Jean-Louis Amiel

Dissociation of natural killer cell activity and antibody-dependent cell-mediated cytotoxicity in kidney allograft recipients receiving high-dose immunosuppressive therapy.

Peripheral blood lymphocytes (PBLs) of normal subjects and of kidney allograft recipients treated with immunosuppressive drugs (azathioprine and prednisone) were tested for natural killer (NK) cell activity against K562 cells, and for killer (K) cell activity against L-1210 cells in the presence of rabbit anti-L-1210 antiserum. It was found that the natural cell-mediated cytotoxicity (NCMC) was abolished in the immunosuppressed patients while the antibody-dependent cell-mediated cytotoxicity (ADCC) remained normal. Furthermore, no correlation was observed between both activities in the treated group, whereas a strong positive correlation did exist in the control population. Uremic routinely hemodialyzed patients tested for NK cell activity did not exhibit any significant difference with the control group. These data indicate that NCMC and ADCC are different functions, apparently correlated in normal population but discriminated by immunosuppressive medical treatment. The abrogation of NCMC in patients in whom the risk of malignancy is highly increased strengthens the concept of a crucial role of NK cells in the in vivo surveillance toward malignancies.

Cisplatin, vinblastine, and bleomycin combination in the treatment of resistant high-risk. Gestational trophoblastic tumors

Eight patients with high‐risk gestational trophoblastic tumors (GTT) resistant to multiagent chemotherapy were treated with the combination of cisplatin, vinblastine, and bleomycin (PVB). All patients had a metastatic disease including three patients with two metastatic sites and two patients with brain metastases. Four patients achieved complete remission (CR) with the PVB regimen (50%). Three additional patients had partial remission (PR) of whom two were converted into CR by surgery of resistant residual lesions. One patient relapsed and the remaining five patients in CR were cured (62%). A multimodal approach was necessary in most patients as five of them had hysterectomy and two patients had a whole‐brain irradiation. Toxicity was mild with no treatment related deaths.

Treatment of high-risk gestational trophoblastic disease with chemotherapy combinations containing cisplatin and etoposide

The authors have treated 22 patients with high‐risk gestational trophoblastic disease (GTD) by cisplatin‐etoposide‐containing combinations. Sixteen patients were treated with dactinomycin, platinum, and etoposide combination (APE regimen) and six patients had platinum and etoposide combination (PE regimen). Fourteen patients were treated for resistant or relapsing GTD after first‐line therapy, and eight patients initially. All 22 patients were high risk according to the World Health Organization prognostic score values. Sustained complete remission was achieved in 19 patients (86%). All eight patients who received treatment as initial therapy were cured (100%) whereas only 11 patients were cured among the 14 patients who failed prior chemotherapy (78%). Hematologic and renal toxicities were limited and no treatment‐related deaths occurred in this group of patients. Cisplatin and etoposide could be more widely used in chemotherapeutic combinations for high‐risk gestational trophoblastic disease.

Low natural killer cell activity in patients with malignant lymphoma

Natural killer (NK) cell activity was found decreased (mean value: 27.5%) in peripheral blood lymphocytes from 59 untreated patients with malignant lymphoma, when compared to 112 healthy subjects (46.3%) and to 75 cancer patients with nonlymphoid tumors (43.7%) (P > 0.001). NK cell values were similar in patients with Hodgkins disease (25.5%) and with non‐Hodgkins lymphoma (28.2%). Decreased NK cell activity was not correlated with age, lymphoma extension or leukocyte counts. A physiological role for NK cells in the immune surveillance against lymphoid neoplasias is discussed.

Prognostic factors in gestational trophoblastic tumors. A multivariate analysis

One hundred sixty‐two gestational trophoblastic tumors (GTT) were treated at the Institute Gustave‐Roussy, Villejuif, France, from 1975 to 1985. Sustained complete remission (CR) was obtained in 146 patients (90%). All 97 patients with no histologic diagnosis of choriocarcinoma were cured, including 19 patients considered at high risk initially. Among 65 histologic chariocarcinoma patients, 16 died (CR, 75.5%) including seven initially nonmetastatic patients. Using a univariate analysis, all factors tested in the whole group of patients were more or less significant except for age and parity. However, when the same variables were tested in patients considered at high risk initially, only three factors were statistically significant. Those three factors were the only ones associated with a statistically significant higher relative death risk (RR) on multivariate analysis and are as follows: an antecedent nonmolar pregnancy (RR = 4.3; P < 0.01); initial presentation with more than one metastatic organ (RR = 7.4; P < 0.01); and primary resistance to single agent (RR = 18.8; P < 0.0001) or multi‐agent chemotherapy (RR = 26.1; P < 0.0001). It seems that those three factors, together with a histologic diagnosis of choriocarcinoma, are the prognostic factors that discriminate patients with unfavorable outcomes among the high‐risk group.

Pharmacokinetics of 2-methyl-9-hydroxyellipticinium acetate (NSC-264137) in cancer patients (phase I study)

In 12 cancer patients we studied the pharmacokinetics of a new antitumor compound, elliptinium, which is a quaternary ammonium derivative of ellipticine, after i.v. infusion. The main parameters were calculated by means of the ADAPT program based upon plasma concentrations and urinary elimination determined by a high performance liquid chromatographic assay and fluorescence detection. The mean apparent volume of distribution for the central compartment, V1, is 2.8 l, the total plasma clearance is 971 ml/min, with a renal clearance of 127 ml/min. The mean elimination half-life, t1/2, z, is 23.7 hr, but shows a large interindividual variation. Urinary elimination is quite low (16%), with the main part (12%) excreted in the first 24 hr. In vitro plasma protein binding (78%) was found to be independent of the concentration (0.1-5.0 micrograms/ml).

Phase II Trial with High-Dose Elliptinium Acetate in Metastatic Renal Cell Carcinoma

Sixteen patients with adult metastatic renal cell carcinoma were treated with elliptinium acetate, 80 mg/m2.day, for 3 consecutive days every 3 weeks. Among the 14 patients evaluable, no objective effects were observed. The toxicity was mild and no patients experienced intravascular hemolysis.