Hematology Reports

9 pages, 3261 KiB

Open AccessArticle

Comprehensive Genomic Profiling in Non-Myeloid Hematologic Malignancies Identifies Variants That Can Alter Clinical Practice

by Chenyu Lin, Katherine I. Zhou, Michelle F. Green, Bennett A. Caughey, John H. Strickler, Michael B. Datto and Matthew S. McKinney

Hematol. Rep. 2024, 16(4), 603-611; https://doi.org/10.3390/hematolrep16040059 - 30 Sep 2024

Abstract

Background: Comprehensive genomic profiling (CGP) is frequently adopted to direct the clinical care of myeloid neoplasms and solid tumors, but its utility in the care of lymphoid and histiocytic cancers is less well defined. Methods: In this study, we aimed to evaluate the [...] Read more.

Background: Comprehensive genomic profiling (CGP) is frequently adopted to direct the clinical care of myeloid neoplasms and solid tumors, but its utility in the care of lymphoid and histiocytic cancers is less well defined. Methods: In this study, we aimed to evaluate the frequency at which mutations identified by CGP altered management in non-myeloid hematologic malignancies. We retrospectively examined the CGP results of 105 samples from 101 patients with non-myeloid hematologic malignancies treated at an academic medical center who had CGP testing between 2014 and 2021. Results: CGP revealed one or more pathogenic or likely pathogenic variant in 92 (88%) of samples and 73 (72%) of tested patients had one or more mutations with diagnostic, prognostic, or therapeutic significance. The identification of a resistance variant resulted in the suspension of the active treatment or affected subsequent treatment choice in 9 (69%) out of 13 patients. However, the presence of a therapy sensitizing variant only led to consideration of a biomarker-directed therapy in 6 (10%) out of 61 patients. Conclusions: Overall, CGP of non-myeloid hematologic malignancies identified clinically significant variants in 72% of patients and resulted in a change in management in 22% of patients. Full article

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10 pages, 999 KiB

Open AccessArticle

The Real-World Outcomes of Relapsed/Refractory Multiple Myeloma Treated with Elotuzumab, Pomalidomide, and Dexamethasone

by Hitomi Nakayama, Yoshinobu Aisa, Chisako Ito, Aki Sakurai and Tomonori Nakazato

Hematol. Rep. 2024, 16(4), 593-602; https://doi.org/10.3390/hematolrep16040058 - 30 Sep 2024

Abstract

Introduction: A combination of elotuzumab, pomalidomide, and dexamethasone (EPd) was approved for the treatment of relapsed/refractory multiple myeloma (RRMM) following the ELOQUENT-3 phase II clinical trial. However, the clinical experience with this therapy is still limited. In this retrospective study, we analyzed [...] Read more.

Introduction: A combination of elotuzumab, pomalidomide, and dexamethasone (EPd) was approved for the treatment of relapsed/refractory multiple myeloma (RRMM) following the ELOQUENT-3 phase II clinical trial. However, the clinical experience with this therapy is still limited. In this retrospective study, we analyzed the efficacy and safety of EPd in a real-world cohort of RRMM patients. Patients and Methods: The medical records of 22 patients who received EPd for RRMM at Yokohama Municipal Citizen’s Hospital (Japan) between January 2020 and July 2021 were reviewed. Results: The median age of our cohort was 73.5 years. The overall response rate was 55%. With a median follow-up of 20.2 months, the median progression-free survival (PFS) was 9.1 months (95% confidence interval [CI], 2.5–23.0 months). The median PFS was shorter in patients with a poor performance status (PS) than in those with favorable PS (2.5 vs. 10.8 months; p < 0.01). Patients with prior daratumumab had significantly shorter PFS than those without prior daratumumab (2.1 vs. 23.0 months; p < 0.01). Additionally, patients with prior pomalidomide had significantly shorter PFS (1.7 vs. 10.3 months; p < 0.01). In the multivariate analysis, poor PS (hazard ratio [HR] = 4.1, 95% CI: 1.1–15.6; p = 0.04) and prior exposure to daratumumab (HR = 3.8, 95% CI: 1.1–13.8; p = 0.04) remained significantly associated with shorter PFS. Conclusions: The results of our study suggest that EPd is an active and well-tolerated regimen in RRMM, even in real-world patients. Furthermore, EPd may be useful, especially in daratumumab-naïve patients. Full article

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8 pages, 874 KiB

Open AccessCase Report

Two Cases of Immune Thrombocytopenia (ITP) Related to Viral Vector Vaccination ChAdOx1-S (AstraZeneca) and a Good Response after Thrombopoietin Receptor Agonist (TPO-RA) Therapy

by Konstantina Salveridou, Theodoros Tzamalis, Maika Klaiber-Hakimi, Sabine Haase, Stefanie Gröpper and Aristoteles Giagounidis

Hematol. Rep. 2024, 16(4), 585-592; https://doi.org/10.3390/hematolrep16040057 - 27 Sep 2024

Abstract

Background: In 2019, a new coronavirus disease emerged in Wuhan, China, known as SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, and caused an ongoing pandemic. Symptomatology of the syndrome is variable, with complications extending to hematopoiesis and hemostasis. Approximately a year after onset [...] Read more.

