title: 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.
authors.affiliation: Centro Trapianti di Midollo Osseo, Istituto di Ematologia, IRCCS Policlinico S. Matteo, Pavia, Italy. alessandrino@smatteo.pv.it
authors.forename: E P
authors.initials: EP
authors.lastname: Alessandrino
authors.forename: P
authors.initials: P
authors.lastname: Bernasconi
authors.forename: A A
authors.initials: AA
authors.lastname: Colombo
authors.forename: D
authors.initials: D
authors.lastname: Caldera
authors.forename: M
authors.initials: M
authors.lastname: Bonfichi
authors.forename: G
authors.initials: G
authors.lastname: Pagnucco
authors.forename: L
authors.initials: L
authors.lastname: Malcovati
authors.forename: M
authors.initials: M
authors.lastname: Varettoni
authors.forename: M
authors.initials: M
authors.lastname: Lazzarino
authors.forename: C
authors.initials: C
authors.lastname: Bernasconi
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D013852:Thiotepa / Q000008:administration & dosage; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D013852:Thiotepa; D014740:Vidarabine; C024352:fludarabine