By Michael Williams, MD
2008-01-01
Dr. Williams indicated no relevant conflicts of interest.
Montoto S, Canals C, Rohatiner
AZ, et al. Long-term follow-up of
high-dose treatment with autologous haematopoietic progenitor cell support in
693 patients with follicular lymphoma: an EBMT registry study. Leukemia. 2007;
21:2324-31.
Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma responsive to a
variety of chemoimmunotherapeutic approaches. However, the lack of cure with
these treatments has led to a number of clinical trials over the past 20 years
investigating the role of high-dose therapy (HDT) and autologous stem cell
transplantation (ASCT) in first or subsequent remission, with no consensus
benefit for overall survival (OS) and with concerns regarding early and late
toxicities. Montoto and colleagues report a retrospective analysis and
long-term follow-up of 693 patients with FL from the European Blood and Marrow
Transplantation Registry who received HDT-ASCT in first remission or after
relapse and subsequent treatment. As a registry-based analysis, induction
treatments and the type of HDT conditioning regimens varied. Fifty-eight
percent received total-body irradiation (TBI) as part of HDT, 81 percent of
patients were treated after 1990, and all patients in the analysis had at least
five years of follow-up; 30 percent of patients had received only a single line
of treatment prior to HDT-ASCT, and 19 percent were in first complete remission
(CR1). Half of the patients relapsed following HDT-ASCT at a median of 1.5
years, with lower relapse rates among those patients who received TBI
conditioning regimens (53 percent vs. 43 percent; p=.05). Progression-free
survival (PFS) and OS were improved for patients transplanted in CR1 (Figures
1a and 1b). Ninety-three patients (13 percent) died within one year of HDT from
a cause other than lymphoma, most due to infection, and 40 (6 percent) died of
a non-lymphoma cause more than one year post-HDT, most due to second
malignancy. The latter was significantly more common in TBI-treated patients
and contributed to an inferior long-term survival for TBI versus non-TBI
conditioning regimens despite the lower relapse rates.
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These results support previous findings that HDT-ASCT may
result in durable remission and possible cure for a subset of patients with FL.
Patients who received a transplant in CR1, and those who had received fewer
lines of pre-transplant chemotherapy or were younger than 45 at transplant, had
improved outcomes. The analysis also verifies excess late mortality due to
second malignancies including MDS/AML, primarily in those treated with TBI; as
such, TBI should no longer be utilized in conditioning regimens and has been
largely abandoned. Although this is the largest series to date evaluating
HDT-ASCT in FL and having the benefit of very long follow-up, caveats include
the retrospective and non-randomized nature of this study, the lack of central pathology
review, and the varying induction and conditioning regimens utilized. Previous
prospective randomized clinical trials of HDT-ASCT for FL in CR1 failed to show
a benefit in OS and also showed excess late, second malignancies.1
However, these prospective trials and the current retrospective analysis only
included patients treated in the pre-chemoimmunotherapy era. Further
prospective clinical trials will be necessary to assess whether HDT-ASCT will
evolve to become a reliably curative approach via induction chemoimmunotherapy
and "in vivo purging" with
monoclonal antibody therapy prior to stem cell collection, or will become
extinct if comparably long PFS and OS is achievable with more effective and
less toxic induction therapies, consolidative immunotherapy with monoclonal
antibodies or idiotype vaccines, or the availability of more effective regimens
for patients who relapse.
- Bowles K, Hodson D, Marcus R.
Follicular lymphoma. Lymphoma: Pathology, Diagnosis and Treatment, R Marcus et
al., Eds. pp 119-122. Cambridge
Univ. Press, 2007.
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