There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®), eltrombopag (Revolade®), and ...avatrombopag (Doptelet®). However, comparative clinical data between these TPO-RAs are limited. Therefore, the purpose of this study was to perform a literature review and seek expert opinion on the relevance and strength of the evidence concerning the use of TPO-RAs in adults with ITP. A systematic search was conducted in PubMed and Embase within the last 10 years and until June 20, 2022. A total of 478 unique articles were retrieved and reviewed for relevance. The expert consensus panel comprised ITP senior hematologists from eight countries across Central Europe. The modified Delphi method, consisting of two survey rounds, a teleconference and email correspondence, was used to reach consensus. Forty articles met the relevancy criteria and are included as supporting evidence, including five meta-analyses analyzing all three European-licensed TPO-RAs and comprising a total of 31 unique randomized controlled trials (RCTs). Consensus was reached on seven statements for the second-line use of TPO-RAs in the management of adult ITP patients. In addition, the expert panel discussed TPO-RA treatment in chronic ITP patients with mild/moderate COVID-19 and ITP patients in the first-line setting but failed to reach consensus. This work will facilitate informed decision-making for healthcare providers treating adult ITP patients with TPO-RAs. However, further studies are needed on the use of TPO-RAs in the first-line setting and specific patient populations.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The diagnosis of immune thrombocytopenia consists in the combination of laboratory and clinical pictures of thrombocytopenia while eliminating other disorders characterized by low levels of ...thrombocytes. The treatment initiation in patients with ITP is recommended when the thrombocyte count has dropped below 20-30 × 109/l, when hemorrhagic manifestations occur and depending on the patient's risk profile. Corticoids and IVIG are used as first-line treatment. Second-line treatment includes splenectomy, immunosuppressive therapy and administration of thrombopoietin receptor agonists. A new drug in the treatment of ITP is fostamatinib. Key words: corticoids - eltrombopag - fostamatinib - immune thrombocytopenia - IVIG - rituximab - romiplostim - sustainable remission - splenectomy.
Thrombopoietin-receptor agonists (TPO-RAs) are highly effective in immune thrombocytopenia (ITP). Recently, reports of sustained remission after TPO-RA discontinuation in adult ITP have been ...reported. We aimed to describe the subset of patients in whom TPO-RA therapy may induce a durable response. We retrospectively analyzed all of our adult ITP patients treated with TPO-RAs, and focused on patients with discontinued TPO-RA therapy due to treatment response. Forty-six relapsed or refractory ITP patients were treated with TPO-RAs. In 11 of these cases, TPO-RA therapy (seven romiplostim; four eltrombopag) was stopped after achieving treatment response. No side effects of TPO-RAs were observed. These patients were pretreated with 1–3 therapy lines plus splenectomy in six patients prior to TPO-RA administration. None of these patients experienced disease relapse after therapy discontinuation over a median follow-up of 33 months (16–54). Substantial proportion of ITP patients receiving TPO-RAs can maintain a durable response after treatment discontinuation. Sustained ITP remission probably does not depend on previous treatment, splenectomy, or disease duration.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The effects of romiplostim on bone marrow morphology were evaluated in adults with immune thrombocytopenia (ITP). Patients with platelet counts <50 × 10
9
/L, ≥1 prior ITP therapies, and no collagen ...at baseline received weekly subcutaneous romiplostim starting at 1 μg/kg, adjusted to maintain platelet counts between 50 and 200 × 10
9
/L. Biopsies were scheduled after 1, 2, or 3 years of romiplostim (cohorts 1, 2, and 3, respectively). Irrespective of scheduled time, biopsies were performed earlier if patients discontinued or failed to achieve/maintain a response to romiplostim. Reticulin (silver stain) and collagen (trichrome stain) were graded by two hematopathologists using the modified Bauermeister scale (0–4). Of 169 patients, 131 had evaluable biopsies; 9/131 (6.9 %) had increases of ≥2 grades on the modified Bauermeister scale (cohort 1: 0/34; cohort 2: 2/39; cohort 3: 7/58), including two with collagen. Three of the nine patients had follow-up biopsies, including one patient with collagen; changes were reversible after romiplostim discontinuation. Of the nine patients, one had neutropenia detected by laboratory test and two had adverse events of anemia, both non-serious and not treatment-related. By actual exposure (as some biopsies did not occur as scheduled), the number of patients with grade increases ≥2 were year 1: 3/41, year 2: 1/38, year 3: 5/52. Twenty-four patients sustained platelet counts ≥50 × 10
9
/L for ≥6 months with no ITP medications after discontinuing romiplostim, i.e., they entered clinical remission of their ITP. In conclusion, in patients with ITP receiving romiplostim, bone marrow changes were observed in a small proportion of patients.
ClinicalTrials.gov identifier: NCT#00907478
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Telomeropathies are associated with a wide range of diseases and less common combinations of various pulmonary and extrapulmonary disorders.
In proband with high-risk myelodysplastic syndrome and ...interstitial pulmonary fibrosis, whole exome sequencing revealed a germline heterozygous variant of
gene (c.1360delG). This "frameshift" variant results in a premature stop codon and is classified as likely pathogenic/pathogenic. So far, this gene variant has been described in a heterozygous state in adult patients with hematological diseases such as idiopathic aplastic anemia or paroxysmal nocturnal hemoglobinuria, but also in interstitial pulmonary fibrosis. Described
gene variant affects telomere length and leads to telomeropathies.
In our case report, we describe a rare case of coincidence of pulmonary fibrosis and hematological malignancy caused by a germline gene mutation in
. Lung diseases and hematologic malignancies associated with short telomeres do not respond well to standard treatment.
Controversies still exist regarding definition of the thrombotic risks in Ph‐ (BCR/ABL1‐) myeloproliferative disorders with thrombocythemia (MPD‐T). Platelet counts at diagnosis are currently not ...taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD‐T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 × 109/L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2V617F mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V ‘Leiden’ and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (± aspirin), we documented a decrease in both venous (6.7‐fold) and arterial events (1.8‐fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Although rituximab has seen increasing use in the treatment of immune thrombocytopenia (ITP) for many years, its therapeutic role in this disease remains unclear. We retrospectively analyzed data of ...all patients with ITP treated with rituximab (375 mg/m
2
once weekly for four consecutive weeks) and consecutively entered the findings into the databases of six large academic centers in the Czech Republic. A total of 114 patients were included in the analysis. All of the patients received rituximab as a second or additional line of therapy. The overall response rate (ORR) after rituximab therapy was 72 % 48 % complete response (CR), 24 % partial response (PR) at month 6, and 69 % (45 % CR, 24 % PR) at month 12. For the group of patients with newly diagnosed (acute) ITP, the results of treatment were significantly better than for the group of patients with persistent or chronic ITP; nonetheless, this group of patients was far too small (
n
= 18) for our findings to be generalized. Multivariate analysis revealed that the ORR was significantly influenced primarily by the number of therapies prior to rituximab (the more previous therapies, the worse treatment response). The results of our analysis “from everyday hematological practice” confirm the high efficiency of rituximab treatment in pretreated adult patients with ITP.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
