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1674 Part XI: Malignant Lymphoid Diseases Chapter 102: Burkitt Lymphoma 1675

THERAPY Rasburicase acts more quickly than allopurinol and should be used if
risk is considered high or if evidence of spontaneous tumor lysis is pres-
GENERAL CONSIDERATIONS ent initially. 51,52 Continuous venovenous hemofiltration has also been
BL is a highly aggressive tumor; however, therapy with multiagent very useful in allowing concomitant full-dose chemotherapy and pre-
venting tumor lysis and renal failure.
53,54
chemotherapeutic programs results in excellent long-term remission
rates and long-term survival of up to 85 percent of children. Applying
the same chemotherapy regimens to adults has shown dramatically
improved response rates. 45–47 Risk stratification allows patients with SPECIFIC REGIMENS
limited disease to be treated with less-intensive therapy than more The specific regimens that have been developed to treat BL have his-
advanced cases and still achieve very high responses, although the vast torically been adapted from pediatric experience; Table 102–2 depicts
majority of patients present with advanced disease. Patients with exten- representative trial results, including adult patients. There are no studies
sive disease can achieve 80 percent long-term survival. The regimens directly comparing these regimens, and comparison among the sin-
employ multiple non–cross-resistant drugs used over a short period. gle-arm studies is difficult because of lack of uniform diagnostic criteria,
These drugs include high-dose cyclophosphamide, methotrexate, vin- staging, and the heterogeneous patient populations studied. In general,
cristine, prednisone, high-dose methotrexate, high-dose cytarabine, shorter durations of chemotherapy (i.e., 6 months) are as good as longer
etoposide, and sometimes ifosfamide. CNS prophylaxis therapy, either (18 months) periods of treatment. Other studies have shown a dramat-
intrathecal or systemic, is given in almost all patients with BL. Radiation ically improved response with use of four cycles of chemotherapy as
therapy does not play a role in the treatment of BL, and use of radiation opposed to 15 cycles. BL has a high proliferative rate, so subsequent
therapy for limited-stage diseases is of no additional benefit. 48,49 chemotherapy cycles should be started as soon as hematologic recovery
occurs. Waiting for a fixed period between cycles may lead to regrowth
of resistant tumor cells between cycles.
TUMOR LYSIS SYNDROME Cyclophosphamide, doxorubicin, vincristine, methotrexate, ifosfa-
The tumor lysis syndrome is a serious metabolic complication of rap- mide, etoposide, and high-dose cytarabine, with intrathecal cytarabine
idly growing tumors, of which BL is a classic example. The syndrome and methotrexate (CODOX-M/IVAC) is among the most commonly
is the result of the rapid destruction of tumor cells, highly sensitive to used regimens in the United States for adults with BL, based upon an
chemotherapy, and can result in hyperuricemia, hyperkalemia, hyper- initial favorable publication from the National Cancer Institute (NCI)
phosphatemia, secondary hypocalcemia, metabolic acidosis, and renal indicating extremely high response rates. Two subsequent, small,
45
failure. In tumors such as BL the cell death rate (and proliferative rate) phase II trials have used this regimen with minor modifications, and
may be so substantial in patients with bulky disease that the tumor have successfully enrolled greater numbers of older patients, demon-
lysis syndrome may occur before therapy, so-called spontaneous tumor strating cure rates of approximately 64 percent. 55,56 These cure rates
lysis. Spontaneous tumor lysis is a highly morbid phenomenon with are substantially less than the initial report, but still better than his-
49
50
a poor prognosis for a salutary outcome from therapy and a compli- torical data with standard-dose regimens. A modification of this regi-
cation with a high death rate. It occurs in patients with a high body men in patients with aggressive lymphomas and high proliferative rate
burden of tumor, usually with abdominal disease, a common situation as measured by Ki-67 fraction has been proposed. BL was strictly
57
in BL. Its principal manifestation is the combination of hyperuricemia defined as the following: germinal center phenotype, BCL2-negative,
and azotemia. In BL a critical part of therapy is recognizing incipient or MYC-rearrangement–positive, and absence of the t(14;18) or abnor-
overt spontaneous tumor lysis rapidly or preventing chemotherapy-in- malities at chromosome 3q27. Overall survival of the subgroup defined
duced tumor lysis. LDH has been used as a surrogate marker for risk of as BL was 67 percent in this group of older patients. Treatment-related
tumor lysis with a serum level twice the upper limit of normal for the mortality was 8 percent. Outcomes were similar among all age groups
laboratory in question being the threshold for urgent concern. The usual with the exception of patients older than age 65 years who clearly had
prophylactic therapy for this situation is carefully monitored hydration an inferior prognosis. These results likely reflect the true outcome of
of at least 3 L of saline per day and either allopurinol or rasburicase to this regimen in practice. Several groups have further modified this reg-
decrease serum uric acid concentration and thereby hyperuricosuria. imen with the addition of rituximab, demonstrating superior outcomes

TABLE 102–2. Outcome of Burkitt Lymphoma in Larger Studies
Citation Regimen No. of Patients 2-Year Outcome
Hoelzer 71 Short duration/dose intensive; pediatric NHL based 35 51% (estimated survival)
Magrath 45 CODOX-M/IVAC 54 89% (actual survival)
Mead 57 CODOX-M/IVAC 58 64% (progression-free survival)
Rizzieri 65 Short duration/dose intensive with rituximab 105 74% (3-year event-free survival)
Thomas 64 Hyper-CVAD with rituximab 31 89% (estimated survival)
Dunleavy 61 Dose adjusted R-EPOCH 29 95% (event-free survival)
Evens 60 R-CODOX-M/IVAC 25 80% (progression-free survival)
CODOX-M/IVAC, cyclophosphamide, doxorubicin, vincristine, methotrexate, ifosfamide, etoposide and high-dose cytarabine, with intrathecal
cytarabine and methotrexate; hyper-CVAD, fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; NHL, non-Hodgkin lym-
phoma; R-CODOX-M/IVAC, rituximab with CODOX-M/IVAC; R-EPOCH, etoposide, vincristine and doxorubicin, with bolus rituximab, cyclophos-
phamide and steroids.

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