Modern approaches to the diagnosis of malignant trophoblastic tumors

Malignant trophoblastic tumors (TO) include invasive and metastatic cystic drift, choriocarcinoma, TO of the placental bed, and epithelioid TO. They are rare, mainly in women of reproductive age, and most importantly, they are always associated with pregnancy. To date, the Blokhin National Medical Research Center of Oncology has accumulated a large and unique experience of modern diagnostics and treatment of patients with various forms of malignant TO. An obligatory stage of the examination is ultrasound diagnostics of the pelvic organs. In addition, performing an ultrasound examination during the treatment period, along with monitoring the level of chorionic gonadotropin, makes it possible to assess the effectiveness of treatment, diagnose tumor resistance and ascertain the onset of remission.

Thalidomide Alone or With Dexamethasone for Previously Untreated Multiple Myeloma

Purpose: To evaluate the activity of thalidomide in patients with asymptomatic multiple myeloma and of thalidomide-dexamethasone in patients with previously untreated symptomatic myeloma. Patients and Methods: Twenty-eight patients with previously untreated asymptomatic myeloma were treated with thalidomide 100 to 200 mg orally (PO) at bedtime (qhs) with serial increments of 50 to 100 mg at weekly intervals, as tolerated to a maximum of 600 mg PO qhs. Forty consecutive previously untreated patients with symptomatic myeloma were also treated as above (maximum dose 400 mg) and received dexamethasone 20 mg/m2 for 4 days beginning on days 1, 9, and 17; the second and third cycles of repeated dexamethasone were begun on day 30. Both groups of patients were treated for at least 3 months. Results: The response rate was 36% for patients treated with thalidomide alone and 72% for patients treated with thalidomide-dexamethasone, the latter including complete remission in 16% of patients. The median time to remission was 4.2 months with thalidomide alone and 0.7 months with thalidomide-dexamethasone. Grade 3 toxicity included infections (nine patients) and thrombotic/embolic events (seven patients). Five deaths have occurred as a result of multiple myeloma (two patients), infection (one patient), unknown cause (one patient), and a possible thromboembolic event (one patient). Conclusion: Thalidomide alone was effective in patients with newly diagnosed myeloma. The combination with dexamethasone induced a high frequency of response, rapid onset of remission, and low incidence of serious irreversible toxicity. These observations support further studies of this promising combination for patients with newly diagnosed multiple myeloma.

Fludarabine therapy in macroglobulinemic lymphoma

Fludarabine, a fluorinated analogue of adenine, was given to 11 patients with macroglobulinemic lymphoma, all but one having failed prior standard chemotherapy. Five patients (45%) responded with more than a 50% reduction of immunoglobulin M (IgM) tumor mass for a projected median duration of longer than 1 year. The onset of remission was usually slow, with a median tumor halving time of 5.2 months in responding patients, emphasizing the importance of repeated courses of treatment. Fludarabine is an important new agent effective against macroglobulinemic lymphoma, and should be evaluated further in combination with other active modalities.

Fludarabine therapy in macroglobulinemic lymphoma

Fludarabine, a fluorinated analogue of adenine, was given to 11 patients with macroglobulinemic lymphoma, all but one having failed prior standard chemotherapy. Five patients (45%) responded with more than a 50% reduction of immunoglobulin M (IgM) tumor mass for a projected median duration of longer than 1 year. The onset of remission was usually slow, with a median tumor halving time of 5.2 months in responding patients, emphasizing the importance of repeated courses of treatment. Fludarabine is an important new agent effective against macroglobulinemic lymphoma, and should be evaluated further in combination with other active modalities.

