Splenectomy Outcomes in Relapsed or Refractory Immune Thrombocytopenia According to First-Line Intravenous Immunoglobulin Response

Introduction: Although splenectomy has long been second-line option for immune thrombocytopenia (ITP) patients, an indicator that reliably predicts the efficacy of splenectomy is still being explored. We investigated the treatment outcomes of splenectomy as a second-line therapy for relapsed/refractory ITP according to first-line intravenous immunoglobulin (IVIG) responses. Methods: Fifty-two adult patients treated with splenectomy as second-line therapy for ITP between 2009 and 2019 were included, and they were classified according to first-line IVIG responses (no response to IVIG: non-responders; only transient IVIG response shorter than 4 weeks: poor responders; IVIG response for a longer period; stable responders). The efficacy of splenectomy was analyzed in the three subgroups. Results: Of the 52 patients, 10 were IVIG non-responders, 34 were poor responders, and the remaining eight were stable responders. Response to splenectomy was observed in 50.0% of IVIG non-responders, 94.1% of poor responders, and 100% of stable responders (p = 0.0030). Among the 45 patients who responded to splenectomy, 51.1% relapsed subsequently, and a significantly lower relapse rate was noted in the stable IVIG responders (12.5%, p = 0.0220) than in non-responders (60.0%) and poor responders (59.4%). Conclusions: First-line IVIG response is indicated as a useful predictive factor for response to splenectomy.

The Prognostic Impact of MYC Gene-Related Abnormalities on Multiple Myeloma Outcome through Fluorescence in situ Hybridization Analysis

Introduction: Chromosomal abnormalities (CAs) have been identified as important factors in determining the biological features and prognostic value of multiple myeloma (MM). MYC gene-related abnormalities (MYC GAs) are one of the CAs, but its unfavorable impact has not been fully investigated in daily clinical practice. Methods: This study retrospectively analyzed the prognostic impact of MYC GAs on 81 patients through fluorescence in situ hybridization analysis in our institute. Results: MYC GAs were associated with poor overall survival (hazard ratio [HR], 3.08; 95% confidence interval [CI], 1.23–7.73; p = 0.017), progression-free survival (PFS) (HR, 2.96; 95% CI, 1.58–5.53; p < 0.001), and time to next treatment (TNT) (HR, 2.11; 95% CI, 1.13–3.93; p = 0.018) in the median follow-up of 34.7 months. Furthermore, MYC GAs with an additional chromosome 8 (MYC-Ch8(+)) were associated with shorter PFS (HR, 3.15; 95% CI, 1.38–7.2; p = 0.0064), whereas MYC GAs without an additional chromosome 8 (MYC-Ch8(−)) were associated with shorter PFS (HR, 3.62; 95% CI, 1.51–8.68; p = 0.004) and shorter TNT (HR, 3.72; 95% CI, 1.41–9.81; p = 0.0078). Conclusion: These findings could help identify high-risk patients with MM. Further prospective studies are needed to confirm the significance of MYC GAs for the MM prognostic effect.

Ruxolitinib Re-Treatment in Patients with Myelofibrosis: Real-World Evidence on Patient Characteristics and Outcomes

Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57–391, OPEN) and 110 (37–148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54–553) and 166 (108–262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.

Romiplostim for Primary Immune Thrombocytopenia (ITP) in Routine Clinical Practice: Results from a Multicentre Observational Study in Germany

Introduction: The effectiveness and safety of romiplostim were evaluated by immune thrombocytopenia (ITP) phase (newly diagnosed/persistent/chronic) at romiplostim initiation. Methods: Post hoc analysis of a prospective, German, multicentre, observational study in adults with ITP who received ≥1 dose of romiplostim. Follow-up data were collected for ≤2 years. Outcomes included overall platelet response (≥1 platelet count ≥50 × 109/L at 2–24 weeks after romiplostim initiation) or durable platelet response (≥75% of measurements ≥50 x 109/L at 14–24 weeks), and adverse drug reactions (ADRs), evaluated by ITP phase. Results: Data from 96 patients were analysed (newly diagnosed, n=18; persistent, n=25; chronic, n=53). During the 2–24-week follow-up, overall platelet response was achieved in 100% (95% confidence interval [CI]: 81.5–100), 100% (86.3–100), and 96.2% (87.0–99.5) of patients with newly diagnosed, persistent, or chronic ITP, respectively; platelet responses were durable in 88.2% (63.6–98.5), 65.0% (40.8–84.6), and 69.4% (54.6–81.7) of patients. During the 2-year follow-up, ADRs occurred in 24.0–35.8% of patients across phases. Two patients with chronic ITP experienced bone marrow ADRs; no thrombotic ADRs occurred. Conclusion: Romiplostim was effective and well tolerated in patients with newly diagnosed, persistent, or chronic ITP in routine clinical practice.