Background: In 2019, a new coronavirus disease emerged in Wuhan, China, known as SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, and caused an ongoing pandemic. Symptomatology of the syndrome is variable, with complications extending to hematopoiesis and hemostasis. Approximately a year after onset of the virus, four vaccination formulas became available to the public, based on a viral vector or mRNA technology. These vaccine formulas have been hampered with hematological complications, like vaccine-induced immune thrombotic thrombocytopenia (VITT) and vaccine-related ITP (immune thrombocytopenic purpura). ITP is a disease with autoimmune pathogenesis characterized by antibody production against platelets and an increased hemorrhagic risk. A decent number of cases have been referred to as possible adverse effects of COVID-19 vaccinations. Case presentation: in this case report, we present two cases of newly diagnosed ITP after vaccination with ChAdOx1-S (AstraZeneca), with a good response to treatment with thrombopoietin-receptor agonists (TPO-RAs). Discussion: we observed an absence of response after corticosteroids and IVIG therapy and a positive therapeutic outcome on TPO-RA. Conclusions: in the ongoing pandemic, there is an urgent need to create therapeutic guidelines for vaccination-related clinical entities and to clarify indications for the vaccination of patients with pre-existing hematological diseases. Full article

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6 pages, 549 KiB

Open AccessCase Report

Complete Remission with Inotuzumab Ozogamicin as Fourth-Line Salvage Therapy in a Child with Relapsed/Refractory Acute Lymphoblastic Leukemia

by Athanasios Tragiannidis, Vassiliki Antari, Eleni Tsotridou, Theodoros Sidiropoulos, Aikaterini Kaisari, Maria Palabougiouki, Timoleon-Achilleas Vyzantiadis, Emmanuel Hatzipantelis, Assimina Galli-Tsinopoulou and Evgenios Goussetis

Hematol. Rep. 2024, 16(4), 579-584; https://doi.org/10.3390/hematolrep16040056 - 27 Sep 2024

Abstract

Background: Despite the progress achieved regarding survival rates in childhood acute lymphoblastic leukemia (ALL), relapsed or refractory disease still poses a therapeutic challenge. Inotuzumab ozogamicin is a CD22-directed monoclonal antibody conjugated to calicheamicin, which has been approved by the Food and Drug Administration [...] Read more.

Background: Despite the progress achieved regarding survival rates in childhood acute lymphoblastic leukemia (ALL), relapsed or refractory disease still poses a therapeutic challenge. Inotuzumab ozogamicin is a CD22-directed monoclonal antibody conjugated to calicheamicin, which has been approved by the Food and Drug Administration for adults and pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia. Case presentation: Herein, we present the case of a 23-month-old girl with high-risk B-ALL who experienced very early isolated medullary relapse; following the failure of conventional chemotherapy according to the ALL-IC REL 2016 protocol, she went on to receive the bispecific T-cell engager (BiTE) blinatumomab and subsequently, due to refractory disease, the combination of fludarabine, cytarabine, and the proteasome inhibitor bortezomib without achieving remission. Given the high CD22 expression by the lymphoblasts, off-label use of inotuzumab ozogamicin (InO) was chosen and administrated in a 28-day cycle as a salvage treatment. The minimal residual disease (MRD) was 0.08% on day 28, and InO was continued, thus achieving MRD negativity; the patient successfully underwent an allogeneic stem cell transplantation from a matched family donor. Conclusions: Our case highlights the efficacy and safety of InO as a salvage treatment in the setting of relapsed B-ALL refractory not only to conventional chemotherapy but also to novel treatments, such as blinatumomab and bortezomib. Full article

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11 pages, 619 KiB

Open AccessArticle

Padua Prediction Score and Hospital-Acquired Proximal and Isolated Distal Deep Vein Thrombosis in Symptomatic Patients

by Michelangelo Sartori, Miriam Fiocca, Mario Soldati, Laura Borgese, Elisabetta Favaretto and Benilde Cosmi

Hematol. Rep. 2024, 16(4), 568-578; https://doi.org/10.3390/hematolrep16040055 - 25 Sep 2024

Abstract

Background: Hospital-acquired deep vein thrombosis (DVT) is an important cause of morbidity and mortality. Objectives: The purpose of this study was to evaluate the prevalence of proximal lower limb DVT and isolated distal DVT (IDDVT) and their relationship to the Padua Prediction Score [...] Read more.

