Exact data on prognosis of children receiving invasive mechanical ventilation (IMV) after allogeneic hematopoietic SCT (HSCT) is lacking. We therefore started a prospective registry in four European university HSCT centers (Leiden, Paris, Prague and Utrecht) and their pediatric intensive care units (PICUs). The registry started in January 2009. In January 2013, the four centers together had treated a total of 83 admissions with IMV. The case fatality rate in these patients was 52%. Mortality 6 months after PICU discharge was 45%. There were significant differences between centers in the proportion of children who received IMV after HSCT (6-23%, Po 0.01), in severity of disease on admission to PICU (predicted mortality 14-37%, P o0.01), in applying noninvasive ventilation before IMV (3-75% of admissions, P o0.01) and in the use of renal replacement therapy (RRT) (8-58% of admissions, P o 0.01). Severe impairment in oxygenation, use of RRT and CMV viremia were independent predictors of mortality. Our study shows that mortality in children receiving IMV after HSCT remains high, but has clearly improved compared with older studies. Patient selection and treatment in PICU differed significantly between centers, which underscores the need to standardize and optimize the PICU admission criteria, ventilatory strategies and therapies applied in PICU.

ObjectiveSubcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration.Patients and methodsDuring January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly – 63% or twice weekly – 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.ResultsThe response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥2 was present in 20% vs 18% and PN grade ≥3 was present in 6% vs 4%.ConclusionsWe conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

We report a case of an 8-year-old girl who underwent a SARS-CoV-2 infection manifesting with atypical symptoms spearheaded by abdominal discomfort and systemic inflammation and partially mimicking hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), which however did not fulfill the HLH/MAS diagnostic criteria. In this case of what has since been described as Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-COV-2 (PIMS-TS) we documented excellent clinical response to immunosuppression with systemic corticosteroids and intravenous immunoglobulins. We show a detailed longitudinal development of neutrophil immunophenotype which suggests activation and engagement of neutrophils during PIMS-TS with compensatory contraction of the response and contra-regulation of neutrophil phenotype during recovery.

Background We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. Methods A total of 344 patients treated with IRD (N = 127) or RD (N = 217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient’s characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05. Results In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1–3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51–0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0% in the IRD group vs 66.2% in the RD group with a complete response rate (CR) of 11.1% vs 8.8%, and very good partial response (VGPR) 22.2% vs 13.9%, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. Conclusions Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.

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SummarySmouldering multiple myeloma (SMM) presents without MM defining symptoms. We aimed to identify patients with SMM with an 80% risk of progression within 2 years using only serum parameters. In total, 527 patients with SMM were included and divided into a training group (287 patients from the Czech Myeloma Group [CMG]) and an independent validation group (240 patients from Heidelberg). The median follow‐up was 2·4 and 2·5 years, respectively. Progression to MM occurred in 51·9% of the CMG and 38·8% of the Heidelberg patients, respectively. The median risk of progression was 11·0% (CMG) and 9·7% (Heidelberg) per year, during the 5 years after diagnosis. A serum involved/uninvolved free light‐chain ratio of >30, immunoparesis, and serum monoclonal (M) protein of ≥2·3 g/dl emerged as powerful predictors of 2‐year progression rate with a hazard ratio (HR) of 2·49 (95% confidence interval [CI] 1·49–4·17), HR of 2·01 (95% CI 1·36–2·96) and HR of 2·00 (95% CI 1·44–2·79) (P < 0·001) in univariate Cox regression analysis, respectively. Based on this, the CMG model identified patients with SMM with a 2‐year risk of progression of 78·7% (95% CI 53·1–95·7; HR 6·8; P < 0·001, CMG) and 81·3% (95% CI 47·1–98·8; HR 38·63; P < 0·001, Heidelberg). Serum parameters in the CMG model allow identification of patients with SMM with an 80% risk of progression to symptomatic MM within 2 years.

Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4Á38, 95% confidence interval (CI): 2Á46-7Á80, P < 0Á0001], high lactate dehydrogenase (LDH) levels (>5 lkat/l; OR 2Á07, 95% CI: 1Á51-2Á84, P < 0Á0001), extensive osteolytic activity (OR 2Á21, 95% CI: 1Á54-3Á15, P < 0Á001), and immunoglobulin A (IgA; OR 1Á53, 95% CI: 1Á11-2Á11, P = 0Á009) or the non-secretory type of MM (OR 2Á83; 95% CI: 1Á32-6Á04, P = 0Á007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression-free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13Á8 months (95% CI: 11Á4-16Á3) vs 18Á8 months (95% CI: 17Á7-19Á9), P = 0Á006; mOS: 26Á7 months (95% CI: 18Á1-35Á4) vs 58Á7 months (95% CI: 54Á8-62Á6), P < 0Á001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops.