Blood advances
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Comparative Study
Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia.
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. ⋯ Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.
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Comparative Study
Comparison of reversal activity and mechanism of action of UHRA, andexanet, and PER977 on heparin and oral FXa inhibitors.
Anticoagulants such as unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and direct oral anticoagulants (DOACs) targeting thrombin (IIa) or factor Xa (FXa) are widely used in prevention and treatment of thromboembolic disorders. However, anticoagulant-associated bleeding is a concern that demands monitoring and neutralization. Protamine, the UFH antidote, has limitations, while there is no antidote available for certain direct FXa inhibitors. ⋯ For UHRA and andexanet, an affinity at or below the micromolar level was found to correlate with neutralization activity, while no reversal activity was observed for the PER977/anticoagulant systems. Standard metrics of clot structure were found to correlate weakly with PER977's activity. This is the first study comparing 3 antidotes in development, with each exerting activity through a distinct mechanism.
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Multicenter Study
Risk stratification of smoldering multiple myeloma: predictive value of free light chains and group-based trajectory modeling.
We investigated the predictive role for serum free light chain ratio (FLCr) ≥100, bone marrow plasma cell (BMPC) ≥60%, and evolving biomarkers through group-based trajectory modeling (GBTM) as high-risk defining events in 273 smoldering multiple myeloma (SMM) patients with a median follow-up of 74 months. FLCr ≥100 was confirmed as a marker for high-risk progression with a median time to progression (TTP) of 40 months with a 44% risk of progression of disease (PD) at 2 years; however, 44% of FLCr ≥100 also did not progress during follow-up. ⋯ Of all the variables examined, we identify a model where immunoparesis, eHb, eMP, and edFLC were significant predictors for ultra-high-risk progression with a median TTP of only 13 months with 3 or more variables present. Our results not only confirm a more modest 2 year PD associated with FLCr ≥100 and BMPC ≥60 but also suggest that eHb, eMP, and edFLC may help identify an ultra-high-risk SMM group.
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Amyloid light-chain (AL) amyloidosis is a rare disease caused by extracellular deposition of misfolded immunoglobulin light chains. This study aimed to provide an up-to-date estimate of prevalence and incidence of AL amyloidosis in the United States. Using claims databases from years 2007 to 2015, adults ≥18 years old with AL amyloidosis were included if they had (1) at least 1 inpatient or 2 outpatient claims consistent with AL amyloidosis and (2) received 1 AL-specific treatment. ⋯ The incidence ranged from 9.7 to 14.0 cases per million person-years (APC, 3%; P = .114) with no statistically significant increase. There was an increase in AL amyloidosis prevalence over a 9-year period coupled with stable incidence rates. Although there is no diagnosis code specific to AL amyloidosis and no validated method for identifying this condition using claims data, extrapolating from our data, there are at least 12 000 adults in the United States living with AL amyloidosis, and the number seems likely to rise.
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We evaluated the impact of light chain type, lambda (λ) or kappa (κ), on disease features and outcomes in patients with immunoglobulin light chain (AL) amyloidosis receiving stem cell transplant at the Mayo Clinic between October 2002 and August 2016. Patients with λ AL amyloidosis had higher rates of renal and neurological involvement (λ 69% vs κ 57%, P = .02 and λ 16% vs κ 9%, P = .03, respectively). Patients with κ AL amyloidosis had more hepatic involvement (λ 7% vs κ 18%, P = .0003). ⋯ Conditioning dose predicted survival in the λ cohort only (median OS 149 months for melphalan 200 mg/m2 vs 50 months for melphalan <200 mg/m2, P < .0001; median OS κ not reached for melphalan 200 mg/m2 or <200 mg/m2, P = .38). On multivariate analysis, light chain type remained an independent predictor of survival. Light chain type predicts organ involvement and survival in patients with AL amyloidosis receiving stem cell transplant.