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The association between Epstein-Barr virus subtype, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder was examined in a group of 25 bone marrow transplant recipients. A highly statistically significant correlation was observed between the human leukocyte antigen B51 allele and development of posttransplantation lymphoproliferative disorder (P=.0016). This study provides, to our knowledge, the first evidence that the human leukocyte antigen B51 allele might predispose bone marrow transplant recipients to Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder. [ABSTRACT FROM AUTHOR]

Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study., (© 2021 by The American Society of Hematology.)

Background: Persistent polyclonal B-cell lymphocytosis (PPBL) is a benign condition associated with smoking., Case Report: A 42-year-old woman was referred to an internist because of an abnormal blood test outcome identified during routine sampling. She had no symptoms; she had smoked for thirty pack years. Physical examination revealed no abnormalities. Laboratory analysis showed absolute lymphocytosis. A blood smear identified binuclear ('buttock') cells. The diagnosis of persistent polyclonal B-cell lymphocytosis (PPBL) was made, with nicotine abuse as the probable cause. The patient was advised to quit smoking., Conclusion: Polyclonal B-cell lymphocytosis is a benign condition that is characterised by: (a) polyclonal increase of B-lymphocytes in peripheral blood; (b) the presence of binuclear lymphocytes (buttock cells) in microscopic differentiation; (c) polyclonal increase in IgM. Recognition is important for the prevention of unnecessary diagnostic testing.

A 69-year-old man of Jewish descent with a second local relapse of rectal carcinoma was found to have a markedly prolonged activated partial thromboplastin time (aPTT). Further evaluation revealed a homozygous factor XI deficiency. Despite various operations in the past he had never displayed any bleeding problems. Severe factor XI deficiency did not prevent venous thrombosis in this patient. The management of patients with prolonged aPTT is described and insight into the pathophysiology of factor XI deficiency is provided. The differential diagnosis in patients with a prolonged aPTT depends on their bleeding tendency. There is a large variability in bleeding tendency in patients with factor XI deficiency. Patients with factor XI deficiency and an increased bleeding tendency can be treated with antifibrinolytic agents prior to small interventions, such as tooth extraction, or with plasma prior to surgery.

A 57-year-old woman without significant medical history presented. She had suffered from dyspnoea for the past 2 days and persistent spasmodic abdominal complaints for the past 2 weeks. Physical examination revealed tachypnoea, tachycardia and slight abdominal tenderness. Laboratory investigations revealed hypoxaemia and a strongly elevated D-dimer level. Thorax radiography revealed no abnormalities and no indications for pulmonary embolism were revealed by the CT. Abdominal ultrasound revealed multiple enlarged lymph nodes. Shortly after admission and despite resuscitation the patient died. Autopsy revealed massive pulmonary tumour embolism that originated from a primary lymphogenic metastasized coecum carcinoma. Pulmonary tumour embolism is characterised by tumour cells in the pulmonary vascular system, which exhibit no continuity with parenchymal metastases. Due to the less than specific findings revealed by history taking, physical examination and additional tests, the condition is rarely diagnosed ante mortem.

Pulmonary hypertension (PHT) occurs in approximately 30% of adults with sickle cell disease (SCD) and is an independent risk factor for early death. In this study, we aimed to determine the value of general laboratory testing, plain chest radiography, electrocardiography (ECG), high-resolution computer tomography (HRCT) of the thorax, pulmonary function testing, and plasma N-terminal brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in patients with SCD-related PHT. A cohort of 85 ambulatory sickle cell patients were prospectively screened for PHT with echocardiography (defined as a tricuspid regurgitation flow velocity of > or =2.5 m/sec). All patients were systematically evaluated by the aforementioned diagnostic tests comparing patients with and without PHT. The prevalence of PHT was 41% in HbSS/HbSbeta(0)-thalassemia patients and 13% in HbSC/HbSbeta(+)-thalassemia patients. No statistically significant differences were detected in ECG, chest radiography, HRCT, and pulmonary function testing between patients with and without PHT. The degree of anemia and renal dysfunction, but not the presence of PHT, were the most important determinants of plasma (NT-pro)BNP levels. The performed imaging and functional studies do not seem to be of value in identifying etiological conditions (such as airflow obstruction or parenchymal lung disease) nor do they offer clues to the presence of mild PHT in SCD., (Copyright 2008 Wiley-Liss, Inc.)

