Acute Leukemias - Republican Scientific Medical Library

Minimal Residual Disease Studies
in Acute Lymphoblastic Leukemia
Syed Abutalib, Wendy Stock
Contents
20.1 Introduction ................... 247
20.2 Methods for Detection of MRD ..... 249
20.2.1 Flow Cytometric Detection of MRD 249
20.2.2 PCR-based MRD Detection ..... 250
20.3 MRD Monitoring in Clinical Trials
of ALL ....................... 251
20.3.1 MRD Studies in Pediatric ALL . . . 251
20.3.2 MRD Studies in Adult ALL .....
20.3.3 MRD Monitoring in Selected Dis-
254
ease Subsets: t(4;11) and t(9;22) .
20.3.4 Prognostic Significance of MRD
in Patients Undergoing Stem Cell
255
Transplantation .............
20.3.5 The Future: Risk-Adapted Therapy
256
Based on MRD ............. 257
20.4 Summary ..................... 257
References ......................... 259
20.1 Introduction
Considerable progress has been made in the treatment
of both childhood and adult acute lymphoblastic leukemia
(ALL) during the past two decades. The majority of
both children and adults achieve a complete remission
(CR) while the majority of children are now cured with
current therapies, most adults will ultimately experience
a relapse and die of their leukemia. The ability to distinguish
good-risk patients who are likely to be cured with
conventional chemotherapy from those who are likely
to relapse has important clinical implications.
In both adult and pediatric ALL, relapse is thought
to result from residual leukemia cells (as many as
10 10 ) that remain following achievement of morphologic
remission and are below the limits of detection using
conventional microscopic and cytogenetic assessment
of the bone marrow [1–3]. A variety of sensitive techniques
have been used to monitor the persistence of
the leukemic clone during treatment in an attempt to
identify patients who are in morphologic and cytogenetic
remission, but in whom there is persistence of
subclinical, or minimal residual disease (MRD), and
who may be at increased risk for relapse.
Moreover, MRD studies in ALL have the potential to
provide novel insights into the clinical efficacy of both
standard and novel treatment strategies aimed at improving
the cure rate. Recent prospective studies designed
to validate the clinical significance of MRD detection
in ALL are beginning to answer several important
questions:
1. Does detection of MRD following achievement of
clinical remission predict treatment outcome?
2. If early MRD measurements are predictive of relapse,
can MRD detection be used to guide therapy
(i.e., can therapy be intensified or reduced based on
MRD results)?
3. What is the optimal clinical time-point(s) for MRD
assessment?
4. Does clinical intervention based on MRD result improve
survival?
5. Is it essential to eradicate MRD (as detected by these
highly sensitive assays) in order to achieve a cure?
6. Can peripheral blood monitoring be substitute for
bone marrow MRD evaluation?