Early post-BMT liver function in children conditioned for bone marrow transplantation with busulfan-containing and with hyperfractionated TBI-containing preparative regimens
Abstract
Liver toxicity following preparatory regimen (prep-reg) for bone marrow transplantation (BMT) creates one of the major problems in the early post-BMT period, especially in patients (pts.) with pretransplant HCV and/or HBV infections, and liver dysfunction. This gave rise to the search for prep-reg, that would be less hepatotoxic, but would still have sufficient antileukemic effect. Therefore, we compared liver function in children prepared for allo-BMT with busulfan-containing and with hyperfractionated TBI-containing regimens.
Patients and methods
Seventeen pts. have been conditioned with busulfan-containing prep-reg (10 with BuVpCy, 7 with BuCy) (Bu-group). Diagnosis consisted of ALL (6) and AML (11). All pts. fram Bu-group have been transplanted with bone marrow from HLA-identical, MLC non-reactive siblings. Pretransplant screening showed positive HBsAg in one patient, and HCV antibody in 6 pts. For GvHD prevention CsA+MTX have been given in 12 pts., CsA+MTX+PRED in 3 pts., and CsA alone in 2 pts. Acute GvHD II- IVO occured in 4 pts. Hyperfractionated TBI (hFTBI) (2 × 1,5 Gy on 4 consecutive days) was employed in 10 pts. (hFTBI+Cy in 6 pts., hFTBI+Vp in 4 pts.) (hFTBI-group). Nine pts. were transplanted for ALL, and one child for AML. Nine pts. from hFTBI-graup have been transplanted with bone marraw fram HLA-identical, MLC non-reactive siblings, and one child from a syngeneic twin. For GvHD prevention 5 pts. have been treated with CsA+MTX, 2 with CsA+PRED, and 2 with CsA alone (recipient of syngeneic bone marrow received no GvHD prophylaxis). Acute GvHD IIO was observed in one child. For HVOD prevention in all children from both groups continuous infusion of alprostadil and/or low-dose heparin (100 units/kg/day) has been administered. Total bilirubine concentration, alanine aminotransferase (AIAt) and aspartate aminotransferase (AspAt) activity were measured in serum on day −10, −1, +7, +14, +21, +28 and +35 by automated chemical analysis using standard reagents.
Results
One child (AML, pos. HCV antibody, BuCy, CsA alone for GvHD prevention) from Bu-group developed on day +18 day recurrent form of severe HVOD leading to the death on day +102.
Conclusions
According to liver function parameters observed till day +35 post-BMT, ie. during the period, when the risk of HVOD is highest, hFTBI seems to be less hepatotoxic than busulfan-containing prep-reg. Therefore BM-recipients with liver dysfunction observed prior to BMT should rather be prepared for transplantation with hFTBI.