Journal of hematology最新文献

Background: Immunocompromised individuals with hematological malignancy have increased risk for poor outcomes and death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This special population may mount a suboptimal response to vaccination. We assessed the effectiveness of tixagevimab and cilgavimab (Evusheld), a monoclonal antibody combination against SARS-CoV-2, in conjunction with standard preventative measures, at preventing symptomatic incident infection.

Methods: Patients aged 18 years and older with hematological malignancy consented to receive Evusheld. Patients were followed longitudinally for development of symptomatic incident SARS-CoV-2 infections. Adverse events were monitored.

Results: Two hundred and three patients (94 female) with hematological malignancies and mean age 72 ± 10 years were included. Of the patients, 99.5% had received at least one mRNA vaccination against SARS-CoV-2. Average time of follow-up was 151 ± 50 days. Nineteen patients (9.3%) developed incident symptomatic SARS-CoV-2 infection, with only one (0.5%) requiring hospitalization. During the same follow-up period, local incident rate of infection was 84,123 cases (11.3% of population). Of those, 3,386 cases (4%) of SARS-CoV-2 required hospital admission. The incidence rate ratio was 0.79. No serious adverse events occurred following administration of Evusheld.

Conclusion: Patients with hematological malignancy who received Evusheld infrequently developed symptomatic infections or require hospitalization. The high-risk cohort incidence was at least as comparable to the average risk general population. Evusheld appears effective and is well tolerated, and may be administered in conjunction with vaccination and standard prevention measures, at decreasing incident SARS-Co-V2 cases in this high-risk population.

Bone involvement is a rare extranodal manifestation in patients with malignant lymphoproliferative diseases and has also been noted as a rare event in patients with Waldenstrom macroglobulinemia (WM). However, the actual prevalence has not been previously reported. We describe an unusual case of a patient with WM who presented with lower back pain and focal bone lesions at initial diagnosis. Magnetic resonance imaging (MRI) revealed multiple vertebral fractures. Positron emission tomography (PET) detected only nodal changes without pathological skeletal-related metabolic activity. Lymph node and bone marrow biopsies combined with an immunoglobulin M (IgM) M component revealed the diagnosis of WM. A next-generation sequencing (NGS) analysis using a targeted lymphoma panel of 59 recurrently mutated genes in lymphoid neoplasms showed mutations in the MYD88 and CD79B genes. After treatment with rituximab and bendamustine, the patient achieved a partial remission and pain relief. After 3 years of stable disease, a spontaneous subcapital fracture at the base of the femoral neck and new vertebral compression fractures occurred. Whole-body low-dose computed tomography (WB-LDCT) and bone density (dual energy X-ray absorptiometry (DEXA)) scan revealed marked osteopenia. After insertion of a hip prosthesis, examination of the removed hip showed infiltration of clonal lymphoplasmacytic cells. Our case confirms that one must be aware that bone involvement in patients with WM can occur as a rare manifestation. Interestingly, the MYD88/CD79B-mutated (MCD) genotype in diffuse large B-cell lymphoma is characterized by extranodal involvement and may also be involved in the pathogenesis of skeletal-related disease in the present case. As a follow-up to this unusual case, we have carried out an analysis based on the Danish Lymphoma Registry (LYFO) covering the entire national population in the period 2000 - 2020. The registry study included a cohort of 2,459 patients with WM and lymphoplasmacytic lymphoma. Our data revealed that primary bone involvement at diagnosis occurs in 1.75% of adults with WM. To the best of our knowledge, this is the first report of the prevalence of skeletal-related disease in a large nationwide cohort and defines bone involvement as an exceedingly rare event in WM.

We report the case of a patient with progressive multisystem mixed histiocytosis associating Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) involving the bone marrow, whose lesions harbored the MAP2K1 E102-I103del. After initial improvement under the MEK inhibitor trametinib, the treatment was only partially efficient and poorly tolerated. Eventually, although the trough blood level of trametinib at steady state was within expected ranges, the disease progressed to a life-threatening situation, with peritoneal involvement and anasarca. Switching to the MEK inhibitor cobimetinib as a salvage therapy resulted in a dramatic, rapid disease response, and the patient remains disease-free 3 years later with the treatment. The load of the MAP2K1 deletion in peripheral blood was correlated with the disease activity and strongly declined with cobimetinib, although it remained detectable at the last follow-up.

