Burkitt s lymphoma

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

Epstein-Barr virus (EBV) Burkitt s lymphoma, nasopharyngeal carcinoma, lymphoproliterative disorders in immuno-suppressed patients (e.g., AIDS, transplant recipients) EBNA-1 Inhibition of cell proliferation... 

Epstein-Barr virus (EBV) Enveloped, icosahedral particles 150nm in diameter Infections occur by salivary exchange. In young children they are commonly asymptomatic but the virus persists in a latent form in lymphocytes. Infection delayed until adolescence often results in glandularfever. In tropical Africa, a severe EBV infection early in life predisposes the child to malignant facial tumours (Burkitt s lymphoma)... 

There are certain histologic subtypes of diffuse, aggressive NHL that respond less well to treatment with conventional regimens such as CHOP. Burkitt s lymphoma, lymphoblastic lymphoma, mantel cell lymphoma, and primary CNS lymphoma are examples of disease that benefit from more intensive therapy. Regimens such as hyper-CVAD, which alternate cycles of hyperfractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone with high-dose cytarabine and methotrexate, often are substituted for CHOP. Intrathecal therapy with methotrexate is indicated with documented CNS infiltration of tumor or involvement of the sinuses. The recent appreciation of the etiology of Helicobacter pylori in the etiology of peptic ulcer disease and the association between colonization and mucosal-associated lymphoma (MALT) has spurred... 

Wiels, J., Junqua, S., Dujardin, P., Le Pecq, J.B., and Tursz, T. (1984) Properties of immunotoxins against a glycolipid antigen associated with Burkitt s lymphoma. Cancer Res. 44, 129. 

Lymphoma, Burkitt s Lymphoma, immunoblastic Lymphoma, primary, or brain Mycobacterium avium complex or M. kamasii, disseminated or extrapulmonary M. tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary Pneumocystis carinii pneumonia Pneumonia, recurrent... 

Drut, R. M Day, S., Drut, R., andMeisner, L. (1994) Demonstration of Epstein-Barr viral DNA in paraffin-embedded tissues of Burkitt s lymphoma from Argentina using the polymerase chain reaction and in situ hybridization. Fed. Pathol. 14,101-109. 

As in cancer predisposing syndromes, these genetic alterations are sometimes carried in the germline. Among human tumours, heritable mutations are an exception. Most alterations are acquired in somatic life in the form of chromosomal translocations, deletions, inversions, amplifications or point mutations. Certain oncogenic viruses play important roles in a few human tumours. Examples are human papilloma-virus in cervical cancer and skin tumours, Ep-stein-Barr virus in nasopharyngeal carcinoma and Burkitt s lymphoma, and human T-cell leukaemia viruses (e.g. HTLV-I, HTLV-II) in T-cell leukaemia. 

The association between malaria and Burkitt s lymphoma, and between splenomegaly and chronic lymphocytic leukemia are perhaps the results of the long-term effects of an overworked thymolymphatic system. 

Burkitt s lymphoma is chiefly a disease of children and is more common in Africa than in other parts of the world. Within the last ten years or so, this disease has attracted much attention—most likely because (a) most patients with Burkitt s lymphoma have a rapid tumor regression following chemotherapy, (b) some patients with Burkitt s lymphoma... 

The first report on the concentration of the serum Ig s in children with Burkitt s lymphoma noted that although the serum IgM was depressed in the majority of the patients, both the serum IgA and IgG were largely within normal limits (N3). Furthermore, those sera with high levels of IgM had an inhibitory effect on the growth of Burkitt tumor cells in culture. 

The marked decrease of the serum IgM in patients with Burkitt s lymphoma have been confirmed by Ziegler et al. (Zl) in East Africa, who noticed an impairment of the primary antibody response and low serum IgM levels in untreated patients with Burkitt s lymphoma, but not in patients in remission. They postulated a defect in humoral immunity possibly to impaired IgM synthesis. 

Classification of the Different Types of Immunoglobulin Patterns in Patients with Burkitt s Lymphoma (M16)... 

Five different types of serum immunoglobulin patterns may be observed in patients with Burkitt s lymphoma (Tables 15-19) Type 1... 

Type I Immunoglobulin Deficiency in Burkitt s Lymphoma Low IgM WITH Normal IgG (mg/ml) ... 

