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Immunity to trophoblast neoplasms by the children of choriocarcinoma mothers
SOCIETY
OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
261
employed for the remaining patients were vincristine/actinomycin D/and cytoxan (VAC) in 25, vinblastinei bleomyciniand cis-platinum (VBP) in 2, and VBP/actinomycin D/adriamycin in one patient. Two patients failed initial therapy but had complete remissions with second regimens. Only one patient with a stage IA mixed germ cell tumor has failed multiple regimens. She is alive with disease. Of the 30 patients with ImT, EST, or MGC tumors 24 have had negative second-look laparotomies. One additional patient had a negative second-look laparoscopy and four are scheduled for secondlook procedures. No patients with negative findings at laparotomy have recurred subsequently. In summary 36 of 37 patients with malignant ovarian germ cell tumors remain without evidence of disease with median follow-up of 49 months. The primary tumors were large. Multiple agent chemotherapy has dramatically improved the prognosis of these patients such that survival in this series was independent of prognostic factors including stage and grade of disease. Patients who fail primary chemotherapy can achieve complete remissions with intensive “second-line” regimens. to Trophoblast Neoplasms by the Children of Choriocarcinoma Mothers. R. A. PATTILLO, A.C.F. RUCKERT, AND R. F. MATTINGLY, The Medical College of Wisconsin, Department of Gynecology and Obstetrics, 8700 West Wisconsin Avenue, Milwaukee. Wisconsin 53226.
21. Immunity
The children of postgestational choriocarcinoma mothers have been examined for susceptibility or resistance to the malignancies of their placental cells. Historical evidence would suggest that their placental cells had been transformed to malignancy during their intrauterine life. On the basis of the foregoing premise, three questions can be asked: (I) Did their lymphocytes become sensitized to the malignancy during intrauterine gestation? (2) Did their lymphocytes retain the memory of this event? and (3) Have their lymphocytes retained cytotoxicity to the choriocarcinoma, thus affording resistance to choriocarcinoma? The results were affirmative to each question, In all instances, the mother’s choriocarcinomas had been grown in tissue culture and lymphocytes from the child were incubated to determine their recognition and cytotoxic capacity to kill these malignant cells from their own placenta as well as from other patients with malignant trophoblastic disease. Two of the mothers had died from resistant widespread disease; three were free of disease for up to I1 years. All children showed immunity to choriocarcinoma cells. 22. Plasma Methotrexate (MTX) Levels in Patients with Gestational Trophoblastic Neoplasia (GTN) Treated by Various Methotrexate Regimens. J. ROTMENSCH, N. ROSENSHEIN, R. DANEHOWER, M. AND J. VILLAR, Department of Gynecology and Obstetrics. The Johns Hopkins Hospital, Baltimore, Maryland 21205.
DILLON,
An optimal MTX regimen and mode of administration for the treatment of GTN has not been defined. In an attempt to compare two standard regimens, MTX plasma levels for GTN were measured after intravenous (iv) and intramuscular (im) administration. In Regimen I, MTX (1 mg/kg) on Days I, 3, 5, and 7 and citrovorum factor (CF) on Days 2, 4, 6, and 8 were administered. Each cycle was alternated between iv and im administration every 3 weeks, allowing each patient to be her own control. Five patients were treated with Regimen I for I6 cycles, (8 iv and 8 im). The mean MTX plasma levels were 2.94 x IOe6, 3.53 x 10mR,and 6.46 x IO-’ M after iv MTX administration and 3.87 x 10m6,3.39 x IO-‘, and 4.25 x IO-’ M after im administration at I, 24, and 48 hr, respectively. Four patients were treated with Regimen 2 for I5 cycles (8 iv and 7 im). The mean MTX plasma levels post-MTX administration were 2.04 x lOmh,4.61 x IOmR,and 1.98 x IO-’ M after iv administration and 1.75 x 10e6, 5.87 x IO-‘, and 1.55 x IO-* M after im administration at I, 12, and 24 hr, respectively. No hematological, renal, or hepatic toxicity occurred with either regimen. Only one patient on single-agent MTX had severe stomatitis. The data indicate that in the MTX-CF regimen, MTX plasma levels were statistically greater at I hr after im administration and at 48 hr after iv administration but probably were not of clinical importance. In the single-agent regimen, there were no differences in MTX by iv or im administration. The low MTX concentrations seen at 48 hr in the MTX-CF regimen support the hypothesis that reduced toxicity may be related not to the CF but to the 48-hr administration interval. Prolonged exposures to minimal concentrations of MTX of less than lOen M in the 8-day regimen may explain the reportedly increased resistance in the MTX-CF regimen.
OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
261
employed for the remaining patients were vincristine/actinomycin D/and cytoxan (VAC) in 25, vinblastinei bleomyciniand cis-platinum (VBP) in 2, and VBP/actinomycin D/adriamycin in one patient. Two patients failed initial therapy but had complete remissions with second regimens. Only one patient with a stage IA mixed germ cell tumor has failed multiple regimens. She is alive with disease. Of the 30 patients with ImT, EST, or MGC tumors 24 have had negative second-look laparotomies. One additional patient had a negative second-look laparoscopy and four are scheduled for secondlook procedures. No patients with negative findings at laparotomy have recurred subsequently. In summary 36 of 37 patients with malignant ovarian germ cell tumors remain without evidence of disease with median follow-up of 49 months. The primary tumors were large. Multiple agent chemotherapy has dramatically improved the prognosis of these patients such that survival in this series was independent of prognostic factors including stage and grade of disease. Patients who fail primary chemotherapy can achieve complete remissions with intensive “second-line” regimens. to Trophoblast Neoplasms by the Children of Choriocarcinoma Mothers. R. A. PATTILLO, A.C.F. RUCKERT, AND R. F. MATTINGLY, The Medical College of Wisconsin, Department of Gynecology and Obstetrics, 8700 West Wisconsin Avenue, Milwaukee. Wisconsin 53226.
21. Immunity
The children of postgestational choriocarcinoma mothers have been examined for susceptibility or resistance to the malignancies of their placental cells. Historical evidence would suggest that their placental cells had been transformed to malignancy during their intrauterine life. On the basis of the foregoing premise, three questions can be asked: (I) Did their lymphocytes become sensitized to the malignancy during intrauterine gestation? (2) Did their lymphocytes retain the memory of this event? and (3) Have their lymphocytes retained cytotoxicity to the choriocarcinoma, thus affording resistance to choriocarcinoma? The results were affirmative to each question, In all instances, the mother’s choriocarcinomas had been grown in tissue culture and lymphocytes from the child were incubated to determine their recognition and cytotoxic capacity to kill these malignant cells from their own placenta as well as from other patients with malignant trophoblastic disease. Two of the mothers had died from resistant widespread disease; three were free of disease for up to I1 years. All children showed immunity to choriocarcinoma cells. 22. Plasma Methotrexate (MTX) Levels in Patients with Gestational Trophoblastic Neoplasia (GTN) Treated by Various Methotrexate Regimens. J. ROTMENSCH, N. ROSENSHEIN, R. DANEHOWER, M. AND J. VILLAR, Department of Gynecology and Obstetrics. The Johns Hopkins Hospital, Baltimore, Maryland 21205.
DILLON,
An optimal MTX regimen and mode of administration for the treatment of GTN has not been defined. In an attempt to compare two standard regimens, MTX plasma levels for GTN were measured after intravenous (iv) and intramuscular (im) administration. In Regimen I, MTX (1 mg/kg) on Days I, 3, 5, and 7 and citrovorum factor (CF) on Days 2, 4, 6, and 8 were administered. Each cycle was alternated between iv and im administration every 3 weeks, allowing each patient to be her own control. Five patients were treated with Regimen I for I6 cycles, (8 iv and 8 im). The mean MTX plasma levels were 2.94 x IOe6, 3.53 x 10mR,and 6.46 x IO-’ M after iv MTX administration and 3.87 x 10m6,3.39 x IO-‘, and 4.25 x IO-’ M after im administration at I, 24, and 48 hr, respectively. Four patients were treated with Regimen 2 for I5 cycles (8 iv and 7 im). The mean MTX plasma levels post-MTX administration were 2.04 x lOmh,4.61 x IOmR,and 1.98 x IO-’ M after iv administration and 1.75 x 10e6, 5.87 x IO-‘, and 1.55 x IO-* M after im administration at I, 12, and 24 hr, respectively. No hematological, renal, or hepatic toxicity occurred with either regimen. Only one patient on single-agent MTX had severe stomatitis. The data indicate that in the MTX-CF regimen, MTX plasma levels were statistically greater at I hr after im administration and at 48 hr after iv administration but probably were not of clinical importance. In the single-agent regimen, there were no differences in MTX by iv or im administration. The low MTX concentrations seen at 48 hr in the MTX-CF regimen support the hypothesis that reduced toxicity may be related not to the CF but to the 48-hr administration interval. Prolonged exposures to minimal concentrations of MTX of less than lOen M in the 8-day regimen may explain the reportedly increased resistance in the MTX-CF regimen.