Conversion from calcineurin inhibitors to sirolimus in transplant-associated thrombotic microangiopathy.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a specific complication of allogeneic hematopoietic cell transplantation with a multifactorial etiology. There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitors (CNIs) with other agentsas a widely accepted practice in this disorder; however, there are limited data on the options for immunosuppression manipulation (ISM). In our study, we retrospectively analyzed outcomes of 45 patients with TA-TMA with ISM and substitution either with steroids (steroid group) or anmTOR inhibitor sirolimus (sirolimus group). In our study, sirolimus was associated with significantly better 1-year overall survival (HR 0.3, 95% CI 0.13-0.7, p = .004) and faster time to normalization of LDH (HR 2.2, 95% CI 0.99-4.99, p = .044). Replacing CNIs with sirolimus could be an effective option in patients with TA-TMA. A multicenter confirmatory study of CNIs replacement with sirolimus is justified.

Clinical Correlates and Prognostic Significance of IL-8, sIL-2R, and Immunoglobulin-Free Light Chain Levels in Patients with Myelofibrosis.

BACKGROUND: Chronic myeloproliferative neoplasms are characterized by clonal hematopoiesis and persistent inflammatory reaction. In this study, the clinical significance and prognostic impact of several inflammatory markers were evaluated in patients with BCR/ABL-negative myeloproliferative malignancies. METHODS: Serum levels of interleukin-8 (IL-8) and lymphoid-associated activation markers - soluble interleukin-2 receptor (sIL-2R) and immunoglobulin-free light chains (FLC) - were evaluated in patients with primary myelofibrosis (MF), post-polycythemia vera MF, and post-essential thrombocythemia MF, and compared with the levels in healthy donors. RESULTS: In 57 MF patients, sIL-2R excess correlated with transfusion-dependent anemia (p = 0.03) and splenomegaly (p = 0.02). There were no statistically significant correlations between sIL-2R and IL-8 levels, but the plasma concentration of κ-FLC positively correlated with the IL-8 level (p = 0.027). In univariate analysis, increased levels of IL-8 (p = 0.016) and sIL-2R (p = 0.010) significantly reduced 1-year overall survival. Only elevated sIL-2R rate retained significance (p = 0.02) in multivariate analysis when Dynamic International Prognostic Scoring System plus (DIPSSplus) risk stratification was added. CONCLUSION: We observed an association between FLC and proinflammatory cytokine hyperexpression. Serum cytokine levels and FLC might be a promising approach to predicting and monitoring treatment response in MF patients.