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A non-myeloablative conditioning protocol containing dibromomannitol (DBM/cytosine arabinoside/cyclophosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from sibling donors. Risk factors include: accelerated phase (10 patients), older age (17 patients over >40 years) and long interval between diagnosis and BMT (27 months on average). Severe mucositis did not occur. Venoocclusive liver disease was absent. Infectious complications were rare. Although grade II-IV acute graft-versus-host disease (GVHD) was present in 9 (25%) cases, there were only 2 serious (III-IV) ones. Chronic GVHD occurred in 25 (69%) cases, preceded by acute GVHD in 9 of the 25 affected patients. Early hematological relapse, 7-29 weeks after BMT, developed in 6 patients (17.6%). No relapse was noted in the completely chimeric patients, however molecular genetic residual disease was observed in 6 patients, in most of them after transient short-term mixed chimeric state. Overall actual survival rate is 83.3% for the 36 cases, and leukemia-free survival is 72.2% for the 34 engrafted patients., (Copyright 2001 S. Karger AG, Basel.)

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisits to induce chimerism are immuno-suppression, myeloablation, or severe immunodeficiency of the recipients on the one side and donor originated immuno-hematopoietic cells in the graft on the other. The pathologic or special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion, and various kinds of solid organ grafting. Different types of chimerism are known including complete, mixed and mosaic, or split chimerism. There are various methods used to detect the type of chimera state, depending on the immunogenetic differences between the donor and recipient. The induction of complete or mixed chimerism is first determinated by the effect of myeloablative therapy. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of GVHD, and the rate of relapse. However, the most important contribution of the chimeric state is in development of graft versus leukemia effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.

A new, radiation-free, conditioning protocol, containing the original Hungarian mitobronitol (DBM) (DBM/ cytosine arabinoside/cyclosphosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from HLA identical sibling donors between 1990-1997. In spite of some prognostically disadvantageous factors (half of them were above 40 years, 10 out of 36 patients were in accelerated phase, the disease history was longer than 2 years in average) the overall survival (30/36) and the leukemia free survival rate (26/36) were in accordance with the best international results. Transplantation-related toxicity was remarkably reduced in comparison to bone marrow transplantation performed by total body irradiation/cyclophosphamide (TBI/Cy) or busulphan/cyclophosphamide (Bu/Cy) conditioning protocols. Acute graft versus host disease was present in lower percentage (9/36) and the number of serious cases was only 2/36. Chronic GVH disease, generally known to be associated with antileukemic effect (GVL), occurred in 25 of cases. Early haematological relapse among the 34 patients with functioning graft occurred in 6 patients which rate is slightly higher than reported after TBI/Cy or Bu/Cy conditioning treatment. There was no relapse among patients transplanted within one year post-diagnosis and patients having CML with accelerated phase. The leukemia free post-transplant period was in association with the chronic GVH disease and full chimeric state.