In the US, the estimated 5-year relative survival rate for ALL is 72.0% (2014-2020 data).[10]National Cancer Institute. SEER Explorer: All cancer sites combined. Recent trends in SEER age-adjusted incidence rates, 2000-2020. 2023 [internet publication].
https://seer.cancer.gov/statistics-network/explorer/application.html?site=1&data_type=1&graph_type=2&compareBy=sex&chk_sex_3=3&chk_sex_2=2&rate_type=2&race=1&age_range=1&hdn_stage=101&advopt_precision=1&advopt_show_ci=on&hdn_view=0&advopt_show_apc=on&advopt_display=2#resultsRegion0
Outcome in adult patients is age-dependent. The estimated 5-year relative survival rate (2014-2020 data) is:[10]National Cancer Institute. SEER Explorer: All cancer sites combined. Recent trends in SEER age-adjusted incidence rates, 2000-2020. 2023 [internet publication].
https://seer.cancer.gov/statistics-network/explorer/application.html?site=1&data_type=1&graph_type=2&compareBy=sex&chk_sex_3=3&chk_sex_2=2&rate_type=2&race=1&age_range=1&hdn_stage=101&advopt_precision=1&advopt_show_ci=on&hdn_view=0&advopt_show_apc=on&advopt_display=2#resultsRegion0
81.6% for patients ages <50 years
41.7% for patients ages 50-64 years
25.3% for patients ages 65 years and above
Prognostic factors
Negative prognostic features include older age, elevated white blood cell (WBC) count at presentation, failure to achieve a complete remission (CR), and adverse cytogenetic abnormalities.
Younger patients with WBC less than 30,000/microliter and who respond to treatment within 4 weeks have the best prognosis.[1]Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004 Apr 8;350(15):1535-48.
http://www.ncbi.nlm.nih.gov/pubmed/15071128?tool=bestpractice.com
[90]Pui CH, Evans WH. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006 Jan 12;354(2):166-78.
http://www.ncbi.nlm.nih.gov/pubmed/16407512?tool=bestpractice.com
[177]Thomas X, Le QH. Current therapeutic strategies in acute lymphoblastic leukemia in the adult. Bull Cancer. 2003 Oct;90(10):833-50.
http://www.ncbi.nlm.nih.gov/pubmed/14706913?tool=bestpractice.com
[178]Thomas X, Le QH. Prognostic factors in adult acute lymphoblastic leukemia. Hematology. 2003 Aug;8(4):233-42.
http://www.ncbi.nlm.nih.gov/pubmed/12911941?tool=bestpractice.com
[179]Pui CH, Carroll WL, Meshinchi S, et al. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol. 2011 Feb 10;29(5):551-65.
http://www.ncbi.nlm.nih.gov/pubmed/21220611?tool=bestpractice.com
[180]Rowe JM. Prognostic factors in adult acute lymphoblastic leukaemia. Br J Haematol. 2010 Aug;150(4):389-405.
http://www.ncbi.nlm.nih.gov/pubmed/20573154?tool=bestpractice.com
Individual risk depends on a variety of clinical and biologic factors including:
Age: among children, those ages <1 year are considered very high risk, those ages ≥10 years are considered high risk, and those ages 1-9 years are considered standard risk.[77]Hunger SP, Loh ML, Whitlock JA, et al. Children's Oncology Group's 2013 blueprint for research: acute lymphoblastic leukemia. Pediatr Blood Cancer. 2013 Jun;60(6):957-63.
http://www.ncbi.nlm.nih.gov/pubmed/23255467?tool=bestpractice.com
[181]Smith M, Arthur D, Camitta B, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol. 1996 Jan;14(1):18-24.
http://www.ncbi.nlm.nih.gov/pubmed/8558195?tool=bestpractice.com
Adults ages >35 years are considered high risk, although the impact of age is a continuous variable.[78]Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7.
https://ashpublications.org/blood/article/106/12/3760/109755/Induction-therapy-for-adults-with-acute
http://www.ncbi.nlm.nih.gov/pubmed/16105981?tool=bestpractice.com
[79]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 complete remission, 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 Feb 15;111(4):1827-33.
https://ashpublications.org/blood/article/111/4/1827/133215/In-adults-with-standard-risk-acute-lymphoblastic
http://www.ncbi.nlm.nih.gov/pubmed/18048644?tool=bestpractice.com
WBC count at presentation: a continuous variable, >30,000/microliter for B-ALL and >100,000/microliter for T-ALL are considered high risk for adults, and >50,000/microliter for B-ALL is considered high risk for children.[77]Hunger SP, Loh ML, Whitlock JA, et al. Children's Oncology Group's 2013 blueprint for research: acute lymphoblastic leukemia. Pediatr Blood Cancer. 2013 Jun;60(6):957-63.
http://www.ncbi.nlm.nih.gov/pubmed/23255467?tool=bestpractice.com
Cytogenetic and molecular abnormalities. See Diagnostic criteria.
