VP-16-213 in combination chemotherapy with chest irradiation for small-cell lung cancer: a randomized trial of the Piedmont Oncology Association.

The role of etoposide epipodophyllotoxin (VP-16-213) in a combined modality treatment program incorporating local chest irradiation and combination chemotherapy with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine has been evaluated in a randomized trial of 165 patients with small-cell lung cancer. The overall response rate (complete response [CR] plus partial response [PR]) was significantly greater in the VP-16-213 arm (85% v 64%, P = .005) primarily as a consequence of improved response in patients with extensive disease (85% v 38%, P = .002 and 30% v 8% for CR only, P = .045). No differences in the response rates were observed in limited disease. The duration of response (months) was greater in the VP-16-213 arm (8.6 v 7.0 overall and 14.4 v 11.5 for CR) but not significantly so. Median survival times (months) were consistently greater in the group receiving VP-16-213 when analyzed according to extent of disease and response (10.6 v 9.5 overall; 15.0 v 13.6 for limited disease; 9.0 v 6.7 for extensive disease; 18.5 v 16.2 for CR overall; and 18.6 v 16.1 for CR in limited disease); the results were not statistically significant. The median survival of extensive disease patients attaining a CR was 15.3 months (range 3.2 to 34.3 + months) in the VP-16-213 arm and 7.4+ and 8.1+ months for the two patients with CR in the other group. Anemia and leukopenia occurred to a greater degree in the four-drug regimen, but no unusual or significant compounding toxicity (ie, neurotoxicity) was observed otherwise. Further investigation of this agent in combination chemotherapy programs for small-cell lung cancer appears to be warranted.

Monosomy X as a recurring sole cytogenetic abnormality associated with myelodysplastic diseases.

Solitary loss of the X chromosome is associated with Turner syndrome and not hematological disorders. We describe five patients with non-constitutional loss of the X chromosome as the sole cytogenetic abnormality in their bone marrow. Three of the five patients had myelodysplastic syndrome (MDS), one case had AML M-6 with evidence suggestive of an evolving MDS, and the last patient had a dysplastic marrow. A review of the literature identified sporadic reports of an association of monosomy X and several hematologic disorders, as well as a few solid tumors. In this series of patients, monosomy X as a sole non-constitutional cytogenetic abnormality in bone marrow is associated with myelodysplastic diseases. In addition, fluorescence in situ hybridization analysis with an X centromere probe indicated that monosomy X was present in erythroid precursors, myeloblasts, promyelocytes, myelocytes, metamyelocytes, granulocytes, and monocytes, while mature lymphocytes presented with two copies of the X chromosome. The molecular cytogenetic evidence supports the diagnosis of a myelodysplastic disorder in these cases and documents the potential role of FISH in hematological disease.

Posttransfusion purpura due to an alloantibody reactive with glycoprotein Ia/IIa (anti-HPA-5b).

A 38-year-old woman (JT) was diagnosed with posttransfusion purpura and significant posthysterectomy vaginal bleeding 9 days after the transfusion of 2 U of packed red blood cells. Analysis of JT's serum by a monoclonal antibody-antigen capture enzyme-linked immunosorbent assay method showed the presence of anti-HPA-5b (anti-Bra) antibodies directed against an epitope on platelet glycoprotein (GP) la of the GPIa/IIa complex. The patient's serum immunoprecipitated two proteins from 125I-labeled HPA-5b positive platelets that migrated under both nonreducing and reducing conditions on sodium dodecyl sulfate polyacrylamide gels at molecular weights characteristic of GPIa (150 Kd and 165 Kd, respectively) and GPIIa (120 Kd and 145 Kd, respectively). These bands were not precipitated when 125I-labeled HPA-5b negative platelets were used. Platelet typings performed on JT and her three children showed that the patient was HPA-5b negative and one of her children was HPA-5b positive. Platelets obtained from one of the donors who provided blood for the inciting transfusion also typed as HPA-5b positive. These findings demonstrate that posttransfusion purpura may be induced by antibodies directed against an alloantigenic epitope, namely HPA-5b (Bra), located on GPIa/IIa. Moreover, clinically significant bleeding can be associated with antibody reactions directed against this GP complex.