Multiple myeloma (MM), a plasma cell (PC) malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply scRNA-seq to study the heterogeneity of 40 individuals along MM progression spectrum including 11 healthy controls, demonstrating high interpatient variability that can be explained by expression of known MM drivers and additional putative factors. We identify extensive sub-clonal structures for 10/29 patients. In asymptomatic patients with early disease and in minimal residual disease post-treatment, we detect rare tumor-PC with similar molecular characteristics of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating-tumor-cells (CTC) allows for accurate liquid biopsy and detection of malignant PC, which reflect the patient BM disease. Our work establishes scRNA-seq for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients.

Hypomethylating agents have become the standard therapy for patients with high‐risk myelodysplastic syndrome (MDS). In Israel, azacitidine (AZA) is routinely used. Yet, infectious complications are common during AZA therapy. The current study was aimed to evaluate the incidence and predisposing risk factors for infections in AZA‐treated patients. This retrospective study included patients treated with AZA in 18 Israeli medical institutions between 2008 and 2011. Data on 184 patients [157 high‐risk MDS and 27 acute myeloid leukemia (AML)], with a median age of 71.6 (range 29–92) were recorded. Overall, 153 infectious events were reported during 928 treatment cycles (16.5%) administered to 100 patients. One hundred fourteen, 114/153 (75%) events required hospitalization and 30 (19.6%) were fatal. In a univariate analysis, unfavorable cytogenetics, low neutrophil, hemoglobin (Hb) and platelet (PLT) counts were found to be associated with infections (24.4% vs. 12.9%, P < 0.0001; 27% vs. 13.5%, P < 0.0001; 20.4% vs. 11%, P < 0.0001 and 29.2% vs. 14.2%, P < 0.0001, respectively). In multivariate analysis, only low Hb level, low PLT count, and unfavorable cytogenetics remained significant. Prior to therapy, poor cytogenetics, PLT count below 20 × 109/L and neutrophil count below 0.5 × 109/L were predictive of the risk of infection during the first two cycles of therapy. In conclusion, patients with unfavorable cytogenetics, presenting with low neutrophil and PLT counts, are susceptible to infections. Evaluation of infection risk should be repeated prior to each cycle. Patients with poor cytogenetics in whom AZA is prescribed despite low PLT count are particularly at high risk for infections and infection prophylaxis may be considered. Am. J. Hematol. 88:130–134, 2013. © 2012 Wiley Periodicals, Inc.

In December 2020 the Israeli Health Ministry began a mass vaccination campaign with the BNT162b2 vaccine. This was an important step in overcoming the severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) pandemic. Autoimmune phenomenon have been described after receiving vaccinations. Here we describe a case series of patients who developed acquired Thrombotic Thrombocytopenic Purpura, a rare autoimmune disease, within several days of receiving the BNT162b2 vaccine. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13(ADAMTS13) activity should be evaluated in patients with history of aTTP before and after any vaccination, especially the SARS‐CoV‐2 vaccination, and immunosuppression treatment should be considered before vaccination in cases of low ADAMTS13 activity. Patients should be closely monitored after the vaccine for clinical situation and laboratory data. Post vaccination thrombocytopenia assessment should include immune thrombocytopenic purpura, vaccine‐induced immune thrombotic thrombocytopenia and acquired thrombotic thrombocytopenic purpura.

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