Lymphoreticular Malignancies Research Articles

Neurologic Complications in Patients With Lymphoreticular Malignancy: A Descriptive Cohort Study.

The objectives of this study were to study the spectrum of neurologic complications in children with lymphoreticular malignancy (acute lymphoblastic leukemia, Hodgkin, and non-Hodgkin lymphoma) at diagnosis and during treatment and to determine the etiology of these complications. In this descriptive cohort study, conducted between November 2018 and March 2020, 204 children with a diagnosis of lymphoreticular malignancy were enrolled. The baseline investigations were done in all the cases. Those who developed neurological symptoms were evaluated with cerebrospinal fluid examination and radiologic and electrophysiologic studies as per indication and were managed according to standard management guidelines. Of the 204 patients, 30 (14.7%) developed neurological complications. The majority of these complications (n=20/30; 87%) occurred during the intensive chemotherapy period. Common complications included acute methotrexate neurotoxicity (n=7), vincristine-induced neurotoxicity (n=7), central nervous system (CNS) relapse (n=4), and posterior reversible encephalopathy syndrome (n=2). L-asparaginase-induced thrombosis (n=1), intramedullary compression syndrome (n=1), CNS infection (n=2), CNS hemophagocytic lymphohistiocytosis (n=1), and steroid-induced myopathy (n=1) were also observed. The complications resolved in 21/30 (70%) patients after receiving appropriate treatment while the neurological complication persisted in 2/30 (6.7%) patients. Three patients (10%) abandoned the treatment, and 4 (13.3%) patients expired. Neurologic complications in patients with lymphoreticular malignancy are quite variable, having common presenting symptoms but varying imaging abnormalities. By close follow-up and effective treatment, the morbidity and mortality of these complications can be minimized.

Role of Flow Cytometry in Diagnosis of Non-Hodgkin’s Lymphoma: A Study at RIMS, Ranchi, India

Purpose: Non-Hodgkin’s lymphomas (NHL) are cancers of mature B, T and NK cells. Diagnosis of NHL is based on immunophenotyping by immunohistochemistry of excised lymph node or flow cytometric immunophenotyping. FNA cytology with immunolabelled flow cytometry can in some circumstance serve as a replacement of open biopsy and conventional histology and immunohistochemistry. Method: The present study consisted of 52 patients suffering from lymphoreticular malignancies who attended and/or were admitted in the Rajendra Institute of Medical Sciences, Ranchi, during the period from March 2020 to August 2021. Results: Out of 54 cases suspicious of Lymphoreticular malignancy, 2 were found to be non-lymphoid origin by flow cytometry of fine needle aspirate and sample collection was inadequate in 3 cases (5.5%). On Immunophenotyping, 44 cases (88%) were found to be B-NHL and 5 cases (10%) were T-NHL. Furthermore, it was sublassified as DLBCL 16 cases (32.6%), FL 6 cases (12.2%), MZBCL 3 cases (6.1%), CLL/SLL 5 cases (10.2%), MCL 2 cases (4.08%), Unclassified B-NHL 12 cases (20.3%) and Mature T cell NHL 5 cases (10.2%). Conclusion: Flowcytometry can be a great tool in diagnosis and classification of NHL and can be used alternatively to conventional excisional Lymph node biopsy and immunohisto-chemistry. Keywords: Flow cytometry, immunophenotyping, Non Hodgkin’s Lymphoma, FNA cytology

Predictors of Candidemia during Febrile Episode in Lymphoreticular Malignancy Affecting Paediatric Population.

Limited studies on candidemia in malignancy in the paediatric population from developing countries show a high incidence, high morbidity and a unique epidemiology as compared to developed nations. Our prospective observational study aimed to explore the prevalence of invasive candidiasis, especially candidemia, in febrile paediatric patients with lymphoreticular malignancy. A sample size of 49 children, with 100 recorded febrile episodes was studied. The relevance of candida colonization and mannan antigen detection as indicators of impending candidemia was evaluated. Genotypic identification of the yeast isolates was followed by sequence analysis using the NCBI-BLAST program, and the generation of the phylogenetic tree using MEGA 6.0 software. We observed a 5% prevalence of candidemia among febrile paediatric patients with lymphoreticular malignancy, predominantly caused by non-albicans candida. Colonization at multiple anatomical sites decreased from day 1 to day 8 of febrile episodes. Significant candida colonization (colonization index ≥0.5) was seen in a larger proportion of candidemia patients on day 1 and day 4 (p < 0.001) displaying a definite association between the two. The receiver operator characteristic (ROC) curve analysis for mannan antigen level revealed a cut-off of ≥104.667 pg/mL, suitable for predicting candidemia with a sensitivity of 100%, specificity of 92% and area under ROC value of 0.958 (95% CI: 0.915-1; p < 0.001). A phylogenetic tree with three population groups, clade 1, 2 and 3, consisting of Candida auris (1), Candida tropicalis (2) and Candida parapsilosis (2), respectively, was generated. The diagnosis of candidemia based on mannan antigen detection gives early results and has high negative predictive values. It can be combined with other biomarkers to increase sensitivity, specificity and positive predictive value.

