26 Scientific Program and Abstracts

ADOPTIVE I M M ~ Y AGAINST A ~ O R WIDESPREAD TUMOR OF A HIGHLY MALIGNANTAND POORLY I~ICMOUSE ~IALI210 K.Kawashima, E.Nagura, F.Nagase, I.Nakashima and K.Yamada University of Nagoya, Depts of Int.Med., Clin.Labo. and Inrnunol., Nagoya, Japan

It is generally known that tumor-specific immune cells might play an important role in eliminating minimal residual tumor cells. The aim of this study was to investigate what are the proper route of administration and the proper preparation of effector cells for adoptive inununotherapy. The present work was performed in a highly malignant, poorly imm- unogenic LI210 leukemia/CD2F 1 mice system in which a highly effective, specific anti- tumor ~unity was generated. (Int.J.Cancer 1983) Regardless of the sites of tumor inject ion, i.p., s.c., i.v., or i.c., the tumor was completely rejected in hyperir~nune CD2F 1 mice. In Winn assays as an adoptive immunotherapy, an i.p. or s.c. injection of invnune spleen cells (ISC) was much more effective than its i.v. or i.c. injection. In the latter two groups, even higher-dose ISC revealed no inhibitory effect on leukemia cells dissemi- nated within ~e blood or the CNS. However, by a secondary in vitro culture of ISC with killed LI210 cells, ISC could be rendered more effective in killing the tumor in the CNS. The i.c. administration of secondarily in vitro sensitized ISC might be one way to eradi- cate (INS leukemia. When analysing the phenotype of effector cells by the elimination test, tumor rejection largely depended on Lyt-l+2 - cells. Thus, the choice of the proper route of administration as well as the appropriate in vitro sensitization is crucial for effec- tive in~nunotherapy of a highly malignant tumor.

RADIOLOGICAL BONE CHANGES AS INDICATOR IN RESIDUAL LEUKEMIA

G.G. Munteanu and M.N. Cristescu Hospital of M.T.Tc.no.2, Dept. of Radiotherapy, Bucharest, Rumania. In spite of modern technical investigations for the discovery of Residual Leukemia (RL), we tried to establish - with the same aim - the relation between relapse - remission and pain-bone changes in Acute Leukemia (AL) using the simple classical radiographs of bones. From a retrospective study (1965-1975) of 135 cases with AL, we extract 34 cases (15 ALL, 15 AGL and 3 Di Guglielmo). The treatment was according to that period. The results were: in AGL bone changes and pain appear in most of the cases (6) after Ist relapse. In ALL, most of the cases (4) appear after 3th relapse and the minimum (i) after 5th relapse. In Di Guglielmo, all cases were in clinical and haematological remis- sion without bone changes. Conclusions: the bone pain which occurs in different stages of the disease was reduced after treatment. The bone changes in ALL appear later (3rd relapse) than in AGL (Ist relapse). The type of lesion was the same in ALL and AGL and was dependent on the number and quality of relapses. The maintenance of the radiological findings in bone changes after the clinical and haematological remission may suggest the presence of RL maintained from "sanctuary nidus" hidden in bones.

DETECTION OF RESIDUAL MALIGNANT CELLS IN JUVENILE CHRONIC MYELOGENOUS LEUKEMIA (JCML) Melvin H. Freedman and Zeev Estrov Div of Hematology, Hosp for Sick Children, Univ of Toronto, Toronto, Canada JCML is a hematopoietic malignancy of early childhood with a median survival of 9 mos. Therefore, we initiated intensive chemotherapy and now are ohserving long-term "remissions". To assess completeness of "remission", we used ceil cultures to detect small numbers of JCML malignant cells in bone marrow (BM) and peripheral blood (PB). At diagnosis, BM and PB cells from 9 pts were studied using liquid cultures and assays for CFU-C and CFU-GEMM. All specimens showed 2 reproducible abnormalities; impaired growth of normal hematopoietic progenitors, and cytogeneticaliy-proven, CSA-independent clonal proliferation of monocyte-macrophage colonies in excessive numbers. Co-cultures of BM adherent or non-adherent cells with control BM resulted in suppressed growth of normal hematopoietic colonies, and supernatant from cultured JCML adherent cells or pts' plasma suppressed control BM colony growth in a dose-dependent manner, indicating the secretion of an inhibitory monokine by the malignant cells. Serial studies of "normal" BM and PB from pts in "remission" showed either complete disappearance of all abnormal- ities, or incomplete remission with persistence of abnormal clonal leukemic cell proliferation in culture and production of the monokine. Identification of minimal residual disease has prompted a change or an intensification of therapy. The cell culture results for JCML are striking, unique to this disease, and have important applications as a diagnostic tool and as a monitor of chemotherapy efficacy.