Hematology Reports

COVID-19 and other infectious diseases can exacerbate the course of paroxysmal nocturnal hemoglobinuria (PNH). The efficacy and safety of the Gam-COVID-Vac vaccine in patients with PNH has not been adequately studied. A retrospective, observational, cohort, non-comparative study was performed to assess the course of COVID-19 as well as the safety and efficacy of the Gam-COVID-Vac (Sputnik V) vaccine in patients with paroxysmal nocturnal hemoglobinuria (PNH). The study included data from 52 patients with PNH aged 18 to 75 years, 38 of whom received background therapy with eculizumab (Elizaria^®) between March 2020 and January 2022. COVID-19 was diagnosed according to the results of PCR testing. The patients were divided into two groups for comparison of the incidence of COVID-19. Group 1 included non-vaccinated patients with PNH, and Group 2 included patients vaccinated prior to the onset of COVID-19. According to vaccination, patients were subdivided into non-vaccinated and vaccinated groups without signs of previous COVID-19 at the beginning of the analyzed period, and patients vaccinated half a year or more after recovery from COVID-19. Testing for anti-SARS-CoV-2 IgG levels was carried out in patients with PNH in the year after their COVID-19. Tests for anti-SARS-CoV-2 RBD IgG levels were performed on vaccinated patients. In total, 28 (53.8%) of the enrolled patients had COVID-19, including asymptomatic forms in 7 (25%) and mild forms in 16 (57%) patients. A total of 22 (42.3%) patients were fully vaccinated with Gam-COVID-Vac, of which 13 (25%) patients were vaccinated without the signs of previous SARS-CoV-2infection, and 9 (17.3%) patients were vaccinated after COVID-19. The number of patients who had COVID-19 was about two times higher in Group 1 (non-vaccinated; 24) (61.5%), whereas in Group 2 (vaccinated), the number of patients with COVID-19 was only 4 (30.8%). The proportion and number of patients who did not have COVID-19 was higher in the group of vaccinated patients (9; 69.2%) than in the group of non-vaccinated patients (15; 38.5%) (p = 0.054). In patients who had been infected with COVID-19, maximum concentrations of anti-SARS-CoV-2 IgG were observed 2–3 months after the acute infection phase, followed by a gradual decline by month 9–10. The mean RBD IgG concentration was higher in the group of patients who had been infected by COVID-19 than in the group of patients without COVID-19 (p = 0.047). Therapy type, including eculizumab, did not have a significant impact on RBD IgG titers (p > 0.05). Hospitalization was required in five (18%) patients, all of whom had breakthrough hemolysis and severe lung damage on CT scans. After the first dose, adverse events (AEs) were reported in 41% of the patients (body temperature increased in 18%; headache in 13.6%; and pain in joints in 4.5%; colitis exacerbation was observed in 4.5%). After the second dose, no AEs were reported. The performed study suggests the possible efficacy and demonstrates the safety of Gam-COVID-Vac (Sputnik V) for the prophylaxis of COVID-19 in patients with PNH who experience immunosuppression due to target therapy. Full article

Acute lymphocytic leukemia (ALL) is the most frequent form of all childhood leukemias, mostly affecting children between 2 and 4 years old. Oral symptoms, such as mouth ulcers, mucositis, xerostomia, Herpes or Candidiasis, gingival enlargement and bleeding, petechiae, erythema, mucosal pallor and atrophic glossitis, are very common symptoms of ALL and can be early signs of the disease. Secondary and tertiary complications, a direct effect of chemo and radiotherapy, are associated with more severe bleeding, higher susceptibility to infections, ulcerations, inflammation of the mucous membranes, osteoradionecrosis, xerostomia, taste alterations, trismus, carious lesions and dental abnormalities. Immunotherapy, though less toxic, causes oral dysesthesia and pain. Overall, the effects in the oral cavity are transient but there are long-term consequences like caries, periodontal disease and tooth loss that impair endodontic and orthodontic treatments. Also, dental abnormalities resulting from disturbed odontogenesis are known to affect a child’s quality of life. The medical dentist should identify these complications and perform appropriate oral care in tandem with other health professionals. Thus, poor oral hygiene can lead to systemic ALL complications. The aim of this review is to describe the oral complications in children with ALL who are undergoing chemo, radio or immunotherapy. Full article

