Thiotepa and fludarabine (TT-FLUDA) as conditioning regimen in poor candidates for conventional allogeneic hemopoietic stem cell transplant.

Abstract:

:Standard conditioning for allogeneic bone marrow transplantation induces high transplant-related mortality (TRM) in patients with a poor performance status. Less intensive regimens have been tested to reduce the TRM; our purpose 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/m2 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/m2 i.v. at day -12. Graft-versus-host-disease (GVHD) prophylaxis was performed i.v. 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 methotrexate/m2 at day +1, and 8 mg/m2 at days +3, +6, and +11. Chimerism was studied 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 chimerism in all but one patient who had refractory acute leukemia. No major toxicity was noticed; only one patient died at day +51 of acute GVHD because of early cyclosporine A discontinuation. One patient with refractory non-Hodgkin's lymphoma (NHL) had a testicular relapse at day +180. Three patients (one with mantle cell lymphoma, two with acute myeloid leukemia) are still in continuous complete remission (CR) with complete donor chimerism at days +180, +210, and +450, respectively. TT-FLUDA seems to be well tolerated, allowing engraftment and stable donor chimerism in patients who are poor candidates for conventional conditioning regimens.

journal_name

Ann Hematol

journal_title

Annals of hematology

authors

Alessandrino EP,Bernasconi P,Colombo AA,Caldera D,Bonfichi M,Pagnucco G,Malcovati L,Varettoni M,Lazzarino M,Bernasconi C

doi

10.1007/s002770100344

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

521-4

issue

9

eissn

0939-5555

issn

1432-0584

journal_volume

80

pub_type

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