ClinicalTrials.gov Identifier: NCT02537990.

Outstanding results have been obtained in the treatment of chronic myeloid leukemia (CML) with first-line imatinib therapy. However, approximately 35% of patients will not obtain long-term benefit with this approach. Allogeneic hematopoietic stem cell transplantation (HCT) is a valuable second-and third-line therapy for appropriately selected patients. To identify useful prognostic indicators of transplantation outcome in postimatinib therapeutic interventions, we investigated the role of the HCT comorbidity index (HCT-CI) together with levels of C-reactive protein (CRP) before HCT in 271 patients who underwent myeloablative HCT for CML in first chronic phase. Multivariate analysis showed both an HCT-CI score higher than 0 and CRP levels higher than 9 mg/L independently predict inferior survival and increased nonrelapse mortality at 100 days after HCT. CML patients without comorbidities (HCT-CI score 0) with normal CRP levels (0-9 mg/L) may therefore be candidates for early allogeneic HCT after failing imatinib. IntroductionThe past decade has witnessed a dramatic change in the management of chronic myeloid leukemia (CML) such that the majority of patients initially receive therapy with imatinib rather than being offered allogeneic hematopoietic cell transplantation (HCT). 1 However, approximately 35% of these patients will fail to respond and/or develop intolerance. The treatment choices then include second-generation tyrosine kinase inhibitors and HCT, and the current challenge is to optimize the relative timings of these alternatives.The results of HCT in CML can be predicted using a prognostic score devised by the European Group for Blood and Marrow Transplantation (EBMT) based on 5 variables: donor type, disease phase, recipient age, donor/recipient sex combination, and interval from diagnosis to transplantation. 2 As the variable of disease phase resulted in higher relative risks than other variables in the model, 2 Passweg et al attempted to modify the score for patients in chronic phase for whom the decision of whether to undergo transplantation is most difficult. They found only one parameter with additional prognostic value, the Karnofsky performance score, and after inclusion the improvement over the original EBMT score was minimal. 3 The hematopoietic cell transplantation comorbidity index (HCT-CI) was developed to analyze the impact of comorbidities on outcome of HCT. 4 In several studies, the HCT-CI predicted for nonrelapse mortality (NRM) and overall survival (OS), 5-8 but it has never been studied specifically in patients with CML. C-reactive protein (CRP) is a sensitive marker of inflammation and persons with elevated levels of this acute phase protein are known to have an increased risk of cardiovascular diseases and malignancies. [9][10] We and others have previously shown the value of CRP levels shortly before HCT in predicting its outcomes. 11-12 However, it was unclear whether the elevated CRP was a reflection of an underlying comorbidity. In this study, we investigated the prognostic valu...

SummaryTimely diagnosis and care are major determinants of the outcome in acute promyelocytic leukaemia (APL), a malignancy whose incidence may be increasing. The Canadian Cancer Registry (CCR) and health system represent valuable settings to study APL epidemiology. We analysed the CCR, which contains data on all Canadians with APL. To provide clinical information lacking in the CCR, we obtained data from five leukaemia referral centres during a similar time period. Between 1993 and 2007, there were 399 APL in Canada. Age-standardized incidence was 0Á083/100 000 and was stable over time. The early death (ED) rate was 21Á8% (10Á6% in patients <50 years old and 35Á5% for those aged >50 years), with no improvement over time. Five-year overall survival (OS) was 54Á6% (73Á3% in patients <50 years; 29Á1% older patients). In the referral cohort, 131 patients were diagnosed between 1999 and 2010. ED was 14Á6% and 2-year OS was 76Á5%. Within this cohort, ED and OS improved over time, although advanced patient age remained an adverse determinant of OS. In Canada, APL incidence is unexpectedly low and temporally stable. ED was higher than reported in clinical trials, but similar to reports from other registries. In contrast, ED was lower in referral centres and improved with time.

Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease-modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non-ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P < 0·0001). By multivariate analysis, not receiving ICT independently predicted inferior OS, (hazard ratio for death 2·0, P = 0·03). In matched pair analysis, OS remained superior for ICT patients (P = 0·02). In this prospective, non-randomized analysis, receiving ICT was associated with superior OS in lower IPSS risk MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease-modifying agents. This provides additional evidence that ICT may confer clinical benefit.