Hemoglobin (Hb) Agrinio is a rare non-deletional a-globin mutation observed almost exclusively in Greek, Spanish or other Mediterranean families. The clinical manifestations of a carrier of a single Hb Agrinio mutation (single heterozygosity) depend on the concomitant presence or absence of other mutations or variants in the beta, alpha or other modifying genes. We present a Greek patient harboring a Hb Agrinio variant plus the - -Med alpha deletional allele, having an infrequent severe form of alpha thalassemia, in contrast to the typical alpha thalassemic patient and requiring regular red blood cell (RBC) transfusions and chelation treatment. We also provide a concise literature review regarding alpha thalassemic hemoglobin variants and their molecular and clinical combinations. A phase 2, double-blind, randomized, placebo-controlled, multicenter clinical trial to determine the efficacy and safety of luspatercept (BMS-986346/ACE-536) for the treatment of anemia in adults with alpha thalassemia with the participation of our center is currently recruiting patients (NCT05664737). Full article

Quantitative abdominal adipose tissue analysis is important for obtaining information about prognosis and clinical outcomes on a wide array of diseases. In recent years, the effects of abdominal adipose tissue compartments in patients with lymphoma and the changes in their distribution after therapies have been studied. This information could facilitate the improvement of therapies in patients with lymphoma, to prevent or treat both visceral obesity and sarcopenia. Opportunistic analysis of body composition on computed tomography (CT) images might contribute to the improvement of patient management and clinical outcomes together with implementation of targeted patient-tailored therapies. The purpose of this literature review is to describe the role of CT to evaluate abdominal adipose tissue quantity and distribution in patients with lymphoma. Full article

Background and Objectives: Relapsed/refractory extramedullary myeloma (RREMM) is an uncommon and aggressive subtype of multiple myeloma defined by plasma cell proliferation outside the bone marrow. Therapeutic options for RREMM are limited, and the prognosis is generally unfavorable. This research aimed to assess the effectiveness of the bendamustine, pomalidomide, and dexamethasone (BPD) regimen in patients with RREMM. Material and Methods: We carried out a retrospective investigation of 11 RREMM patients who underwent BPD treatment. The primary endpoint was progression-free survival. The secondary endpoints of the study were two-year survival and overall response rate (ORR). We analyzed the sociodemographic and clinical features of the patients. Results: The average age of the patients was 62 years. They had a median of four prior treatment lines, and eight patients had previously received autologous stem-cell transplantation. After eight BPD treatment cycles, the ORR stood at 54%, with one very good partial response (VGPR), five partial responses (PR), three progressive diseases (PD), and two stable diseases (SD). The median follow-up was 15 months, with a two-year PFS rate of 71.3% and a two-year survival rate of 81.8%. Conclusions: The BPD regimen demonstrated promising effectiveness in RREMM patients, yielding favorable ORR and survival rates. To corroborate these findings and explore additional treatment alternatives for this patient group, larger prospective studies are required. Full article

Chronic lymphocytic leukemia (CLL), is a hematologic malignancy characterized by the uncontrolled proliferation of mature B lymphocytes. CLL is the most prevalent leukemia in Western countries. Its presentation can range from asymptomatic with the incidental finding of absolute lymphocytosis on a routine blood test, to symptomatic disease requiring immediate intervention. Prognosis of the disease is defined by the presence or absence of specific mutations such as TP53, chromosomal abnormalities such as del(17p), a type of IGHV mutational status, and elevation of B2M and LDH. Treatment of CLL in the United States and Europe has evolved over the recent years thanks to the development of targeted therapies. The standard of care has shifted from traditional chemoimmunotherapy approaches to targeted therapies including Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitors, administered either as monotherapy or in combination with CD20 monoclonal antibodies. Several clinical trials have also recently evaluated combinations of BTKi and venetoclax and showed the combination to be well tolerated and able to induce deep remissions. Targeted therapies have a good safety profile overall; however, they also have unique toxicities that are important to recognize. Diarrhea, fatigue, arthralgia, infections, cytopenias, bleeding, and cardiovascular toxicities (including atrial fibrillation, ventricular arrhythmias, and hypertension) are the adverse events (AEs) commonly associated with BTKis. Initiation of therapy with venetoclax requires close monitoring because of the risk for tumor lysis syndrome associated with this agent, particularly in patients with a high disease burden. Development of newer target therapies is ongoing and the therapeutic landscape in CLL is expanding rapidly. Full article

Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening, rare acute thrombotic microangiopathy (TMA), caused by a severe ADAMTS13 deficiency. As the COVID-19 pandemic rapidly spread around the globe, much data about the pathogenicity of this virus were published. Soon after the detection of the first cases of COVID-19, it was clear that there was a wide range of COVID coagulopathy manifestations, such as deep venous thrombosis, pulmonary thromboembolism, and thrombotic microangiopathies. In the literature, little data have been reported about the association between TTP and COVID-19, and the treatment of COVID-19-associated TTP is still under debate. Here we present the case of a 46-year-old woman who developed a COVID-associated TTP, successfully treated with plasma exchange (PEX), steroids, and caplacizumab. Full article

Acute promyelocytic leukemia (APL) is a rare and aggressive form of acute myeloid leukemia (AML). Instead of cytotoxic chemotherapy, a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) represents front-line therapy in low-risk patients. However, the therapeutic approach could be challenging in the case of a concomitant diagnosis of Brugada syndrome (BrS), a genetic disease characterized by an increased risk of arrhythmias and sudden cardiac death. Here, we present the case of a BrS patient who has been diagnosed with low-risk APL and treated with ATRA and ATO without observing arrhythmic events. In particular, we highlight the difficulties encountered by clinicians during the diagnostic work-up and the choice of the best treatment for these patients. Full article

The β-thalassemias are a group of monogenic hereditary hematological disorders caused by deletions and/or mutations of the β-globin gene, leading to low or absent production of adult hemoglobin (HbA). For β-thalassemia, sirolimus has been under clinical consideration in two trials (NCT03877809 and NCT04247750). A reduced immune response to anti-SARS-CoV-2 vaccination has been reported in organ recipient patients treated with the immunosuppressant sirolimus. Therefore, there was some concern regarding the fact that monotherapy with sirolimus would reduce the antibody response after SARS-CoV-2 vaccination. In the representative clinical case reported in this study, sirolimus treatment induced the expected increase of fetal hemoglobin (HbF) but did not prevent the production of anti-SARS-CoV-2 IgG after vaccination with mRNA-1273 (Moderna). In our opinion, this case report should stimulate further studies on β-thalassemia patients under sirolimus monotherapy in order to confirm the safety (or even the positive effects) of sirolimus with respect to the humoral response to anti-SARS-CoV-2 vaccination. In addition, considering the extensive use of sirolimus for the treatment of other human pathologies (for instance, in organ transplantation, systemic lupus erythematosus, autoimmune cytopenia, and lymphangioleiomyomatosis), this case report study might be of general interest, as large numbers of patients are currently under sirolimus treatment. Full article

A relationship between microvascular disorders and sensorineural hearing loss (SNHL) has been widely proposed. The vascular hypothesis, theorized for the onset of sudden SNHL (SSNHL), is among the most acknowledged: a localized acute cochlear damage, of ischemic or haemorrhagic nature, could be considered a causative factor of SSNHL. The aim of this review is to assess (i) the effect on hearing in patients affected by blood coagulation disorders (prothrombotic or haemorrhagic) and (ii) the possible etiopathogenetic mechanisms of the related hearing loss. A PRISMA-compliant review was performed. Medline, Embase, and Cinahl databases were searched from inception to 31 January 2023, and a total of 14 studies have been included in the review. The available data suggest that it is possible to consider clotting disorders as a potential condition at risk for sensorineural hearing loss; in particular, coagulation tests and eventually the assessment of genetic and acquired prothrombotic factors should be recommended in patients with SSNHL. Also, an audiological evaluation should be recommended for patients with blood coagulation disorders presenting cochlear symptoms, especially in those suffering from clotting diseases. Full article

Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a new entity described in the fifth edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors (WHO-HAEM5). It refers to malignant lymphoma present with symptoms of serous effusions in body cavities (pleural, peritoneal, and/or pericardial) in the absence of an identifiable tumor mass. We present a case of an 82-year-old man with a history of atrial fibrillation and atrial flutter, status post-ablation, essential hypertension (HTN), hyperlipidemia (HLD), and diabetes mellitus (DM) type 2 who was referred to our hospital for shortness of breath due to recurrent pleural effusion. Right video-assisted thoracoscopy with right pleural biopsy was performed. Histopathological examination of the pleural biopsy revealed dense fibrous tissue, chronic inflammation, lymphoid aggregates, and granulation tissue, with no evidence of lymphoma. Cytology of the right pleural fluid revealed large lymphoid cells, which were positive for CD45, CD20, PAX-5, MUM-1, BCL2, BCL6, and MYC protein. They were negative for CD3, CD10, CD138, and HHV-8 by immunohistochemistry (IHC). Epstein–Barr virus (EBV) was negative by in situ hybridization (ISH). Due to the absence of any evidence of lymphoma elsewhere, a diagnosis of fluid overload-associated large B-cell lymphoma (FO-LBCL) was made. We provide a synopsis of the main clinicopathological features of FO-LBCL and the two main differential diagnoses, primary effusion lymphoma (PEL) and diffuse large B-cell lymphoma (DLBCL). Full article

