American journal of blood research最新文献

Follicular lymphoma (FL) originates from germinal center B cells, is the most prevalent form of indolent non-Hodgkin's lymphoma. Upfront management is based on stage, grade, and disease burden. Radiotherapy may be curative in limited disease while chemoimmunotherapy is preferred in advanced disease. Maintenance therapy is routinely administered but its role is debatable. Relapses are common and interval from initial therapy to relapse is most important prognostic factor for relapsed FL. Management of relapsed patients is based on the initial management, the interval from prior therapies, and the toxicity of available therapies. Multiple agents are available for patients after two or more lines of therapy, but sequencing remains poorly defined.

Avascular necrosis (AVN) is a critical health condition associated with local death of the bone tissue resulting in multifocal osteonecrosis (MFON). After a prior patient's consent, we present a case of sickle cell anemia associated with severe MFON that affected both long bones and short bones. She had a positive history of DVT. Initially, she presented with generalized severe bone pain with fever for seven days that got worse on the day of admission, a picture suggestive of sickle cell anemia-induced vaso-occlusive crisis. She was treated with adequate hydration, morphine, enoxaparin (a low molecular weight heparin), paracetamol and ceftriaxone. She got improved on treatment. On 5^th day after admission, she developed sudden severe local tenderness at the distal tibia above the medial malleoli in both legs and she was unable to put a weight on her feet and could not stand up or walk. Plain X-ray films were not diagnostic. Complete liver function tests and kidney function tests were normal. The patient had leukocytosis, high serum urate and high serum LDH (may reflect cellular damage in bone cells). MRI scans revealed an evidence of bilateral multiple avascular necrosis in both femoral heads, left shoulder, left knee, and pelvic bones were evident. The patient's condition was evaluated and the diagnosis of MFON associated with sickle cell crisis was established. This patient responded well to same treatments and her condition got improved. In conclusion, MFON should be considered after vaso-occlusive crisis of sickle cell anemia. Plain X-ray is non-conclusive in diagnosing bony lesions induced by AVN while MRI is diagnostic.

Aberrant Wnt signaling has been found in many solid organ cancers, as well as hematological malignancies. However, its role in classic Hodgkin lymphoma (CHL) remains unclear. We evaluated the expression of Wnt signaling components LEF1, β-catenin, FZD6 and Wnt5a/b and their correlation with the prognosis in 50 CHL patients by immunohistochemical stains. The neoplastic Hodgkin/Reed-Sternberg (HRS) cells showed expression of LEF1, FZD6, and Wnt5a/b but absent nuclear β-catenin. Wnt5a/b expression was seen in a significantly higher percentage of stage IV patients (67%) compared to other stages (p=0.03). However, there was no correlation between the expression of LEF1, FZD6 and Wnt5a/b and patients' stage or survival. In summary, our results confirmed decreased β-catenin expression in HRS. Non-canonical Wnt pathway may play a role in the microenvironment that facilitates HRS migration, however, it is not sufficient to consider LEF1, β-catenin, FZD6 and Wnt5a/b as prognostic factors for CHL.

Primary lymphoma in soft tissue is very rare. In order to understand the clinicopathological features of primary lymphoma in soft tissue, we found 13 cases (0.3%) of primary lymphoma in soft tissue by reviewing 4303 lymphomas diagnosed in our institution from 2010 to 2019. Tumors were found in the following sites: 8 in lower extremity (2 in leg, 1 in calf, 1 in knee and 4 in buttock), 1 in upper extremity (left shoulder) and 4 in the trunk (3 in waist and 1 in thoracolumbar). The most common histologic type was DLBCL (7/13, 54.8%). 6 cases of which had follow-up information. 25 patients were also selected by screening the English literature search (from Jan 2010 to December 2019) including 1102 studies. Compared to the results of literature review, our results are similar with them. The tumor sites were as follows: 10 in lower extremity, 4 in upper extremity, 9 in the trunk and 2 in masticatory muscle. The most common histological type was also DLBCL (n=11/25, 44%). Overall survival analysis of all 31 patients including our 6 cases with primary lymphoma in soft tissue showed no significant difference between different histological type (Log Rank P=0.120, Breslow P=0.157). The differential diagnosis includes malignant melanoma, rhabdomyosarcoma and metastatic carcinoma in soft tissue.

