The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome‐negative cells

Abstract

BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)‐negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph‐negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph‐negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall‐Wallis test), exposure to cytotoxic drugs (chi‐square test), and overall and progression‐free survival (Kaplan‐Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic‐phase CML who were treated with imatinib mesylate after failure of interferon‐α according to whether they attained a major cytogenetic response (MCR) (n = 324 patients), an MCR with CCA/Ph‐negative status (n = 30 patients), or no MCR (n = 161 patients). RESULTS. CCA/Ph‐negative status most frequently involved chromosomes Y, 8, and 7. No significant differences in pretherapeutic risk factors were detected between patients who attained an MCR with and without CCA/Ph‐negative cells, except that exposure to alkylating agents was more frequent in patients with CCA/Ph‐negative cells, and overall and progression‐free survival were identical. With a median follow‐up of 51 months, only 2 patients developed myelodysplastic syndromes (MDS). CONCLUSIONS. The overall prognosis for patients who had CML with CCA/Ph‐negative status was good and was driven by the CML response to imatinib mesylate. Isolated CCA/Ph‐negative cells in the absence of morphologic evidence of MDS do not justify a change in therapy. Cancer 2007. © 2007 American Cancer Society.

BCR/ABL promotes accumulation of chromosomal aberrations induced by oxidative and genotoxic stress

“…13,16,17 However, the former speculation cannot be ruled out because chromosome abnormalities were detected in t(9;22)-negative metaphases appearing during imatinib therapy in patients with newly diagnosed CML-CP. 18,19 To test the hypothesis that BCR/ABL facilitates the accumulation of ROS-induced chromosomal aberrations, freshly established 32Dcl3-BCR/ABL and parental 32Dcl3-neo cells were continuously cultured in vitro for 8 weeks in the presence or absence of an antioxidant, vitamin E (VE) as described before, 20 and then analyzed by SKY (spectral karyotype analysis) to detect acquired chromosomal aberrations. Although parental cells did not contain consistent chromosomal aberrations, one or two additional chromosomes 12 ( þ 12, þ 12 Â 2) were detected in all metaphases of 32Dcl3-BCR/ABL cells maintained in regular medium ( Table 1, VE in vitro, P-C and B/A-C, respectively).…”

Myelodysplastic Syndrome with Ph Negative Monosomy 7 Chromosome following Transient Bone Marrow Dysplasia during Imatinib Treatment for Chronic Myeloid Leukemia

“…The clinical implications of such a phenomenon are still unclear. Clinical courses in such patients were reported to usually be similar to patients without chromosomal aberration, and some are transient (14). However rare cases with chromosomal abnormality developed myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) (15)(16)(17)(18).…”

Mexican Guidelines for the Diagnosis and Treatment of Chronic Myeloid Leukaemia

“…The most common alteration is trisomy 8 and the one with the worst prognosis is the loss of −7 chromosome, with a potential myelodysplastic syndrome [43].…”