2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Fig. 1. Proposed algorithm to incorporate the use of hematopoietic cell transplantation in patients with indolent B-cell non-Hodgkin
lymphoma. ^ As the best treatment for relapsed indolent lymphoma remains unclear, these patients should be treated in the context of a clinical
trial if feasible. * If a patient has not responded to second-line chemotherapy or has significant disease burden, enrollment in a clinical trial
should be strongly considered before use of HCT. Either auto or allo HCT could then be considered to consolidate a response to this intervention.
Abbreviations: HCT, hematopoietic cell transplantation; CR1, first complete remission; HCT-CI, hematopoietic cell transplant-comorbidity
index; auto, autologous; allo, allogeneic; RI, reduced-intensity; MA, myeloablative; BSC, best supportive care; WIS, withdrawal of immunosuppression;
DLI, donor lymphocyte infusion.
reviewed in this article, though these relapses were often
salvageable with further immunomanipulation (see additional
details below). It is noteworthy that none of these
prospective studies showed that the presence of either acute
or chronic GVHD was associated with decreased relapse or
improved disease-free survival.
With these data suggesting that relapse rates are higher
in patients not in CR, investigators hypothesized that radioimmunotherapy
(RIT) as part of the preparative regimen
could deliver targeted radiation to tumor sites with minimal
nonhematologic toxicity to improve early post-transplant
disease control and potentially lead to improved PFS.
Bethge et al performed a phase II study of yttrium-90
conjugated to the anti-CD20 antibody ibritumomab tiuxetan
(90-YIT) plus RI allo HCT. 28 A total of 40 patients were
accrued (17 with FL, 1 with MZL, 1 with LPL, 13 with CLL,
and 8 with mantle cell lymphoma). All had received at least
two prior chemotherapy regimens, and 82% had active
disease at the time of HCT. This treatment approach yielded
2-year estimated EFS of 43% and OS of 51% for the entire
cohort. NRM at 2 years was relatively high compared with
other studies at 45%, which the authors attributed to a
relatively high-risk patient population and high frequency
(68%) receiving grafts from unrelated donors. Additionally, a
cohort of 40 patients with high-risk B-cell lymphomas was
treated at FHCRC with 90-YIT along with RI allo HCT, 45%
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of whom had indolent histologies. 29 For the indolent subset,
only 17% (3 patients) had chemotherapy-sensitive disease at
the time of HCT, but the 3-month response rate was still
83%, with over 75% alive and approximately 50% alive and
progression-free at 2.5 years. The cumulative incidence
estimate of NRM at 2.5 years was 16%, more in line with
other studies reported here. These studies suggest the
feasibility and potential efficacy of the use of RIT added to RI
preparative regimens for patients with indolent B-NHL not
in CR.
Management of Relapse after Allo HCT
Relapse of hematologic malignancies after allo HCT poses
a particularly daunting challenge, and indolent lymphomas
are no exception. Apart from additional chemoimmunotherapy
or radiation, manipulation of the allografted immune
system is an intervention unique to this particular
disease state. This can be attempted using withdrawal of
immunosuppression (WIS) or donor lymphocyte infusion
(DLI). Many of the studies mentioned above include a small
population of patients where such interventions were performed
with or without additional anticancer therapy, occasionally
with dramatic and durable responses. 21,26 DLI in
particular is advocated in patients who received alemtuzumab
as part of their transplant conditioning. A recent
publication from FHCRC specifically analyzed their experi-