Background: Low albumin and high ferritin levels have negative effects on survival in acute myeloid leukemia (AML). In this study, the aim is to determine the role of these factors on survival in patients over 50 years of age with AML.

Methods: Eighty patients followed up between January 2014 and July 2019 were included in the study. Patients were categorised into three subgroups: The favorable, intermediate and high-risk groups.

Results: The overall survival of the favorable group was found to be longer in a statistically significant way.

Conclusion: In this study, it has been shown that serum albumin and ferritin values are useful and simple laboratory values to show prognosis in AML over 50 years of age.

Introduction: Emicizumab is a bispecific monoclonal antibody with the ability to bridge FIXa and FX, mimic FVIII, and restore normal hemostasis in patients with hemophilia A. Moreover, substantial evidence has shown that emicizumab-treated patients do not require monitoring, except before surgery or invasive procedures. However, introducing this novel drug to the market poses some challenges to physicians and clinical laboratories due to its interaction with conventional coagulation tests.

Methods: Given the challenges and laboratory interactions posed by this novel drug, there is an unmet clinical need to develop clear recommendations for emicizumab laboratory monitoring to highlight which laboratory tests should be used, which tests should be avoided, and when these tests should be performed. These expert recommendations are essential to prevent inappropriate testing or misleading interpretations and reduce the extra costs of unnecessary monitoring.

Results: A consensus meeting was conducted in December 2019, including top experts on hemophilia from Saudi Arabia, to discuss this issue.

Conclusion: The experts agreed that, aPTT (activated Partial Thromboplastin Time)-based tests are not suitable for laboratory monitoring patients treated with emicizumab. Only FVIII chromogenic assays based on bovine FIX and FX proteins can be used to measure FVIII levels. They reviewed and recommended the type and time of testing for anti-factor VIII antibodies. Drug levels should be measured using the recommended test only when the anti-drug antibody (ADA) is clinically suspected and after excluding other causes (such as patient non-compliance).

Background and objectives: To determine the seroprevalence of SARS-CoV-2 antibodies and the associated risk factors among healthy blood donors from Peshawar Pakistan, during the second and third waves of the COVID-19 pandemic.

Methods: The study was conducted on 4047 healthy (with no history or symptoms of COVID-19) blood donors attending regional blood center Peshawar between Nov 2020 and June 2021. Demographic data was collected and donors were screened for the presence of anti-SARS-CoV-2 antibodies using electrochemiluminescence immunoassay (ECLIA).

Results: The mean age of the participants was 27.27±7.13 and the majority (99%) were males. Overall, 59% (2391/4047) of the blood donors were reactive for SARS-CoV-2 antibodies. An increasing trend in seropositivity was observed from 45.5% to 64.8% corresponding to the second and third wave of the pandemic in Pakistan. Logistic regression analysis revealed significantly higher odds of seropositivity among male donors compared to females. Similarly, in multivariable analysis, the odds ratio for seropositivity among blood types AB, A, and B were, 1.6, 1.4, and 1.3 (CI 95%) times higher compared to blood group O (P-value ≤0.0001).

Conclusions: Seropositivity of SARS-CoV-2 antibodies among blood donors gradually increased during the second and third wave of the pandemic in Pakistan indicating a widespread prevalence of Covid-19 in the general population. Susceptibility to SARS-CoV-2 varies with ABO blood types, with blood group O associated with low risk of infection.

T-follicular helper cells (TFH) are a unique subset of T-cells with varied transcriptional profiles and functions. In the last 2016 WHO classification, lymphomas arising from TFH were included as a broad category and emphasis was given to separating them from other peripheral T cell lymphomas. The neoplasms derived from these mainly comprise angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma with T-follicular helper cell phenotype, follicular T-cell lymphoma, and cutaneous CD4+ small-medium sized lymphoproliferative disorders. The TFH lymphomas comprise both indolent and aggressive forms. Additional immunohistochemistry to identify TFH cells like CD10, BCL6, ICOS, PD1, CXCL13 and mutations like RHOA, IDH2 is required for diagnosis and prognostication. The understanding of these has evolved over the years, and currently we review the updates and pathobiology of the above.