STAT3 Promotes Cell Proliferation by Potentiating the CCL4 Transcriptional Activity in Diffuse Large B-Cell Lymphoma

STAT3 is a transcription factor and a candidate therapeutic option for human cancers. However, the underlying mechanism of STAT3 in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has yet to be established. We studied here whether STAT3 contributes to CCL4 transcription elevation in DLBCL. Our established protein-protein interactions (PPI) network revealed the overexpression of STAT3 and CCL4 in DLBCL. Mechanistically, STAT3 activated CCL4 transcription to induce the Wnt/β-catenin pathway. The prognostic analysis exhibited that the overall survival of patients with high STAT3 and CCL4 were poorer than those with low STAT3 and CCL4 expression. In addition, silencing of STAT3 reverted the malignant phenotype in DLBCL cells. CCL4 overexpression partly weakened the si-STAT3-mediated anti-tumor effects on DLBCL cells. Tumor xenograft models showed that si-STAT3 inhibited tumor growth in vivo and decreased proliferative and mitogenic activities in tumor tissues, findings that were consistent with the in vitro data. Hence, this study provides new evidence that STAT3 and CCL4 may be new prognostic biomarkers and therapeutic targets for treating DLBCL.

Real-World Use of Fostamatinib in Patients with Immune Thrombocytopenia and Thrombotic Risk

Patients with immune thrombocytopenia (ITP) are at increased risk for bleeding and are paradoxically at increased risk for thrombosis. Many patients with ITP have underlying cardiovascular (CV) disease and/or other thrombotic risk factors for which considerable attention to selecting a therapeutic agent to manage ITP is needed. Fostamatinib, a spleen tyrosine kinase inhibitor, may reduce the risk of thrombosis while not interfering with hemostasis. We present a case series of 5 patients with ITP who had significant CV histories; each had at least 2 thrombotic risk factors. After unsuccessful management of ITP with other treatments, fostamatinib was initiated, was observed to be tolerable, and provided a durable platelet response without associated thromboembolic events. Fostamatinib may be the treatment of choice for patients with ITP in whom use of prothrombotic treatments should be avoided and/or continued use of antiplatelet or anticoagulant medication is needed.

Using Circ-ANAPC7 as a Novel Type of Biomarker in the Monitoring of Acute Myeloid Leukemia

<b><i>Introduction:</i></b> Circular RNAs (circRNAs) are a novel class of RNAs which occupy gene expression at the transcriptional or post-transcriptional level, involve in many physiological processes, and participate in many diseases, especially in cancer. Our previous study showed 1 altered circRNA named circ-anaphase promoting complex subunit 7 (ANAPC7) that was upregulated in acute myeloid leukemia (AML). To further clear the expression and clinical significance of circ-ANAPC7, we enlarged the sample size and illuminated the diagnostic and monitoring value of circ-ANAPC7 in AML. <b><i>Methods:</i></b> Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was supposed to confirm the expression of circ-ANAPC7 of AML patients. We assessed the correlation of circ-ANAPC7 and clinical variables using the Spearman correlation test. The receiver operating characteristic (ROC) curve was carried out to evaluate the diagnostic value. <b><i>Results:</i></b> Circ-ANAPC7 was first found to be upregulated in AML, and its expression was correlated to white blood cell counts in peripheral blood and blast percentage in bone marrow. ROC curve analysis revealed that circ-ANAPC7 has a significant value of auxiliary AML diagnosis (area under the curve = 0.915, <i>p</i> &#x3c; 0.001). Furthermore, the expression level of circ-ANAPC7 was changed accompanied with disease condition transformation. <b><i>Conclusion:</i></b> Circ-ANAPC7 was upregulated in newly diagnosed and relapsed AML. It may serve as potential biomarkers for AML patient’s diagnosis and monitoring.

