[Bestatin therapy of chronic myelogenous leukemia].
We proposed a new approach to treat chronic myelogenous leukemia using a combination of busulfan and Bestatin. Twenty-three patients with Ph1 positive CML including 20 in the chronic phase and 3 in the accelerated phase, were treated with the combination therapy. Complete hematologic remission was obtained in all patients. Complete cytogenetic response (CCR) was obtained in 6 patients (26%), partial cytogenetic response (PCR) in 1 (4%), and minor cytogenetic response (MCR) in 6 (26%). In particular, of 13 patients in early chronic phase, 5 (39%) achieved CCR, 1 PCR, 3 MCR. Complete suppression of Ph1+clone was further confirmed by molecular analysis. Cytogenetic conversion to a normal diploid state persisted for 6-41+ months (median 22 months+). Three year survival rate was 86.6 +/- 9.0% (95% confidence limit). Furthermore, the long-term complete hematologic remission in the accelerated phase patients without progression of the disease may be indicative of a long-term survival. We conclude that Bestatin effectively controls CML and allows reappearance of diploid hemopoietic cells in some patients. The rationale for this combination therapy is that busulfan suppresses the proliferation of leukemic progenitors and decreases tumor burden to the level where Bestatin exhibits its antiproliferative effects. Bestatin is not merely antiproliferative but provides more complex biological properties capable of enhancing repopulation of normal residual stem cells.
Uzuka
Y
Y
Sendai Hematologic Disorders Clinic, Japan.
Saito
Y
Y
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy / Q000401:mortality; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate
D000903:Antibiotics, Antineoplastic; D002066:Busulfan; D007930:Leucine; C012211:ubenimex