Background: Hospital-acquired deep vein thrombosis (DVT) is an important cause of morbidity and mortality. Objectives: The purpose of this study was to evaluate the prevalence of proximal lower limb DVT and isolated distal DVT (IDDVT) and their relationship to the Padua Prediction Score (PPS) in acutely ill, hospitalized patients. Methods: In a single-center cross-sectional study, all inpatients from medical departments with suspected lower-extremity DVT were evaluated with whole-leg ultrasonography during 183 days from 2016 to 2017. Results: Among the 505 inpatients (age 78.0 ± 13.3, females 59.2%) from medical departments, 204 (40.2%) had PPS ≥ 4, but only 54.4% of them underwent pharmacological thrombo-prophylaxis. Whole-leg ultrasonography detected 47 proximal DVTs (9.3%) and 65 IDDVTs (12.8%). Proximal DVT prevalence was higher in patients with high PPS vs. those with low PPS (12.7% vs. 7.0% p = 0.029, respectively), whereas IDDVT prevalence was similar in patients with high and low PPS (14.7% vs. 11.6% p = 0.311, respectively). The area under the receiver operating curve (AUC) for the PPS was 0.62 ± 0.03 for all DVTs, 0.64 ± 0.04 for proximal DVTs, and 0.58 ± 0.04 for IDDVTs. Conclusions: In hospitalized patients, IDDVT had similar prevalence regardless of PPS risk stratification. Adherence to thrombo-prophylaxis in patients was still far from optimal. Full article

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9 pages, 563 KiB

Open AccessCase Report

How We Treat Hemolytic Anemia Due to Pyruvate Kinase Deficiency

by Sara Tama-Shekan, Valeria Moreno, Ludovic Saba and Chakra P. Chaulagain

Hematol. Rep. 2024, 16(3), 559-567; https://doi.org/10.3390/hematolrep16030054 - 31 Aug 2024

Abstract

Background: Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones, thrombosis, and transfusional iron overload. Previously, treatments aimed at symptomatic management [...] Read more.

Background: Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones, thrombosis, and transfusional iron overload. Previously, treatments aimed at symptomatic management with RBC transfusions, phototherapy, folic acid supplementation, splenectomy, and iron chelation therapy when iron overload was documented. Mitapivat, a recently approved medication for treatment of PK-deficiency hemolytic anemia, is an oral allosteric activator of wild-type and mutant RBC PK enzymes. In this paper, we describe three cases of PK-deficiency anemia treated with mitapivat and describe modern management of this rare hemolytic disorder. Methods: A retrospective healthcare database analysis was conducted to extract relevant information. Both quantitative and qualitative methods were integrated to provide a more comprehensive understanding of the cases. Results: Two patients responded well to treatment with mitapivat, noted by an increase in hemoglobin levels, improvements in hemolytic markers, less frequent or no RBC transfusion requirements, and improvements in fatigue. One patient carrying two non-missense mutations of the PKLR gene did not respond to treatment with mitapivat. As variations in patient-specific factors (including genotype) can lead to different clinical manifestations and responses to treatment, we recommend considering both the phenotype (clinical symptoms and signs) and the genotype of the PKLR gene when making therapeutic decisions about starting a patient on mitapivat. Conclusions: While mitapivat addresses the previously unmet needs of most patients with PK deficiency as the first and only disease-modifying medication to receive approval for this condition, not all patients with PK deficiency are amenable to treatment with mitapivat. Full article

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7 pages, 523 KiB

Open AccessCase Report

Hyperbaric Oxygen Therapy during Pregnancy for Critical Anemia Secondary to Sickle Cell Disease with Post-Transfusion Hyperhemolysis: A Case Report

by Shawn Khan, Connor T. A. Brenna, Jacob Pendergrast, A. Kinga Malinowski, Marcus Salvatori, Rita Katznelson and Jordan Tarshis

Hematol. Rep. 2024, 16(3), 552-558; https://doi.org/10.3390/hematolrep16030053 - 30 Aug 2024

Abstract

Background: Sickle cell disease is the most common human monogenetic disease, and its risks are amplified during pregnancy. Methods: This report describes a 35-year-old woman with HgbSS sickle cell disease who developed hyperhemolysis syndrome after undergoing an exchange transfusion during pregnancy. Results: [...] Read more.

