Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous reports suggest that TA-TMA is caused by complement activation by complement-related genetic variants; however, this needs to be verified, especially in adults. Here, we performed a nested case-control study of allo-HSCT-treated adults at a single center. Fifteen TA-TMA patients and 15 non-TA-TMA patients, matched according to the propensity score, were enrolled. Based on a previous report showing an association between complement-related genes and development of TA-TMA, we first sequenced these 17 genes. Both cohorts harbored several genetic variants with rare allele frequencies; however, there was no difference in the percentage of patients in the TA-TMA and non-TA-TMA groups with the rare variants, or in the average number of rare variants per patient. Second, we measured plasma concentrations of complement proteins. Notably, levels of Ba protein on Day 7 following allo-HSCT were abnormally and significantly higher in TA-TMA than in non-TA-TMA cases, suggesting that complement activation via the alternative pathway contributes to TA-TMA. All other parameters, including soluble C5b-9, on Day 7 were similar between the groups. The levels of C3, C4, CH50, and complement factors H and I in the TA-TMA group after Day 28 were significantly lower than those in the non-TA-TMA group. Complement-related genetic variants did not predict TA-TMA development. By contrast, abnormally high levels of Ba on Day 7 did predict development of TA-TMA and non-relapse mortality. Thus, Ba levels on Day 7 after allo-HSCT are a sensitive and prognostic biomarker of TA-TMA.

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Calorie restriction (CR) has been studied as a way to prolong longevity, and CR before chemotherapy can reduce hematological toxicity in cancer patients. We investigated the influence of fasting on immune cells and immature hematopoietic cells. In fasted mice, there was a significant reduction in the hematopoietic stem cell count but no significant difference for progenitor cells. Colony assays showed no difference and the rates of early and late apoptosis were almost identical when comparing fasted and control mice. DNA cell cycle analysis of immature bone marrow (BM) cells showed that CR caused a significant increase in the percentage in the G0/G1 phase and decreases in the S and G2/M phases. We detected a remarkable increase of T cells in the BM of fasted mice. CD44– naïve CD8+ T cells were more numerous in fasted BM, as were naïve CD4+ T cells, and part of those T cells showed less tendency in the G0/G1 phase. Immature hematopoietic cells remained in a relatively quiescent state and retention of colony-forming capacity during CR. The number of naïve T cells in the BM of fasted mice increased. These findings imply immature hematopoietic cells and some lymphoid cells can survive starvation, whilst maintaining their function.

Chronic myeloid leukemia (CML) accounts for approximately 15-20% of all leukemias in adults. 1 CML is characterized by the BCR-ABL1 fusion gene encoding a constitutively active tyrosine kinase. 2 Tyrosine kinase inhibitor (TKI) can help to improved the survival time in CML patients to expect almost normal life expectancy; however, the risk of secondary malignancies due to TKIs has not been completely eliminated. It is reported that second malignancies developed in 3.1-4.5%

A 73-year-old man previously treated with rituximab for his mucosa-associated lymphoid tissue lymphoma suffered a suboptimal humoral immune response against an acquired SARS-CoV-2 infection. A detailed serological description revealed discrepant antigen-specific humoral immune responses. The titer of spike-targeting, “viral-neutralizing” antibodies remained below the detection level, in contrast to the anti-nucleocapsid, “binding” antibody response, which was comparable in both magnitude and kinetics. Accordingly, viral neutralizability and clearance was delayed, leading to prolonged RNAemia and persistent pneumonia. The present case highlights the need to closely monitor this unique population of recipients of B-cell-targeted therapies for their neutralizing antibody responses against SARS-CoV-2.