2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

ROLE OF HCT FOR INDOLENT LYMPHOMA
ence with managing lymphoma relapsing after allo HCT,
revealing that those with indolent histologies had significantly
less mortality compared to aggressive NHL in a
multivariate model (p � 0.008). 30 This analysis also demonstrated
potential benefit of WIS and DLI. In the absence of
significant GVHD, WIS and/or DLI should be considered in
patients with indolent lymphoma who have relapsed after
allo HCT and desire further treatment of their disease.
Special Circumstance: Histologic Transformation
One of the most challenging aspects of managing indolent
lymphoma is the occurrence of histologic transformation
(HT) to an aggressive large-cell lymphoma. The general
treatment approach is similar to that for diffuse large B-cell
lymphoma (DLBCL), with one notable exception. Since HT
is thought to have a worse prognosis than de novo DLBCL,
the NCCN guidelines recommend considering consolidation
with either auto or allo HCT in first remission (either
complete or partial). 11 This may be particularly true for
patients who are unable to receive anthracycline-based
therapy. Few of the studies mentioned above included patients
with HT, as this manifestation takes on the characteristics
of an intermediate- or high-grade lymphoma. A
recent prospective study in Norway evaluated 47 patients
with indolent B-NHL that had relapsed with HT following
chemotherapy. 31 All patients treated in this trial received
salvage chemotherapy with a plan to consolidate responders
with auto HCT; however, only 30 met this criterion and
received sufficient treatment to be included in the analysis.
Among these transplanted patients, the 5-year PFS and OS
rates were 32% and 47%, respectively, with a plateau in the
PFS curve at 30% beyond 3.5 years. It is noteworthy that, in
the 17 patients from the initial cohort who did not undergo
auto HCT, there were three patients (18%)—referred to by
the doctors as “long-term survivors”—who received salvage
chemotherapy and/or radiation alone. The adverse prognosis
of HT before RI allo HCT was evaluated by Rezvani et al,
noting that the risk of relapse was nearly 5 times higher for
HT than for those with nontransformed relapsed/refractory
indolent lymphoma (p � 0.001). 22 Moreover, OS at 3 years
Authors’ Disclosures of Potential Conflicts of Interest
Employment or
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Advisory Role
for relapsed/refractory indolent disease was 52% compared
with 18% for HT (p � 0.02). Although these data underscore
the poor prognosis following HT, long-term remissions are
possible in a subset of patients if aggressive therapy can be
tolerated.
Conclusion
Although the long-term prognosis of indolent lymphomas
has improved with standard chemoimmunotherapy approaches
alone, HCT does offer the potential for durable
remissions for a subset of patients who are eligible for such
treatment. Figure 1 shows a proposed algorithm for the
application of HCT in the management of these diseases,
conceding that rigorous prospective trials are not readily
available for all decision points. It is important to remember
that both auto and allo HCT require a large amount of
preparation (both for the provider and for the patient), so
their application should be considered early in the course of
treating patients with indolent lymphoma.
In summary, auto HCT for chemotherapy-sensitive relapse
can provide improved outcomes, though concerns regarding
secondary malignancies remain. The development
of RI allo HCT has allowed the benefits of GVL and a
potential cure to be offered to patients that would have been
deemed too unfit for traditional MA conditioning. However,
despite this advance, GVHD remains a significant cause of
morbidity and mortality. Challenges also remain in improving
disease control for those with chemotherapy-resistant or
transformed disease as well placing HCT in the context of
ever-expanding nontransplant options for patients with indolent
B-NHL. Despite these hurdles, both auto and allo
HCT remain viable, effective options for many patients with
indolent lymphoma.
Acknowledgment
Dr. Cassaday is supported by the National Institutes of
Health T32 training grant number T32CA009515–27. Dr. Gopal
is supported by the following: P01 CA044991, Leukemia &
Lymphoma Society SCOR grant 7040, and a gift from Frank and
Betty Vandermeer. Dr. Gopal is a Scholar in Clinical Research
of the Leukemia & Lymphoma Society.
Stock
Ownership Honoraria
Author
Ryan D. Cassaday*
Ajay K. Gopal Seattle Genetics Millennium;
Seattle Genetics
*No relevant relationships to disclose.
1. Swerdlow SH, Campo E, Harris NL, et al (eds). WHO Classification of
Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France; International
Agency for Research on Cancer: 2008.
2. Khouri IF, Keating M, Korbling M, et al. Transplant-lite: Induction of
graft-versus-malignancy using fludarabine-based nonablative chemotherapy
and allogeneic blood progenitor-cell transplantation as treatment for lymphoid
malignancies. J Clin Oncol. 1998;16:2817-2824.
REFERENCES
Research
Funding
Abbott
Laboratories;
Biomarin;
Cephalon;
GlaxoSmithKline;
Merck; Pfizer;
Piramal; Seattle
Genetics;
Spectrum
Pharmaceuticals
Expert
Testimony
Other
Remuneration
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