Effect of chemotherapy with alkylating agents on the yield of CD34+ cells in patients with multiple myeloma. Results of the Spanish Myeloma Group (GEM) Study.
OBJECTIVE
Although alkylating agents are clearly beneficial in multiple myeloma (MM), their deleterious effect on bone marrow hematopoietic progenitor cells usually precludes their use as front-line therapy in patients scheduled to undergo autologous stem cell transplantation (ASCT). We analyzed the impact of first-line chemotherapy with alkylating agents on stem cell collection in MM patients.


METHODS
Seven hundred and eighty-nine patients included in the Spanish multicenter protocol GEM-2000 underwent mobilization therapy after four courses of alternating VBMCP/VBAD chemotherapy.


RESULTS
The mobilization regimens consisted of standard or high-dose granulocyte colony-stimulating factor (G-CSF) in 551 (70%) patients, and chemotherapy and G-CSF in 206 (26%) patients. The CD34+ cell yield was lower than 4x10(6)/kg in 388 patients (49%), and equal or greater than 4x10(6)/kg in 401 patients (51%). Multivariate analysis indicated that advanced age (p<0.0001) and longer interval between diagnosis and mobilization (p=0.012) were the two variables associated with a lower CD34+ cell yield. Significant differences in CD34+ cell yield were not observed between the mobilization regimens. Of the 789 patients included in the protocol, 726 (92%) underwent the planned ASCT, whereas 25 (3%) patients did not because of the low number of CD34+ cells collected. Following ASCT, 0.5x10(9) neutrophils/L could be recovered after 11 days (median time; range, 5-71 days) and 20x10(9) platelets/L could be recovered after 12 days (median time; range, 6-69 days).


CONCLUSIONS
A short-course of therapy with alkylating agents according to the GEM-2000 protocol was associated with an appropriate CD34+ cell collection, and allowed the planned ASCT to be performed in the majority of MM patients.
de la Rubia
Javier
J
Grupo Español de Mieloma. delarubia_jav@gva.es
Bladé
Joan
J
Lahuerta
Juan-José
JJ
Ribera
Josep M
JM
Martínez
Rafael
R
Alegre
Adrián
A
García-Laraña
José
J
Fernández
Pascual
P
Sureda
Anna
A
de Arriba
Felipe
F
Carrera
Dolores
D
Besalduch
Joan
J
García Boyero
Raimundo
R
Palomera Bernal
Luis
L
Hernández
Miguel T
MT
García
Paz Ribas
PR
Pérez-Calvo
Javier
J
Alcalá
Antonio
A
Casado
Luis Felipe
LF
San Miguel
Jesús
J
D000328:Adult; D000367:Age Factors; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001772:Blood Cell Count; D002330:Carmustine / Q000008:administration & dosage / Q000494:pharmacology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation; D011241:Prednisone / Q000008:administration & dosage / Q000494:pharmacology; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology
D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan; D002330:Carmustine; D011241:Prednisone