Background: Sickle cell disease is the most common human monogenetic disease, and its risks are amplified during pregnancy. Methods: This report describes a 35-year-old woman with HgbSS sickle cell disease who developed hyperhemolysis syndrome after undergoing an exchange transfusion during pregnancy. Results: In addition to conventional medical treatment, the patient received prepartum hyperbaric oxygen therapy (HBOT), totaling 17 treatments for the indication of severe anemia. She experienced significant clinical improvement while undergoing HBOT and ultimately delivered a healthy preterm infant by cesarean section. Conclusions: The risks, benefits, and challenges of using HBOT in this unique context are discussed. Full article

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11 pages, 2081 KiB

Open AccessCase Report

IgG-k/IgG-λ Para-Osseous Plasmacytoma Relapsed as Soft-Tissue Plasmacytoma with IgA-k Immunophenotype: A Case Report and Review of the Literature on Related Biochemical Aspects

by Manlio Fazio, Chiara Maria Catena Sorbello, Vittorio Del Fabro, Alessandra Romano, Maria Teresa Cannizzaro, Nunziatina Laura Parrinello, Benedetta Esposito, Sara Frazzetto, Federica Elia, Francesco Di Raimondo and Concetta Conticello

Hematol. Rep. 2024, 16(3), 541-551; https://doi.org/10.3390/hematolrep16030052 - 29 Aug 2024

Abstract

Neoplastic plasma cells (PCs) proliferation at anatomic sites dislocated from the bone marrow (BM) or their contiguous growth from osseous lesions that disrupt the cortical bone is termed extramedullary multiple myeloma (EMD). EMD still remains challenging from a therapeutic and biological perspective. Pathogenesis [...] Read more.

Neoplastic plasma cells (PCs) proliferation at anatomic sites dislocated from the bone marrow (BM) or their contiguous growth from osseous lesions that disrupt the cortical bone is termed extramedullary multiple myeloma (EMD). EMD still remains challenging from a therapeutic and biological perspective. Pathogenesis has not been completely clarified, and it is generally associated with high-risk cytogenetics (HRCAs). In order to emphasize the clinical and biochemical complexity of this disease, we have decided to describe the case of a patient affected by relapsed-refractory (RR) EMD, which presented as para-osseous plasmacytoma with a bi-phenotypical immunoglobulin (Ig) component and lately relapsed as soft-tissue plasmacytoma with a total immunophenotype switch. We have also hypothesized a correlation between Ig patterns and prognosis and suggested the possible inclusion of these biochemical features in the general risk assessment. Full article

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12 pages, 2480 KiB

Open AccessArticle

First-Line Combination with Proteasome Inhibitor-Based Treatment and Zoledronic Acid Is Effective in Reducing Later Fractures in Multiple Myeloma Irrespective of Multiple Myeloma Bone Disease at Diagnosis

by Veera Eskelinen, Elise Nivakoski, Kirsi Launonen, Anu Partanen, Sakari Kakko and Milla E. L. Kuusisto

Hematol. Rep. 2024, 16(3), 529-540; https://doi.org/10.3390/hematolrep16030051 - 6 Aug 2024

Abstract

The present study provides real-world evidence on the treatment of multiple myeloma (MM) bone disease with various bisphosphonates combined for different myeloma-specific treatments as no validated data regarding the best combination treatment for bone disease associated with MM are available. We examined retrospectively [...] Read more.

The present study provides real-world evidence on the treatment of multiple myeloma (MM) bone disease with various bisphosphonates combined for different myeloma-specific treatments as no validated data regarding the best combination treatment for bone disease associated with MM are available. We examined retrospectively 345 MM patients treated with autologous stem cell transplantation in Finland during 1996–2020. The median age of the patients was 60 years with a median follow-up time of 50 months (1–339). At diagnosis, 72.1% of the patients had myeloma-associated bone disease and 45.8% had fractures. Most patients (58.8%) received proteasome inhibitor (PI)-containing treatment at first line. MM bone disease was treated in 91.6% of the patients; 49.9% received zoledronic acid (ZA) and 29.9% pamidronate. Inferior overall survival was associated with MM bone disease at diagnosis (p = 0.005) or a fracture at diagnosis (p = 0.003). A later fracture was identified in 29% of the patients, and in those patients without MM bone disease at diagnosis later fractures were less common after ZA treatment (p = 0.049). PI-based treatment plus ZA (p = 0.019) seemed to be the best combination to prevent later fractures, even though the same patient subgroup was more likely to experience relapse (p = 0.018), and also when excluding patients with previous induction therapy without novel agents (p = 0.008). To conclude, this study suggests that the best therapy to prevent later fractures in MM might be PI-based treatment combined with ZA. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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6 pages, 509 KiB

Open AccessCase Report

Lymphocytic Lymphoma Transforming into Hodgkin Lymphoma in Sub-Saharan Africa: Case Report and Literature Review

by Sokhna Aïssatou Touré, Dibor Niang, Serigne Mourtalla Gueye, Mohamed Keita, Alioune Badara Diallo, Elimane Seydi Bousso, Fatma Dieng, Blaise Felix Faye, Moussa Seck and Saliou Diop

Hematol. Rep. 2024, 16(3), 523-528; https://doi.org/10.3390/hematolrep16030050 - 5 Aug 2024

Abstract

The Hodgkin variant Richter syndrome (HvRS) is an infrequent complication occurring in 1% of lymphocytic lymphoma/chronic lymphocytic leukemia patients. We report a case of HvRS diagnosed in Sub-Saharan Africa. A 63-year-old patient was consulted for the investigation of an abdominal mass that had [...] Read more.

