CD19 chimeric antigen receptor (CAR) T-cell therapy has shown great success against B-cell acute lymphoblastic leukemia (B-ALL). Tandem and sequential CD19/CD22 dual-target CAR T-cell therapies have been developed to reduce the possibility of CD19-negative relapse; however, the superior strategy is still uncertain. This study screened 219 patients with relapsed/refractory B-ALL who were enrolled in clinical trials of either CD19 (NCT03919240) or CD19/CD22 CAR T-cell therapy (NCT03614858). The complete remission (CR) rates in the single CD19, tandem CD19/CD22, and sequential CD19/CD22 groups were 83.0% (122/147), 98.0% (50/51), and 95.2% (20/21), respectively (single CD19 vs. tandem CD19/CD22, P = 0.006). Patients with high-risk factors achieved a higher rate of CR in the tandem CD19/CD22 group than in the single CD19 group (100.0% vs. 82.4%, P = 0.017). Tandem CD19/CD22 CAR T-cell therapy was one of the significant favorable factors in the multivariate analysis of the CR rate. The incidence of adverse events was similar among the three groups. Multivariable analysis in CR patients showed that a low frequency of relapse, a low tumor burden, minimal residual disease-negative CR and bridging to transplantation were independently associated with better leukemia-free survival. Our findings suggested that tandem CD19/CD22 CAR T-cell therapy obtains a better response than CD19 CAR T-cell therapy and a similar response to sequential CD19/CD22 CAR T-cell therapy.

We analyzed the outcomes of 44 patients with paroxysmal nocturnal hemoglobinuria (PNH) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) (haploidentical [haplo]-donors, 25; matched sibling donors [MSDs], 15; and matched unrelated donors, 4) between July 2007 and May 2018. All patients achieved successful donor engraftment. The median time was 12 days (range, 7 to 26) for myeloid engraftment and 13 days (range, 11 to 75) for platelets. The cumulative incidences were 15.91% and 2.27% for grades II to IV and grades Ill to IV acute graft-versus-host disease (GVHD), respectively, with a median follow-up time of 36 months (range, 4 to 132). The cumulative incidences were 26.73% for chronic GVHD and 9.70% for moderate to severe chronic GVHD. No patients relapsed. The probabilities of 3-year overall survival (OS) and GVHD-free, failure-free survival (GFFS) were 90.4 +/- 4.6% and 85.6 +/- 5.4%, respectively. The 3-year OS rates of the haplo-donor and MSD groups were 86.5 +/- 7.3% versus 93.3 +/- 6.4% (P=.520). The 3-year GFFS rates of the haplo-donor and MSD groups were 78.3 +/- 8.6% versus 92.9 +/- 6.9% (P=.250). The preliminary results indicated that allo-HSCT is a feasible option for patients with PNH; however, this should not be considered as a first-choice therapy, because the results seemed to only suggest rather than confirm that haplo-HSCT and MSD-HSCT exerted similar therapeutic efficacies. (C) 2019 American Society for Blood and Marrow Transplantation.

Background: Allogeneic stem cell transplantation (allo-SCT) remains the only effective curative therapy for primary myelofibrosis. Utilization and efficacy of allo-SCT are limited by lethal complications, including engraftment failure, and acute (aGVHD) and chronic graft-versus-host disease (cGVHD). Several clinical trials have explored the use of mesenchymal stem cells (MSCs) in allo-SCT to prevent hematopoietic stem cell (HSC) engraftment failure and control GVHD.Methods: Clinical data of 17 patients with primary myelofibrosis who underwent allo-SCT combined with ex vivo expanded MSC transfusion in four centers from February 2011 to December 2018 were retrospectively analyzed.Results: All patients received myeloablative conditioning regimen. The median number of transplanted nucleated cells (NCs) per kilogram body weight was 11.18 × 10⁸ (range: 2.63–16.75 × 10⁸), and the median number of CD34⁺ cells was 4.72 × 10⁶ (range: 1.32–8.4 × 10⁶). MSCs were transfused on the day of transplant or on day 7 after transplant. The median MSC infusion number was 6.5 × 10⁶ (range: 0.011–65 × 10⁶). None of the patients experienced primary or secondary graft failure in the study. The median time to neutrophil engraftment was 13 days (range: 11–22 days), and the median time to platelet engraftment was 21 days (range: 12–184 days). The median follow-up time was 40.3 months (range: 1.8–127.8 months). The estimated relapse-free survival (RFS) at 5 years was 79.1%, and overall survival (OS) at 5 years was 64.7%. Analysis showed that the cumulative incidence of aGVHD grade II to IV was 36% (95% CI: 8%–55%) and that of grade III to IV was 26% (95% CI: 0%–45%) at day 100. The cumulative incidence of overall cGVHD at 2 years for the entire study population was 63% (95% CI: 26%–81%). The cumulative incidence of moderate to severe cGVHD at 2 years was 17% (95% CI: 0%–42%). Seven patients died during the study, with 5 patients succumbing from non‐relapse causes and 2 from disease relapse.Conclusion: The findings of the study indicate that allo-SCT combined with MSC transfusion may represent an effective treatment option for primary myelofibrosis.