Background: The purpose of this study was to investigate the association between anticoagulant dosing intensity in coronavirus disease 2019 (COVID-19) infected patients and its outcomes on venous thromboembolism (VTE) and all-cause mortality.

Methods: This is a retrospective observational study that examined different anticoagulation regimens among COVID-19 patients for prophylaxis of VTE. Primary outcomes of the study were VTE incidence and all-cause mortality for patients receiving prophylaxis-intensity (PPX) and therapeutic-intensity (TX) anticoagulation. Secondary outcomes were incidence of hemorrhagic events and hospital length of stay. Patients were matched (1:1) based on age and Charlson comorbidity score. Sub-group analyses evaluated outcomes within critically ill patients, between specific anticoagulant agents and comorbid conditions.

Results: The primary outcome of VTE occurred in six patients within the prophylactic dose group and eight patients in the therapeutic-intensity dose group (risk ratio (RR): 2.02 (95% confidence interval (CI): 0.7 - 5.2); P = 0.2). Bleeding occurred in 15 (11%) patients in the prophylactic group and 27 (19%) patients in the therapeutic group (RR: 0.5 (95% CI: 0.3 - 1.0); P < 0.049). Hospital length of stay was shorter by 4 days in those treated with prophylactic-intensity anticoagulation (P = 0.003). Intensive care unit admission and ventilation were negatively correlated with mortality in a multivariate analysis.

Conclusions: Among hospitalized COVID-19 patients, the use of therapeutic-intensity anticoagulation did not show any benefits in reducing the occurrence of VTE. An increase in mortality and in the incidence of hemorrhagic events was statistically significant in the therapeutic-intensity group. Future prospective studies are warranted to evaluate anticoagulation therapy in COVID-19 infected patients.

Numerous hemoglobin (Hb) gene mutations have been identified, leading to a spectrum of phenotypes ranging from asymptomatic carrier states to complicated hemolytic anemias. We report a rare case of asymptomatic hypoxemia in a father and his teenage daughter both of whom were found to be carriers of Hb gene variant Zara. Workup for alternative cardiovascular causes of hypoxemia was unremarkable. Further sequencing of the alpha globin locus showed both individuals to be heterozygous for the Hb Zara c.274C>A (p.Leu92Ile) variant of unknown significance in the alpha2-globin gene. This is the first documented association of this Hb variant with familial asymptomatic hypoxemia, highlighting the importance of evaluating for hemoglobinopathies in patients with reduced oxygen saturation.

Vaso-occlusive crisis (VOC) is the leading cause of hospitalization in sickle cell disease (SCD). Intravenous fluid (IVF) administration is the usual practice during VOC episodes to slow the sickling process. In the absence of an evidence-based, clear-cut consensus on the optimal choice, route, and rate of fluid administration, there has been a wide variability in the practice of IVF administration in the treatment of VOC. However, there are growing concerns about the safety of this practice. This systematic review summarized the current evidence on the risk of negative outcomes in SCD patients treated for VOC with IVFs. A database search of Medline/PubMed, EMBASE, Scopus, Web of Science, CINAHL, Wiley Cochrane Library, Clinicaltrials.gov, and conference proceedings of the European Hematology Association (EHA) and American Society of Hematology (ASH) were performed. The results were presented using narrative analysis of quantitative data. Of the 2,821 identified records, a total of three eligible retrospective cohort studies with a total demographic population of 549 SCD patients were included in this review. Normal saline, a frequently used IVF for VOC may be associated with adverse outcomes such as poor pain control and volume overload. Volume overload, new oxygen requirement, acute chest syndrome, and acute kidney injury are potential adverse outcomes of inappropriate IVF use in VOC. There is limited evidence supporting the current practice of IVF use in VOC. Randomized controlled trials are required to fully clarify the place and safety of IVF in the management of VOC.

Background: A combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard treatment for diffuse large B-cell lymphoma (DLBCL). However, no standard treatment has been established for older patients (age ≥ 75 years). This study retrospectively analyzed different treatment strategies in older patients with DLBCL with different chemotherapy regimens and compared the survival rate of patients using oral or intravenous form cyclophosphamide and etoposide in a single center.

