acute lymphocytic leukemia
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Transcript of acute lymphocytic leukemia
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