Should dexamethasone alone or in combination be the initial steroid for adult ITP: Still a relevant question.

Corticosteroids are used in first-line treatment in newly diagnosed immune thrombocytopenia. The goal of treatment is primarily to decrease autoantibody-mediated platelet clearance. Ideally initial treatment would not just increase the platelet count but also provide a long-term sustained remission. While many clinicians use prednisone (PDN) as their first choice of corticosteroid, others prefer dexamethasone. The controversy is the subject of debates. Short courses of higher-dose corticosteroids were first reported by the Andersen study in 1994. The study posited high-dose dexamethasone as a 'cure' for all ITP patients. Later, studies addressed the number of dexamethasone cycles, indications to repeat cycles and timing between cycles, with varied long-term results. The results with dexamethasone were compared to PDN in some studies: the four-day cycles of dexamethasone work faster in increasing platelet counts and appear to reduce the occurrence of severe adverse events. Therefore, it is probably a better option for patients with low platelet counts and bleeding diathesis; however, curative superiority, the initial reason to administer it, compared to PDN is not well demonstrated. Across the studies, treatment with high-dose dexamethasone seems to be safer, with lower incidence of all adverse events compared to PDN, which might be a reflection of shorter treatment duration and possibly also lower cumulative steroid dose. Dexamethasone in combination with rituximab in first-line treatment produced higher response rates with better long-term results compared to high-dose dexamethasone alone and is a particularly good option in younger women.

CD56 Expression Is an Important Prognostic Factor in Multiple Myeloma Even with Bortezomib Induction.

OBJECTIVES: In this retrospective study, we evaluated the impact of CD56, CD117, and CD28 expression on clinical characteristics and survival in newly diagnosed myeloma patients treated with bortezomib-based induction therapy. METHODS: We analyzed 110 myeloma patients. Immunophenotype was determined using panels consisting of CD19/CD38/CD45/CD56/CD138 and CD20, CD28, and CD117 were used additionally. All samples were tested for recurrent chromosomal aberrations. RESULTS: CD56, CD117, and CD28 expression rates were 71, 6, and 68%, respectively. The lack of CD56 expression was associated with light chain myeloma. The lack of CD117 expression was associated with elevated creatinine levels (p = 0.037). We discovered the correlation between CD 28 expression and female gender. The median progression-free survival (PFS) for patients with revised International Staging System stage 2 disease with CD56 expression or the lack of CD56 expression was 20.5 vs. 13.8 months (p = 0.03). In patients undergoing autologous hematopoietic stem cell transplantation (aHSCT), we found no difference in PFS and overall survival regarding the CD56 expression. We found no impact of CD117 and CD28 expression on PFS in patients regarding aHSCT. CONCLUSIONS: Induction treatment incorporating bortezomib diminishes the negative impact of the lack of CD117 expression and aberrancy of CD28 but does not overcome the negative impact of the lack of CD56 expression.

Mobilization with cyclophosphamide reduces the number of lymphocyte subpopulations in the leukapheresis product and delays their reconstitution after autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

BACKGROUND: Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation. PATIENTS AND METHODS: In total 48 patients were prospectively enrolled in three different mobilization regimens; (i) filgrastim (20), (ii) pegfilgrastim (19) and (iii) cyclophosphamide + filgrastim (9). Lymphocytes, CD16+/56+ natural killer and CD4+/CD25high T regulatory cells were determined by flow cytometry. RESULTS: We found a statistically significant difference between the mobilization regimens. Cyclophosphamide reduced lymphocyte and natural killer (NK) cell counts on collection day (lymphocytes 1.08 × 109/L; NK cells 0.07 × 109/L) compared to filgrastim (lymphocytes 3.08 × 109/L; NK cells 0.52 × 109/L) and pegfilgrastim (lymphocytes 3 × 109/L; NK cells 0.42 × 109/L). As a consequence lymphocyte and NK cell counts were also lower in the leukapheresis products following cyclophosphamide mobilization regimen (lymphocytes 50.1 × 109/L; NK cells 4.18 × 109/L) compared to filgrastim (lymphocytes 112 × 109/L; NK cells 17.5 × 109/L) and pegfilgrastim (lymphocytes 112 × 109/L; NK cells 14.3 × 109/L). In all mobilization regimens T regulatory cells increased 2-fold on collection day, regarding the base line value before mobilization. There was no difference in T regulatory cell counts between the regimens. CONCLUSIONS: Mobilization with cyclophophamide reduces the number of mobilized and collected lymphocytes and NK cells as compared to mobilization with growth factors only and results in their delayed reconstitution following autologous hematopoietic stem cell transplantation. We found no difference between filgrastim and pegfilgrastim mobilization.

Amplification of Chromosome 1q Predicts Poor Overall Survival in Newly Diagnosed Multiple Myeloma Patients.

Background: Chromosome 1q copy number alterations are common in newly diagnosed patients with multiple myeloma, and in most published studies, there is no distinction made between three copies or the addition of at least four copies. The impact of these copy number alterations on patient outcome and optimal treatment is not fully understood. Methods: We retrospectively analyzed 136 transplant eligible patients with newly diagnosed multiple myeloma from our national registry, who were treated with first autologous stem cell transplantation (aHSCT) between January 1, 2018, and December 31, 2021. The primary endpoint was overall survival. Results: Patients with at least four copies of chromosome 1q had the poorest prognosis, with an overall survival of only 28.3 months. In multivariate analysis, four copies of chromosome 1q were the only statistically significant factor for overall survival. Conclusions: Despite the use of novel agents, transplantation, and maintenance therapy, patients with a gain of four copies of chromosome 1q have a very poor survival rate. Therefore, prospective studies using immunotherapy in this patient population are necessary.

