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

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. 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. 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. LALA-94 Comparisons of treatment
Thomas X, et al. JCO 2004, Khaled SK, et al. Curr Opin Oncol 2012

5. AlloSCT for high-risk ALL patients in CR1
Yanada M, et al. Cancer 2006

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. 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

9. AlloSCT versus Maintenance Chemotherapy
• ALL CR1 studies
Lazarus HM, et al. Hematology 2012

10. 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

11. PETHEMA ALL-93 trial: disease-free survival
Ribera et al, Haematologica 2005

12. 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

13. MRC UKALLXII/ECOG E2993 Study

14. MRC UKALLXII/ECOG E2993 Study
Goldstone, et al. Blood 2008

15. MRC UKALLXII/ECOG E2993 Study
Goldstone, et al. Blood 2008; Khaled, et al. Curr Opin Oncol 2012

16. 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

17. HOVON Studies: DFS
Comelisson et al, Blood 2009

18. HOVON Studies: OS
Comelisson et al, Blood 2009

19. HOVON Studies: Outcomes
Comelisson et al, Blood 2009

20. 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

21. 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

22. The End
Thank you