SAN DIEGO--With the incidence of non-Hodgkins lymphoma (NHL)
increasing throughout the United States, researchers have been
searching for better ways to decrease the mortality rate of this
cancer, which claims approximately 23,800 Americans each year.
Trials involving high-dose therapy and autologous stem cell
transplant (HDT/ASCT) have shown promising results in these patients,
said Arturo Molina, MD, of the City of Hope National Medical Center,
"The results of most studies of high-dose therapy and stem cell
transplantation in poor-risk NHL in first complete remission have
been very encouraging, particularly in patients with
high-intermediate and high-risk diffuse aggressive NHL," Dr.
Molina said at the Sixth In-ternational Symposium on Recent Ad-vances
in Hematopoietic Stem Cell Transplantation, sponsored by the
University of California, San Diego.
The results of single-institution studies have produced excellent
overall and event-free survival rates, ranging from 60% to more than
80% in first-remission patients with poor-risk features, he said. In
contrast, survival for conventional anthracycline-containing regimens
for the same type of patients is less than 50%.
So far, these results have come from several small pilot trials of
HDT/ASCT in patients who have achieved complete remission.
Dr. Molina said that the International Prognostic Index (IPI) and the
age-adjusted IPI can be used to identify patients with poor-prognosis
aggressive lymphoma. This bad prognosis is due to an increased risk
of death from both a lower complete response rate and a higher risk
of relapse after a complete response.
Unfortunately, Dr. Molina said, most of the handful of randomized
trials that have compared conventional chemotherapy with up-front
HDT/transplant have not selected patients based on these
poor-prognostic factors. Groups that have been pursuing research in
this field include the Groupe dEtude Lymphomes de lAdulte
(GELA) in France and researchers at Dr. Molinas own
institution, the City of Hope.
The City of Hope recently reported the results of HDT/ASCT in 42
poor-risk patients with intermediate- and high-grade NHL in complete
remission, who were classified into the IPI high and
high-intermediate risk groups. Another 10 patients with poor-risk
small noncleaved cell lymphoma also participated.
In the subset of patients with intermediate-grade and immunoblastic
lymph-oma, the 3-year disease-free survival rates were 89% for all
patients, 87% for high-risk patients, and 92% for high-intermediate
risk patients. Based on these results, Dr. Molina said, "we are
participating in a randomized cooperative group study, sponsored by
the Southwest Oncology Group (SWOG), that will compare standard CHOP
chemotherapy with the early use of HDT/ASCT as initial therapy for
diffuse aggressive lymphoma."
Dr. Molina also discussed another important study in Europe that
focused on relapsed non-Hodgkins lymphoma patients. The
multicenter prospective PARMA trial showed a quite dramatic outcome
difference between patients treated with a conventional salvage
regimen vs HDT with autologous bone marrow transplant (BMT).
The 215 study patients had intermediate- or high-grade NHL and were
in relapse after an initial remission with a doxorubicin-containing
regimen. Patients who responded to two cycles of DHAP (dexamethasone,
cytarabine, cisplatin) chemotherapy were then randomized into two
groups. One received four more cycles of DHAP, while the other
patients underwent high-dose therapy using the BEAC regimen (BCNU,
cytarabine, cyclophosphamide) with transplantation using unpurged
With a median follow-up of 63 months, event-free survival and overall
survival were 46% and 53%, respectively, among patients receiving
HDT/BMT, compared with just 12% and 32%, respectively, in the DHAP
This represented the first randomized trial in which high-dose
therapy was shown to improve disease-free and overall survival,
compared with a conventional salvage regimen, Dr. Molina said.
Mantle Cell Lymphoma
Not all the studies, however, have clearly favored transplantation
and high-dose therapy. For instance, most of the phase II studies
using HDT/ASCT in mantle cell lymphoma have produced inconclusive or
One such study of 13 patients--9 were in either first complete
remission or partial remission--has had a median follow-up of just 18
months. During that time, 10 patients were disease free.
The City of Hopes experience with the same type of patients has
been similar, but longer follow-up is necessary to determine if there
is a plateau in the disease-free-survival curve.
At the Dana-Farber Cancer Institute, a retrospective review of
results of high-dose therapy with antibody-purged autologous BMT in
28 patients with mantle cell lymphoma found no evidence of long-term
Small Noncleaved Cell Lymphomas
There also are few data on using transplants and high-dose therapy in
patients with small noncleaved cell lymphomas. Because small
noncleaved cell lymphomas and lymphoblastic lymphomas are rare in
adults, Dr. Molina said that it will be very difficult to develop
randomized studies to address unresolved treatment issues in these
In general, he recommends that high-dose therapy and stem cell
transplantation--autologous or allogeneic--be offered to patients in
their first complete response if they exhibit poor-prognostic
features that put them at a high risk of relapse after treatment with