Methods: We reviewed the records of older patients with DLBCL, aged ≥ 75 years, from January 2010 to August 2019. The different treatment combinations, clinical characteristics, response rates, and toxicity profiles were analyzed. The median overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier (KM) method. Cox regression model was used to identify the risk factors.

Results: Eighty-four patients were included. One-quarter of the patients received cytoreduction treatment because of their poor medical condition at the time of diagnosis. Twenty-six percent of the patients were aged ≥ 85 at the time of diagnosis and 46.7% completed the treatment course. Patients receiving non-anthracycline-containing (non-ACR) treatment had worse Charlson comorbidity index, worse PFS, lower body mass index, or were older. The mean anthracycline accumulative dose in the anthracycline-containing (ACR) group was 134 mg/m². The median OS was 17.2 months and median PFS was 7.7 months. The PFS of R-CHOP is better than R-mini-CHOP and R-CVOP without statistical significance, but OS of R-CHOP is not better than the other regimens.

Conclusion: The toxicity, efficacy, and KM curve for OS and PFS in the non-ACR group were lower compared to ACR group, without statistical significance. R-CVOP had similar OS with R-mini-CHOP in our study. The result does not mean etoposide could totally substitute for anthracycline, but etoposide did have lower early progression rate (12.5%), and it may be an option for frail patients with comorbidity. Oral form cyclophosphamide and etoposide could be considered as a substitute for intravenous administration because of the similar effect and toxic profile.

Coronavirus disease 2019 (COVID-19) has spread tremendously since its first appearance in December 2019. Infected individuals can experience a wide range of systemic complications, including thrombotic microangiopathy (TMA). Like the other forms of TMA, COVID-19-associated TMA is characterized by thrombocytopenia, hemolytic anemia, and organ failure (such as acute kidney injury). The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in COVID-19-associated TMA is most probably dual: it can act either as a trigger to an underlying condition or as a cause of TMA. As opposed to the majority of other reported cases, it may be that in our case COVID-19 was the only cause of TMA. We present a case of a 32-year-old previously healthy man who was treated for acute kidney injury associated with TMA, which we believe was caused by COVID-19. Thrombotic thrombocytopenic purpura, as well as other possible known causes of typical and atypical hemolytic-uremic syndrome, was excluded. During his hospitalization, three negative nasopharyngeal swabs for SARS-CoV-2 were obtained, but serological tests showed the presence of IgG and IgA antibodies. After initial treatment known to be helpful in other forms of TMA (therapeutic plasma exchange and methylprednisolone), his renal function and platelet count recovered completely. Our case illustrates the importance of quickly recognizing this life-threatening complication of COVID-19 and using treatment that has been shown to be beneficial in other forms of TMA. Future studies of the pathophysiology and subsequent targeted treatment of this novel disease are needed.

Programmed cell death protein 1 (PD-1) checkpoint inhibitors such as pembrolizumab are novel therapeutics used to treat various advanced malignancies and have been shown to increase patient survival in several studies. However, these drugs have a toxicity profile that ranges from mild side effects such as dermatitis to life-threatening complications. We present a case of pembrolizumab-induced hemophagocytic lymphohistiocytosis (HLH) in an 80-year-old patient with squamous cell carcinoma (SCC) of presumed cutaneous primary. This patient initially presented with weakness and pancytopenia, thought to be immune-related. She developed progressive anemia, after which further workup revealed concern for HLH. She recovered after a course of steroids, tocilizumab, and etoposide. To our knowledge, this patient's course is among a few rare cases of immune checkpoint inhibitor (ICI)-mediated HLH. This case highlights the need for early diagnosis and recognition of HLH as a potential toxicity related to ICI therapy.

Light chain deposition disease (LCDD) is a rare hematologic disorder that can affect any organ but predominantly involves the kidneys. Existing literature is limited to case reports and small single-center retrospective series, explaining the lack of any treatment algorithms and management guidelines for patients with this disorder. In this systematic review of literature, we explored the role of standard and high-dose chemotherapy-autologous stem cell transplant for LCDD. A total of 11 studies were identified to evaluate the hematologic and renal responses to various treatment regimens. Autologous stem cell transplant and bortezomib-based regimens appear to have reasonable safety and efficacy for this rare hematologic disorder, albeit some statistical and analytical limitations. Large multicenter retrospective and prospective studies are needed to better elucidate the role of various chemotherapy regimens as well as autologous stem cell transplant for patients with LCDD.