Antibody waning after immunosuppressive chemotherapy and immunomodulators, re-immunization considerations in pediatric patients with malignancy and chronic immune thrombocytopenic purpura.

INTRODUCTION: Immunosuppressive chemotherapy increase the risk of vaccine-preventable infectious diseases in children; nevertheless, chemotherapy may result in delay or miss updated immunization schedules. The predictable antibody waning after incomplete primary immunization series may be intensified at the end of chemotherapy. This study aimed to investigate post-chemotherapy vaccine immunity waning at the end of immunosuppressive therapy in children with malignancy and hematologic disorders. MATERIALS AND METHODS: Children with malignancies and hematologic disorders including chronic immune thrombocytopenic purpura (ITP) younger than 18 years old were enrolled from September 2015 to August 2019. Eligible patients who completed their treatment protocol for at least 6 months were recruited. The patient information, including sex, age at the date of diagnosis, number of chemotherapy sessions, underlying disease, and vaccination history, was taken by chart review using predefined questionnaires. The patient's blood samples were obtained, and serum IgG antibody titer checked against diphtheria, tetanus, hepatitis B virus (HBV), mumps, measles, and rubella (MMR) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: 110 children receiving immunosuppressive chemotherapy were recruited. Forty-four (40%) of the children tested were girls and 66 (60%) were boys. The mean age of patients was 5.5 years with a range of 2 to 13 years. Of 110 studied children, 27.3% were seronegative for all antibodies. On average, patients undergo 19 episodes of chemotherapy. The mean chemotherapy sessions were significantly greater in children who were seronegative for all tested antibodies (mean: 36.2, 95% CI 33.16 to 39.24, p-value < 0.001). No statistically significant differences were observed regarding the patient's sex and age between the seropositive and seronegative groups (p-value 0.513 and 0.060, respectively). Based on Poisson regression model analysis, the female gender was associated with 37% lower odds of seronegativity (incidence rate ratio (IIR): 0.63; [95% conf. interval: 0.39 to 1.01, p-value: 0.55]), while chemotherapy sessions 30 or more was associated with significant odds of seronegativity for all tested vaccines (IIR: 25.41; [95% conf. interval: 6.42 to 100.57, p-value < 0.001]). CONCLUSION: Our results reemphasized planned catchup immunization in children undergoing immunosuppressive chemotherapy for malignancy, especially against tetanus, diphtheria, and hepatitis B at least 6 months after the end of chemotherapy sessions.

Management of Maxillary Deformity with Segmental Osteotomy followed by Implant Insertion in ß-Thalassemia Major Patient.

AIM: The aim of this report is to present the management of the maxillary deformity and subsequent implant therapy of a case with ß-thalassemia major. BACKGROUND: ß-thalassemia is a hematologic disorder that results from the abnormality of the ß-globulin chain synthesis. The best known thalassemia-induced dentofacial problem is the maxillary enlargement, and this undesirable growth of maxilla affects not only the facial esthetics but also dental occlusion, and leads to functional deficiency. CASE DESCRIPTION: A 16-year-old female patient with ß-thalasse-mia major was referred with the complaints of severe facial deformity and malocclusion, resulting in psychosocial and functional problems for her. The dentofacial deformity was characterized by an excessive premaxillary growth both in sagittal and vertical planes. Anterior maxillary osteotomy was performed with bilateral canines extraction, and dental implants were inserted to the canine regions, following bone healing. Postoperative course was free of problems with the crown restorations in function. Recurrence has not been occurred at 6 years follow-up. CONCLUSION: With maintaining hemoglobin level over 10 gm/dl, correction of maxillary defects is stable for long-term in ß-thalassemia major patient. Implant application to these patients may lead to unforeseeable results. CLINICAL SIGNIFICANCE: Although having some difficulties, such as overbleeding and stability problems, maxillary enlargement can be treated by segmental osteotomies successfully in ß-thalassemia major patient. Implant failure frequency may be higher, but many other studies are needed for determining implant survival rate in ß-thalassemia major patients.

Immunotactoid Glomerulopathy.

