A large number of pathologic entities share an aggressive natural history; median survival untreated is 6 months, and nearly all untreated pts are dead within 1 year. Pts may present with asymptomatic adenopathy or symptoms referable to involvement of practically any nodal or extranodal site: Mediastinal involvement may produce superior vena cava syndrome or pericardial tamponade; retroperitoneal nodes may obstruct ureters; abdominal masses may produce pain, ascites, or GI obstruction or perforation; CNS involvement may produce confusion, cranial nerve signs, headache, seizures, and/or spinal cord compression; bone involvement may produce pain or pathologic fracture. About 45% of pts have B symptoms.
Diffuse large B-cell lymphoma is the most common histologic diagnosis among the aggressive lymphomas, accounting for 35-45% of all lymphomas. Aggressive lymphomas together account for ∼60% of all lymphoid tumors. About 85% of aggressive lymphomas are of mature B-cell origin; 15% are derived from peripheral (postthymic) T cells.
| APPROACH TO THE PATIENT | ||
Aggressive LymphomaEarly diagnostic biopsy is critical. Pt workup is directed by symptoms and known patterns of disease. Pts with Waldeyer's ring involvement should undergo careful evaluation of the GI tract. Pts with bone or bone marrow involvement should have a lumbar puncture to evaluate meningeal CNS involvement. |
| TREATMENT | ||
Aggressive LymphomasLocalized aggressive lymphomas are usually treated with four cycles of CHOP combination chemotherapy ± involved-field radiation therapy. About 85% of these pts are cured. CHOP + rituximab appears to be even more effective than CHOP + radiation therapy. The specific therapy used for pts with more advanced disease is controversial. Six cycles of CHOP + rituximab is the treatment of choice for advanced-stage disease. Outcome is influenced by tumor bulk (usually measured by LDH levels, stage, and number of extranodal sites) and physiologic reserve (usually measured by age and Karnofsky status) (Table 67-4 International Prognostic Index for NHL). CHOP + rituximab cures about two-thirds of pts. Infusional chemotherapy regimens like dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) plus rituximab may be more effective in the more aggressive double-hit lymphomas that have mutations in c-Myc and bcl-6. The use of a sequential high-dose chemotherapy regimen in pts with high-intermediate and high-risk disease has yielded long-term survival in about 75% of pts in some institutions. Other studies fail to confirm a role for high-dose therapy. About 30-45% of pts not cured with initial standard combination chemotherapy may be salvaged with high-dose therapy and autologous hematopoietic stem cell transplantation. Specialized approaches are required for lymphomas involving certain sites (e.g., CNS, stomach) or under certain complicating clinical circumstances (e.g., concurrent illness, AIDS). Lymphomas occurring in iatrogenically immunosuppressed pts may regress when immunosuppressive medication is withheld. Lymphomas occurring post-allogeneic marrow transplant may regress with infusions of donor leukocytes. Pts with rapidly growing bulky aggressive lymphoma may experience tumor lysis syndrome when treated (Chap. 27 Oncologic Emergencies); prophylactic measures (hydration, urine alkalinization, allopurinol, rasburicase) may be lifesaving. |
Section 6. Hematology and Oncology