Reduced intensity thiotepa-cyclophosphamide conditioning for allogeneic haemopoietic stem cell transplants (HSCT) in patients up to 60 years of age.
Transplant-related mortality (TRM) remains a major problem in older patients undergoing allogeneic haemopoietic stem cell transplants (HSCTs). We have therefore explored a less intensive conditioning in 33 patients with a median age of 52 years (range 43-60) transplanted from human leucocyte antigen (HLA)-identical siblings. The underlying disease was chronic myeloid leukaemia (n = 15), acute myeloid leukaemia (n = 6), myelodysplasia (n = 7) or a chronic lymphoproliferative disorder (n = 5); 15 patients (45%) had advanced disease. The regimen consisted of thiotepa (THIO; 10 mg/kg) on day -5 and cyclophosphamide (CY; 50 mg/kg) on days -3 and -2 (total dose 100 mg/kg). The source was bone marrow (BM) (n = 17) or granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) (n = 16), which were infused without manipulation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and a short course of methotrexate. Mean time to achieve a neutrophil count of 0.5 x 109/l was 17 d (range 11-23) and full donor chimaerism was detected in 79% of patients by day 100. Acute GVHD grade III or IV occurred in 3% of patients. Chronic GVHD was seen in 45% of patients, with a significant difference for PB (69%) compared with BM transplants (23%) (P = 0.009). For BM grafts, the actuarial 2-year TRM was 6%, the relapse 56% and survival 87%; for PB grafts, these figures were, respectively, 27%, 33% and 68%. Twenty-five patients are alive at a median follow-up of 762 d (range 216-1615) and 20 patients (60%) remain free of disease. Thirteen patients (39%) received donor lymphocyte infusion (DLI) either for persisting or relapsing disease and six patients had complete remission.


CONCLUSIONS
(i) patients up to the age of 60 years can be allografted with reduced intensity conditioning; (ii) the procedure was associated with a low transplant-related mortality, particularly for bone marrow grafts, because of a lower risk of chronic GVHD; and (iii) DLI were required after transplant in half the patients for persisting disease or relapse.
Dipartimento di Ematologia (DEMA), Ospedale San Martino, Dipartimento Medicina Interna (DIMI) and Cattedra Medicina Legale, Univesita', Genova, Italy. emato2@smartino.ge.it
A M
AM
Raiola
M T
MT
Van Lint
T
T
Lamparelli
F
F
Gualandi
N
N
Mordini
G
G
Berisso
S
S
Bregante
F
F
Frassoni
M
M
Sessarego
G
G
Fugazza
F
F
Di Stefano
A
A
Pitto
A
A
Bacigalupo
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000601:surgery; D007951:Leukemia, Myeloid / Q000401:mortality / Q000601:surgery; D008232:Lymphoproliferative Disorders / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000601:surgery*; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D013852:Thiotepa