The Hodgkin variant Richter syndrome (HvRS) is an infrequent complication occurring in 1% of lymphocytic lymphoma/chronic lymphocytic leukemia patients. We report a case of HvRS diagnosed in Sub-Saharan Africa. A 63-year-old patient was consulted for the investigation of an abdominal mass that had been evolving for 5 years prior to admission. His history revealed night sweats, 13% weight loss in 3 months and persistent pruritis. Examination revealed bilateral cervical axillary and inguinal macroadenopathies, painless abdominal distension, pruritic lesions and WHO 2 PS. The blood count showed anemia at 9.5 g/dL. Histology revealed a lymphomatous proliferation of diffuse architecture, nodular in places, with Hodgkin and Sternberg cells associated with small lymphocytes, histiocytes and eosinophilic polymorphs. Immunohistochemistry showed CD20, PAX5, BCL2, CD5, CD23 and MYC positivity; Ki67 at 10% and cyclin D1, BCL6 and CD10 negativity; CD30 positivity on Hodgkin and Sternberg cells that remained CD20 negative; difficulty interpreting CD15; EBV positivity (EBERs); and CD3 and CD5 positivity on reactive T cells. CD138 and kappa and lambda light chains were non-contributory. The extension work-up classified the patient as Ann Arbor stage III B with a Hasenclever score of 3/7. This case illustrates the difficulties in diagnosing HvRS in our countries, where the number of haematopathologists is insufficient and the technical facilities are limited. Full article

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11 pages, 535 KiB

Open AccessArticle

Investigation of Delayed Transfusion Reactions in Sickle Cell Disease Patients Polytransfused in the Brazilian Amazon

by Lorena Alves Santos, Anne Cristine Gomes de Almeida, Andrea Monteiro Tarragô, Nina Rosa Gonçalves da Silva, Juliana Nascimento Vitoriano da Silva, Mônica Moura de Souza, Monik Oney Oliveira Nascimento, Marcelo Reis do Nascimento, Ana Caroline dos Santos Castro, Cinthia Xerez de Albuquerque, Evilázio Cunha Cardoso, José Pereira Moura Neto and Sérgio Roberto Lopes Albuquerque

Hematol. Rep. 2024, 16(3), 512-522; https://doi.org/10.3390/hematolrep16030049 - 1 Aug 2024

Abstract

Background: Sickle cell disease (SCD) affects approximately 100,000 people in the United States and millions worldwide, with the highest prevalence of 70% of SCD being found in individuals of African ethnicity. Delayed hemolytic, alloimmunization, and anamnestic transfusion reactions in multiple transfusion patients need [...] Read more.

Background: Sickle cell disease (SCD) affects approximately 100,000 people in the United States and millions worldwide, with the highest prevalence of 70% of SCD being found in individuals of African ethnicity. Delayed hemolytic, alloimmunization, and anamnestic transfusion reactions in multiple transfusion patients need to be investigated and managed to avoid a worsening of the patient’s clinical status. Objective: This paper aims to investigate delayed transfusion reactions in SCD patients who were polytransfused in the Brazilian Amazon. Material and Methods: The clinical and laboratory indicators of SCD patients with more than four transfusions were investigated. The patients were treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Estado do Amazonas, Brazil. Results: A total of 44 polytransfused patients with SCD were followed. Regarding Rh phenotype, it was possible to observe a frequency of 26.6% (12) patients with the RZRZ (DCE/DCE) phenotype, in addition to 4.5% (two) patients with RH and RHCE variants. It was also possible to observe 20.5% (nine) patients with an alloimmunization reaction, who presented the following alloantibodies: anti-RhD, anti-E, anti-K, anti-Jk^b, anti-N, anti-S, and anti-Di^a, two of which are unidentified. Of these, four (44.4%) patients also presented autoantibodies, anti-e, and three unidentified antibodies, and four (44.4%) patients presented an anamnestic reaction, with anti-RhD, K, and Jkb antibodies. Of the 44 patients monitored, 54.4% (24) had clinical and laboratory indicators of a delayed hemolytic reaction. Conclusion: Delayed transfusion reactions, often neglected, occur frequently. Therefore, transfusions need to be monitored for at least 28 days, with medical investigation of clinical and laboratory indicators to make greater use of this therapeutic resource. Full article

