acute lymphocytic leukemia


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What to do in minimal residual disease in acute lymphocytic leukemia?
Maintenance Therapy: Raymond Wong, MD
Transplant: Pankaj Malhotra, MD

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acute lymphocytic leukemia

  1. 1. What to do in minimal residual disease in acute lymphocytic leukemia? Maintenance Therapy Dr. Raymond SM Wong Department of Medicine & Therapeutics Prince of Wales Hospital The Chinese University of Hong Kong
  2. 2. Acute lymphoblastic leukemia (ALL) • ALL is a heterogeneous disease affected by many patient- and disease-related factors, including age, immunologic subtype, and clinical, genetic, and molecular features Lazarus HM, Advani AS, Hematology 2012
  3. 3. Acute lymphoblastic leukemia (ALL) • Most children, adolescents and young adults with acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) have an excellent prognosis with multi-agent chemotherapy in induction, consolidation, re-induction and maintenance therapy • There is a subset of patients with a more guarded prognosis using this approach, who may benefit from haematopoietic allogeneic stem cell transplantation (alloHSCT)
  4. 4. LALA-94 Comparisons of treatment Thomas X, et al. JCO 2004, Khaled SK, et al. Curr Opin Oncol 2012
  5. 5. AlloSCT for high-risk ALL patients in CR1 Yanada M, et al. Cancer 2006
  6. 6. Allogeneic stem cell transplantation (AlloHSCT) • AlloHSCT is the treatment of choice for patients with ALL after first relapse, and is also recommended for high-risk patients in first complete remission (CR1). • There is no consensus on early transplant for standard risk patients • The curative potential of alloHSCT must be balanced against the disadvantages (mortality of 20% to 30%, morbidity, late complications, reduced quality of life) and assessed in relation to the improved outcome by chemotherapy regimens
  7. 7. Minimal residual disease (MRD) and ALL • MRD evaluation and monitoring is developing as an important prognostic factor • May be used to improve risk stratification and to determine which patients, especially those with standard risk, might require alloHSCT • MRD assessment may not be routinely available in all centers Brüggemann M, et al. Blood 2006
  8. 8. AlloSCT versus Maintenance Chemotherapy • ALL CR1 studies Lazarus HM, et al. Hematology 2012
  9. 9. PETHEMA ALL-93 trial • A total of 222 valid high-risk ALL patients recruited • Patients in complete remission after induction chemotherapy (CR1) were assigned to alloHSCT (n = 84) if they had an HLA-identical family donor • The remaining were randomized to • autologous SCT (n=50) or • delayed intensification followed by maintenance chemotherapy up to 2 years in complete remission (n=48) Ribera et al, Haematologica 2005
  10. 10. PETHEMA ALL-93 trial: disease-free survival Ribera et al, Haematologica 2005
  11. 11. MRC UKALLXII/ECOG E2993 Study • ALL in CR1 • N = 1031 • Age: 15 – 64 years • AlloHSCT: 15-59 years • 443 patients with donor • 588 patients had no donor Goldstone, et al. Blood 2008
  12. 12. MRC UKALLXII/ECOG E2993 Study
  13. 13. MRC UKALLXII/ECOG E2993 Study Goldstone, et al. Blood 2008
  14. 14. MRC UKALLXII/ECOG E2993 Study Goldstone, et al. Blood 2008; Khaled, et al. Curr Opin Oncol 2012
  15. 15. HOVON Studies • Newly diagnosed patients with precursor B-cell or precursor T-cell ALL included in the HOVON-18 ALL (HO18) and HOVON-37 ALL (HO37) studies between November 1992 and November 2005 • myeloablative alloHSCT in CR1 patients aged 15-55 years • N = 257 • Donor = 96 • No donor = 161 Comelisson et al, Blood 2009
  16. 16. HOVON Studies: DFS Comelisson et al, Blood 2009
  17. 17. HOVON Studies: OS Comelisson et al, Blood 2009
  18. 18. HOVON Studies: Outcomes Comelisson et al, Blood 2009
  19. 19. Findings of recent studies • Survival benefits appears to be greater for patients with standard-risk rather than high-risk ALL patients. • In the older randomized trials and a meta-analysis, high-risk rather than standard-risk patients benefited from alloHSCT • Age as a high-risk feature accounts for much of the data showing that the standard-risk group benefited the most • Likely reflects the increased treatment-related mortality (TRM) in the high-risk group that negated the GVL effect in these patients • Inclusion of the younger patients in the recent randomized trials, may have biased the results in favor of alloHSCT
  20. 20. Summary • ALL is a heterogenous disease and management should be tailored for each patient • The benefits of alloSCT in high risk patients appeared conflicting in various studies • The risk in transplant related mortality needs to be carefully balanced against the disease free survival benefit • There is a dilemma when a patient has standard risk for relapse especially when MRD assessment is not available • Maintenance chemotherapy is still an options in patients with ALL in CR1
  21. 21. The End Thank you