Immunotactoid glomerulopathy (ITG) is a rare glomerular disease that typically presents with proteinuria, hematuria, and kidney dysfunction. A kidney biopsy is essential to establish the diagnosis of ITG. ITG is characterized by glomerular electron-dense immunoglobulin deposits with hollow-cored microtubules. ITG is classified as either monoclonal or polyclonal based on immunofluorescence staining of the immunoglobulin deposits. Monoclonal ITG is associated with an underlying hematologic disorder in two-thirds of the cases, lymphoma and plasma cell dyscrasias being the most common. Polyclonal ITG is associated with autoimmune diseases but can be seen with hematologic disorders and chronic infections. Due to the preponderance of hematologic disorders in both monoclonal and polyclonal ITG, a thorough hematologic workup must be performed in all cases of ITG. In monoclonal ITG with a detectable clone, clone-directed therapy is administered to achieve hematologic remission, as the renal response is highly dependent on the hematologic response. In clone-negative monoclonal ITG, anti-B cell therapy is often used as a first-line therapy. Management of polyclonal ITG without an underlying hematologic disorder is poorly defined. Compared to monoclonal ITG, patients with polyclonal ITG have a higher risk of progression to end-stage kidney disease. Recurrence of ITG following kidney transplantation is common and is often associated with hematologic relapse.

Risk factors associated with infection-related mortality of Bacillus cereus bacteremia in hematologic disorders.

The mortality risk factors in B. cereus bacteremia in hematologic disorders are still unknown. In this study, patients with B. cereus bacteremia in hematologic disorders were selected in St. lukes international hospital and from electronic databases. A total of 176 patients [median age, 41 years (3-88 years); 99 (56%) males] were included. Of these patients, 141 (80%) had acute leukemia, and 93 (53%) died. Univariate analysis showed that neutropenia, CNS, gastrointestinal, and respiratory infections/symptoms were significantly associated with infection-related death. Meanwhile, glycopeptide use and management with source control were protective factors. Multivariate logistic regression analysis showed that infection-related death was significantly associated with CNS [odds ratio (OR): 3.49, 95% confidence interval (CI) 1.25-9.80], gastrointestinal (OR: 5.22, 95% CI 1.82-8.99), and respiratory infections/symptoms (OR: 8.98, 95% CI 1.62-49.9), as well as glycopeptide use (OR: 0.10, 95% CI 0.03-0.31) and source control (OR: 0.11, 95% CI 0.03-0.37). In conclusion, early glycopeptide administration and source control should be performed upon detection of infections suspicious for B. cereus.

Characteristics of Poor Prognosis in Patients with Cerebral Venous Sinus Thrombosis: A Multicenter Retrospective Study.

Purpose: The present study aimed to identify the characteristics, predictors, and imaging features of poor recovery in cases of cerebral venous sinus thrombosis (CVST). Patients and Methods: A total of 290 consecutive adult patients with CVST were enrolled from January 2017 to December 2021 from five hospitals in Nanning, Guangxi. According to the modified Rankin scale (mRS) score at hospital discharge, the patients were classified into good prognosis (GP, mRS ≤2) groups and poor prognosis (PP, mRS>2) groups. Logistic regression was used to identify factors associated with clinical outcomes. Results: Of the 290 patients, 35 were assigned to the PP group and 255 to the GP group. No significant difference in sex was observed between the two groups. Headache (76.21%) was the most frequent symptom of CVST, and local head and neck infection was the major comorbidity (26.21%). Approximately half of the patients (48.62%) had brain injury lesions <1 cm, and the most commonly affected sinus was the lateral sinus (81.03%). Less-common headaches (odds ratio [OR]: 2.769, p=0.046), altered mental status (OR: 0.122, p<0.001), hematologic disorder (OR: 0.191, p=0.045), and injury to multiple lobes (OR: 0.166, p=0.041) were associated with poor clinical outcomes. Conclusion: Headache was the most common and protective manifestation of CVST, and disturbances in consciousness were an important indication of poor clinical prognosis. Patients with hematologic diseases also tended to have poor outcomes. No significant correlation was found between the number and location of venous sinus thromboses and clinical prognosis; however, intracranial injury involving multiple lobes was often associated with poor prognosis.

Invasive Trichosporonosis in Neonates and Pediatric Patients with Malignancies or Hematologic Disorders.

(1) Background: Trichosporon species have emerged as important opportunistic fungal pathogens, with Trichosporon asahii being the leading and most frequent cause of invasive disease. (2) Methods: We performed a global review focused on invasive trichosporonosis in neonates and pediatric patients with malignancies or hematologic disorders. We reviewed case reports and case series of trichosporonosis due to T. asahii published since 1994, the year of the revised taxonomic classification. (3) Results: Twenty-four cases of invasive trichosporonosis were identified in neonates with the presence of central venous catheter and use of broad-spectrum antibiotics recognized as the main predisposing factors. Thirty-two cases were identified in children with malignancies or hematologic disorders, predominantly with severe neutropenia. Trichosporon asahii was isolated from blood in 24/32 (75%) pediatric cases. Cutaneous involvement was frequently observed in invasive trichosporonosis. Micafungin was the most commonly used prophylactic agent (9/22; 41%). Ten patients receiving prophylactic echinocandins were identified with breakthrough infections. A favorable outcome was reported in 12/16 (75%) pediatric patients receiving targeted monotherapy with voriconazole or combined with liposomal amphotericin B. Overall mortality in neonates and children with malignancy was 67% and 60%, respectively. (4) Conclusions: Voriconazole is advocated for the treatment of invasive trichosporonosis given the intrinsic resistance to echinocandins and poor susceptibility to polyenes.