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8 pages, 1971 KiB

Open AccessCase Report

Persistently High Platelet Factor 4 Levels in an Adolescent with Recurrent Late Thrombotic Complications after SARS-CoV-2 mRNA Vaccination

by Yoichi Haga, Akira Ohara, Tsuneyoshi Yakuwa, Akari Yamashita, Midori Udo, Masaki Matsuoka, Hiroshi Ohara, Atsushi Yasumoto and Hiroyuki Takahashi

Hematol. Rep. 2024, 16(3), 504-511; https://doi.org/10.3390/hematolrep16030048 - 29 Jul 2024

Abstract

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients with a thrombophilic predisposition. Herein, we present a 17-year-old female who had underlying antiphospholipid syndrome (APS) and developed deep vein thrombosis (DVT) 6 months after her second BNT162b2 [...] Read more.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients with a thrombophilic predisposition. Herein, we present a 17-year-old female who had underlying antiphospholipid syndrome (APS) and developed deep vein thrombosis (DVT) 6 months after her second BNT162b2 vaccine dose. Although she had no family history of thrombosis, she had previously developed DVT at 6 years of age, with thrombus formation in the right common iliac vein and the inferior vena cava, along with concomitant left pulmonary infarction. The patient had received anticoagulant therapy for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine was hypothesized to exacerbate the patient’s APS by activating coagulation. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development. Full article

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17 pages, 1150 KiB

Open AccessReview

Hemophagocytic Lymphohistiocytosis Triggered by Herpes Simplex Virus 1 and 2: A Narrative Review

by Andria Papazachariou and Petros Ioannou

Hematol. Rep. 2024, 16(3), 487-503; https://doi.org/10.3390/hematolrep16030047 - 26 Jul 2024

Abstract

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterized by an uncontrolled hyperinflammatory reaction. HLH is classified into primary (familial) and secondary (acquired). Secondary HLH is commonly triggered by infections, with viral infections being a leading cause. Its epidemiology and clinical [...] Read more.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterized by an uncontrolled hyperinflammatory reaction. HLH is classified into primary (familial) and secondary (acquired). Secondary HLH is commonly triggered by infections, with viral infections being a leading cause. Its epidemiology and clinical features in cases associated with herpes simplex virus 1 and 2 remain underexplored. This study aimed to review all previously described cases of HSV-1 or -2-triggered HLH and provide information about this syndrome’s epidemiology, microbiology, clinical characteristics, treatment, and outcomes. Methods: A narrative review was performed based on a search in PubMed, the Cochrane Library, and Scopus. Studies published until 27 April 2024 providing relevant data for HLH due to HSV 1 and 2 in humans were included. Results: We identified 29 eligible studies reporting HLH due to HSV 1 and 2, involving 34 patients. Half of them were adults, and half were neonates. Fever and splenomegaly were the most common clinical findings. Most patients were diagnosed with HSV-1 (64.7%), with PCR being the primary diagnostic method. The median duration of in-hospital treatment was 21 days, with acyclovir and steroids being the mainstays of therapy. The overall mortality rate was 41.2%, and AST levels emerged as an independent predictor of mortality. Conclusions: Our findings underscore the need for heightened awareness surrounding HLH triggered by HSV 1 and 2 and the importance of prompt diagnosis and tailored treatment approaches. Full article

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8 pages, 459 KiB

Open AccessStudy Protocol

Identifying Candidates for Effective Utilization of Stored Autologous PBSCs in Salvage Transplantation for Multiple Myeloma: Who Benefits Most?

by Amany R. Keruakous, Laura Walker, Molly Denlinger, Mohammad A. H. Mian, Danielle Bradshaw, Vamsi K. Kota and Anand P. Jillella

Hematol. Rep. 2024, 16(3), 479-486; https://doi.org/10.3390/hematolrep16030046 - 12 Jul 2024

Abstract

Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT’s efficacy in MM, including its potential as salvage therapy after prolonged remission. [...] Read more.

Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT’s efficacy in MM, including its potential as salvage therapy after prolonged remission. Peripheral blood stem cells (PBSCs) are now the primary source of hematopoietic stem cells for ASCT. Collecting additional PBSCs post-initial myeloablative conditioning is challenging, leading many centers to adopt the practice of collecting and storing excess PBSCs during initial therapy to support tandem transplants or salvage treatments. The use of salvage ASCT may diminish in the face of novel, highly effective treatments like bispecific antibodies and cellular therapies for relapsed/refractory MM (RRMM). Despite available stored PBSC grafts, salvage ASCTs are underutilized due to various factors, including declining performance status and therapy-related comorbidities. A cost utilization analysis from 2013 revealed that roughly 70% of patients had unused PBSC products in prolonged cryopreservation, costing a significant portion of total ASCT expenses. The average cost for collecting, cryopreserving, and storing PBSCs exceeded $20,000 per person, with more than $6700 spent on unused PBSCs for a second ASCT. A more recent analysis from 2016 underscored the declining need for salvage ASCT, with less than 10% of patients using stored PBSC grafts over a decade. Methods: To address the dilemma of whether backup stem cells remain necessary for myeloma patients, the study investigated strategies to reduce the financial burden of PBSC collection, processing, and storage. It evaluated MM patients undergoing frontline ASCT from January 2012 to June 2022, excluding those with planned tandem transplants and those who had a single ASCT with no stored cells. Discussion: Among the 240 patients studied, the median age at PBSC collection was 61. Notably, only 7% underwent salvage ASCT, with nearly 90% of salvage ASCT recipients being ≤ 61 years old at the time of initial ASCT. The study revealed a decreasing trend in salvage ASCT use with increasing age, suggesting that PBSC collection for a single transplant among elderly patients (>60 years old) could be a cost-effective alternative. Most transplant centers aimed to collect 10 × 10⁶ CD34 + cells/kg, with patients over 65 often requiring multiple collection days. Shifting towards single-transplant collections among the elderly could reduce costs and resource requirements. Additionally, the study recommended implementing strategies for excess PBSC disposal or repurposing on the collection day to avoid additional storage costs. In summary, the decreasing utilization of salvage ASCT in MM, alongside financial considerations, underscores the need for revised stem cell collection policies. Conclusions: The study advocates considering single-transplant PBSC collections for elderly patients and efficient management of excess PBSCs to optimize resource utilization. Full article

(This article belongs to the Special Issue Stem Cell Transplantation in Cancer Treatment: Current Status and Future Direction)

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14 pages, 1437 KiB

Open AccessArticle

Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case–Control Study

by Nawaf Alanazi, Abdulaziz Siyal, Sulman Basit, Masood Shammas, Sarah Al-Mukhaylid, Aamer Aleem, Amer Mahmood and Zafar Iqbal

Hematol. Rep. 2024, 16(3), 465-478; https://doi.org/10.3390/hematolrep16030045 - 8 Jul 2024

Abstract

Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the [...] Read more.

Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients’ blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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11 pages, 494 KiB

Open AccessReview

Goal-Directed Use of Prothrombin Complex Concentrates in Liver Transplantation: Is a Plasma-Free Procedure Feasible?

by Giovanni Punzo, Valeria Di Franco and Paola Aceto

Hematol. Rep. 2024, 16(3), 454-464; https://doi.org/10.3390/hematolrep16030044 - 8 Jul 2024

Abstract

Background: Fresh frozen plasma (FFP) transfusions have been the mainstay of hemostatic intervention for the treatment of bleeding and coagulation abnormalities arising during liver transplantation (LT) for decades. However, numerous clinical studies showed that FFP has many side effects, including the risk of [...] Read more.

Background: Fresh frozen plasma (FFP) transfusions have been the mainstay of hemostatic intervention for the treatment of bleeding and coagulation abnormalities arising during liver transplantation (LT) for decades. However, numerous clinical studies showed that FFP has many side effects, including the risk of pathogen transmission, transfusion-associated circulatory overload (TACO), transfusion-related immunomodulation (TRIM), and transfusion-related acute lung injury (TRALI). These adverse events are particularly challenging in patients undergoing LT, who often suffer from severe portal hypertension, poor renal function and coexisting cardiac disease.The aims of this review are to summarize the pharmacological properties of currently available PCCs, to represent the theoretical benefits and the possible risks related to the use of these drugs in patients undergoing LT, and, finally, to review the current literature on the topic in order to highlight the evidence that currently supports PCC use in LT patients. Methods: The current literature on the topic was reviewed in order to highlight the evidence that currently supports PCC use in LT patients. Results: Prothrombin complex concentrates (PCCs) may offer several advantages when compared to FFP. Indeed, PCCs have been shown to reduce the risk of TACO, which during liver transplantation may deteriorate portal hypertension, increase intraoperative bleeding, and possibly reduce survival rates. One of the major concerns for PCC use is thrombogenicity. However, currently available PCCs are much safer as they contain inactivated forms of the vitamin K-dependent coagulation factors and protein C, protein S, antithrombin and/or heparin. Nowadays, the use of PCCs to correct coagulation abnormalities that occur during LT is an increasingly widespread practice. However, it is not yet clear what level of evidence supports this practice, and what the risks associated with it are. Conclusions: Administration of PCC in LT patients to correct haemostatic abnormalities seems to be well-tolerated, but the relationship between PCC use and thromboembolic events in the postoperative period remains unclear. Adequately powered, methodologically sound trials are urgently required for more definitive conclusions about the efficacy and safety of PCCs in a broad phenotype of LT recipients. Full article

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14 pages, 649 KiB

Open AccessReview

Blood Microbiota and Its Products: Mechanisms of Interference with Host Cells and Clinical Outcomes

by Luigi Santacroce, Ioannis Alexandros Charitos, Marica Colella, Raffaele Palmirotta and Emilio Jirillo

Hematol. Rep. 2024, 16(3), 440-453; https://doi.org/10.3390/hematolrep16030043 - 6 Jul 2024

Abstract

In healthy conditions, blood was considered a sterile environment until the development of new analytical approaches that allowed for the detection of circulating bacterial ribosomal DNA. Currently, debate exists on the origin of the blood microbiota. According to advanced research using dark field [...] Read more.

