Recurrent hemorrhagic pericardial effusion in a child due to diffuse lymphangiohemangiomatosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Recurrent hemorrhagic pericardial effusion in children with no identifiable cause is a rare presentation.</p> <p>Case presentation</p> <p>We report the case of a 4-year-old Indian girl who presented with recurrent hemorrhagic pericardial effusion. Diffuse lymphangiomatosis was suspected when associated pulmonary involvement, soft tissue mediastinal mass, and lytic bone lesions were found. Pericardiectomy and lung biopsy confirmed the diagnosis of diffuse lymphangiohemangiomatosis. Partial clinical improvement occurred with thalidomide and low-dose radiotherapy, but our patient died from progressive respiratory failure.</p> <p>Conclusion</p> <p>Diffuse lymphangiohemangiomatosis should be considered in the differential diagnosis of hemorrhagic pericardial effusion of unclear cause.</p

IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia

IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r). Patients with B-ALL and IKZF1 deletion (n = 133) were included. IKZF1 ∆1-8 were associated with large alterations within chromosome 7: monosomy 7 (18%), isochromosome 7q (10%), 7p loss (19%), and interstitial deletions (53%). The latter included COBL-r, which were found in 12% of the IKZF1 ∆1-8 cohort. Patients with COBL-r are mostly classified as intermediate cytogenetic risk and frequently harbor ETV6, PAX5, CDKN2A/B deletions. Overall, 56% of breakpoints were located within COBL intron 5. Cryptic recombination signal sequence motifs were broadly distributed within the sequence of COBL, and no enrichment for the breakpoint cluster region was found. In summary, a diverse spectrum of alterations characterizes ΔIKZF1 and they also include deletion breakpoints within COBL. We confirmed that COBL is a hotspot associated with ΔIKZF1, but these rearrangements are not driven by RAG-mediated recombination

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

Epigenetic regulation of cathepsin L expression in chronic myeloid leukemia

The expression and significance of cathepsin L (CTSL) has been extensively studied in solid tumours. However no such information in chronic myeloid leukaemia (CML) was available. We investigated the activity and expression of this protease in peripheral blood mononuclear cells (PBMCs) of 47 adult CML patients. Thirty adults suffering from systemic diseases and 50 healthy volunteers served as controls. The mRNA levels of CTSL, its specific endogenous inhibitor cystatin C and transcriptional up-regulator vascular endothelial growth factor (VEGF) were quantitated by real-time qPCR. CTSL protease activity and its mRNA expression were significantly higher in CML chronic phase (CP) patients compared to CML accelerated phase/blast crisis (AP/BC) patients and controls (P ≤ 0.001). VEGF whose expression was most pronounced in CP and declined (P ≤ 0.001) in the advanced phases of the malignancy exhibited a strong positive correlation with CTSL expression (r= 0.97; P ≤ 0.001). Cystatin C expression was significantly lower (P ≤ 0.001) in CML and displayed inverse correlation with CTSL (r=−0.713; P ≤ 0.001) activity. CTSL promoter was significantly hypomethylated in CML CP compared to CML AP/BC patients as well as controls. K562, a BC CML cell line displayed CTSL activity, expression and methylation status of CTSL promoter that was comparable to CML AP/BC patients. Treatment of these cells or PBMCs isolated from CML AP/BC patients with 5'-aza-cytidine resulted in a dramatic increase in CSTL activity and/or expression thereby demonstrating the role of promoter methylation in the stage specific expression of CTSL in CML. Differential expression of CTSL in CML at various stages of malignancy may prove useful in identification of the high-risk patients thereby facilitating better management of disease

Giant recurrent retroperitoneal liposarcoma presenting as a recurrent inguinal hernia

Retroperitoneal liposarcoma presenting as an inguinal hernia is a rare entity. We present the first case of Giant recurrent liposarcoma presenting as a recurrent inguinal hernia in a 40-year-old male. Physical examination showed an irreducible lump in the right inguinal region and a scar in the right lumbar and right inguinal region. Computed tomography (CT) scan of abdomen revealed it to be a retro peritoneal mass extending into the right inguinal region along and involving the cord structures. Wide local excision of the tumour with right orchidectomy and inguinal hernioplasty was performed. Histo-pathology confirmed it to be a liposarcoma. Patient received postoperative radio therapy. Follow up of two years has shown him to be disease free. Retroperitoneal liposarcoma can grow along cord structures into the inguinal canal and mimic an irreducible indirect inguinal hernia

Superior vena cava syndrome and poor performance status at presentation affect survival in mediastinal T-lymphoblastic lymphoma-a single institute experience from India

Analysis of mediastinal T-lymphoblastic lymphomas (T-LBL) with T-acute lymphoblastic leukemia has precluded identification of prognostic factors. Newly diagnosed T-LBL patients presenting with mediastinal mass and &#60;20 % bone marrow involvement were analyzed for clinical features and outcome. In 55 patients with median age 18 years, 39 (71 %) had “B” symptoms, 46 (83.6 %) had bulky mediastinal mass and two thirds of patients (n = 36) had superior vena cava syndrome/superior mediastinal syndrome (SVCS/SMS). With acute lymphoblastic leukemia (ALL)-like protocols in majority, complete remission was achieved in 58.2 % patients. Estimated 5-year overall survival (OS) and event-free survival (EFS) were 59.8 and 51.6 % (median follow-up—35 months). On multivariate analysis, poor Eastern Cooperative Oncology Group (ECOG) performance status (PS &#62; 2; n = 14) affected OS (p = 0.007), while Poor ECOG PS and SVCS/SMS affected EFS (p = 0.008 and p = 0.035, respectively). Combination of baseline-poor PS and presence of SVCS/SMS predicted poor EFS in a prognostic model (HR 6.20; p = 0.002). This is the first outcome study from Asia which has been able to predict baseline ECOG PS and presence of SVCS/SMS as prognostic factors affecting EFS