Hereditary platelet delta (δ)-storage pool deficiency is a rare condition in which there are fewer dense granules in platelets disrupting primary hemostasis. It can cause a mild–moderate bleeding tendency with normal coagulation studies; hence, it is an underdiagnosed diagnostic challenge. The authors present three patients with hereditary platelet delta (δ)-storage pool deficiency who had heavy menstrual bleeding, excessive bleeding following surgery, mucocutaneous bleeding, and a bleeding score greater than or equal to 6. These cases reveal the susceptibility of underdiagnosing platelet disorders and the significance of utilizing a bleeding assessment tool to help guide further workup with transmission electron microscopy to visualize the fewer dense granules in platelets. Although bleeding is typically moderate, it can be severe in certain scenarios, like after mucosal surgeries, and can lead to death, highlighting the importance of the condition’s recognition and prophylactic treatment. Full article

Patients with myeloproliferative neoplasms (MPNs) are at increased risk of cardiovascular disease (CVD), including acute coronary syndrome (ACS). However, data on long-term outcomes of patients with MPN who have had ACS and risk factors for all-cause death or CV events post-ACS hospitalization are lacking. We conducted a single-center study of 41 consecutive patients with MPN with ACS hospitalization after MPN diagnosis. After a median follow-up of 80 months after ACS hospitalization, 31 (76%) experienced death or a CV event (myocardial infarction, ischemic stroke, or heart failure hospitalization). After multivariable Cox proportional hazards regression, index ACS within 12 months of MPN diagnosis (HR 3.84, 95% CI 1.44–10.19), WBC ≥ 20 K/µL (HR 9.10, 95% CI 2.71–30.52), JAK2 mutation (HR 3.71, 95% CI 1.22–11.22), and prior CVD (HR 2.60, 95% CI 1.12–6.08) were associated with increased death or CV events. Further studies are warranted to improve cardiovascular outcomes in this patient population. Full article

The Medical Directors of nine Italian Hemophilia Centers reviewed and discussed the key issues concerning the replacement therapy of hemophilia patients during a one-day consensus conference held in Rome one year ago. Particular attention was paid to the replacement therapy needed for surgery using continuous infusion (CI) versus bolus injection (BI) of standard and extended half-life Factor VIII (FVIII) concentrates in severe hemophilia A patients. Among the side effects, the risk of development of neutralizing antibodies (inhibitors) and thromboembolic complications was addressed. The specific needs of mild hemophilia A patients were described, as well as the usage of bypassing agents to treat patients with high-responding inhibitors. Young hemophilia A patients may take significant advantages from primary prophylaxis three times or twice weekly, even with standard half-life (SHL) rFVIII concentrates. Patients affected by severe hemophilia B probably have a less severe clinical phenotype than severe hemophilia A patients, and in about 30% of cases may undergo weekly prophylaxis with an rFIX SHL concentrate. The prevalence of missense mutations in 55% of severe hemophilia B patients allows the synthesis of a partially changed FIX molecule that can play some hemostatic role at the level of endothelial cells or the subendothelial matrix. The flow back of infused rFIX from the extravascular to the plasma compartment allows a very long half-life of about 30 h in some hemophilia B patients. Once weekly, prophylaxis can assure a superior quality of life in a large severe or moderate hemophilia B population. According to the Italian registry of surgery, hemophilia B patients undergo joint replacement by arthroplasty less frequently than hemophilia A patients. Finally, the relationships between FVIII/IX genotypes and the pharmacokinetics of clotting factor concentrates have been investigated. Full article

Amyloidosis is a term describing the extracellular deposit of fibrils composed of subunits of several different normal serum proteins in various tissues. Amyloid light chain (AL) amyloidosis contains fibrils that are composed of fragments of monoclonal light chains. Many different disorders and conditions can lead to spontaneous splenic rupture, including AL amyloidosis. We present a case of a 64-year-old woman with spontaneous splenic rupture and hemorrhage. A final diagnosis of systemic amyloidosis secondary to plasma cell myeloma was made with infiltrative cardiomyopathy and possible diastolic congestive heart failure exacerbation. We also provide a narrative review of all documented cases of splenic rupture associated with amyloidosis from the year 2000 until January 2023, along with the main clinical findings and management strategies. Full article