Study of Extramedullary Lymphoblastic Lymphoma (LBL) Diagnosed by Flowcytometric Immunophenotyping (FCI) on Fine Needle Aspirate (FNA) Sample-A Case Series of 18 Cases.

Lymphoblastic lymphoma (LBL) accounts for about 2% of all lymphomas. Recognition of T/B-LBL albeit of their rareness is very important as they present as localized diseases with low tumor burden. They can present both at nodal and extranodal sites. Limitation of diagnosis and classification of lymphoma on fine needle aspirate (FNA) can be minimized by clubbing it with flowcytometric immunophenotyping (FCI) to ensure diagnostic accuracy rapidly. Study of a series of 18 cases of LBL to assess the utility of FCI on FNA and effusion samples in extramedullary LBL. FCI was done on FNA and effusion samples from 130 morphologically diagnosed/suspicious cases of lymphoreticular malignancy, followed by peripheral blood and bone marrow (BM) examination. The patients diagnosed to have B/T LBL, based on WHO 2017 classification, were selected for further analyses. FCI of 130 cases showed 91 mature and 18 precursor lymphoid neoplasms. These 18 cases were from lymph nodes (11), pleural fluid (03), and soft tissue masses (04). Peripheral blood and BM of 15/18 cases were normal of which FCI revealed T-LBL (11) and B-LBL (04). Two cases (both T LBL) showed BM involvement (<25%), while one case of B-LBL which was misdiagnosed as mature lymphoma by immunohistochemistry (IHC) evolved as B ALL. Diagnosis of extramedullary B/T-LBL needs comprehensive evaluation of clinical presentation, cytomorphology, and immunophenotyping. Rapid and accurate diagnosis by FCI on FNA and effusion samples allows early therapeutic decisions, thereby avoiding leukemic dissemination.

P399 Diagnostic value of Candida coloni zation index and serum Candida mannan antigen for candidemia in febrile episodes of pediatric lymphoreticular malignancies

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjective: To evaluate the diagnostic performance of Candida colonization index and serum Candida mannan antigen predicting candidemia in febrile episodes of pediatric lymphoreticular malignanciesMethodsIt was a prospective observational study done for 18 months, from November 2018 to April 2020 at the pediatric oncology unit of a multispecialty tertiary care center. Based on our patient load, duration of the proposed study, and available resources, a sample size of 49 (n = 49) was decided and 100 febrile episodes in children with lymphoreticular malignancy were studied. Children below 12 years, receiving chemotherapy for hematological malignancy having oral or axillary temperature ˃38.3°C for ˃1 h were included in this study. Children receiving the antifungal treatment in last 7 days were excluded from the study. Blood collected on day1 and day4 was cultured in BACTEC-9120. For colonization, swabs and samples were collected and cultured on SDA on day1, day4, and day8. All Candida isolates were subcultured on SDA and subjected to Gram's stain, germ tube test followed by Microscan identification. DNA sequencing followed by phylogenetic analysis was done for all the isolates of Candida recovered from blood. Antifungal susceptibility of yeast stains was done. Serum collected on day1 was used for C. mannan antigen detection using ELISA system.ResultsPrevalence of candidemia was 5%. Non-albicans Candida spp were isolated from blood cultures on day 4. Candida colonization decreased from day1 to day8. Colonization index (CI) day1 showed 80% sensitivity 98.9% specificity, and 98.9% negative predictive value. Significant colonization (CI ≥0.5) was seen in a larger proportion of cases that developed candidemia. There was a significant association of Candida colonization (CI ≥0.5) with occurrence of candidemia on day1 and day4. A total of 4 (80%) of candidemia episodes were positive for serum mannan antigen while 1 (20%) was negative. Mannan antigen was detected earlier with 80% sensitivity, 92.6% specificity, and 98.9% negative predictive value. All Candida isolates were sensitive to fluconazole, amphotericin-B, and caspofungin.Receiver operator characteristic curves for diagnostic performance of various parameters in predicting candidemia show the following trends:Best parameter in terms of AUROC is the CI (Day 1).Best parameters in terms of sensitivity are the CI (Day 1), CI (Day 4), and mannan antigen level.Best parameter in terms of specificity is the CI (Day 8).Best parameter in terms of positive predictive value is the CI (Day 1).Best parameters in terms of negative predictive value are the CI (Day 1), CI (Day 4), and mannan antigen level.Best parameters in terms of diagnostic accuracy are the CI (Day 1), CI (Day 8).ConclusionThe CI can predict candidemia but the threshold value needs to be explored in pediatric patients with lymphoreticular malignancies. Mannan antigen detection gives early results with a high negative predictive value.

