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
Nov 02, 2014
What to do in minimal residual disease in acute lymphocytic leukemia?Maintenance TherapyDr. Raymond SM WongDepartment of Medicine & TherapeuticsPrince of Wales HospitalThe Chinese University of Hong Kong
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
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)
LALA-94 Comparisons of treatment
Thomas X, et al. JCO 2004, Khaled SK, et al. Curr Opin Oncol 2012
AlloSCT for high-risk ALL patients in CR1
Yanada M, et al. Cancer 2006
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
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
AlloSCT versus Maintenance Chemotherapy
• ALL CR1 studies
Lazarus HM, et al. Hematology 2012
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
PETHEMA ALL-93 trial: disease-free survival
Ribera et al, Haematologica 2005
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
MRC UKALLXII/ECOG E2993 Study
MRC UKALLXII/ECOG E2993 Study
Goldstone, et al. Blood 2008
MRC UKALLXII/ECOG E2993 Study
Goldstone, et al. Blood 2008; Khaled, et al. Curr Opin Oncol 2012
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
HOVON Studies: DFS
Comelisson et al, Blood 2009
HOVON Studies: OS
Comelisson et al, Blood 2009
HOVON Studies: Outcomes
Comelisson et al, Blood 2009
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
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
The EndThank you