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1632 Part XI: Malignant Lymphoid Diseases Chapter 98: Diffuse Large B-Cell Lymphoma and Related Diseases 1633

developed to minimize the toxicity associated with standard high-dose TABLE 98–5. International Prognostic Factor Index for
chemotherapy, achieve sufficient engraftment to prevent graft rejection 93
and exploit the graft-versus-tumor effect of allo-HSCT. In a prospec- Non-Hodgkin Lymphoma
tive study, 31 patients with DLBCL and one patient with Burkitt lym- Risk factors
phoma received allo-HSCT following 2 Gy total-body irradiation with Age older than 60 years
or without fludarabine. Twenty-four patients had undergone prior
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ASCT. With a median followup of 45 months, 3-year OS and PFS were Serum lactic dehydrogenase greater than twice normal
45 percent and 35 percent, respectively. Three-year cumulative inci- Performance status ≥2
dences of relapse and nonrelapse mortality were 41 percent and 25 Stage III or IV
percent, respectively. Cumulative incidences of acute graft-versus-host
disease (GVHD) grades II to IV, grades III and IV, and chronic GVHD Extranodal involvement at more than 1 site
were 53, 19, and 47 percent, respectively. In another study, 48 consec- Each factor accounts for 1 point, for a total score that ranges from 0 to
utive patients with relapsed or refractory DLBCL (30 patients with de 3 for patients younger than 61 years of age. The latter age-adjusted
novo disease and 18 patients with transformed follicular lymphoma) index includes all variables except for age and extranodal sites. For
90
underwent transplantation with an alemtuzumab-containing regimen. patients 61 years of age and older, a total score ranges from 0 to 5
The PFS and OS rates after 4 years were 48 and 47 percent, respectively. and includes each variable shown in this table.
Seventeen percent of patients developed grades II to IV acute GVHD,
and 13 percent experienced extensive chronic GVHD. Four-year esti-
mated nonrelapse mortality was 32 percent, and relapse risk was 33 used, except for age and presence of extranodal sites. The 5-year survival
percent. Although these results are promising, allo-HSCT cannot be rates for patients age 60 years or younger with IPI scores of 0, 1, 2, and
recommended before ASCT except in the context of a clinical trial. 3 were 83, 69, 46, and 32 percent, respectively (Table 98–6). To better
93
estimate prognosis among modern DLBCL patients, a revision of the IPI
Radioimmunotherapy was recently developed by the National Comprehensive Cancer Network
95
Radioimmunotherapy as monotherapy is not recommended for (the NCCN-IPI). This model employs the same five risk factors but uses
DLBCL but its role as part of a conditioning regimen prior to ASCT a different scoring algorithm, and improves discrimination of groups
has been encouraging. A phase II trial evaluated the safety and efficacy treated with rituximab-containing chemoimmunotherapy.
90
of combining Y-ibritumomab tiuxetan with high-dose carmustine,
cytarabine, etoposide, and melphalan (BEAM) and ASCT in patients
with lymphoma who were considered ineligible for total-body irradi- GENE-EXPRESSION PROFILING AND
90
ation because of older age or prior radiotherapy. The addition of Y- DETERMINATION OF DIFFUSE LARGE B-CELL
91
ibritumomab tiuxetan to BEAM with ASCT was feasible and the tox- LYMPHOMA SUBTYPES
icity and tolerability profile similar to that observed with BEAM alone.
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Similarly, I-tositumomab (up to 0.75 Gy) was combined with BEAM Gene-expression profiling has also been used to delineate groups of
followed by ASCT for the treatment of chemotherapy-resistant relapsed patients with DLBCL who may differ in their response to therapy and
or refractory lymphoma. Short-term and long-term toxicities were sim- prognosis (Fig. 98–2). 14–17,96,97 Six genes identified by gene-expression
ilar to that in patients previously treated with BEAM alone, with an OS analysis and detected by quantitative real-time polymerase chain reac-
98
rate of 55 percent and an EFS rate of 39 percent. 92 tion can identify three prognostic groups in patients with DLBCL. The
six genes that were used in this model occur in the germinal center B-cell
signature (LMO2, BCL6), activated B-cell signature (BCL2, CCND2,
Summary of Approach to Patients with Relapsed Disease SCYA3), and lymph node signature (FN1). In this study, expression of
Patients with relapsed disease should receive multidrug chemotherapy, LMO2, BCL6, and FN1 correlated with prolonged survival, whereas
such as R-ICE or R-DHAP. If chemosensitivity is demonstrated and no expression of BCL2, CCND2, and SCYA3 correlated with short survival.
contraindications are present, ASCT should be performed. If patients are Protein immunohistochemistry (IHC) has also been used to delineate
elderly or have comorbid conditions the goal should be palliation. Radio- DLBCL subtypes, but shows imperfect concordance with gene expres-
therapy can be used to alleviate symptoms at particular sites of involvement sion results. Even though various algorithms have been developed for
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in patients with relapsed DLBCL and single-agent therapy can be used but subtyping DLBCL by IHC, further refinement is needed prior to relying
with low expected response rates and duration of responses. on IHC for management decisions and prognostication.

COURSE AND PROGNOSIS SERUM LACTIC DEHYDROGENASE AND
β -MICROGLOBULIN
INTERNATIONAL PROGNOSTIC INDEX 2
2
In 1993, a model was proposed to assign a prognosis to patients Patients with an elevated β -microglobulin level and high serum LDH
have a poor prognosis, with a 26 percent survival compared to 81
with aggressive lymphoma undergoing treatment with doxorubicin- percent survival in patients without elevation of either of these markers. 93,99
containing chemotherapeutic regimens termed the international prog-
nostic index (IPI). 93,94 The model used clinical data, including (1) tumor
stage, (2) serum LDH level, (3) number of extranodal disease sites PRESENCE OF MYC GENE REARRANGEMENT
involved, (4) performance status, and (5) patient age. This model resulted
in the IPI, which is used to forecast the behavior of aggressive lymphoma OR ELEVATED PROTEIN EXPRESSION
(Table 98–5 and Fig. 98-1). For patients younger than age 60 years, an Approximately 10 percent of DLBCL patients harbor a translocation
age-adjusted IPI has been proposed in which all the factors of the IPI are involving the MYC gene. Patients with a MYC rearrangement detected

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