Deficiency of Human Adenosine Deaminase Type 2 - A Diagnostic Conundrum for the Hematologist.

Deficiency of adenosine deaminase type 2 (DADA2) was first described in 2014 as a monogenic cause of polyartertitis nodosa (PAN), early onset lacunar stroke and livedo reticularis. The clinical phenotype of DADA2 is, however, very broad and may involve several organ systems. Apart from vasculitis, children may present with i) Hematological manifestations (ii) Lymphoproliferation and iii) Immunodeficiencies. Patients with DADA2 can have variable patterns of cytopenias and bone marrow failure syndromes. Patients with DADA2 who have predominant haematological manifestations are associated with ADA2 gene variants that result in minimal or no residual ADA2 activity. Lymphoproliferation in patients with DADA2 may range from benign lymphoid hyperplasia to lymphoreticular malignancies. Patients may present with generalized lymphadenopathy, splenomegaly, autoimmune lymphoproliferative syndrome (ALPS) like phenotype, Hodgkin lymphoma, T-cell large granular lymphocytic infiltration of bone marrow and multicentric Castleman disease. Immunodeficiencies associated with DADA are usually mild. Affected patients have variable hypogammaglobulinemia, decrease in B cells, low natural killer cells, common variable immunodeficiency and rarely T cell immunodeficiency. To conclude, DADA2 has an extremely variable phenotype and needs to be considered as a differential diagnosis in diverse clinical conditions. In this review, we describe the evolving clinical phenotypes of DADA2 with a special focus on haematological and immunological manifestations.

Coronavirus disease 2019-associated mucormycosis in children

Background Coronavirus disease 2019 (COVID-2019) was declared as a pandemic on March 11, 2020 by the WHO. This disease was complicated by its association with an opportunistic fungal infection, termed as COVID-19-associated mucormycosis (CAM). CAM is well described in adults, but only a few case reports and series were published about pediatric CAM. Objectives This systematic review aimed to describe the clinical spectrum and outcome of CAM cases in children. Patients and methods A systematic review of literature was done in agreement with PRISMA guidelines to understand the clinical profile of pediatric CAM. Pubmed, Scopus, Google Scholar databases, and news websites were searched to identify any relevant article on pediatric CAM.. References within the included articles were reviewed. All articles that met the criteria were analyzed for demographics, clinical, laboratory, radiographic, treatment, and outcome data. Results We retrieved a total of 13 cases of pediatric CAM, which were included in this systematic review. The mean age at presentation was 11.6 years (range, 5–16 years). Diabetes mellitus was the underlying cause in four cases, whereas three of them presented with diabetic ketoacidosis. Five children were immunocompromised, which included two cases of acute lymphoreticular malignancy. Rhinocerebral, orbital, and gastrointestinal mucormycosis was seen in three, two, and one case, respectively. Out 13 cases, two succumbed to the illness. Conclusion Most children with CAM had definite underlying risk factors like diabetes mellitus, lymphoreticular malignancies, and immunodeficiency status. The clinical presentation and outcome in children were similar to adults.

Lymphoreticular malignancies in serous effusions: Cytomorphologic, flow cytometric and immunocytochemical analysis.

