Natural killer (NK) cell based immunotherapy is an emerging strategy in hematologic malignancies because allogeneic NK cells can provide potent antitumor immunity without inducing graft-versus-host disease. Thus, we expanded cord blood-derived NK (CB-NK) cells ex vivo from random (MHC mismatched and KIR mismatched) donors, and investigate the feasibility and efficacy of repeated infusions CB-NK cells as maintenance therapy after autologous hematopoietic stem cell transplantation (ASCT). Thirty-one patients with acute myeloid leukemia and high-risk lymphoma received ASCT and the adoptive CB-NK cell multiple infusions for maintenance therapy. Patients received a median dose of 5.98 × 10 7 /kg (range, 1.87-17.69 × 10 7 /kg) CB-NK cells and 23 patients completed four infusions, 8 patients received three infusions. Only mild infusion reactions occurred in 15.5% of 116 infusions. Compared to a contemporaneous cohort of 90 patients who did not receive NK cell therapy, the adoptive transfer of CB-NK cells as maintenance treatment showed a tendency of difference in decreasing the relapse rate between CB-NK group and control group (9.7% vs 24.4%). The patients who receiving NK cell infusions had a better PFS and OS than controls (4 year PFS, 84.4 ± 8.3% vs 73.5 ± 5.4%; and 4 year OS, 100% vs 78.1 ± 5.4%) . These findings demonstrate safety and validity of maintenance therapy using CB-NK cells multiple infusions after ASCT, and it is worthy of further clinical trial verification.

Background: Myelodysplastic syndromes (MDS) encompass a group of heterogeneous haematopoietic stem cell malignancies characterised by ineffective haematopoiesis, cytological aberrations, and a propensity for progression to acute myeloid leukaemia. Diagnosis and disease prognostic stratification are much based on genomic abnormalities. The traditional metaphase cytogenetics analysis (MC) can detect about 40-60% aberrations. Single-nucleotide polymorphism arrays (SNP-A) karyotyping can detect copy number variations with a higher resolution and has a unique advantage in detection of copy number neutral loss of heterozygosity (CN-LOH). Combining these two methods may improve the diagnostic efficiency and accuracy for MDS. Methods: We retrospectively analysed the data of 110 MDS patients diagnosed from January 2012 to December 2019 to compare the detection yield of chromosomal abnormalities by MC with by SNP-A, and the relationship between chromosomal abnormalities and prognosis. Results: Our results showed that SNP-A improved the detection yield of chromosomal aberrations compared with MC (74.5 vs. 55.5%, p<.001). In addition, the positive yield could be further improved by combining MC with SNP-A to 77.3%, compared with MC alone. Univariate analysis showed that age >65years, bone marrow blasts >= 5%, with acquired CN-LOH, new aberrations detected by SNP-A, TGA value>the median (81.435Mb), higher risk by IPSS-R-MC, higher risk by IPSS-R-SNP-A all had poorer prognosis. More critically, multivariable analysis showed that age >65years and higher risk by IPSS-R-SNP-A were independent predictors of inferior OS in MDS patients. Conclusion: The combination of MC and SNP-A based karyotyping can further improve the diagnostic yield and provide more precise prognostic stratification in MDS patients. However, SNP-A may not completely replace MC because of its inability to detect balanced translocation and to detect different clones. From a practical point of view, we recommend the concurrent use of SNP-A and MC in the initial karyotypic evaluation for MDS patients on diagnosis and prognosis stratification. KEY MESSAGES SNP-A based karyotyping can further improve the MDS diagnostic yield and provide more precise prognostic stratification in MDS patients. Acquired CN-LOH is a characteristic chromosomal aberration of MDS, which should be integrated to the diagnostic project of MDS. The concurrent use of SNP-A and MC in the initial karyotypic evaluation for MDS patients can be recommended.

The use of hypomethylating agents (HMAs) prior to hematopoietic stem cell transplantation (HSCT) in patients with myelodysplastic syndromes (MDS) was still controversial. Therefore, we sought to evaluate the impact of hypomethylation therapy before HSCT, with a special focus on long-term outcome. Databases, including PubMed, Embase Ovid, and the Cochrane Library, were searched for studies published up to 4 November 2018. Overall survival (OS) was selected as the primary endpoint, and relapse-free survival (RFS) was the secondary endpoint. A total of 6 cohort studies were included in the final meta-analysis. Our results showed that the outcome of patients with MDS using HMAs prior to HSCT was similar compared to those who did not with OS (HR = 0.81, 95% CI 0.63–1.04, p = 0.104) and RFS (HR = 0.96, 95% CI 0.72–1.26, p = 0.749). The pooled HR of OS in the older patients was 0.75 (95% CI 0.57–0.98, p = 0.035). No evidence showed that patients with MDS will benefit from using HMAs before HSCT in long-term survival (OS and RFS) compared to chemotherapy or best supportive therapy, though older patients were more likely to benefit from pre-transplantation HMAs treatment in terms of long-term survival. Our conclusions await further validation by prospective studies with larger sample size and randomized-controlled design. Particularly, to clarify whether the older patients who are candidates for HSCT could benefit from this bridging treatment will be of great interest.

RATIONALE:The balanced translocation t(8;21;22)(q22;q22;q11.2) is not reported previously, although t(8;21)(q22;q22) is seen in approximately 7% of adults and most frequent abnormality in children with newly diagnosed acute myeloid leukemia (AML). AML-associated hemophagocytic lymphohistiocytosis (HLH) is a rare event, reported only of limited numbers. The present study reports a very rare case of t(8;21;22)(q22;q22;q11.2) with AML, not reported previously, and developed HLH at the same time.PATIENT CONCERNS AND DIAGNOSIS:A 15-year-old girl presented with a history of bleeding gums and high fever, leukocytosis, anemia, and thrombocytopenia. While waiting the result of bone marrow aspirate, the HLH-associated examinations were abnormal. Bone marrow aspirate showed a hypercellular marrow with 1% myeloblasts. The cytogenetic and molecular studies revealed the presence of abnormal karyotype-46, XX, t(8;21;22)(q22;q22;q11.2) and RUNX1-RUNX1T1 fusion gene. Genetic detections of HLH showed heterozygous genetic variants in lysosomal trafficking regulator (LYST). Hence, she was diagnosed with AML with t(8;21;22)(q22;q22;q11.2) and HLH.INTERVENTIONS AND OUTCOMES:All HLH clinical symptoms disappeared after the 4 weeks treatment of HLH. Then the patient received standard AML induction chemotherapy and the leukemia relapsed after 2 cycles of high-dosed consolidation therapy. Eventually, the patient received emergent paternal haploidentical hematopoietic stem cell transplantation based on the complex variant translocation, leukemia replased state and HLH with compound heterozygotes mutation, and achieved sustained remission with RUNX1-RUNX1T1 negative for more than 1 year.LESSONS:Patients with some specific recurrent cytogenetic abnormalities should be diagnosed with AML regardless of the blast count, for example t(8;21). We should improve the understanding of complex variant translocations. HLH-related genetic mutations were not only found in primary HLH, but also in second HLH.