Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy.
Eighty-two patients with advanced multiple myeloma (MM) were enrolled in 2 sequential clinical studies of 1 or 2 courses of myeloablative therapy with stem cell support. Conditioning regimens consisted of high-dose melphalan (MEL) with or without total body irradiation (TX1 = 35) and MEL as the first preparative regimen, followed within 6 months by busulfan and melphalan (TX2 = 47). On the basis of adequate stem cell harvest, 31 patients (TX1 = 13; TX2 = 18) were transplanted with highly purified CD34+ cells. Positively selected stem cells did not adversely affect hematopoietic reconstitution compared with unmanipulated peripheral blood stem cell. Overall, the complete remission (CR) rate of evaluative patients was 13.8% and 41% for single and double autotransplant, respectively (P =.04). Moreover, 3 patients undergoing TX2 achieved molecular remission and 2 remain PCR-negative after 36 and 24 months from autograft. The median event-free survival (EFS) durations for TX1 and TX2 were 17 and 35 months, respectively (P =.03). Actuarial 3-year overall survival for patients treated with 1 or 2 transplants are 76% and 92%, respectively (P = NS). On multivariate analysis, superior EFS was associated with low beta2 microglobulin (beta2-M) level at diagnosis and TX2, whereas overall survival was correlated with beta2-M. Positive selection of CD34+ cells did not influence the achievement of clinical or molecular CR, as well as remission duration or survival of MM patients. Thus, whereas multiple cycles of high-dose therapy may be beneficial for patients with myeloma, the clinical impact of tumor cell purging remains highly questionable.
Lemoli
R M
RM
Institute of Hematology, Department of Pediatrics, University of Bologna, Bologna, Italy.
Martinelli
G
G
Zamagni
E
E
Motta
M R
MR
Rizzi
S
S
Terragna
C
C
Rondelli
R
R
Ronconi
S
S
Curti
A
A
Bonifazi
F
F
Tura
S
S
Cavo
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D002066:Busulfan; D008558:Melphalan