Advances in Hematology最新文献

Fostamatinib is a small molecule spleen tyrosine kinase (Syk) inhibitor that was approved for the treatment of adult patients with immune thrombocytopenia (ITP) in second-line therapy. Syk inhibition prevents cytoskeletal rearrangements during phagocytosis, allowing platelet survival in ITP. However, fostamatinib treatment in elderly patients with ITP has not been well established. We performed a retrospective review of all elderly patients (age greater than or equal to 65 years) who had started on fostamatinib for the treatment of ITP at a single tertiary care centre to evaluate its efficacy and safety. Seven patients, median age 80 years (range 78-94), four women and three men, all of Caucasian background, with various comorbidities, started fostamatinib 100 mg orally twice daily as second or subsequent line therapy. Patients had a diagnosis of ITP for a median of 6 years (range approximately 6 months-30 years), had six comorbidities (range 2-14), and experienced 2 unique prior lines of ITP therapy (range 1 to 6). Over 1290 days of fostamatinib exposure, two patients required dose escalation to 150 mg orally twice daily, while five patients remained on the initial starting dose of 100 mg twice daily. The median platelet count at the time of initiating fostamatinib was 25 × 10⁹/L (range less than 10-193). The median time to response (defined as any first platelet count greater than or equal to 30 × 10⁹/L) was 19 days (range 0-181 days), with two patients responding rapidly (5 days and 19 days). Two patients required dose escalation and rescue therapy, and these same two patients discontinued fostamatinib after 175 days and 216 days of treatment. Treatment was tolerated in all patients with no thromboembolic events observed. One death was noted and unrelated to treatment. Overall, fostamatinib was effective and safe for the majority of these very elderly patients with ITP.

Background: Convalescent plasma obtained from individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains neutralizing antibodies to the virus and has been frequently used as a treatment in hospitalized patients with severe COVID-19.

Methods: We conducted a retrospective, observational cohort study involving 96 hospitalized patients with severe COVID-19 who were allocated in a 1 : 1 ratio to having received either high antibody concentration convalescent plasma or low antibody concentration convalescent plasma. Quantitative measurements of IgG to the receptor-binding domain (RBD), the S1 subunit of the spike protein, and the SARS-CoV-2 nucleocapsid (N) protein were determined from donor plasma samples. The primary outcome was all-cause mortality within 30 days following convalescent plasma administration in regard to each of the three antibody domains.

Results: Within the nucleocapsid antibody domain, death occurred in 22.2% of patients in the low antibody concentration group versus 23.5% in the high antibody concentration group (p=0.88). Within the RBD antibody domain, death occurred in 22.9% of patients in both the low and the high antibody concentration groups (p=1.0). Within the S1 subunit antibody domain, death occurred in 27.1% of patients in the low antibody concentration group versus 18.8% in the high antibody concentration group (p=0.33).

Conclusions: No significant differences were observed between low and high concentration convalescent plasma in regard to overall mortality at 30 days, hospital length of stay, number of ventilator days, and subsequent receipt of invasive mechanical ventilation in patients who were previously not receiving mechanical ventilation. Trial Registration. This study was not associated with a clinical trial due to the retrospective nature of study design.

Background: Bone marrow infiltration of lymphoma cells is a candidate risk factor for infusion-related reactions (IRRs) in patients with CD20-positive B-cell non-Hodgkin lymphoma (B-NHL). However, despite with the lack of sufficient data, the effect of bone marrow infiltration of B-NHL cells on the incidence rate of grade 2 or higher IRRs with the administration of rituximab has been retrospectively studied in this paper.

Methods: Patients with CD20-positive B-NHL who received the rituximab induction therapy for the first time were enrolled in this study. To evaluate the bone marrow infiltration of B-NHL cells, May-Giemsa stain of bone marrow films and flow cytometry examination of bone marrow aspiration samples were performed. IRR grade was determined using the IRR criteria in the Common Terminology Criteria for Adverse Events version 4.0.

Results: A total of 127 patients were eligible for this study. Grade 2 or higher IRRs were observed in 43 (34%) patients. In univariate analysis, use of glucocorticoid before rituximab infusion was a strong risk-avoiding factor for grade 2 or higher IRRs. Advanced stage of disease (Ann Arbor: stages III and IV) or bone marrow infiltration of B-NHL cells revealed the risk factors, regardless of glucocorticoid premedication. Using multivariate analysis, bone marrow infiltration was found to be an independent risk factor for patients without prior glucocorticoid use.

Conclusion: Bone marrow infiltration of B-NHL cells is a risk factor for grade 2 or higher IRRs at the first rituximab induction therapy without glucocorticoid premedication.

