Myeloablative treatments for multiple myeloma: update of a comparative study of different regimens used in patients from the Spanish registry for transplantation in multiple myeloma.
After a previous analysis that did not detect clear differences in the results of three conditioning regimens used for autologous stem cell transplantation (ASCT) in patients from the Spanish Registry for Transplant in Multiple Myeloma (MM), we have updated the registry, including a larger number of cases and a fourth conditioning regimen with a longer follow-up. We evaluate 472 MM patients treated with 200 mg/m2 melphalan (MEL200), 135 patients treated with 140 mg/m2 melphalan plus total body irradiation [(MEL140 + TBI)], 186 patients treated with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL) and 28 patients treated with 14 mg/kg busulphan followed by cyclophosphamide 120 mg/kg (BUCY). There were no significant differences in respect to either transplant related death or haematological recovery, regardless of growth factor use, between the four conditioning programs. Nevertheless, hospitalization time with MEL200 was less than with BUMEL when growth factors were used (19+/-9 vs. 25+/-9 days, P = 0.009) and less than with MEL140 + TBI without growth factors (20+/-8 days vs. 27+/-9 days, P = 0.002). In patients with measurable disease at ASCT (non-complete remission [CR]), BUMEL achieved a 51% CR vs. 43%-31% in the other groups (P = 0.007). The response rate for patients in partial remission (PR) at ASCT was 100% with BUMEL vs. 93%-86% in the other groups (P between 0.02 and 0.0007). The median overall survival (OS) for the BUMEL group was 57 months (95% confidence interval [CI]: 51-78) as compared to 45 (CI: 36-64) months for the MEL200 group and 39 (CI: 28-72) months for the MEL140 + TBI and BUCY groups. The median event free survival (EFS) was longer in the BUMEL group [30 (CI: 22-44) mo] than in the MEL200 [22 (CI: 18-26) mo], BUCY [23 (CI: 11-50) mo] or MEL140 + TBI groups [20 (CI: 15-29) mo]. Nevertheless, the differences in OS and EFS did not reach statistical significance in either the univariate analysis or the multivariate analysis adjusted with other high prognostic weight factors. As in the initial study, differences in regards to the anti-myeloma effect of the conditioning regimens are not conclusive. However, the better response rates associated with the favorable tendency in outcome achieved with BUMEL, continue to justify further prospective studies.
Lahuerta
Juan José
JJ
Spanish Stem Cell Transplantation Group (GETH), Spanish Society of Hematology, Madrid. jjlahuerta@terra.es
Grande
Carlos
C
Blade
Joan
J
Martínez-López
Joaquín
J
de la Serna
Javier
J
Alegre
Adrian
A
Garcia
Laraña Jose
LJ
Caballero
Dolores
D
de la Rubia
Javier
J
Marín
Julián
J
Perez-Lopez
Cristina
C
Sureda
Anna
A
Escudero
Antonio
A
Cabrera
Rafael
R
Conde
Eulogio
E
García-Ruiz
Juan Carlos
JC
Pérez-Equiza
Katty
K
Hernandez
Fernado
F
Palomera
Luis
L
León
Angel
A
Giraldo
Pilar
P
Solano
Carlos
C
Bargay
Joan
J
San
Miguel Jesús
MJ
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000592:standards / Q000633:toxicity; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D019653:Myeloablative Agonists / Q000592:standards / Q000627:therapeutic use* / Q000633:toxicity; D012042:Registries; D012074:Remission Induction / Q000379:methods; D013030:Spain; D033581:Stem Cell Transplantation / Q000379:methods / Q000401:mortality / Q000592:standards; D016019:Survival Analysis; D013810:Therapeutic Equivalency; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality / Q000592:standards; D014916:Whole-Body Irradiation
D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D002066:Busulfan; D008558:Melphalan