Frequencies of glycosylphosphatidylinositol (GPI)-deficient cells using high-sensitivity flow cytometry as per the 2018 ICCS/ESCCA consensus guideline in patients with hematologic malignancy, aplastic anemia, or cytopenia.

OBJECTIVES: We examined the frequencies and sizes of glycosylphosphatidylinositol (GPI)-deficient cells as per the International Clinical Cytometry Society/European Society for Clinical Cell Analysis (ICCS/ESCCA) consensus guidelines for the high-sensitivity detection of GPI-deficient cells. METHODS: In 2018, the ICCS/ESCCA guidelines for the high-sensitivity detection of GPI-deficient cells were published. We evaluated frequencies and sizes of GPI-deficient red blood cells (RBCs), neutrophils, and monocytes as determined using the ICCS/ESCCA guidelines and Clinical and Laboratory Standards Institute (CLSI) guidelines in patients with a hematologic malignancy, aplastic anemia, or cytopenia. RESULTS: A total of 106 (38.7%) patients exhibited GPI deficiency in at least one blood cell lineage. GPI-deficient cells of one or more lineages were found in 62.7% of patients with a hematologic malignancy, 51.1% of patients with aplastic anemia, and 23.4% of patients with cytopenia. GPI-deficient monocytes were most frequently detected in all three groups. By population size, GPI-deficient clones (>1%) in monocytes were mostly detected in patients with a hematologic malignancy or aplastic anemia. Rare cells with GPI deficiency (<0.1%) in monocytes were most common among patients with cytopenia. CONCLUSION: High-sensitive flow cytometry analysis including monocytes may be necessary for patients with a hematologic disorder.

Secondary Acute Myeloid Leukemia (sAML): Similarly Dismal Outcomes of AML After an Antecedent Hematologic Disorder and Therapy Related AML.

Therapy related acute myeloid leukemia (tAML) and secondary AML after an antecedent hematologic disorder (sAML-AHD) are often addressed together, blurring any clinical and prognostic differences. Among 516 AML patients, we compared characteristics and outcomes of 149 patients with "sAML" (sAML-AHD: 104, tAML: 45), uniformly and intensively treated during the last 2 decades at 1 center. Clinical outcomes of the whole "sAML" cohort were significantly inferior compared to de novo AML and in both intermediate and poor cytogenetic risk groups. Adverse karyotype had no effect on survival in tAML, while it was a negative predictor in sAML-AHD. Both groups showed similarly dismal outcome, with low complete remission rates (CR 44% vs. 41%) and median overall survival (OS 7 vs. 10.5 months). Allogeneic hematopoietic cell transplantation (alloHCT) recipients in CR1 had superior median OS (24 vs. 8 months). By multivariate analysis, alloHCT was an independent predictor of outcome, while karyotype was for sAML-AHD only. In conclusion, both "sAML" groups have inferior outcomes after chemotherapy, with adverse karyotype affecting primarily sAML-AHD. Until new treatment approaches are available, only alloHCT offers a survival advantage.

Hematopoietic Stem Cells and Their Roles in Tissue Regeneration.

Hematopoietic stem cells (HSCs) are regarded as one of essential cell sources for treating regenerative diseases. Among many stem cells, the feasibility of using adult-derived hematopoietic stem cells in therapeutic approaches is very diverse, and is unarguably regarded as an important cell source in stem cell biology. So far, many investigators are exploring HSCs and modified HSCs for use in clinical and basic science. In the present review, we briefly summarized HSCs and their application in pathophysiologic conditions, including non-hematopoietic tissue regeneration as well as blood disorders. HSCs and HSCs-derived progenitors are promising cell sources in regenerative medicine and their contributions can be properly applied to treat pathophysiologic conditions. Among many adult stem cells, HSCs are a powerful tool to treat patients with diseases such as hematologic malignancies and liver disease. Since HSCs can be differentiated into diverse progenitors including endothelial progenitors, they may be useful for constructing strategies for effective therapy.

