Prospective evaluation of variables affecting platelet function in patients with newly diagnosed chronic myeloid leukemia.

: Platelet function in chronic myeloid leukemia (CML) could be affected by either hyperleucocytosis, clonal megakaryopoiesis, or tyrosine kinase inhibitors. However, these variables have never been prospectively evaluated. We conducted a prospective study over a period of 1.5 years in a tertiary care center of north India. Patients with CML in chronic phase, more than 18 years, and treated with imatinib were enrolled (n = 32). Age, and sex-matched controls were also included. Platelet function test was performed using two-channel Chrono-Log aggregometer 490 at four time-points: first, at diagnosis; second, after leucoreduction (total leucocyte count, <10 × 10/l) achieved with hydroxycarbamide; third, on-imatinib at BCR-ABL less than 1%; and fourth, in an independent cohort (off-imatinib) at deep molecular response (DMR) (BCR-ABL < 0.01%). Statistical analysis was performed using IBM SPSS statistics (version 22.0). Median age of patients was 42 years (15-65), and M : F ratio was 1 : 1. At diagnosis, platelet function correlated negatively with total leucocyte count, but not with platelet count. As compared with baseline, platelet aggregation with ADP (2.5 µl), and collagen (2.5 µl) improved significantly after leucoreduction (P = 0.05 and 0.009, respectively). Imatinib further caused significant impairment of aggregation with ADP (2.5 µl), collagen (2.5 µl), and collagen (1 µl) (P = 0.04, 0.008, and 0.02, respectively). Patients in DMR also demonstrated a significant impairment of platelet aggregation with all the agonists as compared with controls. While leucoreduction alone can improve the baseline platelet function derangement in CML, imatinib further impairs it. Residual CML stem cells, or effect of imatinib on normal common myeloid progenitors might account for platelet function derangement at DMR.

Comparative evaluation of galactomannan test with bronchoalveolar lavage and serum for the diagnosis of invasive aspergillosis in patients with hematological malignancies.

INTRODUCTION: Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies. In recent years, testing for values of galactomannan (GM) in serum and bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA for such patients, but global experience and consensus on optical density (OD) cutoffs, especially for BAL galactomannan remains lacking. METHODS: We performed a prospective case-control study to determine an optimal BAL GM OD cutoff for IPA in at-risk patients. Cases were subjects with hematological diagnoses who met established revised definitions for proven or probable IPA established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/MSG, 2008), without the use of BAL GM results. Exclusion criteria included the use of piperacillin/tazobactam and use of antifungals that were active against Aspergillus spp. before bronchoscopy. There were two control groups: patients with hematological diagnoses not meeting definitions for proven or probable IPA and patients with nonhematological diagnoses with no evidence of aspergillosis. Following bronchoscopy and BAL, GM testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions. RESULTS: There were 51 cases and 20 controls. Cases had higher BAL fluid GM OD indices (ODIs) (mean: 1.27 and range: 0.4-3.78) compared with controls (mean: 0.26 and range: 0.09-0.35). Receiver operating characteristic analysis demonstrated an optimum ODI cutoff of 1.0, with high specificity (100%) and sensitivity (87.5%) for diagnosing IPA. CONCLUSIONS: Our results support BAL GM testing as a reasonably safe test with higher sensitivity compared to serum GM testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid overdiagnosis of IPA.