NON-SUPRALETHAL MITOBRONITOL CYTARABINE CYCLOPHOSPHAMIDE CONDITIONINGWITHOUT IRRADIATION BEFORE BONE-MARROW TRANSPLANTATION FOR ACCELERATED CHRONIC GRANULOCYTIC-LEUKEMIA - APPARENT ABSENCE OF ACUTE GRAFT-VERSUS-HOST DISEASE

Cytostatic chemotherapy instead of supralethal total body irradiation (TBI) has been increasingly used as an alternative myeloablative regim en before bone marrow transplantation (BMT). While irreversible azoosp ermia/amenorrhoea seems to occur less frequently with such conditionin g, graft-versus-host disease (GVHD) remains unaffected. Five-year dise ase-free survival in accelerated chronic granulocytic leukemia (CGL), after BMT with matched sibling grafts has been 0.1 0-0.30. Mitobronito l, cytosine arabinoside, and cyclophosphamide were used for conditioni ng. Patients were transplanted with unmanipulated HLA/MLC identical si bling bone marrow. For recovery, a pathogen-low room was available wit hout air filtering and laminar airflow. Seven of eight accelerated-CGL patients were engrafted: full allogeneic reconstitution was detected in four and mixed chimerism in three patients. Five out of the seven e ngrafted patients survived at least nine months (median = 42 months), two are considered cured (8-9 years survival). The four leukemia-free survivors displayed full allogeneic reconstitution and presented sympt oms of chronic GVHD. One patient became a genetically verified father. Acute GVHD and veno-occlusive liver disease (VOLD) were absent in all patients, diffuse interstitial pneumonitis (IP) occurred in one case. Non-supralethal conditioning with mitobronitol/cytarabine/cyclophosph osphamide in accelerated-CGL allows allogeneic bone marrow reconstitut ion with survival and cure rates comparable to those achieved with oth er protocols using TBI or busulphan conditioning. Unlike the latter tr eatments, however, our protocol leads to fewer transplant-related comp lications including acute GVHD, IP, VOLD, and azoospermia/amenorrhoea.