The expression of bcl-2 mRNA may serve as a prognostic factor predicting remission outcome and long-term prognosis in AML.

The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell-depleted allogeneic graft from a HLA-identical family donor (n ‫؍‬ 15) or an alternative donor (n ‫؍‬ 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day ؉30 and day ؉100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate. (Blood. 2001;98:565-572)

The tumor suppressor gene wt1 (Wilms' tumor gene) encodes for a zinc finger DNA-binding protein with predominantly transcription repressing properties. Because wt1 has been shown to be expressed in the vast majority of patients with acute myeloid leukemias (AML), we investigated the relevance of wt-1 mRNA expression regarding prognosis and possible prediction of relapse during follow-up. Totally bone marrow-derived blasts of 139 AML patients (129 newly diagnosed AML patients, 22 AML patients again in first relapse, and 10 AML patients analyzed primarily in first relapse) were studied for wt1 mRNA expression. Seventy-seven patients were analyzed for wt1 mRNA expression during follow-up. wt1-specific reverse transcription-polymerase chain reaction (RT-PCR) was performed and the amplification product was visually classified as not, weakly, moderately, or strongly amplified, as described previously. PCR products were quantitated by competitive PCR using a shortened homologous wt1 construct standard in representative cases. The expression of wt1 transcripts was correlated to age, French-American-British (FAB) subtype, phenotype, karyotype, and long-term survival. wt1 mRNA was detectable in 124 of 161 (77%) samples at diagnosis and in first relapse. wt1 expression was independent from age, antecedent myelodysplastic syndrome or FAB subtype, with the exception of a significant difference in M5 leukemias showing wt1 transcripts in only 40% (P = .0025). There was no correlation between the level of wt1 mRNA and response to treatment or the prognostic groups defined by the karyotype. Concerning long-term survival, patients with high levels of wt1 had a significantly worse overall survival (OS) than those with not detectable or low levels. The 3-year OS for all newly diagnosed AMLs was 13% and 38% (P = .038), respectively, and 12% and 43% (P = .014) for de novo AMLs. The difference was more distinct in patients less than 60 years of age. During follow-up, all patients achieving complete remission became wt1 negative. Reoccurrence of wt1 transcripts predicted relapse. The data indicate that high expression of wt1 mRNA is associated with a worse long-term prognosis.

Results of the randomized trial comparing CHOP-like chemotherapy with early HDT do not support the use of HDT with carmustine, etoposide, cytarabine, and melphalan following shortened standard chemotherapy.