MINIMAL RESIDUAL DISEASE IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

MICHAEL J BOROWITZ MD PhD PROFESSOR OF PATHOLOGY JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE

Improved Survival in Childhood ALL by Study Era 100

1996-2000 (n=3421) 1989-1995 (n=5121)

80

1983-1988 (n=3711) 60

1978-1983 (n=2984) 1975-1977 (n=1313)

40

1972-1975 (n=936) 1970-1972 (n=499)

20

1968-1970 (n=402)

0 0

2

4

6

8

Years From Study Entry

10

12

PROGNOSTIC FACTORS IN CHILDHOOD ALL • NCI Risk Group – Standard Risk: 19 y, WBC < 50K – High Risk: 10 y or WBC> 50K – Infants are poor risk; often considered separately

• Cytogenetics

• •

– BCR-ABL – TEL-AML1 – hyperdiploidy – MLL CNS or testicular disease Initial response to therapy

Rate of Initial Response is Strong Predictor of Event-Free-Survival .01% is sufficiently poor to warrant intervention Day 8 MRD will also be employed in risk stratification “Best of the best” group: NCI SR with favorable genetics, and absence of both d8 and d29 MRD (98% 4y EFS) will not be assigned to treatment protocol and treated off study with low intensity therapy Day 8/15 bone marrows for morphology will be dropped

CONCLUSIONS I

• Minimal residual disease in ALL can be • •

detected by flow cytometry or molecular methods. Flow methods are somewhat less sensitive than optimal molecular methods but are faster and cheaper End-induction MRD is the most important prognostic factor in multivariate analysis

CONCLUSIONS II

• MRD measured during induction therapy also

•

stratifies patients into good, intermediate and poor risk groups that could potentially allow for even earlier therapy. Optimal risk assignment requires more than a single MRD measurement and can include some combinations of other factors and/or MRD at additional timepoints

ACKNOWLEDGEMENTS • Cheryl Willman • David Viswanatha • Drew Carroll • Ed Weir

• • • •

Karen Bowles Shirley Fuller Kathy Cowan Emily Bright

• Brent Wood

• Jon Shuster • Mini Devidas • Steve Linda • • • • • •

Bruce Camitta Jeanette Pullen Paul Bowman Bill Carroll Steve Hunger Naomi Winick

NIH R01 CA86011 R21 CA110344 U10 CA98543