Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase

Abstract

BackgroundPublished criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.MethodsThis is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10–29%, basophils ≥ 20%, platelets > 1 × 106/μL or <1 × 105/μL and white blood cells > 1 × 105/μL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin < 10 g/dL, time between diagnosis of chronic myeloid leukemia and imatinib treatment, and hematologic toxicity.ResultsRisk factors for poor survival in multivariate analysis were Grades 3–4 hematologic toxicity (p-value = 0.001), blasts 10–29% (p-value = 0.023), and hemoglobin < 10 g/dL (p-value = 0.04). Risk factors for not achieving major cytogenetic response were blasts 10–29% (p-value = 0.007), hemoglobin < 10 g/dL (p-value = 0.001), and previous use of interferon (p-value = 0.032). Risk factors for progression to the blast phase were hemoglobin < 10 g/dL (p-value = 0.005), basophils ≥ 20% (p-value = 0.023), and time from diagnosis of chronic myeloid leukemia to imatinib treatment > 12 months (p-value = 0.030).ConclusionThese data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.

Prognostic impact of Additional Chromosomal Abnormalities in Egyptian Chronic Myeloid Leukemia Patients

“…We also report that CP patients who were tolerant to their received TKIs tended to develop ACAs less (14/34, 17%) than their counterparts who were defined as intolerant to TKIs (2/6, 33%). These observations could be matched with previous studies [10], [28], [29]. An interesting observation that we report in this study is the near significance higher median OS and EFS of CML-CP patients who had a shift to a different generic IM during their treatment course due to the unavailability of Glivec ® (p = 0.087 and p = 0.100, respectively).…”

“…Patients with thrombocytopenia (<100×109/L) had a lower median OS than patients who presented with higher platelet counts (p = 0.07) and was found to be an independent poor prognostic factor in Egyptian CML patients upon the log-rank statistical test of the impact of variables on OS (p=0.082). This correlation was similar to a previously reported significant correlation between thrombocytopenia at presentation and unresponsiveness to TKI therapy and lack of MCyR which was consequently and significantly correlated with OS and EFS [28]. A higher percentage of CML-CP patients who failed to achieve optimal response to TKI therapy had ACAs (42%) compared to (28%) of optimal responders.…”

Management of Chronic Myeloid Leukemia in Advanced Phase

“…Early studies in AP-CML patients not previously exposed to other TKIs showed that imatinib determined 60–85% rates of complete hematologic response (CHR, 16–45% of complete cytogenetic response (CCyR) and 19–34% of major molecular response (MMR) (56–60, 63). OS ranged from 74% at 12 months to around 40–50% at 5–7 years, an outcome clearly less favorable as compared to CP patients.…”

A British Society for Haematology Guideline on the diagnosis and management of chronic myeloid leukaemia

“…Molecular monitoring should be performed by reverse transcriptase quantitative PCR (RT-qPCR) from total peripheral blood leucocytes using standardised methodologies that adhere to national and international guidelines (see Fig 1). 35,[37][38][39]46 Assessment by digital PCR as an alternative to RT-qPCR may increase in the future, but irrespective of the method used, results should be expressed on the International Scale (IS) 68 and indicate the molecular response (MR) level.…”

“…33 Studies of TKIs in advanced phase. Imatinib in de novo AP CML 46,67,86,89,144,153 and in BC. 42,87,122,141,144,149 Dasatinib and nilotinib in imatinib failure, in AP 3,34,53,82,84,117 and in BC.…”