Clinical Hematology International最新文献

Health disparities in multiple myeloma (MM) disproportionately affect minorities. Characterization of health disparities encountered by Hispanic Americans with MM is necessary to identify gaps and inform future strategies to eliminate them. We performed a systematic review of publications that described health disparities relevant to Hispanic Americans with MM through December 2021. We included all original studies which compared incidence, treatment, and/or outcomes of Hispanic Americans with other ethnic groups. Eight hundred and sixty-eight articles were identified of which 22 original study articles were included in our systematic review. The number of publications varied over time with the highest number of studies (32%) published in 2021. Most of the published studies (59%) reported worse outcomes for Hispanic Americans with MM compared to other ethnic groups. There is growing evidence that Hispanic Americans with MM are facing a multitude of disparities that require immediate attention and solutions.

With the rising number of patients undergoing hematopoietic stem cell transplantation (HSCT), clinicians are more likely to encounter infectious complications in immunocompromised hosts, particularly cytomegalovirus (CMV) infection. Besides the high mortality of CMV end-organ disease, patients with detectable CMV viremia may have worse outcomes and decreased survival even in the absence of end-organ disease. In view of the implications on morbidity and mortality, clinicians should maintain a high index of suspicion and initiate antiviral drugs promptly when CMV infection is confirmed. High-risk patients should be identified in order to provide optimal management. Additionally, novel antiviral agents with a good safety profile and minor adverse events are now available for prophylaxis in high-risk patients and for treatment of resistant or refractory CMV infection. The following review provides concise, yet comprehensive, guidance on the burden and risk factors of CMV in this population, as well as an update on the latest evidence for the management of CMV infection.

Introduction: This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody.

Methods: RO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model.

Results: Overall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%).

Conclusions: RO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma.

Trial registration: ClinicalTrials.gov: NCT04434469; Registered June 16, 2020; https://www.

Clinicaltrials: gov/ct2/show/NCT04434469 .

Myelodysplastic neoplasms, formerly known as myelodysplastic syndromes (MDS), represent a group of clonal disorders characterized by a high degree of clinical and molecular heterogeneity, and an invariable tendency to progress to acute myeloid leukemia. MDS typically present in the elderly with cytopenias of different degrees and bone marrow dysplasia, the hallmarks of the disease. Allogeneic hematopoietic stem cell transplant is the sole curative approach to date. Nonetheless, given the disease's demographics, only a minority of patients can benefit from this procedure. Currently used prognostic schemes such as the Revised International Prognostic Scoring System (R-IPSS), and most recently the molecular IPSS (IPSS-M), guide clinical management by dividing MDS into two big categories: lower- and higher-risk cases, based on a cut-off score of 3.5. The main clinical problem of the lower-risk group is represented by the management of cytopenias, whereas the prevention of secondary leukemia progression is the goal for the latter. Herein, we discuss the non-transplant treatment of MDS, focusing on current practice and available therapeutic options, while also presenting new investigational agents potentially entering the MDS therapeutic arsenal in the near future.

Introduction: Despite the implementation of new therapeutic agents, management of relapsed multiple myeloma (MM) remains a challenge. Salvage autologous hematopoietic cell transplant (AHCT) remains a valid therapeutic option for eligible patients who achieve prolonged response after a first AHCT. However, a second graft is not always available, and these patients may need a second mobilization.

Patients and methods: This prospective, non-interventional, multicenter study aimed to collect data on the feasibility of salvage AHCT using a plerixafor-based hematopoietic cell mobilization in relapsed MM, according to the plerixafor label in France. Adult patients with relapsed MM eligible for a second AHCT and mobilized using granulocyte- colony stimulating factor (G-CSF) and plerixafor were included.

Results: Of the 23 patients, 17 achieved a successful hematopoietic cell mobilization and 13 were able to proceed to a second AHCT. Median age was 62.9 years (min-max 51-71). Ten patients (77%) were male. Eleven (85%) received AHCT as a third-line treatment or more. Median time between first and second AHCT was 5.4 years (range, 2.6-16.3). Among 18 evaluable patients, mobilization was successful for 17 (94%) of them [95% CI 84-100], with no reported side effects. Among the 13 patients who underwent salvage AHCT, the median time to engraftment was 14 days (min-max 11-29). One-year progression-free and overall survival were 88.9% [95% CI 43.3-98.4] and 100%, respectively.

Conclusion: This study demonstrated that plerixafor allows safe and efficient mobilization in relapsed MM patients who are candidates for a salvage AHCT.

Trial registration: NCT02439476 Registered 8 May 2015, https://clinicaltrials.gov/ct2/show/NCT02439476 .

The imaging appearances of the skeletal system have been well documented in sickle cell disease (SCD) but there is limited information about the impact of SCD treatments on skeletal abnormalities. We present two patients with SCD maintained on long-term erythrocytapheresis and the changes to their skeletal abnormalities on neuroimaging with this treatment. We observed a reversal of the bone marrow conversion process and the skull appearance was age appropriate without any radiographic findings of iron overload in the patients.

Multiple myeloma (MM) is a prevalent hematological malignancy. Resource-constrained settings such as the Middle East are particularly burdened by the increasing trends in MM morbidity and mortality in addition to challenges in the management of MM. It thus becomes necessary to identify and address debatable areas of current practice and gaps in the management of MM in the Middle East. With a special focus on the Lebanese situation, the first-line treatment of the very elderly (> 80 years old) is discussed, in addition to the impact of relapse type (biochemical or clinical relapse) on maintenance therapy, the choice of first relapse therapy in relation to maintenance therapy, and the role of MRD in the MM treatment landscape. The need for realistic management guidelines accounting for local resources and expertise, in addition to the reflection of drug accessibility and cost on clinical practice are recognized.

The multicenter observational BiRD study investigated the real-world effectiveness and safety of ibrutinib in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia (WM) in Belgium. This interim analysis reports results for patients with CLL, with a median follow-up of 34 months. Overall, patients had predominantly relapsed/refractory disease (73%) and were elderly (median age 72 years) with high-risk features such as del17p and/or TP53 mutations (59%). Patients were included either prospectively or retrospectively, and the total patient population effectiveness results were adjusted with left truncation. In the effectiveness population (N = 221: prospective, n = 71; retrospective, n = 150), the overall response rate was 90.0%. Median progression-free survival was 38.3 months (prospective, not estimable; retrospective, 51.5 months) and median overall survival was not yet estimable in the total, prospective and retrospective groups. Treatment-emergent adverse events (TEAEs) for the prospective and retrospective groups are reported separately. Any-grade TEAEs of interest in the prospective/retrospective groups included infections (67.1%/60.1%), diarrhea (20.5%/10.5%), hypertension (16.4%/9.8%) and atrial fibrillation (12.3%/7.2%). Major bleeding was reported in 5.5%/3.3% of prospective/retrospective patients, with little difference observed between those receiving versus not receiving antithrombotic treatment. Discontinuations due to toxicity were reported in 10.5% of patients. Results from this interim analysis show treatment with ibrutinib to be effective and tolerable, with no new safety signals observed. Future analyses will report on longer-term follow-up.