Rebound Thrombocytosis Is an Independent Predictor of Good Prognosis in AML Patients Attaining First Complete Remission

We investigated the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in post-chemotherapy newly diagnosed AML patients. De novo AML patients who were diagnosed between October 2002 and December 2013 were evaluated retrospectively. The patients who attained first complete remission (CR) after one or two induction therapies were selected and their marrow aplasia periods preceding CR were considered. The patients who were transplanted were excluded. Neutrophil (NRT) and platelet recovery times (PRT) were accepted as the periods between neutrophil nadir and ³1000/µl neutrophil count and platelet nadir and ³50000/µl platelet count, respectively. The platelet nadir-to-first consolidation (PCT) and neutrophil nadir-to-first consolidation times (NCT) were computed. RN and RT thresholds were accepted as 7000/µl and 450000/µl respectively.

There were 100 patients suitable for inclusion. The frequency of RT was 11/31, 6/19, 5/50 in patients with favorable ELN cytogenetic categories, normal karyotype, other cases, respectively (p=0.1). Cox regression analysis using need of reinduction therapy as stratification parameter revealed RT as the only parameter predicting both OS (p=0.06) and DFS (p=0.024). After understanding that RT₅₂₅ (threshold 525000/ µl) is an independent prognostic parameter in AML patients, we tried to find its prognostics value in subgroups. There were 15 APL patients. Prognostic value of RT₅₂₅ could not be determined due to low event rates. Only two patients experienced an event. Both events were mortalities during consolidation. There was one mortality in RT₅₂₅ and no- RT₅₂₅ groups each. There were 16 CBF-type AML patients. Four patients experienced an event. All events were relapses. All four events occurred in 12 cases without RT₅₂₅ while none of four patients with RT₅₂₅ experienced an event. However, statistical significance was not observed between groups in DFS (figure 1) and OS comparisons due to low event rates (p=0.17 and p=0.18 respectively). In other AML patients, there were 35 events (25 relapse, 10 deaths in CR). All of the events occurred in no-RT₅₂₅ group. All RT₅₂₅ cases in this group were living with CR at last follow-up. Both DFS (median [95% confidence interval] not reached versus 13.2 (6.1 - 20.2) months, p=0.004) (figure 2) and OS (not reached versus 17.0 (0 - 34.6) months, p<0.001) rates were higher in RT₅₂₅ cases. In order to understand whether RT or RN were related to better marrow capacity or late consolidation, we considered NRT and PRT and nadir-first consolidation durations in all patients cohort. For RT group, the PRT was 10.3±5.2 days whereas it was 12.8±8.5 days for no-RT group (p=0.43). The NRT was 15.8±7.8 and 20.3±9.7 days in RN and no-RN groups respectively (p=0.07). For RT group, the PCT was 27.8±7.9 whereas it was 29.1±15.2 days for the group with no-RT (p=0.07). NCT was 30.2±11.2 and 34.6±18.2 days for RN and no-RN groups respectively (p=0.12). Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients.

To our knowledge, this is the first study that reports a correlation between RT/RN and prognosis in AML. Interestingly, RT was the only significant independent parameter in multivariate analyses also including classical prognostic risk factors for OS and DFS. The favorable prognosis associated with RT₅₂₅ was evident in AML patients other than APL and CBF-type disease. However it could not be demonstrated in APL and CBF-type disease probably due to low event rates. In accordance with this suggestion there was a trend towards statistical significance in CBF-type disease (0/4 versus 4/12 relapses in RT₅₂₅ and no-RT₅₂₅ cases respectively, p=0.17). The marrow recovery time and the duration between marrow aplasia and first consolidation were shorter in RT and RN cases indicating better healthy hematopoiesis/marrow capacity in this group. As RT and RN are very easy to detect, they can be used as prognostic indicators in countries with limited laboratory facilities. These findings should be confirmed in other patient cohorts and preferably prospective studies.

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