Involvement of body fluids by lymphoreticular malignancies (LRM) is rare and often associated with poor prognosis and decreased overall survival. The present study was conducted to analyze the characteristic cytomorphologic, flow cytometric and immunocytochemical features of LRMs in serous effusions. This was a three-year retrospective study. A total of 218 effusion samples, reported as involved by lymphoreticular malignancies, on cytology, were reviewed. All the cases wherein the cytological diagnosis was confirmed by flow cytometric (FCM) and/or immunocytochemical (ICC) studies were retrieved and studied in detail. FCM and/or ICC were performed in a total of 51/218(23.4%) samples, including 30 pleural (58.8%), 18 peritoneal (35.3%), and 3 pericardial fluid (5.9%) samples. The cytomorphologic diagnoses included infiltration by non-Hodgkin lymphoma (NHL;n = 27), infiltration by LRM (n = 19), infiltration by chronic lymphocytic leukemia (CLL;n = 2), Hodgkin's lymphoma (HL;n = 1) and suggestive of infiltration by LRM (n = 2). FCM and/or ICC confirmed the diagnoses as infiltration by T-cell lymphoblastic lymphoma in 18; mature B-cell NHL in 10; Burkitt lymphoma in 7; diffuse large B-cell lymphoma in 4; follicular lymphoma, T- cell NHL and CLL in 2 samples each and hairy cell leukemia, plasmablastic lymphoma and HL in 1 sample each. 94.1% concordance was noted between the initial and final cytologic diagnosis. Involvement of body fluids and effusions by LRMs, though rare, carries an immense prognostic significance and hence the prompt detection is crucial. Detection of these malignancies by cytologic examination of effusions is challenging yet potentially useful and the least invasive method available to establish an early diagnosis.

Clinical profile and management of dengue in lymphoreticular malignancy- A case series

Clinical profile and management of dengue in lymphoreticular malignancy- A case series

Procalcitonin Clearance, CD64, and HLA-DR as Predictors of Outcome in Febrile Neutropenic Children With Lymphoreticular Malignancies.

Febrile neutropenia (FN) is a dreaded complication of cancer chemotherapy. There has been a lot of improvement in supportive care in FN that has drastically reduced the infection-related mortality in these patients. The focus now is on reducing infection-related morbidity, healthcare costs and optimizing the quality of life of the child as well as their family during these episodes. In this study, biomarkers were studied as predictors of outcome so that outcome can be predicted earlier, and treatment modified accordingly. To measure procalcitonin levels (at baseline and day 3), procalcitonin clearance, neutrophil CD64 expression levels (at baseline) and monocyte HLA-DR expression levels (at baseline), and their correlation with outcome. Tertiary care hospital. Cross-sectional observational study. Sixty-five episodes of FN in children below 12 years with lymphoreticular malignancies. Children receiving antibacterial and/or antifungal treatment within the last 7 days were excluded from the study. The subjects recruited into the study had undergone complete clinical and laboratory evaluation as per hospital protocol. Procalcitonin (day 0 and 3), neutrophil CD64 expression, and monocytic HLA-DR expression levels were measured in these patients. Sixty-five episodes of FN were studied in children with lymphoreticular malignancy. It was found that procalcitonin and HLA-DR are very good markers of outcome, whereas CD64 although a good marker, was inferior to procalcitonin and HLA-DR in predicting outcome. Procalcitonin clearance was found to be superior to single value of procalcitonin. Furthermore, procalcitonin on day 3 was found to be a better predictor of outcome compared with its baseline value. Also, it was found that procalcitonin and HLA-DR had a significant correlation with baseline C-reactive protein levels. On the basis of the findings of the study we suggest that serial monitoring of procalcitonin levels be used in febrile neutropenic children with cancer. Procalcitonin levels on day 3 alone can be offered in resource poor setting. The role of HLA-DR and CD64 also seems promising and needs to be further explored in larger multicentric studies.

Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations

Ligase IV (LIG4) syndrome is a rare disorder of DNA damage repair caused by biallelic, pathogenic variants in LIG4. This is a phenotypically heterogeneous condition with clinical presentation varying from lymphoreticular malignancies in developmentally normal individuals to significant microcephaly, primordial dwarfism, radiation hypersensitivity, severe combined immunodeficiency and early mortality. Renal defects have only rarely been described as part of the ligase IV disease spectrum.We identified a consanguineous family where three siblings presenting with antenatal growth retardation, microcephaly, severe renal anomalies and skeletal abnormalities, including radial ray defects. Autozygosity mapping and exome sequencing identified a novel homozygous frameshift variant in LIG4, c.597_600delTCAG, p.(Gln200LysfsTer33), which segregated in the family. LIG4 is encoded by a single exon and so this frameshift variant is predicted to result in a protein truncated by 678 amino acids. This is the shortest predicted LIG4 protein product reported and correlates with the most severe clinical phenotype described to date. We note the clinical overlap with Fanconi anemia and suggest that LIG4 syndrome is considered in the differential diagnosis of this severe developmental disorder.

Neonatal thymectomy in children—accelerating the immunologic clock?

The thymus is critical for central tolerance and diverse T-lymphocyte repertoire development, to provide lifelong defense against pathogens while maintaining self-tolerance. Peak thymic output occurs in utero, during infancy, and in early childhood, diminishing throughout life. Infants with congenital heart disease requiring sternotomy often undergo thymectomy to clear the surgical field. The long-term effects of early thymectomy are just being appreciated. Many patients remain asymptomatic despite immunologic findings mirroring those of immunosenescence. Few develop increased infection or lymphoreticular malignancy risk. When considering the effects of infant thymectomy, patients with partial DiGeorge syndrome or hypomorphic recombination-activating gene (RAG) mutations may be instructive. These patients are lymphocytopenic, with increased early-onset infection and autoimmunity risk that is not seen in most patients who underwent thymectomy during infancy. The thymic structure of patients with partial DiGeorge syndrome or hypomorphic RAG is abnormal, with disrupted architecture inclining to perturbation of central tolerance. Similar findings may be seen in patients with myasthenia gravis, although disrupted peripheral tolerance may play a greater role in autoimmunity development. In conclusion, thymectomy during infancy may increase future risk of infection or autoimmunity, with premature immunosenescence mediated through disruption of central and peripheral tolerance mechanisms initiated by early cessation or diminution of thymic output. Ideally, some thymic tissue should be preserved at the time of surgery.

HLH Masquerading Lymphoma: Diagnostic Dilemma and Treatment Outcomes.

A case series to illustrate difficulties faced in diagnosis, management and subsequent therapeutic approach patients presenting with HLH secondary to lymphoma. A retrospective review of patients treated for HLH and lymphoma in Clinical Hematology department of a tertiary care hospital in North India, was performed from Jan 2017 to April 2019. Follow up was included till September 2019. Diagnosis of HLH was made using HLH 2004 criteria along with H score. Only patients who fulfilled HLH 2004 criteria were included. Nine patients were treated during above period, three patients with Hodgkins lymphoma, two patients had DLBCL and four patients had T-cell lymphoma. All patients presented with features of HLH and underlying lymphoma was detected on further evaluation. All patients had H score above the cut off value for diagnosis of HLH. Out of 9 patients, 6 received lymphoma directed chemotherapy and 1 was given only steroids, 1 received IVIG with steroids. 1 died early, before institution of therapy. Out of the 6 patients who received chemotherapy, all attained remission status but two patients had early relapse. In the remaining 3 patients who could not be started on chemotherapy, all died within 3weeks of presentation. Underlying lymphoreticular malignancy should be actively searched in adult patients presenting with HLH. Early diagnosis and initiation of disease specific therapy with or without specific HLH directed treatment can improve the historical poor prognosis.

Epidemiology of Gastrointestinal Malignancies in Nigeria:Port Harcourt Cancer Registry Study

Background: Undocumented observations suggest a rising incidence of gastrointestinal tract cancers (GITc) among urban dwellers in Nigeria. Aim: The aim is to report on the incidence and clinic-pathological characteristics of GITc in Port Harcourt and its environs. Materials and Methods: Clinical, pathological, and demographic information on cancer patients obtained from various hospitals, radiology centers, and pathology laboratories within Port Harcourt and Obio-Akpor local government areas of Rivers state between 2008 and 2017 were reviewed. The information was coded using the International Classification of Diseases for Oncology, 3rd Edition and stored in Canreg 4 software in the Port Harcourt cancer registry. Results: GITc constituted the third-most common systemic cancers consisting of 12.2% (328 cases) with a male-to-female ratio of 1.05:1. The annual age-standardized rate ranged between 1.1–21.6/100,000 for females and 1.8–15.9/100,000 for males, with the highest rate recorded in 2017. The mean age was 51.2 ± 15.8 years with bimodal peak age groups of 50–54 and 55–59 years. The most common sites for GITc were colorectal followed by the liver and stomach consisting of 44.5%, 16.5%, and 15.2% of cases, respectively. Epithelial malignancies, i.e., carcinomas markedly predominated over malignancies of other cell types such as mesenchymal cell malignancies, lymphoreticular cell malignancies, and germ cell malignancies and constituted 92.4% of total GITc. Conclusion: GITc is posing a public health challenge in Port Harcourt and environs. A government-sponsored health plan on cancer control, including awareness campaigns on the adoption of more healthy lifestyles, hepatitis B vaccination, colonoscopy screening with prompt treatment, is advocated.