Immunophenotypic subtype: CD20 expression is associated with a poor prognosis.[80]Jeha S, Behm F, Pei D, et al. Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2006 Nov 15;108(10):3302-4.
https://ashpublications.org/blood/article/108/10/3302/22786/Prognostic-significance-of-CD20-expression-in
http://www.ncbi.nlm.nih.gov/pubmed/16896151?tool=bestpractice.com
Response to induction therapy: patients receiving induction therapy who do not achieve a CR, or who respond poorly, are considered high risk.
Presence of measurable residual disease (MRD; e.g., ≥0.01%) following induction therapy: persistent MRD after induction is associated with poor outcomes.[81]Dekker SE, Rea D, Cayuela JM, et al. Using measurable residual disease to optimize management of AML, ALL, and chronic myeloid leukemia. Am Soc Clin Oncol Educ Book. 2023 Jun;43:e390010.
https://ascopubs.org/doi/10.1200/EDBK_390010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/37311155?tool=bestpractice.com
Central nervous system (CNS) involvement
CNS involvement is a major complication of ALL occurring in 5% to 7% of patients at diagnosis; incidence is higher in patients with T-ALL (8%) and mature B-ALL (Burkitt lymphoma/leukemia, 13%).[50]Reman O, Pigneux A, Huguet F, et al. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis and/or at first relapse: results from the GET-LALA group. Leuk Res. 2008 Nov;32(11):1741-50.
http://www.ncbi.nlm.nih.gov/pubmed/18508120?tool=bestpractice.com
[51]Lazarus HM, Richards SM, Chopra R, et al. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993. Blood. 2006 Jul 15;108(2):465-72.
https://ashpublications.org/blood/article/108/2/465/109893/Central-nervous-system-involvement-in-adult-acute
http://www.ncbi.nlm.nih.gov/pubmed/16556888?tool=bestpractice.com
[52]Pui CH. Central nervous system disease in acute lymphoblastic leukemia: prophylaxis and treatment. Hematology Am Soc Hematol Educ Program. 2006 Jan;(1):142-6.
https://ashpublications.org/hematology/article/2006/1/142/19688/Central-Nervous-System-Disease-in-Acute
http://www.ncbi.nlm.nih.gov/pubmed/17124053?tool=bestpractice.com
[53]Lamanna N, Weiss M. Treatment options for newly diagnosed patients with adult acute lymphoblastic leukemia. Curr Hematol Rep. 2004 Jan;3(1):40-6.
http://www.ncbi.nlm.nih.gov/pubmed/14695849?tool=bestpractice.com
[54]Richards S, Pui CH, Gayon P, et al. Systematic review and meta-analysis of randomized trials of central nervous system directed therapy for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2013 Feb;60(2):185-95.
https://onlinelibrary.wiley.com/doi/10.1002/pbc.24228
http://www.ncbi.nlm.nih.gov/pubmed/22693038?tool=bestpractice.com
CNS involvement can lead to severe neurologic morbidity (i.e., cranial nerve palsies), and is a major obstacle to cure, accounting for up to 40% of initial relapses in clinical trials.[82]Krishnan S, Wade R, Moorman AV, et al. Temporal changes in the incidence and pattern of central nervous system relapses in children with acute lymphoblastic leukaemia treated on four consecutive Medical Research Council trials, 1985-2001. Leukemia. 2010 Feb;24(2):450-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820451
http://www.ncbi.nlm.nih.gov/pubmed/20016529?tool=bestpractice.com
[83]Laningham FH, Kun LE, Reddick WE, et al. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae. Neuroradiology. 2007 Nov;49(11):873-88.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386669
http://www.ncbi.nlm.nih.gov/pubmed/17924103?tool=bestpractice.com
[84]Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol. 2008 Mar;9(3):257-68.
http://www.ncbi.nlm.nih.gov/pubmed/18308251?tool=bestpractice.com
Studies have shown that use of intensive regimens in patients with CNS involvement at diagnosis results in similar outcomes (i.e., CR, disease-free survival, and overall survival) to patients without CNS involvement at diagnosis, particularly among adults.[50]Reman O, Pigneux A, Huguet F, et al. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis and/or at first relapse: results from the GET-LALA group. Leuk Res. 2008 Nov;32(11):1741-50.