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m² during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505.

Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials (https://Clinicaltrials.gov Identifier https://clinicaltrials.gov/ct2/show/NCT02315768).

Background: The stress of academic life may predispose young adults to poor dietary habits, which could potentially precipitate nutritional deficiencies, such as iron deficiency. This study evaluated factors predictive of optimal iron stores as well as changes in haematological parameters over the course of an academic year in a cohort of tertiary students.

Materials and methods: The repeated-measure cohort study recruited 117 undergraduate students from September 2018 to May 2019. Venous blood samples were drawn for full blood count estimation, qualitative glucose-6-phosphate dehydrogenase (G6PD) status, haemoglobin variants, and blood group determination during the first 2 weeks of semester 1. However, anthropometric parameters as well as full blood counts were determined for each participant during the first week and last week of semesters 1 and 2. Additionally, semistructured questionnaires were used to capture sociodemographic data. Also, serum ferritin was estimated for each participant using enzyme-linked immunosorbent assay.

Results: Overall, 23.1% and 15.5% of participants inherited G6PD defect (G6PDd) or haemoglobin variants, respectively. However, group O (68/117; 58.1%) was the predominant ABO blood group and an overwhelming 90.6% (106/117) inherited Rh D antigen. The prevalence of anaemia increased from 20% at the beginning of the first semester to 45.1% at the latter part of the second semester. G6PDd participants had significantly higher median serum ferritin than G6PD normal participants (p = 0.003). Also, a significantly higher proportion of females were iron depleted (25% vs. 2.3%) or iron deficient (14.3% vs. 9.3%) compared to males. Moreover, being male, G6PD deficient, or 21-25 years was associated with increased odds of participants having optimal serum ferritin levels.

Conclusion: The progression of anaemia prevalence from mild to severe public health problem over the course of one academic year should urgently be addressed.

Of the variety of immunoglobulin related amyloidosis (AL), immunoglobulin M (IgM) related AL represents only 6 to 10% of affected patients, and the majority of these cases are associated with underlying non-Hodgkin's Lymphoma including Waldenström's macroglobulinemia (WM). Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors approved for certain indolent B cell non-Hodgkin's lymphoma (NHL). BTK is a nonreceptor kinase involved in B-cell survival, proliferation, and interaction with the microenvironment. We retrospectively evaluated the tolerability and effectiveness of BTK inhibitors ibrutinib and acalabrutinib therapy in (n = 4) patients with IgM-related AL amyloidosis with underlying WM. Treatment was well tolerated with both hematologic and organ response in patients with AL amyloidosis in the setting of WM. Atrial fibrillation led to the discontinuation of ibrutinib in one patient, and acalabrutinib caused significant thumb hematoma needing dose reduction in another patient. All patients evaluated had the MYD88 mutation. This may explain the good response to BTK inhibitors therapy in our series. BTK inhibitors should be further investigated in larger prospective studies for treatment of AL amyloidosis in patients with lymphoplasmacytic lymphoma/WM.

Purpose: There remains a lack of consensus among experts regarding the optimal therapeutic approach for Mantle cell lymphoma (MCL) after failure of covalent Bruton Tyrosine Kinase inhibitor (cBTKi)-based therapy. This study was designed to examine patient characteristics, current treatment patterns, and clinical outcomes using a real-world database to evaluate how MCL is currently managed post-cBTKi therapy in the U.S.

Methods: A large, deidentified U.S. electronic medical record (EMR) oncology database (ConcertAI) with data from January 2011 to July 2021 was utilized for this study. Eligible patients were adults with MCL who had received at least one cBTKi. Descriptive statistics were used to evaluate patient characteristics and treatment patterns. Time-to-event real-world outcomes of duration of therapy, time to next treatment discontinuation, and overall survival was evaluated using the Kaplan-Meier method.

Results: A total of 946 patients met eligibility criteria. Of these, 739 (78.1%) discontinued cBTKi treatment before the end of the follow-up period, while the remaining 207 (21.9%) were still receiving cBTKi therapy at the end of the follow-up period. Among those who had discontinued the cBTKi, 352 (47.6%, 352/739) received at least one subsequent (post-cBTKi) treatment. The median duration of the immediate post-cBTKi therapy was 2.6 months (n = 352). Among the 739 patients who discontinued cBTKi treatment, the median time from cBTKi discontinuation to next treatment discontinuation or death was 3.9 months and the median overall survival was 10.3 months.

Conclusions: This study demonstrates the poor outcomes experienced by patients after cBTKi therapy. There is an urgent need for safe and effective treatments for patients with recurrent or progressive MCL.