Cytotherapy (2002) Vol. 4, No. 3, 205–215
205
© 2002 ISCT
Autologous hematopoietic transplantation
for low-grade lymphomas
JG Gribben
Department of Adult Oncology, Dana-Farber Cancer Institute, Department of Medicine,
Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Correspondence to: John G Gribben, Department of Adult Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham
and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Background
Autologous stem cell transplantation (SCT) has become the treatment of
choice for patients with relapsed chemo-sensitive intermediate grade
lymphoma, but its role in the treatment of low-grade lymphomas and in
selected patients in first remission remains controversial.
Methods
A large number of clinical trials have evaluated the role autologous
SCT in both low grade and intermediate grade non-Hodgkin’s
lymphomas (NHL). These studies have attempted to evaluate the role of
high dose therapy with stem cell support in comparison to more conven-
tional chemotherapy approaches. Studies have also focused on methods
to assess whether contaminating tumor cells are contained with the stem
cell collection and whether this has impact on outcome. With an
increased number of patients now long term survivors, additional
studies are focusing on long term complications and in particular the
emergence of secondary malignancies.
Results
Virtually all patients now receive peripheral blood stem cells rather
than bone marrow as a source of stem cells. The role of purging of
residual tumor cells remains controversial and no randomized trial
has been published to date that could evaluate the clinical utility of
cell manipulation to attempt to remove contaminating lymphoma
cells. Secondary leukemia is emerging as a major source of
long-term morbidity and mortality after autologous stem cell
transplantation.
Conclusion
Autologous SCT is associated with improved outcome in patients with
relapsed intermediate grade lymphoma and most likely prolongs disease
free survival in patients with low grade NHL. Morbidity and mortality
of the procedure is low and major efforts are being made to attempt to
decrease the major causes of failure, which remain disease relapse and
occurrence of secondary malignancies.
Keywords
Low-grade non-Hodgkin’s lymphoma, CLL, mantle-cell lymphoma,
stem-cell transplantation.
Role of SCT in low-grade lymphoid
malignancies
Although high-dose therapy (HDT) with stem-cell support
has become the treatment of choice for patients with
relapsed intermediate-grade lymphoma [1], the role of
stem- cell therapy (SCT) in the management of patients
with low-grade NHL remains more controversial. As shown
in Table 1, there are many reasons why SCT has been used
less frequently in patients with low-grade lymphoma. There
has been reluctance to perform potentially lethal treatment
procedures in diseases with relatively long natural histories,
which tend to occur in more elderly patients. The very high
incidence of BM infiltration in these diseases has made it
difficult to use autologous stem-cells for rescue after HDT.
Lastly, although the indolent lymphomas are characterized
by initial chemotherapy responsiveness, by the time SCT is
considered as a treatment option, many of these patients are
heavily pre-treated and have acquired chemotherapy resis-
tance and decreased BM reserve. However, the risk of
unacceptable mortality is decreased by judicious patient
selection and improvements in supportive care in transplan-
tation, and increasing numbers of patients with advanced
stage follicular lymphoma (FL), mantle-cell lymphoma
(MCL) and CLL are now undergoing these procedures.
Martin Dunitz
Taylor&Francis
healthsciences