Two Sides of a Coin: Case Report of Unilateral Synangiosis and Contralateral Stroke Highlighting Consequences of Disease Progression and Efficacy of Revascularization in Sickle Cell Disease Associated Moyamoya Syndrome

Moyamoya syndrome increases the risk of stroke in sickle cell disease, but revascularization surgery can modify this risk. Collaborative management between hematology and neurosurgery offers effective strategies to reduce stroke risk in these patients. We describe a challenging case where a patient with sickle cell disease undergoing standard of care management as prescribed by the Stroke Prevention Trial in Sickle Cell Anemia (STOP) and revascularization with pial synangiosis subsequently developed rapidly progressive disease in other cerebral vessels and suffered ischemic hemispheric stroke. This case demonstrates the success of management in accordance with American Heart Association (AHA) and American Stroke Association (ASA) guidelines, but also demonstrates critical areas where we lack understanding of disease progression.

Efficacy of Individualized Preventive Treatment of Patients with Severe Hemophilia A Guided by Multiple Clinical Parameters and Pharmacokinetics

Objective: To investigate the effect of multiple clinical parameters (age, weight, blood types, and bleeding types) on FⅧ pharmacokinetic parameters (PK parameters) in adult patients with severe hemophilia A (SHA), draw up individualized preventive treatment plans, and observe clinical efficacy and economic benefit. Methods: Forty SHA patients treated in our hospital from January 2018 to May 2019 were enrolled, with their age, weight, blood types, bleeding types, and PK parameters measured to analyze the effects of clinical parameters on PK parameters. Individualized preventive treatment was developed, and patients were followed up for 1 year. The annual bleeding times (ABR), annual joint bleeding times (AJBR), and annual FⅧ dosage were observed and compared before and after treatment. Results: Weight, blood types and bleeding types could affect the PK parameters of FVIII. A prevention plan was formulated under the guidance of FVIII half-life. After 1 year of follow-up, ABR decreased by 88.9%, AJBR decreased by 90%, and annual FⅧ dosage increased by 47%. The dosage of FⅧ in 8 patients after was less than that before prevention, and the average half-life time of these 8 patients was 13.32 h. Conclusions: 1. Weight, blood types, and bleeding types of adult SHA patients could affect FVIII half-life. As body mass index increased, FVIII half-life were significantly prolonged. The FVIII half-life of patients with type O blood were significantly shorter than those with other blood types, and the FVIII half-life of knee joint bleeding were conspicuously shorter than those of elbow joint bleeding. 2. Individualized preventive treatment could markedly reduce bleeding times. For patients with a long half-life period, the total annual FⅧ dosage could be reduced to achieve bleeding prevention and economic benefit.

Reproductive Failure and Thrombophilia: Not Enough Evidence for a Tight Bond

<b><i>Objectives:</i></b> The role of hereditary thrombophilia in reproductive failure (RF) is strongly debatable. In this retrospective single-center study, we analyzed pregnancy outcome in 175 women screened for thrombophilia after at least one event of RF. <b><i>Results:</i></b> The prevalence of thrombophilia in our cohort was 33.4%. Pregnancy survival curves were not different according to severity (log-rank, <i>p</i> = 0.302) or type of thrombophilia (log-rank, <i>p</i> = 0.532). In total, 81.7% of 175 subsequent pregnancies were proceeded with LMWH. Concomitant use of ASA was prescribed in 75 pregnancies according to physician choice. The primary endpoint was live birth rate (LBR) that succeeded in 152/175 next pregnancies (86.8%) and late obstetric complications (LOBC) which occurred in 17/175 next pregnancies (9.8%). In logistic regression analysis, neither the severity nor the type of thrombophilia was important for any pregnancy outcome (LBR or LOBC). Considering therapeutic interventions, the use of LMWH ± ASA was not related to LBR or LOBC. The only factor inversely related to LBR was age above the cutoff value of 35.5 years (<i>p</i> = 0.049). <b><i>Conclusions:</i></b> Incidence of thrombophilia is increased among women with RF, but the severity or type of thrombophilia is not related to pregnancy outcome.