[Autologous bone marrow transplantation for patients with chronic myelogenous leukemia after in vitro purging of the graft with bcr/abl antisense oligodeoxynucleotides]

Abstract

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.

Conclusion: ABMT with bcr/abl AS-ODN purged graft can result in quite long duration of MCR and prolonged CP in some patients with CML.