Clinicopathological study of cervical lymphadenopathy at rural tertiary health care centre

Background: The term lymphadenopathy refers to nodes that are abnormal in size, consistency or number. Cervical lymphadenothy is one of the common and important presentations of the underlying pathology of the head and neck region which has large number of differential diagnosis like neoplasms, infections (specific and non-specific) and in immune deficiency disorders and also, the rare disorders like Inflammatory pseudotumour (Plasma cell granuloma) and Kikuchi-Fujimoto diseases. Etiological profile of cervical Lymphadenopathy varies from region to region, in developing countries like India, acute respiratory infection, suppurative skin infection and tuberculosis are the main causes for cervical lymphadenopathy while in developed countries secondary carcinoma are the most frequent causes for cervical lymphadenopathy.Methods: This hospital based cross sectional study was carried out in the Department of Otorhinolaryngology in Rural Tertiary Health Care Centre. The period of the study was from January 2014 to June 2016.Results: In our study of 176 patients the youngest patient was 13year of age and oldest patient was 68 years old. The majority of patients affected were in the age group of 21 to 30 years (30.68%) followed by 13 to 20 years (23.86%). The least affected age group was 60 to 70 years (5.8%). There were 80 men and 96 women. The male to female ratio in present study was 1:1.2 The frequently affected age group was 21 to 30 years in men (26.25%) as well as women (34.38%). In our study Neck swelling was present in all cases (100%). fever was the second most common symptom in 54 cases (30.68%) followed by cough in 45 cases (25.56%). In our study most frequently involved lymph node group was posterior cervical in 68 cases (38.39%), followed by upper deep cervical in 66 cases (37.50%).Conclusions: In the present study it was found that tuberculosis was the most frequent cause of cervical Lymphadenopathy in 48.29% of patients, followed by reactive Lymphadenopathy in 17.34%, metastatic lymphadenopathy in 15.34% chronic nonspecific Lymphadenopathy in 14.77% and primary lymphoreticular malignancy in 4.35%. In our study out of 176 cases of cervical lymphadenopathy 141 cases (80.11%) were non neoplastic and 35 cases (19.88 %) were neoplastic.

Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders

Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150mg/m2 fludarabine or less and 40mg/kg cyclophosphamide or less were used. Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48months (range, 1.5-552months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P=.006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P=.45). Median follow-up was 35months (range, 2-168months). No secondary malignancies were reported during 15years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved. RIC HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended.

Differentiation of secondary involvement of the breast by lymphoreticular malignancy from fibroadenoma using ultrasound elastography: A report of two cases.

Extramedullary lymphoma infiltration of the breast by lymphoblastic lymphoma is very rare and most cases are of B-cell lineage; T-cell neoplasms represent less than 10% of all breast lymphomas. Here, we report one patient with lymphoblastic lymphoma and one patient with leukemia, who have similar lesions in breasts with different ultrasound elastography findings. Ultrasound-guided tru-cut biopsies were performed and the first lesion was confirmed as lymphoma infiltration and the second as fibroadenoma. In cases of breast mass presence in patients with a history of hematologic malignancies such as lymphoma or leukemia, breast infiltration should be kept in mind. Elastography findings can assist in the differentiation of these lesions and further investigations or biopsies can be avoided.

IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo.

