Outcomes of adult acute lymphoblastic leukemia in the era of pediatric-inspired regimens: a single-center experience
Recent data on acute lymphoblastic leukemia (ALL) treatment with multi-agent chemotherapy showed excellent response in pediatric patients in terms of long-term survival; however, the clinical needs for adult patients are still unmet. Adolescent and young adults’ (AYA) ALL could benefit from a pediatric-inspired regimen with a higher rate of long-term remission. This retrospective study sought to investigate the efficacy of treatment of adult ALL in a single center over the past decade. We analyzed 107 ALL patients with a median age of 26 years (range 15–63 years). Of these, 67.3% received adult regimen and 32.7% received pediatric-inspired regimen. The median follow-up time was 11.6 months (range 1–120). Complete remission (CR) was similarly achieved in over 80% in both schemes. Relapse and refractory rates were higher in the adult group (75%) than in the pediatric (45.7%) group. Two-year disease-free survival in the pediatric group was significantly superior to the adult group (47.1% vs 24.7%, hazard ratio [HR], 1.73, 95% CI 1.22–3.03). Two-year overall survival was higher in pediatric group as compared to adult group (50.8% versus 31.2%, HR 1.52, 95% CI 0.83–2.78). Thus, these findings show that the pediatric-inspired regimen should be considered for the treatment of adult ALL.
KeywordsAdult ALL Adolescence and young adults’ (AYA) ALL Treatment outcomes Pediatric-inspired regimen
The authors would like to thank all medical staff, nurses and paramedic team in Chiang Mai University (CMU) Hospital, Chiang Mai, Thailand for their participation in the care of all patients.
TR and AT were responsible for design of the study, data collection, interpretation of the data and writing the manuscript. TR and CC analyzed the data. All authors contributed to the revision of manuscript and approved the final version.
Compliance with ethical standards
Conflict of interest
All of the authors have no conflict of interest.
- 3.Thanawut P, Chansung K, Limwattananon C. Cost analysis for treatment of adult patients with acute leukemia in Thailand 2006. Available from: https://gsbooks.gs.kku.ac.th/51/gradresearch10/file/MMP10.pdf. Accessed 10 Dec 2018
- 8.Kantarjian H, Thomas D, O’Brien S, Cortes J, Giles F, Jeha S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101(12):2788–801.CrossRefGoogle Scholar
- 11.Gleissner B, Gokbuget N, Bartram CR, Janssen B, Rieder H, Janssen JW, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood. 2002;99(5):1536–43.CrossRefGoogle Scholar
- 13.Stock W, La M, Sanford B, Bloomfield CD, Vardiman JW, Gaynon P, 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):1646–54.CrossRefGoogle Scholar
- 15.Hallbook H, Gustafsson G, Smedmyr B, Soderhall S, Heyman M, Swedish Adult Acute Lymphocytic Leukemia G, et al. Treatment outcome in young adults and children > 10 years of age with acute lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and an adult protocol. Cancer. 2006;107(7):1551–61.CrossRefGoogle Scholar
- 17.Rytting ME, Jabbour EJ, Jorgensen JL, Ravandi F, Franklin AR, Kadia TM, 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):819–23.CrossRefGoogle Scholar
- 18.Hayakawa F, Sakura T, Yujiri T, Kondo E, Fujimaki K, Sasaki O, et al. Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group. Blood Cancer J. 2014;4:e252.CrossRefGoogle Scholar
- 20.Nachman JB, La MK, Hunger SP, Heerema NA, Gaynon PS, Hastings C, et al. Young adults with acute lymphoblastic leukemia have an excellent outcome with chemotherapy alone and benefit from intensive postinduction treatment: a report from the children’s oncology group. J Clin Oncol. 2009;27(31):5189–94.CrossRefGoogle Scholar
- 24.Ribera JM, Oriol A, Sanz MA, Tormo M, Fernandez-Abellan P, del Potro E, et al. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol. 2008;26(11):1843–9.CrossRefGoogle Scholar
- 25.Rijneveld AW, van der Holt B, Daenen SM, Biemond BJ, de Weerdt O, Muus P, et al. Intensified chemotherapy inspired by a pediatric regimen combined with allogeneic transplantation in adult patients with acute lymphoblastic leukemia up to the age of 40. Leukemia. 2011;25(11):1697–703.CrossRefGoogle Scholar
- 30.Testi A, Valsecchi M, Conter V, Vignetti M, Paoloni F, Giona F, et al. Difference in outcome of adolescents with acute lymphoblastic leukemia (ALL) enrolled in pediatric (AIEOP) and adult (GIMEMA) protocols [abstract]. Blood. 2004;104(11):Abstract 1954.Google Scholar
- 31.Alves M, Daudt L, Mazzucco K, Taniguchi A, Nava T, Moreno F, et al. Is it better to treat adolescents with acute lymphoblastic leukemia as old children or as young adults? Blood. 2008;112:Abstract 3968.Google Scholar
- 32.Schroder H, Kjeldahl M, Boesen AM, Nielsen OJ, Schmidt K, Johnsen HE, et al. Acute lymphoblastic leukemia in adolescents between 10 and 19 years of age in Denmark–secondary publication. Dan Med Bull. 2006;53(1):76–9.Google Scholar
- 33.Cluzeau T, Dhedin N, Huguet F, Raffoux E, Maury S, Mannone L, et al. Dose- intensity impacts on survival of adolescents and young adults with acute lymphoblastic leukemia treated in adult departments by a pediatric protocol (FRALLE 2000BT) [abstract]. Blood. 2012;120(21):Abstract 3561.Google Scholar
- 34.Stock W, Luger SM, Advani AS, Geyer S, Harvey RC, Mullighan CG, et al. Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of US intergroup trial C10403 [abstract]. Blood. 2014;124(21):Abstract 796.Google Scholar
- 35.Gökbuget N, Beck J, Brandt K, Brüggemann M, Burmeister T, Diedrich H, et al. Significant improvement of outcome in adolescents and young adults (AYAs) aged 15-35 years with acute lymphoblastic leukemia (ALL) with a pediatric derived adult ALL protocol: results of 1529 AYAs in 2 consecutive trials of the German Multicenter Study Group for Adult ALL (GMALL) [abstract]. Blood. 2013;122(21):Abstract 839.Google Scholar
- 36.Albritton K, Caligiuri M, Anderson B, Nichols C, Ulman D, Adams H, et al. Closing the gap: research and care imperatives for adolescents and young adults with cancer: NIH; 2006. Publication no. 06-6067: available from: https://www.cancer.gov/types/aya/research/ayao-august-2006.pdf. Accessed 25 Nov 2018
- 38.Nagura E, Kimura K, Yamada K, Ota K, Maekawa T, Takaku F, et al. Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 1994;33(5):359–65.CrossRefGoogle Scholar
- 41.Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007;109(8):3189–97.CrossRefGoogle Scholar
- 42.Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009;113(19):4489–96.CrossRefGoogle Scholar
- 48.Jabbour E, Kantarjian H, Ravandi F, Thomas D, Huang X, Faderl S, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. Lancet Oncol. 2015;16(15):1547–55.CrossRefGoogle Scholar
- 49.Sasaki K, Jabbour EJ, Ravandi F, Short NJ, Thomas DA, Garcia-Manero G, et al. Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2016;122(23):3650–6.CrossRefGoogle Scholar