Graft-versus-leukemia in rat MHC-mismatched bone marrow transplantation is merely an allogeneic effect.
One of the major problems in the treatment of leukemia with bone marrow transplantation (BMT) remains leukemia relapse. It has been clearly shown that graft-versus-host disease (GVHD) is accompanied by a graft-versus-leukemia reaction (GVLR) which reduces the incidence of leukemia relapse. To date, discussion is still going on as to whether GVHD and GVLR are either two different reactions or are exerting their effects through the same mechanism(s). In two rat leukemia models, namely the Brown Norway acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia L4415, total body irradiation (TBI) was given to induce a state of so-called minimal residual disease (MRD). Subsequently, it was attempted to evoke a GVLR distinct from GVHD by using semi-allogeneic hybrid-to-parent or parent-to-hybrid BMT, with or without the addition of graded numbers of lymphocytes. In both leukemia models applying hybrid-to-parent BMT, the addition of high numbers of semi-allogeneic lymphocytes to the semi-allogeneic graft had no antileukemic effect. In parent-to-hybrid BMT, the grafts sharing their alloantigens with the leukemia cells did not induce an anti-leukemic effect, irrespective of the number of lymphocytes present in the graft or the induction of evident GVHD. When the parental graft was histoincompatible with the leukemia cells, transplantation of bone marrow alone induced a significant increase in life span correlating with 2.8 log leukemia cell kill (LCK).(ABSTRACT TRUNCATED AT 250 WORDS)
Kloosterman
T C
TC
Institute of Hematology, Erasmus University Rotterdam, The Netherlands.
Martens
A C
AC
van Bekkum
D W
DW
Hagenbeek
A
A
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology*; D006087:Graft vs Host Reaction / Q000276:immunology*; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D008285:Major Histocompatibility Complex / Q000502:physiology*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D051381:Rats; D011914:Rats, Inbred BN; D012008:Recurrence; D016019:Survival Analysis; D014184:Transplantation, Homologous