Abstract
Detection of the chronic myelogenous leukemia (CML)-related marker, the bcr/abl m-RNA transcript, in blood or bone marrow of patients with CML in hematologic remission after allogeneic bone marrow transplantation (allo-BMT) may be associated with the presence of minimal residual disease but does not uniformly predict hematologic relapse. In contrast, when there is cytogenetic reappearance of the Philadelphia (Ph1) translocation [t(9;22)(q34;q11)] along with additional cytogenetic abnormalities, especially more than 2 years after BMT, progression to hematologic relapse and acceleration of CML usually occur. An exception to this rule may be our patient, who was a 29-year old white woman diagnosed with Ph1-positive CML by cytogenetics. She was initially treated with hydroxyurea. An allo-BMT was performed 4 months after the diagnosis, while the patient was still in the first chronic phase of her disease, her HLA-identical brother serving as bone marrow (BM) donor. The conditioning regimen for BMT consisted of cytosine arabinoside, cyclophosphamide, total body irradiation, splenic irradiation, and intrathecal methotrexate. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A and methotrexate. Her hospital course was unremarkable and without evidence of acute GVHD. Six months after transplantation, the patient had mild chronic GVHD and was treated with azathioprine and prednisone for 6 months. A year later, she recurred with mild chronic GVHD. She was treated with azathioprine alone for 5 months. Subsequently, she received cyclosporin A and prednisone for 8 months, with resolution of her symptoms. Serial BM cytogenetic studies showed normal male donor karyotypes 12 and 24 months after BMT. At 36, 42, and 50 months after BMT, reappearance of the Ph1 was noted along with some cells with additional cytogenetic abnormalities, including t(6;14)(p21;q32). The breakpoint involvement of 14q32, the heavy chain Ig locus, in the new clone may be indicative of B-lymphoid lineage-based evolution. The abnormal clones disappeared 56 months from BMT and remained absent through 69 months after BMT. The patient has remained in hematologic remission during her entire post-BMT course. Clinically, she continues to do well without immunosuppressants at presently 69 months after BMT. The reappearance of the Ph1 chromosome could be associated with the immunosuppressive therapy given for chronic GVHD. This case supports the concept that immunologic mechanisms may be important in the eradication of CML after allo-BMT, and even cytogenetic evidence of blast crisis CML may spontaneously remit after allo-BMT.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have