At diagnosis, variant Philadelphia (Ph) translocation occurringoccurring in patients (pts) with Chronic Myeloid Leukemia (CML) have been reported in 5-10% of pts. Some studies have suggested that variant Ph translocations may have an adverse prognosis with conventional chemotherapy or -interferon, while others have reported that have no impact on prognosis after Imatinib Mesylate (IM) treatment. Variant translocation could be three-way or four-way translocation (involving chromosomes 9, 22 and 1 or 2 additional chromosome respectively), associated or not with deletions of der(9) chromosome. AIM: To investigate the role of occurrence of variant Ph translocations on the response to IM in early chronic phase (CP) CML pts. Methods. A sub-analysis of 531 evaluable CML pts in early CP, have been performed within 3 simultaneously running trials of the GIMEMA WP on CML (CML/021; CML/022; CML/023). Median observation time was 30 months. Monitoring: hematologic, continuously; CC, FISH and molecular analysis were performed at baseline, 3, 6 and 12 months, and then every 6 months by local or reference labs. Results. At enrollment, 28 pts (5.3%) had variant Ph translocation: 1 showed variant Ph translocation by fluorescence in situ hybridization (FISH) but not by conventional cytogenetic (CC); 2 pts (7.1%) had a four-way translocation; 27 pts (96.2%) had a three-way translocation. In 5 pts (17.8%) translocation was associated with deletion of der(9). Only one carried an additional chromosome abnormality: t(7;19)(q21;p13). The two groups of pts, with or without variant translocation, were similar for age, Sokal risk and IM dose. At 12 months, 23 pts achieved complete cytogenetic response (CCgR; 82.2% vs. 83.9% in pts without variant), 2 pts reached partial cytogenetic response (PCgR; 7.1% vs. 6.6%), in 3 treatment was unsuccessful (10.7% vs. 9.5%). The 2 pts with four-way translocation reached CCgR, and 4 of 5 pts (80%) with deletion of der(9) reached CCgR. Conclusions. In the present large series of pts in early CP treated with IM therapy, we found no difference in cytogenetic response rates between pts with variant translocations and with classic ones. It will be discuss the eventual correlation between the complexity of mechanism of translocation genesis (one or two-step) and response to IM therapy. ACKNOWLEDGMENTS: University of Bologna (RFO), Fondazione del Monte di Bologna e Ravenna, European LeukemiaNet founds, MIUR PRIN 2005, Bologna AIL.

VARIANT PHILADELPHIA TRANSLOCATION IN EARLY CHRONIC PHASE OF CHRONIC MYELOID LEUKEMIA: RESULTS OF IMATINIB MESYLATE THERAPY (A GIMEMA WP ON CML ANALYSIS)

CUNEO, Antonio;
2008

Abstract

At diagnosis, variant Philadelphia (Ph) translocation occurringoccurring in patients (pts) with Chronic Myeloid Leukemia (CML) have been reported in 5-10% of pts. Some studies have suggested that variant Ph translocations may have an adverse prognosis with conventional chemotherapy or -interferon, while others have reported that have no impact on prognosis after Imatinib Mesylate (IM) treatment. Variant translocation could be three-way or four-way translocation (involving chromosomes 9, 22 and 1 or 2 additional chromosome respectively), associated or not with deletions of der(9) chromosome. AIM: To investigate the role of occurrence of variant Ph translocations on the response to IM in early chronic phase (CP) CML pts. Methods. A sub-analysis of 531 evaluable CML pts in early CP, have been performed within 3 simultaneously running trials of the GIMEMA WP on CML (CML/021; CML/022; CML/023). Median observation time was 30 months. Monitoring: hematologic, continuously; CC, FISH and molecular analysis were performed at baseline, 3, 6 and 12 months, and then every 6 months by local or reference labs. Results. At enrollment, 28 pts (5.3%) had variant Ph translocation: 1 showed variant Ph translocation by fluorescence in situ hybridization (FISH) but not by conventional cytogenetic (CC); 2 pts (7.1%) had a four-way translocation; 27 pts (96.2%) had a three-way translocation. In 5 pts (17.8%) translocation was associated with deletion of der(9). Only one carried an additional chromosome abnormality: t(7;19)(q21;p13). The two groups of pts, with or without variant translocation, were similar for age, Sokal risk and IM dose. At 12 months, 23 pts achieved complete cytogenetic response (CCgR; 82.2% vs. 83.9% in pts without variant), 2 pts reached partial cytogenetic response (PCgR; 7.1% vs. 6.6%), in 3 treatment was unsuccessful (10.7% vs. 9.5%). The 2 pts with four-way translocation reached CCgR, and 4 of 5 pts (80%) with deletion of der(9) reached CCgR. Conclusions. In the present large series of pts in early CP treated with IM therapy, we found no difference in cytogenetic response rates between pts with variant translocations and with classic ones. It will be discuss the eventual correlation between the complexity of mechanism of translocation genesis (one or two-step) and response to IM therapy. ACKNOWLEDGMENTS: University of Bologna (RFO), Fondazione del Monte di Bologna e Ravenna, European LeukemiaNet founds, MIUR PRIN 2005, Bologna AIL.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/532879
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