Randomized trial with Poly A-Poly U as adjuvant therapy complementing surgery in patients with breast cancer: in vitro study of cellular immunity.

The immunologic reactivity of patients with initially operable breast cancer was measured by the leukocyte migration inhibition test using autologous tumor extract (T), autologous serum (S), and a combination of both (T + S). These patients formed part of a randomized clinical trial comparing, on the one hand, conventional treatment and, on the other, conventional treatment complemented by injections of poly A-poly U. A sequential study was carried out on 159 patients, testing them 7 days, 2 months, 4 months, and 1 year after the operation. Statistical comparisons revealed no significant difference in the reaction of the two groups. In addition, no significant differences were found between those with lymph node involvement and those without. Radiotherapy given to those with lymph node involvement did not significantly change their reactions. We were able to show that the percentage of patients with a positive leukocyte migration inhibition test (LMIT) increases regularly and significantly with time. This study confirmed the presence in some autologous serum of a synergistic factor (SS factor) which increased the inhibition of migration of leukocytes by autologous tumor extract. This factor was found in 18 patients, equally divided between both therapeutic groups. In the group with SS factor, the percentage with lymph node involvement appeared greater (83% compared with 68% among those patients who had no SS factor), and the incidence of metastases was also increased (44% compared with 21%). This factor seemed to indicate a bad prognosis. However, there was a difference in the results between the two therapeutic groups in patients with the synergistic factor. Of nine patients undergoing conventional treatment, six had devleoped metastases, whereas only two out of the nine patients who also poly A-poly U developed metastases. The same trend was observed in the whole trial population.

Successful infusion of 40 cryopreserved autologous bone-marrows. In vitro studies of the freezing procedure.

Cryopreservation of human bone marrow may be helpful to use supralethal chemoradiotherapy in order to cure malignant diseases. We report here a cryopreservation procedure from large volumes of human bone marrow which can be applied in routinal use. Whole bone marrow in 10% Dimethylsulfoxide (ME2SO) was frozen at an 1 degree C/min. controlled rate and was stored into liquid nitrogen. After thawing and before infusion, both ME2SO and free hemoglobin were removed. The in vitro recovery of nucleated cells and the myeloid stem cell assay (CFC) were performed as quality control. About 60% of the marrow cells and 40% of the total CFC number were recovered at the end of the procedure. Using this technique, 40 patients (25 children with malignant lymphoma and 15 adults with lymphoma and solid tumors) were transplanted with autologous cryopreserved bone marrow after receiving intensive chemotherapy. Three of them received both chemotherapy and a total body irradiation. Engraftment was achieved in all patients. Rise in leucocyte count (greater than 1.10(9)/l) occurred within an average of 17 days. In conclusion, in autologous bone marrow transplantation, this method of cryopreservation is effective to obtain rapid hematological reconstitution in patients treated for malignant diseases by intensive cytoreductive regimens.

Hematopoietic recovery following autologous bone marrow transplantation: role of cryopreservation, number of cells infused and nature of high-dose chemotherapy.

Twenty-nine patients were treated with single or combined high-dose melphalan therapy followed by autologous bone marrow transplantation. Hematopoietic recovery from these treatments was studied. No correlation was found between the number of GM-CFC infused and the time required for hematopoietic recovery. It is suggested that this correlation is only demonstrable for low 'doses' of infused bone marrow cell and/or GM-CFCs. The role of bone marrow cell preservation techniques was examined and results were similar for fresh and cryopreserved bone marrow. The erythrocyte, lymphocyte and granulocyte levels of the patients reported here reached a normal or subnormal hematological steady state 3 months after autograft. Our results confirm the value of cryopreservation techniques. Hematopoietic recovery was short and of the same duration whether the patients were given single or combined high-dose melphalan before autologous bone marrow transplantation. These results also demonstrate the value of such transplantation in shortening the myelosuppression caused by high-dose chemotherapy.

Potential therapeutic role of cisplatinum in autologous bone marrow transplantation: in vitro eradication of neuroblastoma cells from bone marrow.

Cisplatinum may prove to be a valuable agent for the elimination of diseased cells in the bone marrow of patients with neuroblastoma. In this study, we measured the efficacy of cisplatinum on human neuroblastoma cell lines and on normal human bone marrow progenitors, GM-CFC and CFU-F. Data indicate that the therapeutic index of cisplatinum is high. We set up an experimental model consisting of a mixture of human bone marrow and human neuroblastoma cells in order to confirm these preliminary results in purging conditions. Results indicate that cisplatinum exhibits a high and specific tumoricidal property and appears to be valid in bone marrow purging.