To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp and suffer from immunodeficiency with increased risk to develop lymphoreticular malignancies. NK cells from WAS patients fail to form lytic synapses, however, the functional outcome in vivo remains unknown. Here, we show that WASp KO NK cells had decreased capacity to degranulate and produce IFNγ upon NKp46 stimulation and this was associated with reduced capacity to kill MHC class I-deficient hematopoietic grafts. Pre-treatment of WASp KO NK cells with IL-2 ex vivo restored degranulation, IFNγ production, and killing of MHC class I negative hematopoietic grafts. Moreover, WASp KO mice controlled growth of A20 lymphoma cells that naturally produced IL-2. WASp KO NK cells showed increased expression of DNAM-1, LAG-3, and KLRG1, all receptors associated with cellular exhaustion and NK cell memory. NK cells isolated from WAS patient spleen cells showed increased expression of DNAM-1 and had low to negative expression of CD56, a phenotype associated with NK cells exhaustion. Finally, in a cohort of neuroblastoma patients we identified a strong correlation between WASp, IL-2, and patient survival.

An observational study of abdominal organ involvement detected by ultrasound and computed tomography in children suffering from lymphoreticular malignancy at a tertiary care hospital in Eastern India

Abstract Introduction: Abdominal organs are usually involved in lymphoreticular malignancies (LRM), and the detection is crucial for Initial staging, determination of the location and extent of disease, and is the hallmark for the choice of treatment. At present, the established radiological technique for staging Hodgkin's disease is computed tomography (CT) and ultrasonography (USG) in our country. Objective: The objective of the study was to evaluate the pattern of abdominal organ involvement in childhood LRM by USG and CT and to analyze the findings. Methods: The study included 121 children with newly diagnosed childhood LRM who underwent real time USG and contrast enhanced CT scan. The records of the US and CT scanning were analyzed with respect to size, shape, margins, echogenicity/density pattern of various abdominal organs and lymph nodes to evaluate the extent and pattern of abdominal organ involvement by the disease process. Results: Out of 121 cases of LRM, US detected significant portal lymphadenopathy in 9 (7.44%) cases where CT detected enlarged portal nodes in only 3 and missed in 6 cases. However in the retroperitoneal lynphadenopathy CT scored over US, as CT detected 16 (13.22%) cases as against 13 (10.74%) cases detected by US. Conclusion: In our study we observed abdominal organs are commonly involved at the time of initial presentation in childhood LRM, with diffuse organomegaly being commoner than focal lesions. Abdominal symptoms and GIT involvement were also found more common in NHL patients at their initial presentation. There are no characteristic patterns of involvement either on US or CT which are specific to any individual disease entity. Although organomegaly and focal lesions are not diagnostic, but in a known case of childhood LRM these are highly suggestive of involvement by the existing disease process. There is no significant difference in the detection rate of abdominal organ involvement by US and CT in our study. However US being safer and cheaper, US may be suggested as the primary imaging modality to detect abdominal organ involvement in childhood LRM at initial presentation.

Preventive role of carvedilol in adriamycin-induced cardiomyopathy.

Background & objectives:Adriamycin though considered as an effective anticancer drug, leads to irreversible cardiomyopathy (CMP) and congestive heart failure (CHF). The aim of this study was to determine the protective effect of carvedilol in adriamycin (ADR)-induced cardiomyopathy (CMP) in cancer patients.Methods:Patients with lymphoreticular malignancy in whom ADR therapy was planned were randomized into two groups: carvedilol and control. Twenty seven patients each were enrolled in carvedilol and control groups. In the carvedilol group, 12.5 mg once daily oral carvedilol was given during six months. The patients were evaluated by echocardiography before and after chemotherapy. Left ventricular ejection fraction (EF) and systolic and diastolic diameters were calculated.Results:At six months of follow up, six patients in the carvedilol group and five in the control group had died. The mean EF (63.19 vs. 63.88%) and fraction shortening (FS) (34 vs. 34.6) of the carvedilol group were similar at follow up, but in the control group, the mean EF (67.27 vs. 60.82%, P=0.003) and FS (38.48 vs. 34.6, P<0.05) at control echocardiography were significantly lower. In carvedilol group, both systolic and diastolic diameters were not changed, but in control group, systolic diameters were significantly increased compared with basal measures (left ventricular end systolic diameter = 28.26±5.50 mm vs. 31.25± 6.50 mm; P< 0.05).Interpretation & conclusions:Prophylactic use of carvedilol in patients receiving anthracycline protected systolic functions of the left ventricle. Carvedilol can be a potential drug which can ameliorate ADR-induced CMP.