2-chloro-3--deoxyadenosine and Lymphoma

Myasthenia gravis (MG) is an autoimmune disease mediated by antibodies to acetylcholine receptors (AChRs) or muscle specific tyrosine kinase (MuSK). While the frequent association of MG with thymoma in patients aged 40-60 years is well recognized, its occurrence in patients with lymphoma has not been well studied. We review the literature on the association of MG and lymphoid malignancies and report two new patients. MG can occur in a synchronous or non-synchronous fashion with lymphoma. The pathogenesis of MG in lymphoid malignancies is probably heterogeneous and likely relates to perturbations in the immune mechanisms that normally prevent the emergence of autoimmunity. These perturbations could be the result of the lymphoid malignancy per se, or its treatment.

Topics: 2-Chloroadenosine; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cyclosporine; Deoxyadenosines; Fatal Outcome; Female; Humans; Lymphoma; Lymphoma, Follicular; Lymphoproliferative Disorders; Male; Middle Aged; Myasthenia Gravis; Paraneoplastic Syndromes, Nervous System; Prednisone; Pyridostigmine Bromide; Recurrence; Remission Induction; Rituximab; Waldenstrom Macroglobulinemia

Splenic Marginal Zone Lymphoma (SMZL) is a rare clinicopathological entity among marginal zone lymphomas. SMZL is an indolent lymphoma usually treated by splenectomy. A subset of patients is characterized by a more aggressive clinical course and poor prognosis. Treatment of these cases and second-line therapy for relapsed patients have not been yet identified. We report 10 cases treated with cladribrine (5 mg/m(2)/week) for six courses. Six patients (60%) achieved partial response, two patients (20%) achieved a complete response and the two remaining patients did not respond and died as a result of progression of the disease. The treatment was well tolerated. A total of 60% of the patients had an overall survival rate of 48 months and 24 months progression-free-survival was achieved by 37% with a median time of progression-free-survival of 17 months. Interestingly, in addition to a relevant percentage of hematological remission, some patients also experienced a molecular remission. We conclude that this treatment is safe and well tolerated and is able to induce a substantial number of responses. Our results suggest that this schedule is well tolerated and could be an useful alternative to splenectomy.

Topics: 2-Chloroadenosine; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Deoxyadenosines; Female; Humans; Lymphoma; Middle Aged; Splenectomy; Splenic Neoplasms; Survival Analysis; Treatment Outcome

2-CdA is active as a single agent in the treatment of low-grade lymphomas. We analyzed the induction of apoptosis by 2-CdA alone (n=5) and in combination with other drugs in peripheral lymphocytes from 25 patients with leukemic low-grade lymphomas and from 25 healthy volunteers. 2-CdA was tested in 4 escalating concentrations (0.05 microg/ml to 0.4 microg/ml). Linear regressions showed a dose dependent apoptosis rate of 0.29 x microg 2-CdA/ml + 0.11 (r2=0.88, p=0.006) in normal cells and 0.41 x microg 2-CdA/ml + 0.15 (r2=0.88, p=0.005) in leukemic cells. Intracellular metabolization of 2-CdA into 2-CdA-5'mono-, -di- and the active metabolite -triphosphate was analyzed by HPLC and paralleled the dose dependent increase of apoptosis. The combination of 2-CdA with doxorubicin or mitoxantrone had a synergistic effect on the induction of apoptosis (p<0.001) in both normal and neoplastic lymphocytes, whereas 2-CdA plus etoposide or cytosine arabinoside were only additive. Due to the flat slope of the dose response of 2-CdA concentration on apoptosis we assume that higher in vivo dosages of 2-CdA in the treatment of low-grade lymphomas may not result in a higher clinical efficacy. The synergistic lymphocytotoxic effect of 2-CdA combined with doxorubicin or mitoxantrone may be relevant for new treatment approaches.

Topics: 2-Chloroadenosine; Antineoplastic Agents; Apoptosis; Deoxyadenosines; Dose-Response Relationship, Drug; Doxorubicin; Drug Synergism; Humans; Lymphoma; Mitoxantrone; Tumor Cells, Cultured

Topics: 2-Chloroadenosine; Antimetabolites, Antineoplastic; Deoxyadenosines; Humans; Lymphoma; Splenectomy; Splenic Neoplasms

Topics: 2-Chloroadenosine; Antibodies, Monoclonal; Deoxyadenosines; Humans; Immunoconjugates; Immunotoxins; Leukemia, Hairy Cell; Lymphoma; Pentostatin; Ricin