Thrombotic complications from COVID-19 are now well known and contribute to significant morbidity and mortality. Different variants confer varying risks of thrombotic complications. Heparin has anti-inflammatory and antiviral effects. Due to its non-anticoagulant effects, escalated-dose anticoagulation, especially therapeutic-dose heparin, has been studied for thromboprophylaxis in hospitalized patients with COVID-19. Few randomized, controlled trials have examined the role of therapeutic anticoagulation in moderately to severely ill patients with COVID-19. Most of these patients had elevated D-dimers and low bleeding risks. Some trials used an innovative adaptive multiplatform with Bayesian analysis to answer this critical question promptly. All the trials were open-label and had several limitations. Most trials showed improvements in the meaningful clinical outcomes of organ-support-free days and reductions in thrombotic events, mainly in non-critically-ill COVID-19 patients. However, the mortality benefit needed to be more consistent. A recent meta-analysis confirmed the results. Multiple centers initially adopted intermediate-dose thromboprophylaxis, but the studies failed to show meaningful benefits. Given the new evidence, significant societies have suggested therapeutic anticoagulation in carefully selected patients who are moderately ill and do not require an intensive-care-unit level of care. There are multiple ongoing trials globally to further our understanding of therapeutic-dose thromboprophylaxis in hospitalized patients with COVID-19. In this review, we aim to summarize the current evidence regarding the use of anticoagulation in patients with COVID-19 infection. Full article

Anemia is a prominent global health issue with a wide variety of causes and can be associated with decreased quality of life, increased hospitalization, and higher mortality, especially in older individuals. Therefore, studies further shedding light on the causes and the risk factors of this condition should be performed. The aim of the present study was to examine the causes of anemia in hospitalized patients in a tertiary hospital in Greece and identify risk factors related to higher mortality. In total, 846 adult patients with a diagnosis of anemia were admitted during the study period. The median age was 81 years, and 44.8% were male. The majority of patients had microcytic anemia, with the median mean corpuscular volume (MCV) being 76.3 fL and the median hemoglobin being 7.1 g/dL. Antiplatelets were used by 28.6% of patients, while 28.4% were using anticoagulants at the time of diagnosis. At least one unit of packed red blood cells (PRBCs) was transfused in 84.6% of patients, and a median of two PRBCs was used per patient. A gastroscopy was performed in 55%, and a colonoscopy was performed in 39.8% of patients in the present cohort. Anemia was considered to be multifactorial in almost half the cases, while the most commonly identified cause was iron deficiency anemia, more commonly with positive endoscopic findings. Mortality was relatively low, at 4.1%. Multivariate logistic regression analysis identified higher B12 levels and longer duration of hospital stay to be independently positively associated with mortality. Full article

Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators as single agents remain scarce, combination therapies are an area of therapeutic interest. In this review, the author summarizes attractive kinase pathways for therapeutic targets and the combination strategies for these pathways. Specifically, the review focuses on combination therapies targeting the FLT3 pathways, as well as PI3K/AKT/mTOR, CDK and CHK1 pathways. From a literature review, combination therapies with the kinase inhibitors appear more promising than monotherapies with individual agents. Therefore, the development of efficient combination therapies with kinase inhibitors may result in effective therapeutic strategies for AML. Full article

Methemoglobinemia is an acute medical emergency that requires prompt correction. Physicians should have a high degree of suspicion of methemoglobinemia in cases that present with hypoxemia that does not resolve with supplemental oxygenation, and they should confirm this suspicion with a positive methemoglobin concentration on arterial blood gas. There are multiple medications that can induce methemoglobinemia, such as local anesthetics, antimalarials, and dapsone. Phenazopyridine is an azo dye used over-the-counter as a urinary analgesic for women with urinary tract infections, and it has also been implicated in causing methemoglobinemia. The preferred treatment of methemoglobinemia is methylene blue, but its use is contraindicated for patients with glucose-6-phosphatase deficiency or those who take serotonergic drugs. Alternative treatments include high-dose ascorbic acid, exchange transfusion therapy, and hyperbaric oxygenation. The authors report a case of a 39-year-old female who took phenazopyridine for 2 weeks to treat dysuria from a urinary tract infection and subsequently developed methemoglobinemia. The patient had contraindications for the use of methylene blue and was therefore treated with high-dose ascorbic acid. The authors hope that this interesting case promotes further research into the utilization of high-dose ascorbic acid for managing methemoglobinemia in patients who are unable to receive methylene blue. Full article