Problem kontroli leukocytozy u chorego na pierwotne włóknienie szpiku leczonego ruksolitynibem

Ruxolitynib — JAK1/JAK2 inhibitor — registrated for patients with myelofibrosis (MF) IPSS (International Prognostic Scoring System) intermediate-2 or high, with splenomegaly and general symptomatology. Moreover, ruxolitinib is used to reduce splenomegaly and general symptomatology in patients with MF who are candidates for allogeneic hematopoietic stem cells transplantation (allo- -HSCT). Anemia, thrombocytopenia and occasionally leukopenia with neutropenia are observed as a main side effects of ruxolitinib. Moreover, there are problems related to cytokine storm caused by treatment discontinuation. Here we report the patient with MF and important leucocytosis, in whom splenomegaly and general symptoms were reduced due to ruxolitinib. However, ruxolitinib in monotherapy did not reduce the leukocyte count, so the the combined therapy with ruxolitinib plus hydroxycarbamide was initiated. As the result of the treatment, reduction of number of leukocytes was observed, meanwhile the level of hemoglobin was stable and platelets count drop slightly. Thereafter, the patient proceeded to allo-HSCT. So far, there are two cases of patients treated with ruxolitinib plus hydroxycarbamid published in the literature. We think, that all cases treated in that way, should be reporteds, as we can establish the safety of this drug combination.Ruksolitynib to inhibitor JAK1/JAK2 zarejestrowany do terapii mielofibrozy (MF) obarczonej ryzykiem pośrednim-2 lub wysokim według Międzynarodowego Wskaźnika Prognostycznego (IPSS) oraz z towarzyszącą splenomegalią i objawami ogólnymi. Dodatkowo u chorych kwalifikowanych do przeszczepienia allogenicznych krwiotwórczych komórek macierzystych (allo-HSCT) zaleca się stosowanie ruksolitynibu przed transplantacją w celu poprawy stanu ogólnego chorego oraz zmniejszenia śledziony. Do głównych działań niepożądanych ruksolitynibu należą niedokrwistość, małopłytkowość, rzadziej leukopenia z neutropenią. Ponadto poważnym problemem są objawy związane z odstawieniem leczenia spowodowane gwałtownym wzrostem stężenia cytokin prozapalnych, co jest nazywane burzą cytokinową. Poniżej przedstawiono przypadek chorej na MF ze znaczną leukocytozą, u której w wyniku zastosowania ruksolitynibu udało się ograniczyć splenomegalię oraz nasilenie objawów ogólnych. Jednakże ruksolitynib w monoterapii nie spowodował obniżenia liczby leukocytów. W związku z tym u chorej zastosowano terapię łączoną ruksolitynibem i hydroksykarbamidem. Uzyskano znaczną redukcję leukocytozy, przy stabilnym stężeniu hemoglobiny i nieznacznym obniżeniu liczby płytek krwi. Pacjentkę zakwalifikowano do procedury allo-HSCT. Dotychczas w literaturze opisano 2 przypadki terapii łączonej ruksolitynibem z hydroksykarbamidem. Raportowanie opisów przypadków kolejnych chorych leczonych za pomocą powyższego zestawu leków w celu potwierdzenia bezpieczeństwa i skuteczności takiej terapii wydaje się mieć istotne znaczenia dla codziennej praktyki klinicznej

The effect of lipegfilgrastim on hematopoietic reconstitution and supportive treatment after megachemotherapy with autologous peripheral blood stem cell transplantation in patients with lymphoproliferative malignancies

