mitoguazone and Lymphoma--Large-B-Cell--Diffuse

A 62-year-old woman was diagnosed as having malignant lymphoma, diffuse large B-cell type. She underwent chemotherapy with the standard dose of CHOP and MINE regimens, resulting in complete remission. Four months later, the myelodysplastic syndrome of RA (refractory anemia) with pancytopenia developed and rapidly progressed to acute myelogenous leukemia (AML-M6) in 4 months. Cytogenetic analysis for the bone marrow specimens of both periods of MDS and AML-M6 revealed complex karyotypic abnormalities involving chromosome 5, 7, 11q23 and 20q11.2. Neither rearrangement of the MLL gene by Southern blot analysis nor tandem duplication of MLL gene by RT-PCR technique was detected. The patient was died from progression of leukemia and pneumonia. The autopsy showed no residual disease of lymphoma-related disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 5; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Leukemia, Erythroblastic, Acute; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Mitoguazone; Myelodysplastic Syndromes; Neoplasms, Second Primary; Prednisolone; Vinblastine; Vincristine

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl-GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.

Topics: Adult; Aged; Bone Marrow; Digestive System; Guanidines; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Mitoguazone; Time Factors