LGL leukemia is a rare chronic lymphoproliferative disorder of cytotoxic lymphocytes which can be immunophenotypically either T cell or NK cell-derived. According to the World Health Organization classification, it can be divided into three subtypes: chronic T-cell leukemia and chronic natural killer cell lymphocytosis, and aggressive natural killer cell LGL leukemia. Clonal proliferation of large granular lymphocytes can be because of stimulation of various molecular pathways namely JAK-STAT3 pathway, FAS/FAS-L pathway, RAS-RAF-1-MEK1-ERK pathway, PI3K/AKT pathway, NF-KB pathway, and Sphingolipid Rheostat pathways. The most common clinical features presenting with this leukemia are neutropenia, anemia, thrombocytopenia. This leukemia is also associated with various autoimmune conditions. It usually has an indolent course except for the aggressive NK cell LGL leukemia. The cause of death in the indolent cases was mostly due to infectious complications related to the neutropenia associated with the disease. The rarity of the disease coupled with the availability of only a handful of clinical trials has been a hindrance to the development of a specific treatment. Most of the cases are managed with immunomodulators. The advances in the knowledge of molecular pathways associated with the disease have brought few targeted therapies into the limelight. We discuss here the evolution, epidemiology, demographic profile, pathophysiology, differential diagnosis, the available treatment options along with the survival and prognostic variables which may help us in better understanding and better management of the disease and hopefully, paving the way for a targeted clinical approach.

Background: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell neoplasm distinguished by extensive clonal expansion of plasma cells in the bone marrow (BM) and peripheral blood (PB). PCL is divided into two subtypes: primary (pPCL) originates de novo without preceding multiple myeloma, while secondary (sPCL) comprises a leukemic modification that occurs as a late manifestation from previous multiple myeloma (MM). pPCL and sPCL are clinically and biologically two different entities. The molecular mechanisms of the development of PCL, either primary or secondary, remain poorly understood. We aim to present 5 years of data on clinical profiles and treatment outcomes of pPCL and sPCL patients treated at our cancer hospital in India and to find a predictive parameter of the development of PCL in cases of MM.

Methods: In this study, we retrospectively reviewed and evaluated the clinicopathological features, laboratory parameters, immunophenotypic profile, and patient outcomes of 17 PCL cases diagnosed among 180 plasma cell dyscrasia patients during the study period to establish a correlation between pPCL & sPCL for diagnosis and management of PCL.

Results: A total of 17 PCL patients were diagnosed among 180 plasma cell dyscrasia patients during the study period. Among PCL patients, 9 cases had pPCL (52.94% of all PCL patients), and 8 cases had sPCL (47.06% of all PCL patients). Peculiar differences were seen between the two PCL types. Both types of PCL had a younger age at the time of diagnosis, having elevated BM plasma cell infiltration percentage, frequent anemia, thrombocytopenia, elevated beta-2-microglobulin (B2M) levels, raised LDH levels, and positive M-protein in both serum and urine. In addition, SFLC assay and Immunofixation assay showed higher κ and lower λ in pPCL compared with sPCL (P<0.05). Higher Renal insufficiency was also observed in pPCL compared to sPCL (P=0.335). The survival and response to treatment of PCL patients remain considerably poor, sPCL exhibit shorter overall survival (OS) than pPCL with (median 1.75 months vs. 7 months respectively, P=0.1682). Plasma cell leukemia (PCL) needs to be diagnosed early and requires prompt initiation of treatment before patients get complications.

Conclusion: Our study characterizes the clinical and laboratory features of pPCL and sPCL and may aid physicians in prognosticating the course of disease of their patients. However, future multicentre studies are the need of the hour to develop accurate diagnostic criteria and establish the efficacy of therapeutic regimens.