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The NHLs are a heterogeneous group of lymphoid malignancies that share certain features.
Classification of NHLs is controversial and has undergone many revisions. Currently, there
are two complementary approaches: one based on descriptions of lymph node architecture
and histologic features (see Table 74-4) and the other based on the use of immunologic
markers. A new classification based on immunologic markers and histologic features is
shown in Table 74-5.
The cause of most NHLs is unknown. However, immunosuppressed patients (eg, renal
transplant patients) and patients with abnormally high immune function (eg, those with
collagen-vascular disease) are at greater risk, as are those taking hydantoin drugs (eg,
phenytoin), suggesting that the immune system plays a role. A virus is involved in at least
some cases. Burkitt's lymphoma, endemic in Central Africa, is associated with Epstein-Barr
virus infection. An aggressive T-cell leukemia-lymphoma is associated with human T-cell
lymphotropic virus type I (HTLV-I) infection in Japan and the Caribbean. Patients with
HIV often develop aggressive NHL.
Diagnosis
The diagnosis is made by a biopsy of a lymphatic site revealing the histologic features of
malignant lymphoma. Clinical staging of NHL is similar to that of Hodgkin's disease,
although a staging laparotomy is rarely required because the illness is usually disseminated
when discovered. After a complete physical examination, CBC, blood chemistry profile,
bone marrow aspirate, lymph node biopsy, chest x-ray, and abdominal CT scan, about 90%
of patients are found to have stage III or IV disease. Other studies (eg, serum protein
electrophoresis, skeletal x-rays, IV urography) are sometimes useful.
In NHL, indicators of a good prognosis are nodular histologic pattern, limited stage, low
number of extranodal sites, and younger age. Marrow involvement is a poor prognostic
sign for high-grade lymphomas but not for low- or intermediate-grade lymphomas. Other
poor prognostic signs are poor performance status, bulky abdominal disease, Hb < 12 g/dL,
and serum LDH > 250 U/L. The rapidity of response to chemotherapy also predicts
survival.
Chemotherapy has the potential to cure only patients with intermediate- and high-grade
lymphomas. Paradoxically, aggressive therapy does not even prolong survival of patients
with low-grade lymphomas, even though these tumors are extremely sensitive to
chemotherapy. Therefore, therapy should be minimal with low-grade tumors and aggressive
with intermediate- and high-grade tumors. Hemolymphopoietic growth factors may also be
used.
In stages III and IV, most patients experience only lymphadenopathy. Although most
patients respond to chemotherapy, the relapse rate is 10 to 20% annually. Even though 80 to
90% of patients with favorable prognostic histologic findings achieve a complete
remission, only 10 to 20% are without disease after 10 years. Thus, it seems wise to avoid
both the serious systemic toxicity inherent in aggressive combination chemotherapy and the
risk of acute nonlymphocytic leukemia caused by chronic low-dose alkylating agents.
Chemotherapeutic treatment is reserved for patients with progressive disabling
constitutional symptoms. Most oncologists use a single alkylating agent (eg, chlorambucil
0.4 mg/kg as a single dose for 1 day every 28 days). This so-called pulse therapy has less
myelotoxicity and, perhaps, less leukemogenic potential. Some physicians use relatively
mild combination chemotherapy regimens (see Table 74-6). Local radiation can be used to
reduce bulky nodes.
Regimens developed specifically for the elderly are available. One such regimen, as shown
in Table 74-6, uses cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine,
and prednisone (CAP/BOP). However, doxorubicin is not well tolerated by the elderly (nor
is methotrexate because it causes renal complications). Nearly identical complete remission
rates were found for patients > 60 and those < 60 treated with this regimen. The toxicity
was the same in both age groups, as was the duration of remission. Overall survival was
62% for those < 60 but only 35% for those > 60. However, most of the excess morbidity
was related to factors other than lymphoma.