Acute Leukemias - Republican Scientific Medical Library

The Role of Autologous Stem Cell Transplantation
in the Management of Acute Lymphoblastic Leukemia
in Adults
Partow Kebriaei, Sergio Giralt
Contents
18.1 Introduction ................... 229
18.2 Outcome of Autologous SCT in Adult
ALL .......................... 230
18.3 Comparison of Autologous SCT with
Allogeneic SCT and Chemotherapy . . 230
18.4 Factors Influencing Transplant
Outcome ..................... 232
18.4.1 Source of Stem Cells ......... 232
18.4.2 Preparative Regimens ........ 232
18.4.3 Ex Vivo Purging ............ 233
18.5 Novel Transplant Approaches ...... 233
18.5.1 Maintenance Therapy Post-SCT . . 233
18.5.2 Targeted Therapies: Imatinib
Mesylate ................. 234
18.5.3 Immunotherapy ............ 234
18.6 Conclusion .................... 234
References ......................... 235
18.1 Introduction
Recent treatment strategies for adult acute lymphoblastic
leukemia (ALL) have resulted in improved complete
remission (CR) rates of 80–90% [1–3]. However, longterm
disease-free survival (DFS) rates have remained
disappointingly low at 30–40%. Current research efforts
are focused on an improved understanding of the biology
of the disease, and innovative postremission strategies
that will prolong disease-free duration. Stem cell
transplantation (SCT) is one strategy that may improve
disease outcome. Allogeneic SCT has been demonstrated
to improve DFS in high-risk ALL patients in
multiple large series. High risk is defined by specific biologic
and clinical features that have been noted to consistently
influence the outcome of adult ALL (Table
18.1). Age greater than 60 years, an elevated white
blood cell count at presentation, failure to achieve clinical
remission within the first 4 weeks of treatment, and
specific recurring cytogenetic abnormalities are all considered
adverse clinical features. In a multivariate analysis
of risk factors in adult ALL, karyotype was identified
as the most important factor for DFS [4]. In general,
patients with a normal karyotype have improved survival
compared to those harboring a cytogenetic abnormality.
In one series, six abnormalities were noted
to result in unfavorable outcome, defined as having a
0.25 or less probability of continuous CR at 5 years.
These include, in decreasing frequency, patients with
t(9;22)(q34;q11), trisomy 8, t(4;11)(q21;q23), monosomy
7, a hypodiploid karyotype, and t(1;19)(q23;p13) [4–6].
However, in contrast to allogeneic SCT, most prospective,
randomized studies of chemotherapy compared
with autologous and allogeneic SCT have not
Table 18.1. Adverse prognostic features in Adult ALL
Age >60 yrs
WBC count >30000/lL
Cytogenetics: t(9;22)(q34;q11), trisomy 8, t(4;11)(q21;q23),
monosomy 7, a hypodiploid karyotype, t(1;19)(q23;p13)
Delayed time to CR >4 week