In healthy conditions, blood was considered a sterile environment until the development of new analytical approaches that allowed for the detection of circulating bacterial ribosomal DNA. Currently, debate exists on the origin of the blood microbiota. According to advanced research using dark field microscopy, fluorescent in situ hybridization, flow cytometry, and electron microscopy, so-called microbiota have been detected in the blood. Conversely, others have reported no evidence of a common blood microbiota. Then, it was hypothesized that blood microbiota may derive from distant sites, e.g., the gut or external contamination of blood samples. Alteration of the blood microbiota’s equilibrium may lead to dysbiosis and, in certain cases, disease. Cardiovascular, respiratory, hepatic, kidney, neoplastic, and immune diseases have been associated with the presence of Gram-positive and Gram-negative bacteria and/or their products in the blood. For instance, lipopolysaccharides (LPSs) and endotoxins may contribute to tissue damage, fueling chronic inflammation. Blood bacteria can interact with immune cells, especially with monocytes that engulf microorganisms and T lymphocytes via spontaneous binding to their membranes. Moreover, LPSs, extracellular vesicles, and outer membrane vesicles interact with red blood cells and immune cells, reaching distant organs. This review aims to describe the composition of blood microbiota in healthy individuals and those with disease conditions. Furthermore, special emphasis is placed on the interaction of blood microbiota with host cells to better understand disease mechanisms. Full article

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9 pages, 3769 KiB

Open AccessCase Report

Transient Stress Lymphocytosis in a Child: A Case Report and Systematic Review of the Literature

by Alexander Placek, Randall Y. Chan, Maria Vergara-Lluri and Russell K. Brynes

Hematol. Rep. 2024, 16(3), 431-439; https://doi.org/10.3390/hematolrep16030042 - 3 Jul 2024

Abstract

Transient stress lymphocytosis (TSL) is an under-recognized phenomenon associated with an acute stressful event such as physical trauma or various emergency medical conditions. Lymphocytosis generally resolves within several hours to days of the stressor. While most reports of TSL predominantly involve adult patients, [...] Read more.

Transient stress lymphocytosis (TSL) is an under-recognized phenomenon associated with an acute stressful event such as physical trauma or various emergency medical conditions. Lymphocytosis generally resolves within several hours to days of the stressor. While most reports of TSL predominantly involve adult patients, it has only rarely been reported in pediatric patients. Here, we describe the clinical course of a 9-year-old male who developed TSL following a traumatic fall from a second-story balcony and provide a systematic literature review of TSL. Full article

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10 pages, 230 KiB

Open AccessArticle

Double Trouble: COVID-19 Infection Exacerbates Sickle Cell Crisis Outcomes in Hospitalized Patients—Insights from National Inpatient Sample 2020

by Zubair Hassan Bodla, Mariam Hashmi, Fatima Niaz, Austin B. Auyeung, Anuoluwa Oyetoran, Muhammad Jahanzeb Khalil, Muhammad Salman Faisal, Farhan Khalid, Abdel-Rahman Zakieh, Yvette Bazikian and Christopher L. Bray

Hematol. Rep. 2024, 16(3), 421-430; https://doi.org/10.3390/hematolrep16030041 - 29 Jun 2024

Abstract

Background: This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. Methods: A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who [...] Read more.

Background: This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. Methods: A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization. Analyses were conducted with STATA. Multivariate logistic and linear regression analyses were used to adjust for confounding variables. Results: Of 66,415 adult patients with a primary SCC diagnosis, 875 were identified with a secondary diagnosis of COVID-19 infection. Unadjusted mortality rate was higher for SCC patients with COVID-19 (2.28%) compared to those without (0.33%), with an adjusted odds ratio (aOR) of 8.49 (p = 0.001). They also showed increased odds of developing acute respiratory failure (aOR = 2.37, p = 0.003) and acute kidney injury requiring dialysis (aOR = 8.66, p = 0.034). Additionally, these patients had longer hospital stays by an adjusted mean of 3.30 days (p < 0.001) and incurred higher hospitalization charges by an adjusted mean of USD 35,578 (p = 0.005). Conclusions: The SCC patients with COVID-19 presented higher mortality rates, increased morbidity indicators, longer hospital stays, and substantial economic burdens. Full article

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