Unrelated donor haematopoietic cell transplantation after non-myeloablative conditioning for patients with high-risk multiple myeloma.
BACKGROUND
Allografting induces long-term molecular remissions and possibly cure in myeloma patients. The development of non-myeloablative conditionings has reduced the transplant-related mortality (TRM) associated with myeloablation and extended the eligible age for transplantation. Moreover, high response rates are reported especially when allografting is preceded by cytoreductive high-dose chemotherapy. We investigated the feasibility of unrelated donor non-myeloablative transplantation as either part of the initial treatment plan or as salvage treatment in heavily pretreated patients.


METHODS
Twenty-two patients underwent non-myeloablative allografting, 10 as part of their initial treatment and 12 at relapse. Donors were matched for HLA-A, B, C, DRB1 and DQB1 by high-resolution typing. Only one single class I allele disparity was allowed. Conditioning consisted of fludarabine 90 mg/m(2) and 2 Gy total body irradiation. Graft-vs.-host disease (GVHD) prophylaxis included cyclosporin and mycophenolate mofetil.


RESULTS
All patients except two (91%) readily engrafted. After a median follow-up of 20 (10-30) months, incidences of grade II-IV acute and extensive chronic GVHD were 50% and 61%. Overall response (OR) was 55%, with four (20%) complete and seven (35%) partial remissions. However, in patients allografted up-front OR was 89% whereas in the heavily pretreated group OR was 27% (P = 0.01). Two-year overall and event-free survivals were both 79% in the group transplanted up-front and 27% and 25% among relapsed patients (P = 0.025 and P = 0.006, respectively). Overall, six patients died of TRM and three of disease progression.


CONCLUSIONS
Unrelated donor non-myeloablative allografting is feasible in myeloma. Disease control appears more pronounced when patients are treated soon after diagnosis.
Bruno
Benedetto
B
Division of Hematology at the San Giovanni Battista Hospital, University of Torino, Torino, Italy. benedetto.bruno@unito.it
Sorasio
Roberto
R
Patriarca
Francesca
F
Montefusco
Vittorio
V
Guidi
Stefano
S
Busca
Alessandro
A
Scimé
Rosanna
R
Console
Giuseppe
G
Milone
Giuseppe
G
Marotta
Giuseppe
G
Dominietto
Alida
A
Giaccone
Luisa
L
Rotta
Marcello
M
Falda
Michele
M
Bacigalupo
Andrea
A
Bosi
Alberto
A
Corradini
Paolo
P
Fanin
Renato
R
Pollichieni
Simona
S
Boccadoro
Mario
M
D000328:Adult; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D009367:Neoplasm Staging; D012307:Risk Factors; D016879:Salvage Therapy; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome