Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This nonrandomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD − CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD − CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD − CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < .05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD <5% and without poor prognostic markers (P > .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.

Nighttime atmospheric processing enhances the formation of brown carbon aerosol (BrC) in biomass burning plumes. Heterocyclic compounds, a group of volatile organic compounds (VOCs) abundant in biomass burning smoke, are possible BrC sources. Here, we investigated the nitrate radical (NO 3 )-initiated oxidation of three unsaturated heterocyclic compounds (pyrrole, furan, and thiophene) as a source of BrC. The imaginary component of the refractive index at 375 nm (k 375 ), the single scattering albedo at 375 nm (SSA 375 ), and average mass absorption coefficients (⟨MAC⟩ 290−700 nm ) of the resulting secondary organic aerosol (SOA) are reported. Compared to furan and thiophene, NO 3 oxidation of pyrrole has the highest SOA yield. Pyrrole SOA (k 375 = 0.015 ± 0.003, SSA = 0.86 ± 0.01, ⟨MAC⟩ 290−700 nm = 3400 ± 700 cm 2 g −1 ) is also more absorbing than furan SOA (⟨MAC⟩ 290−700 nm = 1100 ± 200 cm 2 g −1 ) and thiophene SOA (k 375 = 0.003 ± 0.002, SSA 375 = 0.98 ± 0.01, ⟨MAC⟩ 290−700 nm = 3000 ± 500 cm 2 g −1 ). Compared to other SOA systems, MACs reported in this study are higher than those from biogenic precursors and similar to high-NO x anthropogenic SOA. Characterization of SOA molecular composition using high-resolution mass spectrometric measurements revealed unsaturated heterocyclic nitro products or organonitrates as possible chromophores in BrC from all three precursors. These findings reveal nighttime oxidation of fire-sourced heterocyclic compounds, particularly pyrrole, as a plausible source of BrC.

No abstract