Canterbury DHB

Overview

• Acute lymphoblastic leukaemia (ALL) has a poor prognosis with less than one third of <60 yrs and <10% of >60 yrs having curable disease. Over 80% achieve a remission but most relapse. Recently, more data have become available to define the role of allogeneic transplant and use of tyrosine kinase inhibitors. For a seminar about ALL, see Malard, F. and M. Mohty (2020). "Acute lymphoblastic leukaemia." Lancet 395(10230): 1146-1162.
• Intensive treatment followed by consolidation and maintenance therapy, the latter for up to 2-3 years, has until recently been the standard management for all adult ALL. Results of such treatment are excellent in childhood, but much less satisfactory in adults. Young adults with ALL do better if they are given paediatric protocols. See Curran, E. and Stock, W. (2015). "How I treat acute lymphoblastic leukemia in older adolescents and young adults." Blood 125: 3702-10. In adults, allogeneic hematopoietic stem cell transplantation has occupied an increasing therapeutic role. See Ribera, J.-M., et al (2021). "Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia." Blood 137(14): 1879-1894.
• Philadelphia chromosome positive ALL (Ph+ ALL), rare in children, occurs in 20-25% of adult patients and carries a very poor outlook. Allogeneic transplantation is recommended for patients with a suitable donor. Data from recent trials indicate that imatinib or dasatinib improves the short-term prognosis for these patients, allowing more patients to receive an allogeneic transplant. See Ravandi, F. (2019). "How I treat Philadelphia chromosome–positive acute lymphoblastic leukemia." Blood 133(2): 130.
• Philadelphia chromosome – like ALL is a newly identified high risk B lineage ALL subtype which account for 15% of children and even more young adults with ALL. It is defined by gene expression and the outlook for these patients is improved with the addition of kinase inhibitors. In Christchurch we are currently unable to identify these patients. See Tran, T.H. and M.L. Loh (2016). "Ph-like acute lymphoblastic leukemia." Hematology Am Soc Hematol Educ Program 2016(1): 561-566.
• CNS involvement is common in ALL if no measures are taken to prevent it. It can be present at diagnosis.
• Patients should be entered into clinical trials where possible. See the Clinical Trials page on the Intranet.
• Identification of minimal residual disease by molecular or immunophenotyping techniques, and stratifying treatment by results, has become standard in managing childhood ALL, but is not yet part of routine care of adults with ALL in Christchurch. See Vora, A., Goulden, N. (2014). "Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial." The Lancet Oncology 15: 809-18.
• There has been great interest in treating acute lymphoblastic leukamia with new or additional drugs such as Rituximab in pre B ALL, and in the case of relapsed or refractory ALL, with bispecific T cell engaging antibodies and chimeric antigen receptor T cells (CAR-T cells). Whereas rituximab is now funded as part of treatment of pre-B ALL, non of the other approaches is funded routinely in NZ. See the following for information:
  • Maury, S., et al. (2016). "Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia." New England Journal of Medicine 375(11): 1044-1053.
  • Gökbuget, N., et al (2018). "Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia." Blood 131(14): 1522-1531.
  • Park, J. H., et al. (2018). "Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia." New England Journal of Medicine 378(5): 449-459.
• For a review of managing adult patients with ALL, see:
  • Ravandi, F. (2019). "How I treat Philadelphia chromosome–positive acute lymphoblastic leukemia." Blood 133(2): 130.
  • Luger, S.M. (2015). "How I treat adults with relapsed or refractory Philadelphia chromosome–negative acute lymphoblastic leukemia." Blood 126: 589-96.
  • O'Dwyer, K. M. (2020). "The challenge to further improvements in survival of patients with T-ALL: Current treatments and new insights from disease pathogenesis." Semin Hematol 57(3): 149-156.
  • Gökbuget, N. (2016). "Treatment of older patients with acute lymphoblastic leukemia." ASH Education Program Book 2016: 573-9.

Topic Code: 8836