Human testicular germ cell tumours of adolescents and adults (TGCTs), the seminomatous and non-seminomatous germ cell tumours, show morphological and biological similarities to normal embryonic development, presumably determined by their supposed cell of origin, the primordial germ cell/gonocyte. Based on this knowledge, OCT3/4, also known as POU5F1, was recently defined as a diagnostic marker for these tumour types. In the adult testis, positive immunohistochemistry for OCT3/4 is an absolute indicator for the presence of the TGCT precursor carcinoma in situ/intratubular germ cell neoplasia undifferentiated (CIS/ITGCNU), seminoma, and/or embryonal carcinoma. Several studies have confirmed this observation, using the same polyclonal antibody. The present study demonstrates the usefulness of OCT3/4 immunohistochemistry in a diagnostic setting of a consecutively collected series of more than 200 testicular tumours and over 80 testicular biopsies. Moreover, it is shown that a monoclonal antibody directed against OCT3/4 is as informative as the polyclonal antibody, both in immunohistochemistry and in western blot analysis. The antibodies are robust and applicable with different methods of pretreatment and storage of tissue. This allows routine application of this diagnostic marker., (Copyright 2005 Pathological Society of Great Britain and Ireland)

Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes are considered pivotal to prevent lymphoproliferative disease (LPD) in allogeneic stem cell transplantation (SCT) recipients. We evaluated the recovery of EBV-specific CD8+ T cells after partially T-cell-depleted SCT and studied the interaction between EBV-specific CD8+ T cells, EBV reactivation, and EBV-LPD. EBV-specific CD8+ T cells were enumerated using 12 class I HLA tetramers presenting peptides derived from 7 EBV proteins. Blood samples were taken at regular intervals after SCT in 61 patients, and EBV DNA levels were assessed by real-time polymerase chain reaction. Forty-five patients showed EBV reactivation, including 25 with high-level reactivation (ie, more than 1000 genome equivalents [geq] per milliliter). Nine of these 25 patients progressed to EBV-LPD. CD8+ T cells specific for latent or lytic EBV epitopes repopulated the peripheral blood at largely similar rates. In most patients, EBV-specific CD8+ T-cell counts had returned to normal levels within 6 months after SCT. Concurrently, the incidence of EBV reactivations clearly decreased. Patients with insufficient EBV-specific CD8+ T-cell recovery were at high risk for EBV reactivation in the first 6 months after SCT. Failure to detect EBV-specific CD8+ T cells in patients with high-level reactivation was associated with the subsequent development of EBV-LPD (P =.048). Consequently, the earlier defined positive predictive value of approximately 40%, based on high-level EBV reactivation only, increased to 100% in patients without detectable EBV-specific CD8+ T cells. Thus, impaired recovery of EBV-specific CD8+ T cells in patients with high-level EBV reactivation may identify a subgroup at very high risk for EBV-LPD and supports that EBV-specific CD8+ T cells protect SCT recipients from progressive EBV reactivation and EBV-LPD.

Recipients of a partially T-cell-depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV-lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD, LPD-mortality, and abrogates viral reactivation in high-risk patients. We monitored 49 recipients of a TCD allo-SCT weekly for EBV reactivation by quantitative real-time polymerase chain reaction (PCR). Preemptive therapy by a single infusion of rituximab was given to patients with viral reactivation more than or equal to 1000 geq/mL. Results were compared with an historical control group of patients retrospectively monitored for EBV reactivation at similar intervals. There were 17 prospectively monitored patients who showed EBV reactivation more than or equal to 1000 geq/mL and 15 received preemptive therapy. Median time to preemptive therapy was 113 days (range, 41-202 days) after SCT. There were 14 patients who showed complete response (CR) as characterized by prevention of EBV-LPD and complete clearance of EBV-DNA from plasma, which was achieved after a median number of 8 days (range, 1-46 days). One patient progressed to EBV-LPD despite preemptive therapy, but obtained CR after 2 infusions of rituximab and donor lymphocyte infusion. There were 2 patients who had already developed EBV-LPD prior to preemptive rituximab, but obtained CR following 2 rituximab infusions. Comparison of this prospectively followed series to our historical cohort with the same high-risk profile showed a reduction of EBV-LPD incidence (18% +/- 9% versus 49% +/- 11%, respectively) and a complete abrogation of LPD-mortality (0% versus 26% +/- 10%, respectively) (P =.04) at 6 months from EBV-DNA more than or equal to 1000 geq/mL. Frequent quantitative monitoring of EBV reactivation and preemptive therapy by rituximab improves outcome in patients at high risk of EBV-LPD. (Blood. 2002;99:4364-4369)