Ep. Alessandrino et al., Thiotepa and fludarabine (TT-FLUDA) as conditioning regimen in poor candidates for conventional allogeneic hemopoietic stem cell transplant, ANN HEMATOL, 80(9), 2001, pp. 521-524
Standard conditioning for allogeneic bone marrow transplantation induces hi
gh transplant-related mortality (TRM) in patients with a poor performance s
tatus. Less intensive regimens have been tested to reduce the TRM; our purp
ose was to evaluate the feasibility and tolerability of a new combination:
thiotepa and fludarabine (TT-FLUDA). Six patients received 5 mg thiotepa/kg
daily from day -8 to -7 and 25 mg fludarabine/m(2) daily from day -6 to -2
followed by an allogeneic peripheral blood progenitor cell infusion; three
of these patients with signs of overt leukemia received 18 mg idarubicin/m
(2) IV at day -12. Graft-versus-host-disease (GVHD) prophylaxis was perform
ed IV with 1 mg cyclosporine A/kg per day from day -5 to the day of marrow
engraftment, then 6 mg/kg per day orally up to day +100, and 10 mg methotre
xate/m(2) at day +1, and 8 mg/m(2) at days +3, +6, and +11. Chimerism was s
tudied with fluorescent in situ hybridization for sex chromosomes (XY FISH)
and minisatellite polymerase chain reaction (PCR) at days +30, +100, +180,
and +360. Engraftment was achieved in all cases with complete donor chimer
ism in all but one patient who had refractory acute leukemia. No major toxi
city was noticed; only one patient died at day +51 of acute GVHD because of
early cyclosporine A discontinuation. One patient with refractory non-Hodg
kin's lymphoma (NHL) had a testicular relapse at day +180. Three patients (
one with mantle cell lymphoma, two with acute myeloid leukemia) are still i
n continuous complete remission (CR) with complete donor chimerism at days
+180, +210, and +450, respectively. TT-FLUDA seems to be well tolerated, al
lowing engraftment and stable donor chimerism in patients who are poor cand
idates for conventional conditioning regimens.