We have analyzed the phenotype, cytokine profile, and mitotic history (telomere length) of monoclonal T-cell expansions in 5 CD3 ؉ T-cell large granular lymphocyte (TLGL) leukemia patients by fluorescence activated cell sorting (FACS) and single-cell polymerase chain reaction (PCR). We confirm that the common phenotype of TLGL leukemia is CD3 ؉ CD8 ؉ CD45RA ؉ CD27 ؊ CD94 ؉ (CD57 ؉ ). Interestingly, the C-type lectin-like type killer cell receptor CD94 was invariably associated with the activating form of its signaltransducing molecule NKG2. Furthermore, when judged by criteria such as interferon gamma (IFN-␥)/tumor necrosis factor (TNF) production, expression of granzyme, FasL, and NKG2D, the TLGL cells had all the features of a cytotoxic effector T cell. Telomere shortening in TLGL cells was in the normal range for CD8 ؉ T cells, indicating that they had not divided significantly more than chronically stimulated CD8 ؉ T cells in healthy individuals. In 25 of 27 controls, cells with a TLGL phenotype occurred at low (1%-3%) frequencies. However, in the other 2 individuals (ages 28-36 years), large stable (> 3 years) monoclonal expansions of CD3 ؉ CD8 ؉ CD45RA ؉ CD27 ؊ CD57 ؉ CD94 ؉ NKG2C ؉ were found which rendered these controls phenotypically indistinguishable from TLGL leukemia patients. We believe that the TLGL clonopathy, rather than being IntroductionLymphoproliferative disorders of large granular lymphocytes (LGLs) are classified as lymphoid neoplasms. 1,2 They are divided into 2 distinct entities: approximately 10% to 20% are of the natural killer (NK) lineage (CD3 Ϫ CD16 ϩ ), whereas the others consist of mature CD3 ϩ T cells expressing either an ␣ or a ␥␦ T-cell receptor (TCR). NK-LGL leukemia is by far the more aggressive form. Most patients have more than 10 ϫ 10 9 /L LGLs in their blood and a significant percentage dies within 2 months after diagnosis. 3 By contrast, CD3 ϩ T-cell LGL (TLGL) leukemia that affects mainly elderly patients progresses in a much milder way. Lymphocytosis is usually modest 4 and many patients may even remain asymptomatic. 3,[5][6][7] Moreover, clinical complications consist primarily of neutropenia or autoimmune features. 8 Therefore, it remains under debate whether this T-cell clonopathy of variable significance 9 should be considered as a malignancy or rather as a secondary reactive phenomenon. 6 Apart from the low malignancy of TLGL leukemia, there are more indications that the clonal expansion is the result of a perhaps rather common dysregulation of CD8 ϩ T cells. In fact, large oligoclonal expansions of CD8 ϩ T cells are quite frequent in elderly people. 10 Such clones that may be maintained by cytokines rather than by antigen 11 are of a phenotype similar to that of normal CD8 ϩ effector T cells of which the clonal size is still controlled through apoptosis. The latter is also true for the TLGL clone. In the majority of patients, these cells are CD8 ϩ CD45RA ϩ CD27 Ϫ , 6,7,12,13 express Fas and FasL,14,15 and may or may not express CD57. 6,7 Therefore, they share m...
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited genetic disorder caused by red cell enzymatic defects and is associated with haemolytic crisis when patients are exposed to oxidative agents (fava beans, drugs, infections).Hydroxychloroquine is suspected to trigger haemolytic crisis in G6PD-deficient patients, and off-label administration of this drug to patients infected with the novel coronavirus (SARS-CoV-2) could cause concern. We report here the first case of severe haemolytic crisis in a patient with G6PD deficiency, initiated by severe COVID-19 infection and hydroxychloroquine use. With worldwide spread of COVID-19, especially in regions with a high prevalence of G6PD deficiency, our case should alert physicians to this possible correlation.
After hematopoietic stem cell transplantation, delayed immune hemolysis may occur when donor-derived B lymphocytes carried with the graft produce immune antibodies against the recipient's incompatible red cells. We report the occurrence of this syndrome in the context of minor blood group incompatibility between donor and recipient after peripheral blood stem cell (PBSC) transplantation. On day 12 post-transplant there was abrupt onset of hemolysis necessitating supportive treatment with hydration and transfusions. Because, as compared to bone marrow, PBSC grafts are enriched with lymphocytes, more frequent and intense delayed immune hemolysis may be anticipated when using PBSC. This complication is described most often when cyclosporine alone is used for immunosuppression following the graft. The addition of methotrexate, which with CyA forms the classic regimen for the prevention of graft-vs-host disease, may diminish the frequence and severity of this adverse reaction.
Geneva University Hospitals, Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and Swiss National Science Foundation.
BackgroundTAFRO syndrome has been reported in Japan among human herpesvirus 8 (HHV-8)-negative/idiopathic multicentric Castleman’s disease (iMCD) patients. To date, the majority of iMCD patients with TAFRO syndrome originate from Japan.Case presentationHerein, we report a 67-year-old HIV/HHV-8-negative Caucasian iMCD patient diagnosed with TAFRO. He presented with marked systemic inflammation, bicytopenia, terminal renal insufficiency, diffuse lymphadenopathies, and anasarca. Lymph node and bone marrow biopsies revealed atrophic germinal centers variably hyalinized and megakaryocytic hyperplasia with mild myelofibrosis. Several other biopsies performed in kidneys, liver, gastrointestinal tract, prostate, and lungs revealed unspecific chronic inflammation. The patient had a complete response to corticosteroids, tocilizumab, and rituximab. He relapsed twice following discontinuation of rituximab. When reviewing the literature, we found seven other Caucasian cases with TAFRO syndrome. There were no significant differences with those described by the Japanese cohort except for the higher frequency of kidney failure and auto-antibodies in Western patients.ConclusionThis case illustrates that patients with TAFRO syndrome can develop non-specific inflammation in several tissue sites. Furthermore, this case and our review of the literature demonstrate that TAFRO syndrome can affect Caucasian and Japanese patients highlighting the importance of evaluating for this syndrome independently of ethnic background.
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