Treatment of Children with Acute Leukemia by Passive Cyclic Immunization with Autoplasma and Autoleukocytes Operated During the Remission Period

The original premise of the recent study is the assumption that under usual conditions, the patient with acute leukemia is immunologically tolerant to his own leukemogenic agent. The antigenic specificity of the leukemogenic factor may change under the influence of drugs (6-mercaptopurine), thus bringing about the possibility of antigenic stimulation. In connection with this it is suggested that the onset of remission in acute leukemia occurs with the participation of humoral and cellular immunologic mechanisms. We have demonstrated that during remission of acute leukemia, the use of cyclic passive immunization with autoplasma and autoleukocytes obtained at earlier stages of the first complete remission leads to a considerable prolongation of the remission periods. Administration of plasma and leukocytes (obtained in the remission period) upon the onset of the acute phase is accompanied in some cases by a short-term effect which manifests itself in the improvement of subjective well-feeling, decreased pain, reduced size of lymph nodes, liver and spleen, and in reduction of the "blast" content of the bone marrow. Intracutaneous injection in the remission period of the extract from bone marrow and leukocytes obtained from patients in the acute phase of leukemia produces a positive skin reaction.

VINCRISTINE IN THE TREATMENT OF ACUTE LEUKEMIA IN CHILDREN

Vcr induced complete marrow remission in 43% of children with all types of acute leukemia who were refractory to other antileukemic therapy. The median duration of disease before Vcr treatment was 13.5 months. The marrow response in those patients achieving an A marrow was rapid with a marked clearing of the blasts by 14 days and a complete remission by 28 days. The median duration of complete remission with and without maintenance therapy was 63.5 and 59 days, respectively. Drug toxicity occurred in about half the patients, limiting the total dose of drug that could be given. Leukopenia, alopecia, gastrointestinal symptoms, and neurotoxicity were the most common problems seen. These were reversible on withdrawal of the drug. Remissions were not improved by increasing the dose of Vcr to 0.1 mg/kg for two or more doses after 4 doses of 0.075 mg/kg. The reduction in dose necessitated by drug toxicity was not detrimental to a good response since the children attaining complete remissions experienced the greatest number of alterations in dose prior to the onset of remission.

ACQUIRED HEMOLYTIC ANEMIA

1. Observations of 11 patients with acquired hemolytic anemia are reported. 2. In contrast to patients with congenital hemolytic jaundice, all patients in this group exhibited evidence of sensitization of their erythrocytes by an antibody-like agent. In all patients studied there was abnormal destruction of transfused cells in vivo. 3. The sensitizing agent was found to be adsorbed on the erythrocytes when it could not be demonstrated in the serum. A rough method of assay of the amount adsorbed was devised by making serial dilutions of the anti-globulin serum. With this technic a fairly consistent correlation was found between the amount of antibody on the cell and activity of the disease. 4. Splenectomy when successful appears to exert a curative effect by sharply reducing the amount of antibody substance on the cell. Patients who had not responded to splenectomy in the past showed evidence of saturation of their cells with adsorbed antibody. The erythrocytes of patients who had responded to splenectomy and were in remission when studied showed distinctly less antibody on the cell by the same technique. 5. Two patients were observed to enter spontaneous remission after a long period of activity. The onset of remission in both was associated with a decrease in the amount of adsorbed immune body. However, one patient has shown evidence of return of antibody production without immediate recurrence of the hemolytic anemia. This inconsistency is not explained. 6. The tendency toward spherocytosis as measured by increased osmotic fragility may or may not be present in acquired hemolytic anemia. Prior to splenectomy the most marked increase in hypotonic fragility was observed in the patient with the most active disease. Continued activity of the disease following splenectomy was productive of the most extreme increases in spherocytosis. This suggests that the spherocytic cells are removed from the circulation by the spleen. 7. Agglutination of red cells when the amount of adsorbed antibody reaches a critical level, together with such other phenomenon as stasis, spherocytosis, increased mechanical fragility and possibly phagocytosis probably explain the increased cell destruction. 8. The occurrence of definite and sustained leukopenia with neutropenia and thrombocytopenia in several patients with hemolytic disease due to an immune body agent raises questions as to the etiology of classic thrombocytopenic purpura and of splenic neutropenia. Patients have been observed who seem to represent transition forms between acquired hemolytic anemia and thrombocytopenic purpura. Abnormal immune mechanisms could account for both excessive destruction of platelets and deficient formation.