http://www.ncbi.nlm.nih.gov/pubmed/18508120?tool=bestpractice.com
[51]Lazarus HM, Richards SM, Chopra R, et al. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993. Blood. 2006 Jul 15;108(2):465-72.
https://ashpublications.org/blood/article/108/2/465/109893/Central-nervous-system-involvement-in-adult-acute
http://www.ncbi.nlm.nih.gov/pubmed/16556888?tool=bestpractice.com
[85]Thomas X, Boiron JM, Huguet F, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004 Oct 15;22(20):4075-86.
https://ascopubs.org/doi/10.1200/JCO.2004.10.050
http://www.ncbi.nlm.nih.gov/pubmed/15353542?tool=bestpractice.com
[86]Petersdorf SH, Kopecky KJ, Head DR, et al. Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study. Leukemia. 2001 Feb;15(2):208-16.
http://www.ncbi.nlm.nih.gov/pubmed/11236936?tool=bestpractice.com
[87]Kantarjian HM, O'Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000 Feb;18(3):547-61.
http://www.ncbi.nlm.nih.gov/pubmed/10653870?tool=bestpractice.com
[88]Hoelzer D, Thiel E, Löffler H, et al. Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood. 1988 Jan;71(1):123-31.
https://www.sciencedirect.com/science/article/pii/S0006497120782339
http://www.ncbi.nlm.nih.gov/pubmed/3422030?tool=bestpractice.com
However, outcomes are often poor in patients with CNS relapse (median overall survival <1 year).[89]Surapaneni UR, Cortes JE, Thomas D, et al. Central nervous system relapse in adults with acute lymphoblastic leukemia. Cancer. 2002 Feb 1;94(3):773-9.
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.10265?sid=nlm%3Apubmed
http://www.ncbi.nlm.nih.gov/pubmed/11857312?tool=bestpractice.com
Patients with CNS involvement (particularly CNS relapse) usually warrant consideration for postremission allogeneic SCT.[59]Hoelzer D, Bassan R, Dombret H, et al. Acute lymphoblastic leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v69-82.
https://www.annalsofoncology.org/article/S0923-7534(19)31639-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27056999?tool=bestpractice.com
[69]Kopmar NE, Cassaday RD. How I prevent and treat central nervous system disease in adults with acute lymphoblastic leukemia. Blood. 2023 Mar 23;141(12):1379-88.
https://ashpublications.org/blood/article/141/12/1379/493851/How-I-prevent-and-treat-central-nervous-system
http://www.ncbi.nlm.nih.gov/pubmed/36548957?tool=bestpractice.com
Relapse/refractory disease
The prognosis in relapsed or refractory disease is generally poor. Median survival is less than 1 year, and less than 25% of patients survive in the long term.[141]Oriol A, Vives S, Hernández-Rivas JM, et al; Programa Español de Tratamiento en Hematologia Group. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica. 2010 Apr;95(4):589-96.
https://haematologica.org/article/view/5555
http://www.ncbi.nlm.nih.gov/pubmed/20145276?tool=bestpractice.com
Long-term survival is dependent upon attaining a complete remission (CR) with subsequent allogeneic stem cell transplantation (SCT).
An individual's risk depends on a variety of clinical and biologic factors including:[182]Teachey DT, Hunger SP. Predicting relapse risk in childhood acute lymphoblastic leukaemia. Br J Haematol. 2013 Sep;162(5):606-20.
https://onlinelibrary.wiley.com/doi/10.1111/bjh.12442
http://www.ncbi.nlm.nih.gov/pubmed/23808872?tool=bestpractice.com
[183]Kebriaei P, Poon LM. The role of allogeneic hematopoietic stem cell transplantation in the therapy of patients with acute lymphoblastic leukemia. Curr Hematol Malig Rep. 2012 Jun;7(2):144-52.
http://www.ncbi.nlm.nih.gov/pubmed/22410763?tool=bestpractice.com
[184]Cassaday RD, Alan Potts D Jr, Stevenson PA, et al. Evaluation of allogeneic transplantation in first or later minimal residual disease - negative remission following adult-inspired therapy for acute lymphoblastic leukemia. Leuk Lymphoma. 2016 Sep;57(9):2109-18.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010422
http://www.ncbi.nlm.nih.gov/pubmed/27002921?tool=bestpractice.com
Age: younger patients are more likely to attain a CR and have better survival.
Long duration of first CR: survival is better for those whose duration of first remission is more than 2 years.
Site of relapse: if there is involvement of additional sites.
Status of disease at SCT: patients who underwent SCT in CR after salvage did better than those who were not in CR at the time of SCT. Patients who achieve MRD-negative remission with salvage therapy prior to SCT may also have better outcomes, but this has not been definitively established in a prospective trial.