Hamartoma of the spleen (splenoma) with calcifications in a child with beta-thalassemia: A case report.

Splenic hamartoma (or splenoma) is a rare, benign, vascular tumor, often incidentally found at imaging, surgery or autopsy. Albeit usually asymptomatic and rare in children, when it occurs in the pediatric population it is more commonly symptomatic. We report a case of a 15-year-old girl with iron-deficiency anemia and beta-thalassemia, who had a large (10 × 8 × 7 cm) splenic lesion with calcifications, incidentally found during follow-up for splenomegaly and histologically characterized as hamartoma with calcified areas. The association of hamartoma and hematological disorders is a very unusual condition in children.

GATA family transcriptional factors: emerging suspects in hematologic disorders.

GATA transcription factors are zinc finger DNA binding proteins that regulate transcription during development and cell differentiation. The three important GATA transcription factors GATA1, GATA2 and GATA3 play essential roles in the development and maintenance of hematopoietic systems. GATA1 is required for the erythroid and megakaryocytic commitment during hematopoiesis. GATA2 is crucial for the proliferation and survival of early hematopoietic cells, and is also involved in lineage specific transcriptional regulation as the dynamic partner of GATA1. GATA3 plays an essential role in T lymphoid cell development and immune regulation. As a result, mutations in genes encoding the GATA transcription factors or alteration in the protein expression level or their function have been linked to a variety of human hematologic disorders. In this review, we summarized the current knowledge regarding the disrupted biologic function of GATA in various hematologic disorders.

Diffuse Presence of Myeloblasts in Chronic Subdural Hematoma of a Young Adult Patient without Systemic Hematologic Disorder.

Objective Myeloblasts are rarely found in the composition of a chronic subdural hematoma (CSH), and reported cases with myeloblasts in CSH have all been associated with systemic hematologic disorders. We present a young man with CSH manifesting the diffuse presence of myeloblasts, although no systemic hematologic disorders were identified. Participant A 27-year-old man, complaining of a headache lasting for a few months, was diagnosed with right CSH, and the aspirated hematoma was sent for cytological evaluation because no apparent etiologic episode was found. The diffuse presence of precursor cells, such as myeloblasts and erythroblasts, mimicking the aspirated bone marrow, was confirmed. This finding was suggestive of a systemic hematologic disorder, although the systemic evaluations were negative. Results The patient's hematoma reaccumulated twice, and finally hematoma and enhanced dura were removed by craniotomy under general anesthesia. Further histologic evaluation did not show any precursor cells, and he has remained asymptomatic for > 2 years without any evidence of the hematologic disorder. Conclusion We believe this is the first case with CSH that contained myeloblasts as well as erythroblasts in an otherwise healthy patient. A possible etiology was considered for the origin of precursor cells in his CSH.

Intracranial Hemorrhage in Patients with Hematologic Disorders

OBJECTIVE: Spontaneous intracranial hemorrhage is still common cause of death in the hematologic disorder including leukemia. The authors examine laboratory & radiological findings in patients with intracranial hemorrhage caused by hematologic disorder. METHODS: From March 1998 to May 2002, 42 patients with hematologic disease complicated by intracranial hemorrhage were transferred from hematology department. The patients were normotensive and had not trauma history. In all patients, intracranial hemorrhages were diagnosed with the brain computerized tomography. Surgical treatment was performed in one case. RESULTS: Underlying hematologic disorders included aplastic anemia (4), acute myeloblastic leukemia (20), acute lymphoblastic leukemia (6), chronic myeloblastic leukemia (8), myelodysplastic syndrome (2), multiple myeloma (1), and polycythemia vera (1). Intracranial hemorrhage subtypes consisted of intracerebral hemorrhage (39) including mainly subcortical lobar hemorrhage (28), and subarachnoid hemorrhage (3). Twenty (48%) of the 42 patients had multifocal hematomas. Thirty six patients (86%) had moderate and severe thrombocytopenia (less than 100x10(9)/L). Twenty four patients (57%) had moderate and severe leukocytosis (greater than 20x109/L). CONCLUSION: It showed that (1) the risk factors of intracranial hemorrhage in hematologic disorders are thrombocytopenia, leukocytosis and disseminated intravascular coagulopathy ; (2) intracerebral hemorrhage in hematologic disorders occur preferentially in the subcortical portion ; (3) intracranial hemorrhage in hematologic disorders consist of various combinations of subcortical lobar hemorrhage, subarachnoid hemorrhage, subdural hemorrhage and intraventricular hemorrhage ; (4) intracerebral hemorrhage in hematologic disorders tend to be multiple.