CASE-REPORT OF SPONTANEOUS REMISSION OF CYTOGENETIC RELAPSE OF CHRONIC MYELOGENOUS-LEUKEMIA SUGGESTIVE OF PROGRESSION TO BLAST CRISIS AFTERALLOGENEIC BONE-MARROW TRANSPLANTATION

Detection of the chronic myelogenous leukemia (CML)-related marker, th e bcr/abl m-RNA transcript, in blood or bone marrow of patients with C ML in hematologic remission after allogeneic bone marrow transplantati on (allo-BMT) may be associated with the presence of minimal residual disease but does not uniformly predict hematologic relapse. In contras t, when there is cytogenetic reappearance of the Philadelphia (Ph(1)) translocation [t(9;22)(q34;q11)] along with additional cytogenetic abn ormalities, especially more than 2 years after BMT, progression to hem atologic relapse and acceleration of CML usually occur. An exception t o this rule may be our patient, who was a 29-year old white woman diag nosed with Ph(1)-positive CML by cytogenetics. She was initially treat ed with hydroxyurea. An allo-BMT was performed 4 months after the diag nosis, while the patient was still in the first chronic phase of her d isease, her HLA-identical brother serving as bone marrow (BM) donor. T he conditioning regimen for BMT consisted of cytosine arabinoside, cyc lophosphamide, total body irradiation, splenic irradiation, and intrat hecal methotrexate. Graft-versus-host disease (GVHD) prophylaxis consi sted of cyclosporin A and methotrexate. Her hospital course was unrema rkable and without evidence of acute GVHD. Six months after transplant ation, the patient had mild chronic GVHD and was treated with azathiop rine and prednisone for 6 months. A year later, she recurred with mild chronic GVHD. She was treated with azathioprine alone for 5 months. S ubsequently, she received cyclosporin A and prednisone for 8 months, w ith resolution of her symptoms. Serial BM cytogenetic studies showed n ormal male donor karyotypes 12 and 24 months after BMT. At 36, 42, and 50 months after BMT, reappearance of the Ph(1) was noted along with s ome cells with additional cytogenetic abnormalities, including t(6;14) (p21;q32). The breakpoint involvement of 14q32, the heavy chain Ig loc us, in the new clone may be indicative of B-lymphoid lineage-based evo lution. The abnormal clones disappeared 56 months from BMT and remaine d absent through 69 months aft er BMT. The patient has remained in hem atologic 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 Ph(1) chromosome could be associat ed with the immunosuppressive therapy given for chronic GVHD. This cas e 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.