Tumor Lysis Syndrome

Tumor lysis syndrome is a common complication after treatment of high-grade, bulky NHLs (because of their exquisite sensitivity to therapy and high proliferative capacity). The syndrome is characterized by renal failure, hyperkalemia, hyperphosphatemia, and hypocalcemia. Measures to prevent this complication include aggressive hydration; allopurinol; alkalinization of the urine; and frequent monitoring of electrolytes, uric acid, and creatinine. Dialysis is sometimes required. Rasburicase, a recombinant urate-oxidase enzyme, is now available for the prevention and treatment of hyperuricemia. (For a more comprehensive discussion of the tumor lysis syndrome, see the “Oncologic Emergencies and Paraneoplastic Syndromes” chapter.)

Lymphoma During Pregnancy

Lymphoma is one of the most common cancers diagnosed during pregnancy, occurring in approximately 1 in every 5,000 gestations. Evens and colleagues recently reported outcomes from a retrospective analysis of 50 patients with NHL that occurred during pregnancy. Median age at diagnosis for B-cell NHL was 29.5 years vs 34 years for T-cell lymphoma (P = .09). The most common NHL diagnosis was DLBCL, which accounted for 56% of all NHLs and 73% of B-cell NHLs. Fifty-four percent of NHL patients had advanced-stage disease, although functional imaging was not performed in any patient. Interestingly, extranodal disease was still frequently identified, with 26% of patients having more than one extranodal site, with several atypical sites seen (eg, vaginal, breast). Diagnosis of lymphoma occurred at a median of 23 weeks, with all but one patient having untreated disease. Pregnancy was terminated in six NHL patients; among the remaining patients, 15 (32%) had therapy deferred until postpartum. In the latter patients, a diagnosis was made at a median of 30 weeks’ gestation compared with 22 weeks’ gestation for patients who received antenatal therapy (P < .001).

Antenatal treatment was started at a median of 25 weeks’ gestation (range, 13 to 37 weeks). Four of the five NHL patients who received antenatal radiotherapy had supra-diaphragmatic stage I-II disease, while most patients who received antenatal therapy were treated with conventional non-antimetabolite chemotherapy regimens (eg, CHOP). The overall response rate for NHL patients who received antenatal therapy was 71% (complete remission 50%). The most common preterm complication was induction of labor (33%), while gestation went to full term in 56% of patients, with delivery occurring at a median of 37 weeks. Interestingly, there were no differences in maternal complications, perinatal events, or median infant birth weight based on deferred vs antenatal therapy. At a median follow-up of 41 months, 3-year progression-free survival and overall survival for NHL patients were 53% and 82%, respectively. On univariate analysis for NHL, radiotherapy predicted inferior progression-free survival, and increased LDH levels and poor ECOG performance status portended worse overall survival. It is highly advocated that patients be managed concurrently with high-risk maternal-fetal medical consultation.

Follow-Up of Long-Term Survivors

Relapse

Among patients with aggressive lymphoma subtypes, most recurrences are seen within the first 2 years after the completion of therapy, although later relapses may occur. Physical examination and laboratory testing at 2- to 3-month intervals and follow-up CT scans (with or without PET scan) at 6-month intervals for the first 2 years following diagnosis are recommended. However, it is recognized that on relapse of disease, the patient usually presents with symptoms rather than the relapse being diagnosed purely on the basis of surveillance scans or routine clinic visits. Early detection of recurrent disease is important because these patients may be candidates for potentially curative high-dose therapy and SCT. Patients with advanced low-grade NHL are at a constant risk of relapse, and late recurrence of disease may be seen, sometimes after more than a decade-old remission.

Treatment Complications

There has been a more selective use of irradiation as part of the initial therapy for NHL; therefore, the risk of certain radiation-induced complications has been reduced or eliminated in patients with more recently diagnosed NHL. Nevertheless, total-body irradiation may be used as a component of myeloablative conditioning regimens. Also, transplant recipients are at increased risk for secondary myelodysplasia and acute myeloid leukemia, regardless of whether they received a radiation-containing conditioning regimen. All individual chemotherapy agents have their own potential long-term morbidity, such as late cardiovascular disease with anthracycline therapy.

Secondary Malignancies

Long-term survivors are at increased risk for second cancers. In a survey of 6,171 patients with NHL who survived 2 or more years, nearly 1,000 patients lived 15 or more years after diagnosis. Second cancers were reported in 541 patients, with significant excesses seen for all solid tumors; acute myeloid leukemia; melanoma; Hodgkin lymphoma; and cancers of the lungs, brain, kidneys, and bladder. The actuarial risk of developing a second malignancy at 3 to 20 years after diagnosis of NHL was 21%, compared with a population-expected cumulative risk of 15%.

Long-term survivors need continued follow-up for possible treatment-related complications. Some of these toxicities may still be unknown. Careful documentation of late complications will be important in the design of future treatment strategies aimed at preserving or improving response rates and the duration of remission while reducing toxicity.