Megachemotherapy with autologous peripheral blood stem cell transplantation (auto-PBSCT) is a standard treatment option in patients below 70 years of age with multiple myeloma (MM) as well as with relapsed and refractory lymphomas. Recombinant granulocyte colony-stimulating factors (G-CSF) are commonly used to accelerate bone marrow recovery after chemotherapy and reduce the duration of severe neutropenia. Lipegfilgrastim is a glicopegylated G-CSF with prolonged action registered for adult patients with malignant neoplasms in order to reduce the duration of neutropenia and the incidence of febrile neutropenia (FN). So far, there is not enough data to confirm the effectiveness and safety of this drug in patients with hematological malignancies including those undergoing auto-PBSCT. The aim of this study was to determine the effect of lipegfilgrastim on hematopoietic regeneration and supportive care after auto-PBSCT in patients with lymphoproliferative malignancies. The study population consisted of 30 patients (12 female and 18 male; median age: 50 years ± 13), including 13 patients with MM, 5 with Hodgkin’s lymphoma (HL) and 12 with non-Hodgkin’s lymphoma (nHL). The median number of transplanted CD34+ cells was 3.96 ± 1.56 × 10^6/kg of body mass. On day +1 after auto-PBSCT, the patients received lipegfilgrastim in a single 6 mg subcutaneous injection. The control group consisted of 32 patients (13 female and 19 male; median age: 50 years ± 6.4), including 13 with MM, 8 with HL and 11 with nHL, who received subcutaneous filgrastim in a dose of 5 μg/kg/day from day +1 after transplantation and continued to an absolute neutrophil count (ANC) > 1.5 × 10^9/L. There was no significant difference in the time of regeneration ANC > 0.5 × 10^9/L which was 10.65 ± 1.00 vs. 11.51 ± 2.29 days respectively in the study and control group. Similar observations were noted regarding the duration of febrile neutropenia (2.16 ± 2.22 vs. 1.70 ± 4.17 days; p = 0.998), regeneration of platelets (PLT) > 20 × 10^9/L (12.41 ± 2.41 vs. 13.82 ± 4.48 days; p = 0.233) and demand for transfusion of red blood cells (0.76 ± 1.07 vs. 1.33 ± 2.33 units; p = 0.414) and platelets (11.5 ± 6.9 vs. 19.2 ± 17.7 units; p = 0.08). Different results were observed for the length of hospitalization, which was significantly shorter in the lipegfilgrastim group (16.14 ± 14 vs. 24.46 ± 6.79 days; p = 0.000). Lipegfilgrastim is as effective as filgrastim with regards to the regeneration of the hematopoietic system, duration of febrile neutropenia, demand for transfusion of blood products and significantly reduces hospitalization in patients with lymphoproliferative malignancies after auto-PBSCT

Asymmetric and symmetric dimethylarginines and mortality in patients with hematological malignancies—A prospective study

<div><p>The study was designed to determine the associations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginines plasma concentrations with all-cause mortality in patients with hematological malignancies. 33 patients with acute myeloid leukemia (AML), 31 patients with non-Hodgkin’s lymphoma (nHL), 32 patients with chronic lymphocytic leukemia (CLL) and 48 patients without malignancy were enrolled into the study. Each patient was followed until death or for at least 14.5 months (range: 14.5–53). Median ADMA and SDMA were significantly elevated in AML, nHL and CLL compared to controls (ADMA: 1.36, 1.24, 1.03, 0.55 μmol/l respectively, p<0.0001; SDMA: 0.86, 0.76, 0.71, 0.52 μmol/l respectively, p<0.0001). High ADMA and SDMA were associated with increased risk for all-cause mortality in CLL group (Hazard ratio (HR) for ADMA: 3.05, 95% CI:1.58–5.88, p = 0.001; HR for SDMA: 4.71, 95% CI:1.91–11.58, p = 0.001). Our study suggests that ADMA and SDMA could be novel prognostic factors for all-cause mortality in CLL patients.</p></div

Correlations between SDMA and L-arginine, ADMA, its metabolites and sVCAM-1 in the study groups (Spearman’s rank correlation test).

<p>Correlations between SDMA and L-arginine, ADMA, its metabolites and sVCAM-1 in the study groups (Spearman’s rank correlation test).</p

Kaplan–Meier survival curve analysis in relation to ADMA and SDMA in hematological groups.

<p>p was calculated using Cox regression analysis.</p