Danazol in the treatment of myelodysplastic syndromes.

20 patients with myelodysplastic syndromes (MDS) were treated with danazol, 800 mg daily in 4 divided doses. 18 patients were evaluable for response. 3 patients (17%), whose principal problem was anemia, responded to treatment, but only with an increase in platelet count. Responses were short-lived and lacked clinical significance. No patients with anemia or leukopenia responded to treatment and none of the 7 patients with a platelet count less than 30 x 10(9)/l responded. Danazol appears to have limited clinical utility in the treatment of MDS. However, occasional patients with thrombocytopenia may benefit.

Chemo-hormonal therapy for metastatic renal cell carcinoma with adriamycin, hydroxyurea, vinblastine, and medroxyprogesterone acetate.

In a phase II study, eight patients with metastatic renal cell carcinoma have been treated with a combination of chemotherapy and hormonal therapy using adriamycin, hydroxyurea, vinblastine, and medroxyprogesterone acetate. Five patients have responded, including one with complete response, one with subjective improvement, and three with partial responses. The median survival was 4 months with a range of 4--11 months. With the exception of mild alopecia and nausea, toxicity was minimal; no significant hematologic toxicity was noted. The initial results of this study suggest that chemo-hormonal therapy plays a significant role in the management of renal cell carcinoma.

Anorectal and perianal complications of hematologic malignant neoplasms.

Among 17 adults with hematologic malignant neoplasms in whom anorectal complications developed, the overall mortality was 53%; for those in whom the disease was not in remission the mortality was 69%, compared with zero for patients who were in remission. All but one of the deaths were directly attributable to septicemia secondary to the anorectal lesion. Over half of the patients had a history of previous anorectal problems or disordered bowel pattern preceding the anorectal complication. The anorectal lesions affecting these 17 patients included prolapsed hemorrhoids (in 5); discrete ulcers in the anal canal and surrounding cellulitis (8); necrosis of the anus and perianal area (2); and perirectal abscesses (2). Only the abscesses responded to surgical drainage. Treatment of the other lesions was conservative: bowel function was maintained as normal as possible, good perineal hygiene was practised and stool softeners were used, while efforts were directed towards achieving remission of the hematologic neoplastic disease.

9-beta-D-arabinofuranosyladenine 5'-phosphate metabolism and excretion in humans.

9-beta-D-Arabinofuranosyladenine (ara-A) was converted chemically to the 9-beta-D-arabinofuranosyladenine 5'-phosphate (ara-A-5'-P) and administered i.v. to four cancer patients in seven experiments. Urinary excretion and plasma levels of radioactivity were monitored for 24 hr in each case. Radioactivity present as unchanged ara-A-5'-P, ara-A, and the deamination product of ara-A, 9-beta-D-arabinofuranosylhypoxanthine, was determined. Excretion was, as in earlier studies with ara-A, given i.v., largely as 6-beta-D-arabinofuranosylhypoxanthine. However, in contrast to the 88 to 97% excretion of ara-A and products in 24 hr when ara-A was given by i.v. push, excretion was 41.47 to 79.1% in 24 hr when ara-A-5'-P was given. With the exception of one experiment at a low dose, where plasma ara-A levels were significant for 6 hr, the plasma levels of ara-A were sustained at significant levels for 24 hr after a single dose of ara-A-5'-P. The doses of ara-A-5'-P given were well tolerated by the four patients. Indications are that this derivative provides important advantages (solubility and sustained blood levels) over ara-A.

Sjögren's syndrome terminating as a myeloproliferative disorder.

A 59 year old female was diagnosed as having Sjögren's syndrome in 1963. A short time later, she developed a refractory sideroblastic anemia. In 1972, she was found to have a preleukemic state with a persistent "shift to the left" of the granulocytic series, terminating early in 1974 as acute myeloblastic leukemia. Although several cases of malignant lymphomata have been described in association with Sjörgen's syndrome, to our knowledge no other example of Sjörgen's syndrome has been described in association with a myeloproliferative disorder. Defective immune surveillance produced by the Sjörgen's syndrome may have permitted the development of the myeloproliferative syndrome. Alternatively, both disorders may have developed from a hemopoietic stem cell defect.