Graft versus host disease (GVHD) and recurrence of basic disease are major
obstacles to a successful allogeneic bone marrow transplantation (BMT) outc
ome. One of the possibilities of maintaining the therapeutic potential of m
arrow allografting in the absence of GVHD is to intensify the conditioning
regimen administered pre-T-cell depleted BMT in order to compensate for the
loss of GVH related graft versus leukemia (GVL) effect. In order to do so
we used a preparative regimen consisting of three alkylating agents-Busulfa
n (BU), Thiotepa (TTP) and Cyclophosphamide (CY)-for T-cell depleted alloge
neic stem cell transplantation (SCT) instead of the standard BU-CY protocol
The effect of this intensified regimen was investigated in 30 consecutive
leukemia patients who underwent T-cell depleted SCT from HLA identical sibl
ings. Sixteen of the patients were males and 14 females, of median age 24 (
5-43) years. Fourteen patients had acute myelogenous leukemia (AML), ten ac
ute lymphoblastic leukemia (ALL), four chronic myelogenous leukemia (CML) a
nd two myelodysplastic syndrome. The conditioning regimen consisted of BU 4
mg/kg x 4 days (- 8 to - 5), TTP 5 mg/kg x 2 days (- 4 and - 3), and CY 60
mg/kg x 2 days (- 2 and - 1). Engraftment was normal, with WBC >1.0 x 10(9
)/1 at day + 18 (10-32), ANC > 0.5 x 10(9)/1 at day +21 (9-33) and platelet
s > 25 x 10(9)/1 at day + 30 (14-69). Regimen related toxicity (RRT) was mo
derate and transplant related complications comparable to other conventiona
l conditioning protocols. Overall survival and disease free survival (DFS)
at 60 months follow up was 50%. Only three patients (10%), with ALL, relaps
ed and subsequently died. From the current data it would appear that TTP do
es not significantly improve BMT outcome in patients with leukemia, when co
mpared to the standard BU-CY conditioning. However, our results with the BU
-TTP-CY combination followed by T-cell depleted allogeneic SCT could provid
e the basis for a prospective randomized study comparing this protocol with
the standard BU-CY regimen. (C) 1999 Elsevier Science Ltd. All rights rese
rved.