Selective lymphoid irradiation. V. Synergism with pretransplant thymectomy or thymic irradiation in cardiac transplantation in rats.

Selective lymphoid irradiation (SLI) using palladium-109-hematoporphyrin (Pd-H), given four days prior to transplantation, combined with two doses of antilymphocyte globulin (ALG) (10 mg, days -2 and -1), was evaluated as a method of induction of permanent heterotopic cardiac allograft survival in the highly histoincompatible rat strain combination of ACI (RT1(1))-to-Lewis (RT1a). Both Pd-H and ALG localize poorly in the thymus, so this study evaluated whether thymic irradiation (TI) or thymectomy (TX) of the adult recipient results in indefinite allograft survival. Immunosuppression with Pd-H or ALG alone gave a mean survival time (MST) of 6.7 +/- 0.6 days, but the combination of the two agents led to an MST of 17.6 +/- 3.4 days. When TI was combined with Pd-H and ALG, cardiac allograft survival was prolonged to 50.2 +/- 13.9 days, but TI alone showed an MST of 10.3 +/- 1.8 days. Permanent cardiac allograft survival (greater than 250 days) was achieved in all thymectomized recipients treated with the combination of Pd-H and a brief course of ALG. These animals also accepted second-set skin grafts and rejected third-party skin grafts following more than 150 days of ACI cardiac allograft survival. Thymic irradiation, although effective in acting synergistically with SLI and ALG, led to prolonged, but limited allograft survival, although thymectomy with SLI and ALG is synergistic in prolonging allograft survival permanently without chronic immunosuppression.

Potential of 109Pd-labeled lymphocytes for selective lymphatic ablation.

The biodistribution of lymphocytes labeled with 109Pd was investigated in Lewis rats to determine if they might be useful for selective lymphoid ablation. 109Pd-labeled lymphocytes demonstrated significant lymphoid localization. However, there was a fall in the accumulation of radiolabeled lymphocytes in lymphoid tissue when the 108Pd carrier dose or the 109Pd radioactive dose incorporated per 10(8) lymphocytes was increased from 0.12 mg to 0.20 mg and from 21.3 microCi to 54.6 microCi, respectively (P less than 0.001). 109Pd-labeled syngeneic and allogeneic lymphocytes demonstrated similar tissue distribution patterns. These results raise the possibility of using 109Pd-labeled lymphocytes for selective lymphoid ablation, but emphasize the need for using high specific activity 109Pd and large amounts of lymphocytes for labeling. This will minimize cell damage and allow maximum therapeutic results to be obtained. The use of large numbers of cells might best be accomplished by using donor lymphocytes.

[A case of advanced gastric cancer with Virchow's node metastasis, responding to concomitant plasma exchange and immunochemotherapy].

We report a case of advanced gastric cancer with Virchow's node metastasis which responded to concomitant plasma exchange and immunochemotherapy. Plasma exchange was conducted three times in total (once a week) using a membrane type plasma separator, with fresh frozen plasma as exchange fluid. Immunochemotherapy was performed simultaneously using MMC, FT and OK-432. By the end of the third plasma exchange, Virchow's node was confirmed by palpation and ultrasonic examination to have vanished. Diminution of the gastric cancer, and improvement of stenosis of the stomach were confirmed under endoscopy. We surmised that plasma exchange eliminated the immunosuppressive substances in serum, and intensified the anticancer effects of MMC and FT, resulting in the disappearance of the Virchow's node and diminution of the gastric cancer itself.

[Hepatic arterial infusion chemotherapy of hepatocellular carcinoma].

In 24 cases of unresectable hepatocellular carcinoma, we performed hepatic arterial catheterization and intra-arterial infusion chemotherapy. Adriamycin (ADM), Mitomycin C (MMC), 5-FU and Lipiodol (LPD) were administered an average of 13.5 times over a mean period of 106 days. Except for 5 unevaluable cases, there were 0 CR, 5 PR, 4 MR, 7 NC and 2 PD cases, for an efficiency rate of 27.8%. Complications thought to be due to the catheter included catheter blockade in 1 case (4.3%) and dermal infection of insertion site in 3 cases (13.0%). As for the results of follow-up study, one-year survival rate with this therapy was 47.8%, which compares favorably with a one-year survival rate of 30.0% in 30 cases treated only with TAE. From the above results, hepatic arterial infusion chemotherapy can be repeatedly performed on an outpatient basis, and it is considered to be a useful therapeutic method for treating unresectable hepatocellular carcinoma.

Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation.

The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators.(ABSTRACT TRUNCATED AT 250 WORDS)

Biodistribution of radiolabeled lymphocytes.

Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes (10(7)-10(9) syngeneic or allogeneic cells; 1-10 microCi [.037-.37 MBq]/10(8) cells) obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. However, In-111 labeled thymocytes or xenogeneic lymphocytes failed to accumulate in lymphoid tissue. In vitro irradiation of the In-111 labeled lymphocytes (100-400 rads [1-4 Gy]) before in vivo administration and increase of the In-111 to 40 microCi [1.48 MBq]/10(8) lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level, and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy.

The biodistribution of radiolabeled antilymphocyte monoclonal antibody in the rat.

The biodistribution of radiolabeled mouse anti-pan T monoclonal antibody (W3/13) against rat lymphocytes was examined in normal rats. Monoclonal antibody to human prostate-associated antigens (PAA) served as a control. In vitro studies demonstrated a 38% maximum binding of radiolabeled W3/13 to lymphocytes, which was significant (P less than 0.001) when compared with the control (PAA) value of 3.4%. In vivo, intravenously administered 111In labeled W3/13 and 131I labeled W3/13 exhibited similar tissue distribution patterns. The localization of W3/13 in lymphoid tissue was significantly greater than that achieved with PAA. W3/13, however, did not demonstrate significant localization in the intact thymus and accumulated to a higher degree (6-10% ID/g) than expected in bone marrow at 24 h. These findings suggest that radiolabeled anti-lymphocyte monoclonal antibodies may not be well suited for the treatment of lymphoreticular neoplasms and allograft rejection in patients.

Transfusión de granulocitos en pacientes neutropénicos febriles / Granulocyte transfusion in febrile neutropenic patients

Desde 1996 a la fecha hemos transfundido con granulocitos a 20 pacientes con 21 episodios de neutropenia febril con criterios de extrema gravedad. 14 episodios correspondieron a sepsis con germen conocido y 7 neutropenia febril sin germen aislado. Los pacientes recibieron un promedio de 3.7 aféresis, con 2.17(potencia 10) granulocitos por cada una. Los donantes fueron seleccionados entre familiares directos con estudios rutinarios para la donaci¢n de sangre, los que fueron condicionados con factor estimulante de colonias granulocíticas previa al procedimiento aferético. 15 pacientes sobrevivieron al episodio neutropénico con resolución de cuadro infeccioso. Las reacciones adversas transfucionales en los receptores fueron leves y no hubo complicaciones clínicas en los donantes. Las transfusiones de granulocitos parecen ser efectivas en pacientes con neutropenia febril sin respuesta a antibióticos