In twelve of sixty-three patients, both the serum IgM and the serum IgG concentrations were depressed. Two of these Burkitt s lymphoma children also had low IgA, but in the other 10 children the scrum IgA was normal. There were 5 known deaths in children classified with this type II deficiency. Seven of these children had tumor classification of the grade III type III immunoglobulin deficiency. There were 14 children with Burkitt s lymphoma classified with this type III immunoglobulin deficiency with moderately reduced levels of scrum IgG and normal levels of IgM. One child in the grouji had a moderately elevated IgA,... 

There was a fifth group of patients with Burkitt s lymphoma who had mostly normal levels of serum immunoglobulin. The majority of these patients were in remission from their tumor. 

It is likely that the IgM in the CSF of patients with Burkitt s lymphoma may be partly derived from subunits of serum IgM crossing the blood-brain barrier, since 4 out of 17 patients with Burkitt s lymphoma had detectable IgM in their urines which emerged from Sephadex G-200 columns in two different peaks, strongly suggesting the occurrence of subunits of the intact molecule (M17). 

Klein (K2) reported IgM absorbed to the surface of fresh Burkitt s lymphoma cells, and it is possible that the low serum IgM values may result from absorption to malignant cells. Zeigler et al. (Zl) postulated that IgM metabolism may be inhibited by active production of IgG in vitro by the Burkitt lymphoma cells (04), and furthermore, that the IgM defect may be either acquired or inherited or an expression of delayed maturity of immunoglobulin metabolism which contributes to the susceptibility of the individual to the oncogenic agent (N3). 

One of the chief causes of early death in patients with Burkitt s lymphoma was renal failure, and it is tempting to suggest that the increased excretion of proteins into the urine may well be related to the damage caused to the kidney (Z2). 

A viral etiology has been implicated in Burkitt s lymphoma, and there is some evidence that Epstein-Barr virus causes infectious mononucleosis in Europe and Burkitt s lymphoma in Africa. It has been suggested that if the cause of the Burkitt s lymphoma is viral, then entry of the virus particles into the lymphoid colls of the body may derange a part of the cell immune process, subsequently affecting the production of the IgM antibody, a theory which is compatible to the dysproteinemia sometimes seen in multiple myeloma and other lymphomas (N2). Also in support of this is the observation that C-reactive protein was markedly elevated in the serum of patients with Burkitt s lymphoma, and disappeared entirely from the blood when they were cured (MIO). The relationship between malarial infection and Burkitt s lymphoma has been dealt with in a previous section on malaria. 

The majority of patients with Burkitt s lymphoma showed an intact delayed hypersensitivity response to DCNB and lymphocyte transformation to phytohemagglutinin was also normal in the majority of patients (Z3). Fass et al. (F2) reported that 12 patients with Burkitt s lymphoma when tested with autologous tumor extracts showed measurable cellular responses of the host against his own tumor. In contrast to patients with Burkitt s lymphoma who have impaired antibody production but normal cellular immunity, patients with other forms of neoplasia of the reticuloendothelial system frequently have impairment of both the humoral and cellular aspects of immunity. 

The serum immunoglobulins, in particular the IgM concentrations, are depressed in patients with Burkitt s lymphoma. All patients with central nervous system (CNS) involvement had IgM in their CSF, and subunits of IgM were detected in the urines of some Burkitt s lymphoma patients. The cellular immune responses were reported to be intact, but the humoral immunity was depressed in most patients with Burkitt s lymphoma. 

In summary, it can be said that the majority of patients with Burkitt s lymphoma have a significant decrease of their serum Ig] I levels. Others have deficiencies of either IgG or both IgG and Ig] I. The CSF and urinary IgM may be related to CNS and renal involvement in patients with Burkitt s lymphoma. 

IgM is frequently detected in the CSF of patients with trypanosomiasis, tuberculous meningitis, Staphlococcus meningitis and in patients with Burkitt s lymphoma with CNS involvement and could very well be of diagnostic significance. 

Malignancies of various types— multiple myelomatosis, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, reticulum cell sarcoma, Hodgkin s disease, Burkitt s lymphoma and other malignancies of the reticuloendothelial system... 

K2. Klein, G., Immunological aspects of Burkitt s lymphoma. Adean. Immunol. 14, 187-250 (1968). 

K3. Klein, G., Klein, E., and Clifford, P., Search for host defences in Burkitt s lymphoma membrane immunofluorescence tests on biopsies and tissue culture lines. Cancer Res. 27, 2510-2520 (1967). 

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