<b><i>Introduction:</i></b> This prospective study evaluated a calcineurin inhibitor-free graft-versus-host disease (GVHD) prophylaxis regimen of ruxolitinib in combination with post-transplant cyclophosphamide (PTCy). <b><i>Patents and Methods:</i></b> Twenty patients with primary or secondary myelofibrosis were prospectively enrolled. Reduced intensity conditioning was performed, followed by allogeneic stem cell transplantation from related (<i>n</i> = 7) or unrelated (<i>n</i> = 13) donors. GVHD prophylaxis included only PTCy and ruxolitinib (45 mg) from day–7 to day–2, and 15 mg from day+5 to day+100. This trial was registered at www.clinicaltrials.gov as #NCT02806375. <b><i>Results:</i></b> Primary engraftment was documented in 17 patients. One patient experienced primary graft failure and 2 died before engraftment. Eleven patients demonstrated severe poor graft function (SPGF), which required ruxolitinib dose reduction. The regimen was well tolerated, with grade 3–4 non-haematological toxicity in 30%, viral reactivation in 45%, and severe sepsis in 15% of patients. The incidence of acute GVHD grade II–IV was 25%, grade III-IV GVHD was 15%, and moderate chronic GVHD was 20%, with no severe cases. Only 2 patients required systemic steroids. Haematological relapse was documented in 1 patient. Two-year non-relapse mortality was 15%, 2-year overall survival was 85%, and 2-year event-free survival was 72%. <b><i>Conclusion:</i></b> GVHD prophylaxis with PTCy and ruxolitinib is associated with low toxicity, good acute and chronic GVHD control, and low relapse incidence. However, the relatively high rate of SPGF should be taken into account. SPGF could possibly be mitigated by ruxolitinib dose reduction.

JAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without (n = 274) or with (n = 277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%, p = 0.05). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%; p = 0.04)] and better 2-year event-free survival (68.9% vs. 53.7%; p = 0.02) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age > 58 years (p = 0.03) and HLA mismatch donor (p = 0.001). RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.

Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and Methods. The retrospective study included 44 adult recipients (allogeneic – 33 [75%] and autologous – 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia – 18 (41%) and lymphoma – 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1–818 days), after HSCT – 507.5 days (14–3723 days). Overall and progression-free survival was assessed using the Kaplan–Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1–3490 days). Twelve patients (27.2%) were in grade 3–4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1–2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1–88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%.

A number of sequencing studies identified the prognostic impact of somatic mutations in myelodysplastic syndrome (MDS). However the majority of them focused on methylation regulation, apoptosis and proliferation genes. Despite the number of experimental studies published on the role of micro-RNA processing and checkpoint genes in the development of MDS, the clinical data about mutational landscape in these genes is limited. We performed a pilot study which evaluated mutational burden in these genes and their association with common MDS mutations. High prevalence of mutations was observed in the genes studied: 54% had mutations in DICER1, 46% had mutations in LAG3, 20% in CTLA4, 23% in B7-H3, 17% in DROSHA, 14% in PD-1 and 3% in PD-1L. Cluster analysis that included these mutations along with mutations in ASXL1, DNMT3A, EZH2, IDH1, RUNX1, SF3B1, SRSF2, TET2 and TP53 effectively predicted overall survival in the study group (HR 4.2, 95%CI 1.3–13.6, p = 0.016). The study results create the rational for incorporating micro-RNA processing and checkpoint genes in the sequencing panels for MDS and evaluate their role in the multicenter studies.

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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.

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