Effectiveness and safety of romiplostim among patients with newly diagnosed, persistent and chronic ITP in routine clinical practice in central and Eastern Europe: an analysis of the PLATON study.

OBJECTIVES: The objective of this analysis was to assess the effectiveness and safety of romiplostim in the real-world by duration of primary immune thrombocytopenia (ITP): <3 ('newly diagnosed'), 3-12 ('persistent'), and >12 ('chronic') months. METHODS: This was a post-hoc analysis of the PLATON single-arm, observational cohort study of adults from five Central and Eastern European countries receiving ≥1 romiplostim dose as second-line therapy, or where surgery was contraindicated. Durable (≥75% of measurements with ≥50 × 109 platelets/L during weeks 14-24) and overall platelet response (≥30 or ≥50 × 109 platelets/L at least once), rescue therapy, bleeding, discontinuation of other ITP medications, and adverse drug reactions (ADRs) were assessed. RESULTS: Of 100 participants, 22.0% had newly diagnosed, 17.0% had persistent, and 61.0% had chronic ITP. Prior splenectomy was most frequently reported in chronic ITP (32.8%), prior bleeding was predominant in newly diagnosed patients (68.2%). Durable platelet response was achieved in 50.0% (95% confidence interval [CI]: 28.2-71.8%) of newly diagnosed, 35.3% (95% CI: 14.2-61.7%) of persistent, and 31.1% (95% CI: 19.9-44.3%) of chronic ITP patients. Overall platelet response was achieved in >80% across all strata. Safety was comparable across groups, with a low incidence of thrombotic ADRs and no bone marrow ADRs. DISCUSSION: In this real-world study, platelet response to romiplostim was consistent across all strata of ITP duration. ADRs were infrequent and similar across ITP settings. CONCLUSION: These findings support the utilization of romiplostim in patients with newly diagnosed and persistent ITP in accordance with recent guidelines and the recent romiplostim label extension.

Severe immune thrombocytopenia in a critically ill COVID-19 patient.

The novel coronavirus SARS-CoV-2 can cause a severe and even fatal respiratory illness named COVID-19. Apart from respiratory failure, COVID-19 may be associated with various autoimmune complications. We present a case of a critically ill patient with COVID-19 who developed severe immune thrombocytopenia that was successfully treated with a concomitant use of corticosteroids and intravenous immunoglobulins.

Filgrastim-alone versus pegylated filgrastim-alone for autologous peripheral blood stem cells mobilization in newly diagnosed multiple myeloma patients.

BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is the recommended standard upfront treatment for transplant eligible myeloma patients. Considering possible complications related to chemotherapy-cytokine mobilization, cytokine-alone mobilization is often used. We compared mobilization with filgrastim alone to pegfilgrastim alone in newly diagnosed myeloma patients after induction treatment with bortezomib and dexamethasone. The comparison was made between peripheral blood stem cell (PBSC) yields, number of apheresis, hematopoietic stem cell subsets, and time to neutrophil and platelet engraftment after aHSCT. METHODS: A total of 42 myeloma patients were prospectively enrolled in the study: 21 received filgrastim, 21 pegfilgrastim. Flow cytometry was used to determine the number of PBSC, myeloid, lymphoid, and megakaryocyte precursors in peripheral blood and apheresis product on day 1 of apheresis. RESULTS: The median number of collected PBSC was 5.05 × 106/kg in the filgrastim and 4.66 × 106/kg in the pegfilgrastim group (p = 0.428). The median number of apheresis was 2.5 in the filgrastim and 2 in the pegfilgrastim group (p = 0.901). The number of megakaryocyte precursors in peripheral blood was significantly higher in the filgrastim group, but not in the apheresis products. There were no statistically significant differences in the myeloid and lymphoid precursors in the peripheral blood and in the apheresis products. The median time to neutrophil and platelet engraftment was 13 days and 16.5 days for filgrastim and 13 days and 16 days for pegfilgrastim group. CONCLUSIONS: We can conclude that pegfilgrastim alone is at least equally successful as filgrastim alone for the PBSC mobilization in newly diagnosed myeloma patients.

Concurrent rearrangements of BCL2, BCL3, and BCL11A genes in atypical chronic lymphocytic leukemia.

The most frequent chromosomal aberrations with the well established prognostic meaning in chronic lymphocytic leukemia (CLL) are +12, del(11q), del(13q), and del(17p). Less common translocations lead to deregulation of genes primarily due to juxtaposition with IGH gene. We present a case of CLL patient with atypical morphology and an aggressive course of disease. In spite of aggressive treatment including allogeneic hematopoietic stem cell transplantation disease progressed into a rare cutaneous Richter's syndrome. Trisomy 12 was found as a sole chromosomal change at initial cytogenetic analysis of lymphoma cells. At progression, besides trisomy 12 three concomitant balanced translocations t(2;14)(p13;q32), t(14;19)(q32;q13), and t(18;22)(q21;q11) were found. The same karyotype was confirmed in cells aspirated from skin infiltrates at Richter transformation. Atypical cytological features, trisomy 12, and a progressive course of disease observed in our case are typical for CLL with each of particular Ig translocations that were concomitantly found in CLL for the first time. Similar to "double hit" lymphoma concurrent rearrangements may be relevant also in CLL.