aged between 15 and 24 years
• The Canadian Cancer Society defines AYA as those aged between 15 and 29 years.
• USA AYA definitions:
• SEER 16-29 years
• National Cancer Institute 15-39 years
• Children’s Oncology Group 15-29 years
• WHO defined adolescent 10-19 years
• In Asian countries, there is no official definition for AYA age ranges in many Asia
countries
Geiger AM, Castellino SM. Delineating the age ranges used to define adolescents and young adults. J Clin Oncol.
2011 Jun 1;29(16):e492-3.
Increasing trend of Adolescents and Young Adults With ALL
The age range of the AYAs was 15 to 39 years. Average percentage change (APC) represents the
mean percentage change of logarithmic values, with APC values and P values for incidence
provided by SEER and calculated by us for new case numbers.
JAMA Oncol. 2018;4(5):725-734. doi:10.1001/jamaoncol.2017.5305
Five year Relative Survival Rate of Patients with ALL by Single
Year of age at diagnosis, 2000 to 2007. Survival Cliff
Data A, Included is joinpoint analysis that created linear regressions for ages 1 to 17 years and 20 to 68 years
and associated statistical variables.
B, The pediatric age-dependent survival trend in A is extrapolated into the adult age range..
JAMA Oncol. 2018;4(5):725-734.
Pediatric and Adult Therapy Regimen Outcomes
in AYAs With ALL or LBL
Children Children
standard High
risk Risk
Roberts, K. G. & Mullighan, C. G. (2015) Genomics in acute lymphoblastic leukaemia: insights
and treatment implicationsNat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2015.38
Outcomes of children,
adolescents, and young
adults with Ph-like ALL. (A)
Patients with Ph-like ALL
have an inferior outcome
compared with patients
with non–Ph-like patients
treated on AALL0232.
Blood 2018;132:351-356.
Asparaginase
• Pediatric trials showed superior outcome in patients treated with asparaginase:
• RCT trials in children with ALL, the asparaginase-containing regimen had 34%
higher 10-year to 20-year overall survival,
• Asparaginase causes more hepatic dysfunction, pancreatitis, and coagulopathies
in AYAs than in younger patients.
• A lower dose and longer intervals between doses of asparaginase prevent drug-
limiting hyperbilirubinemia.
• Several review articles offer practical guidelines for prevention and management
of asparaginase toxicities in AYAs.
• The benefit to toxicity ratio of asparaginase in AYAs with ALL or LBL is favorable.
Adult ALL trials: experience with Asp.
• significant benefit from asparaginase in a Cancer and Leukemia Group B trial, the 22
patients who had less asparagine depletion had a lower overall survival (hazard ratio [HR],
2.37; P = .002) and disease-free survival (HR, 2.21; P = .01) than 63 patients who did
achieve asparagine depletion.
• In a multi-institutional study, 60 of 95 adult patients with T-cell ALL or T-cell LBL, those
who received asparaginase had statistically improved relapse-free survival (HR, 2.65;
P = .01) and overall survival (HR, 2.30; P = .02), even after adjusting for other variables.
• Overall survival was greater in asparaginase-treated patients younger than 40 years (HR,
3.4; 95% CI, 1.2-9.5) than in older adults.
• In another multi-institutional study, 61 adults with early T-cell precursor ALL had a
statistically significant better progression-free survival and overall survival if they
received asparaginase.
• The primary objective of this study was to assess DFS rate and its secondary aims were to
assess toxicity, the CR rate and OS rate.
• The CR rate was 94%, The 5-year DFS and OS rates were 67% and 73% respectively.
• Severe adverse events were observed at a frequency that was similar to or lower than that
in children treated with the same protocol.
77.9%
75.3%
Factors contributing to difference in outcome
• adherence to dose intensity and differences in psychosocial care.
• AYA are at higher risk of toxicity, including VCR and Asp, pediatric oncologists may be
more comfortable with continuing intensive treatment and maintaining dose intensity in
the face of such toxicity.
• Dose reductions of these agents may have contributed to outcome differences. In the
DFCI Protocol 91‐01, patients who tolerated <25 weeks of asparaginase had a
significantly inferior EFS (73% ± 7% vs 90% ± 2%; P < 0.1
• AYA have been shown to have lower rates of medication adherence as compared to
younger children. Rates of 6‐MP nonadherence of >5% have been associated with a
threefold increase in the risk of relapse.
• Given lower patient volumes in pediatric centers, AYA at risk of nonadherence may be
more easily identified and referred to the appropriate psychosocial supports
Collaboration with pediatric oncologists
• The challenge of the pediatric regimen to adult oncologists: becoming
knowledgeable and comfortable with the complexity of pediatric regimen.
•
• Adult-treating oncologists benefit from the collaboration with and support
of pediatric oncologists and their staff in applying a pediatric regimen, as
well as from organizational modifications of their ambulatory clinics to
support effective and manageable delivery of the pediatric regimen.
• In 2016, the NCCN added hyper-CVAD plus rituximab to its AYA ALL guidelines but
specified that it was for CD20-positive ALL only
• and that the pediatric regimens for all forms of Ph chromosome-negative ALL were
“preferred.”
• CART THERAPY
Conclusions and Recommendations
• the development of protocols to address important treatment issues and
subgroups in AYA with ALL is necessary
• The survival cliff and accrual cliff and other data provide the rationale to treat
AYAs with newly diagnosed ALL on either a pediatric-inspired regimen or an
approved national clinical trial designed for this patient group, referral to a
specialized center with access to these trials should be arranged.
• Outcome should include better quality of life during and after therapy, as
indicated by hospitalization time, readmission for treatment complications, and
late adverse effects, such as infertility and second malignant neoplasms.
Thank you
谢谢