[Autologous bone marrow transplantation for patients with chronic myelogenous leukemia after in vitro purging of the graft with bcr/abl antisense oligodeoxynucleotides].
OBJECTIVE
To investigate the efficacy of autologous bone marrow transplantation (ABMT) for patients with chronic myelogenous leukemia (CML) after in vitro purging of the graft with bcr/abl antisense oligodeoxynucleotides (AS-ODN).


METHODS
Five CML patients, 2 in chronic phase (CP), 1 in accelerated phase (AP) and 2 in blast crisis (BC), all confirmed the presence of b3a2 bcr/abl mRNA by RT-PCR (reverse transcriptase-polymerase chain reaction). Patients had received 2 courses of intensive chemotherapy for "in vivo purging" before bone marrow harvesting. The autologous bone marrow cells were concentrated by CS3000plus and then incubated with 18-mer phosphorothioate bcr/abl AS-ODN (40 - 60 microg/ml, for 48 - 60 h). Conditioning regimens were TBI + Cy (total body irradiation + cyclophosphamide) or MAC + CCNU.


RESULTS
After intensive chemotherapy, ph(+) cells in bone marrow reduced to 34% (24% - 46%) and the numbers of bcr/abl mRNA (+) CFU-GM to 45.6% (33% - 58%). After bcr/abl AS-ODN in vitro purging, two patients were bcr/abl mRNA negative and three positive with the number of bcr/abl mRNA (+) CFU-GM markedly reduced. Delayed hematopoietic reconstitutions were observed in all patients after ABMT. During a more than 2 years follow-up period, three patients obtained major cytogenetic remission (MCR) and lasted for 9 - 12 months and the durations of CP after ABMT were longer than that before ABMT. One of this three in BC before ABMT being survived disease-freely for 37 months with bcr/abl mRNA (-) after ABMT. Another patient in BC had a short duration of MCR and relapsed at +7 months. One patient died from severe infection and bleeding at day +74 because of delayed reconstitution.


CONCLUSIONS
ABMT with bcr/abl AS-ODN purged graft can result in quite long duration of MCR and prolonged CP in some patients with CML.
Sun
J
J
Department of Hematology, Nanfang Hospital, the First Military Medical University, Guangzhou 510515, China.
Wu
B
B
Liu
Q
Q
Feng
R
R
Liu
X
X
Meng
F
F
Zhou
S
S
D000293:Adolescent; D000328:Adult; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl