Manish Butte

HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN PREGNANT AND POSTPARTUM WOMEN.

Wiad Lek. 2020;73(9 cz. 1):1844-1847

Authors: Obuchowska A, Kamiński M, Kimber-Trojnar Ż, Grzesik P, Standyło A, Turżańska K, Leszczyńka-Gorzelak B

Abstract
OBJECTIVE: Introduction: Haemophagocytic lymphohistiocytosis (HLH) is an extremely rare, life-threatening disease, caused by uncontrolled activation of lymphocytes T and macrophages. This situation leads to cytokine storm, infiltration and internal organs failure. HLH can be categorised into either primary (familiar) or secondary which may be associated with infections, immunodeficiency syndromes, autoimmune diseases and malignancy. The secondary HLH is difficult to diagnose due to nonspecific symptoms and complicated differential diagnostics. The aim: To conduct a comparative analysis of pregnant and puerperal patients diagnosed with HLH.
PATIENTS AND METHODS: Material and methods: Review of available literature on haemophagocytic lymphohistiocytosis during pregnancy and the puerperium.
RESULTS: Results: Review of the latest literature shows that HLH can occur at any time during pregnancy and in the puerperium. Symptoms of the disease are non-specific: fever not responding to antibiotic therapy, sometimes hectic, hepatosplenomegaly, swelling, lymphadenopathy, disseminated intravascular coagulation, multi-organ failure and death. In laboratory tests, worsening bicytopenia or pancytopenia, increasing indicators of organ damage, hypertriglyceridemia, hypofibrinogenemia and abnormally high serumferritin levels are observed.
CONCLUSION: Conclusions: HLH, due to non-specific symptoms and rarity, is often overlooked in the diagnostic process. Due to the high mortality and morbidity rates of HLH during pregnancy for mother and foetus, timely diagnosis and the inclusion of specialist treatment are particularly important. An interdisciplinary approach to the patient is necessary to make an accurate diagnosis. The assessment of serum ferritin concentrations facilitates diagnosis. The bone marrow is essential to diagnosis and should be performed as early as possible.

PMID: 33099527 [PubMed – in process]

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Primary hypoparathyroidism in a patient with common variable immunodeficiency associated enteropathy.

Rom J Intern Med. 2020 Oct 23;:

Authors: Ismayilov R, Simsir IY, Akyol D, Ardeniz FO

Abstract
BACKGROUND: Common variable immunodeficiency (CVID) is a rare disease characterized by humoral immunodeficiency, often causing sinopulmonary and gastrointestinal infections, and may cause enteropathy in some patients, which leads to severe malnutrition and electrolyte deficiencies. Although many autoimmune diseases are seen with increased frequency in CVID patients, primary hypoparathyroidism is extremely rare.
CASE PRESENTATION: A 50-year-old man with CVID presented with diarrhea. The patient had complaints for 2 years and was cachectic. He had severe electrolyte and vitamin deficiencies that did not respond to oral treatment. The diarrhea causes such as celiac, inflammatory bowel diseases, and gastrointestinal infections were excluded and the endoscopy showed enteropathic changes in the duodenum and colon. Concomitant hypoparathyroidism was also detected in the patient with hypocalcemia despite adequate replacement.
CONCLUSION: Parenteral therapy should be considered in the management of CVID enteropathy cases that do not respond to oral replacement. Although very rare, hypoparathyroidism should be considered in the differential diagnosis of CVID patients with treatment-resistant hypocalcemia.

PMID: 33098635 [PubMed – as supplied by publisher]

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Renal Infiltration as a Primary Presentation of Burkitt Lymphoma Secondary to Systemic Lupus Erythematosus: A Rarity Unto a Rarity.

Cureus. 2020 Sep 17;12(9):e10512

Authors: Irshad Y, Tariq EF, Asif H, Anwar MM, Khan UA

Abstract
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin B-cell lymphoma characterized by the translocation and deregulation of the MYC (MyeloCytomatosis) gene on chromosome 8. Three distinct clinical forms of BL are recognized: endemic (African), sporadic (non-endemic), and immunodeficiency-associated. Bilateral renal infiltration leading to acute kidney injury (AKI) is a rare initial presentation of BL. Diagnosis is usually made after evaluating the histology and immunophenotyping of the affected tissue. We report a case of a 46-year-old male who presented with symptoms of AKI resulting from infiltrative disease, a primary presentation of lymphoma. The patient was a known case of systemic lupus erythematosus (SLE) for the last five years and was referred to the nephrology department due to acute elevation in creatinine, from 0.8 mg/dL to 3.57 mg/dL. On physical examination, there was no lymphadenopathy. Nephrology and SLE workup revealed low complement protein levels and absolute neutrophils, lymphocytes, and metamyelocytes. Renal ultrasound (USG) showed both kidneys with symmetric and edematous appearance. Biopsy affirmed high-grade B-cell lymphoma, positive for BCL-6 (B-cell leukemia/lymphoma) and CD-10 (cell surface marker) and negative for BCL-2 (B-cell leukemia/lymphoma). PET (positron emission tomography) scan showed extensive hypermetabolic lymphadenopathy in multiple areas. The patient was started on chemotherapy and on continuous renal replacement therapy. He improved clinically, and his creatinine lowered down to 0.8 mg/dL. Repeat USG showed decreased edematous appearance of both kidneys. Primary renal infiltration by BL is a rare presentation in adults. Prompt renal biopsy will change the course of treatment and can affect the prognosis. It is thoroughly advised to keep this malignancy in mind when making a diagnosis for AKI.

PMID: 33094053 [PubMed]

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Haploidentical Stem Cell Transplant With Post-transplant Cyclophosphamide for Chediak-Higashi Syndrome: A Very Rare Case Report.

J Pediatr Hematol Oncol. 2020 Oct 21;:

Authors: Sachdev M, Bansal M, Chakraborty S, Hamal S, Bhargava R, Dua V

Abstract
Chediak-Higashi syndrome is a rare immunodeficiency disorder for which hematopoietic stem cell transplant (HSCT) is the only curative treatment option. HSCT only corrects the hematological and immunologic manifestations of the disease but neurological complications may still progress after transplant. Haploidentical HSCT (haplo-HSCT) has evolved as a feasible alternative for patients with primary immunodeficiency. More recently, there has been use of haplo-HSCT with post-transplant cyclophosphamide. However, only 4 cases of Chediak-Higashi syndrome have been reported using this approach. Here, the authors describe a case of a 17-month-old boy who was successfully treated by haplo-HSCT with reduced-toxicity conditioning (fludarabine/treosulfan/melphalan) and post-transplant cyclophosphamide.

PMID: 33093354 [PubMed – as supplied by publisher]

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Early-onset autoimmunity associated with SOCS1 haploinsufficiency.

Nat Commun. 2020 Oct 21;11(1):5341

Authors: Hadjadj J, Castro CN, Tusseau M, Stolzenberg MC, Mazerolles F, Aladjidi N, Armstrong M, Ashrafian H, Cutcutache I, Ebetsberger-Dachs G, Elliott KS, Durieu I, Fabien N, Fusaro M, Heeg M, Schmitt Y, Bras M, Knight JC, Lega JC, Lesca G, Mathieu AL, Moreews M, Moreira B, Nosbaum A, Page M, Picard C, Ronan Leahy T, Rouvet I, Ryan E, Sanlaville D, Schwarz K, Skelton A, Viallard JF, Viel S, Villard M, Callebaut I, Picard C, Walzer T, Ehl S, Fischer A, Neven B, Belot A, Rieux-Laucat F

Abstract
Autoimmunity can occur when a checkpoint of self-tolerance fails. The study of familial autoimmune diseases can reveal pathophysiological mechanisms involved in more common autoimmune diseases. Here, by whole-exome/genome sequencing we identify heterozygous, autosomal-dominant, germline loss-of-function mutations in the SOCS1 gene in ten patients from five unrelated families with early onset autoimmune manifestations. The intracellular protein SOCS1 is known to downregulate cytokine signaling by inhibiting the JAK-STAT pathway. Accordingly, patient-derived lymphocytes exhibit increased STAT activation in vitro in response to interferon-γ, IL-2 and IL-4 that is reverted by the JAK1/JAK2 inhibitor ruxolitinib. This effect is associated with a series of in vitro and in vivo immune abnormalities consistent with lymphocyte hyperactivity. Hence, SOCS1 haploinsufficiency causes a dominantly inherited predisposition to early onset autoimmune diseases related to cytokine hypersensitivity of immune cells.

PMID: 33087723 [PubMed – in process]

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Haploidentical transplantation in pediatric non-malignant diseases: a retrospective analysis on behalf of the Spanish Group for Hematopoietic Transplantation (GETH).

Eur J Haematol. 2020 Oct 21;:

Authors: Torres Canizales J, Ferreras C, Pascual A, Alonso L, Regueiro A, Plaza M, Pérez Hurtado JM, Benito A, Couselo JM, Fuster JL, Díaz-Almirón M, Bueno D, Mozo Y, Gómez López A, Vicario JL, Balas A, Sisinni L, de Heredia CD, Pérez-Martínez A

Abstract
OBJECTIVE: Describe the GETH haploidentical stem cell transplantation (haplo-HSCT) activity in non-malignant disease (NMDs).
METHODS: We retrospectively analyzed data from children with NMDs who underwent haplo-HSCT.
RESULTS: From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo-HSCT through ex vivo T-cell-depleted (TCD) graft platforms or post-transplantation cyclophosphamide (PT-Cy) at 7 Spanish centers. Five cases employed unmanipulated PT-Cy haplo-HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+ CD19+ depletion, TCRαβ+ CD19+ selection or naive CD45RA+ T-cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo-HSCT, and bone marrow was the source for one PT-Cy haplo-HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis and thalassemia. The 1-year cumulative incidence of graft failure was 27.4%. The 1-year III-IV acute graft-versus-host disease (GvHD) and 1-year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2-year overall survival was 44.9% for PIDs, and the 2-year graft-versus-host disease-free and relapse-free survival rate was 37.6% for the other NMDs. The transplantation-related mortality at day 100 was 30.8%.
CONCLUSION: Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise.

PMID: 33084101 [PubMed – as supplied by publisher]

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TPPP3 Associated with Prognosis and Immune Infiltrates in Head and Neck Squamous Carcinoma.

Biomed Res Int. 2020;2020:3962146

Authors: Yang Z, Li X, Li J, Su Q, Qiu Y, Zhang Z, Zhang L, Mo W

Abstract
Tubulin polymerization promoting protein family member 3 (TPPP3) is a kind of protein that can mediate the dynamics and stability of microtubules. However, the correlations of TPPP3 between prognosis and immune infiltrates in different tumors are still unclear. The analysis of TPPP3 expression was performed via Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) website. We also used GEPIA to assess the impact of TPPPT3 on clinical outcomes. The related pathways involved in TPPP3 were analyzed by gene-set enrichment analysis (GSEA), and the correlation between TPPP3 and immune infiltration was studied by Tumor Immune Estimation Resource2.0 (TIMER 2.0). The TPPP3 expression was significantly reduced in head and neck squamous carcinoma (HNSC) compared to adjacent tissues. In addition, the low expression of TPPP3 in HNSC was significantly associated with prognosis. The pathways closely related to the low expression of TPPP3 are “Antigen Processing and Presentation,” “Primary Immunodeficiency,” and so on. The TPPP3 expression was negatively correlated with the level of CD8+ T cell, B cell, and myeloid dendritic cell infiltration in HNSC. The TPPP3 expression is closely related to multiple immunomarkers in CD8+ T cell and Myeloid dendritic cells. These data indicate that TPPP3 is associated with multiple cancers and involves multiple immune-related pathways, and TPPP3 is associated with immune infiltration levels. Besides, the TPPP3 expression may help regulate tumor-associated CD8 + T cells, DC cells in HNSC. We conclude TPPP3 can be considered as a biomarker for predicting head and neck squamous cell carcinoma prognosis and immune infiltration.

PMID: 33083464 [PubMed – in process]

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Hematopoietic stem cell transplantation positively affects the natural history of cancer in Nijmegen breakage syndrome.

Clin Cancer Res. 2020 Oct 20;:

Authors: Wolska-Kusnierz B, Pastorczak A, Fendler W, Wakulinska A, Dembowska-Baginska B, Heropolitanska-Pliszka E, Piatosa B, Pietrucha B, Kalwak K, Ussowicz M, Pieczonka A, Drabko K, Lejman M, Koltan S, Gozdzik J, Styczynski J, Fedorova A, Miakova N, Deripapa E, Kostyuchenko L, Krenova Z, Hlavackova E, Gennery A, Sykora KW, Ghosh S, Albert MH, Balashov D, Eapen M, Svec P, Seidel MG, Kilic SS, Tomaszewska A, Wiesik-Szewczyk E, Kreins A, Greil J, Buechner J, Lund B, Gregorek H, Chrzanowska K, Mlynarski W

Abstract
PURPOSE: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematological malignancies.
EXPERIMENTAL DESIGN: We describe the natural history of NBS, including cancer incidence, risk of death and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency.
RESULTS: Among two hundred forty-one (n=241) patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were diagnosed with cancer. Incidence rates for primary and secondary cancer, tumor characteristics, and risk factors affecting overall survival (OS) were estimated. The cumulative cancer incidence was 40.21% ±3.5% and 77.78% ±3.4% at 10 years and 20 years of follow-up, respectively. Most of the tumors n=95 (62.9%) were non-Hodgkin lymphomas. Overall, 20 (13.2%) secondary malignancies occurred at a median age of 18 (IQR, 13.7-21.5) years. The probability of 20-year overall OS for the whole cohort was 44.6±4.5%. Patients who developed cancer had a shorter 20-year OS than those without malignancy (29.6% vs. 86.2%; p<10-5). Forty-nine NBS patients underwent HSCT, including fourteen patients transplanted before malignancy. NBS patients with diagnosed cancer who received HSCT had higher 20-year OS than those who did not (42.7% vs. 30.3%; p=0.038, respectively). Among patients who underwent pre- emptive transplantation, only one patient developed cancer, which is 6.7 times lower as compared to non-transplanted patients (incidence rate ratio 0.149 (95% CI: 0.138-0.162), p<0.0001).
CONCLUSIONS: There is a beneficial effect of HSCT on the long-term survival of NBS patients transplanted in their first complete remission of cancer.

PMID: 33082212 [PubMed – as supplied by publisher]

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