Positive T-cell Research Articles

Long Term Outcome Patterns and Risk Factors for Early Mortality and Disease Progression in ALK-Positive Anaplastic Large Cell Lymphoma

Long Term Outcome Patterns and Risk Factors for Early Mortality and Disease Progression in ALK-Positive Anaplastic Large Cell Lymphoma

False positive T-cell Cytotoxicity crossmatch results suggestive of autoantibodies in Korean Network for Organ Sharing crossmatch tests for deceased donor organ transplantation

False positive T-cell Cytotoxicity crossmatch results suggestive of autoantibodies in Korean Network for Organ Sharing crossmatch tests for deceased donor organ transplantation

Tre-P-05 - Use of mogamulizumab for refractory Sézary syndrome in real clinical practice: report of three cases

Sézary syndrome (SS) is a cutaneous T cell lymphoma (CTLC) with poor prognosis which can present de novo or secondary to mycosis fungoides (MF). We report our experience treating patients with SS with mogamulizumab (n=3). <h3>Case 1:</h3> A 76-year-old woman presented with an 8-year history of refractory erythroderma. Skin biopsy showed dermal lymphocytic infiltrate with aberrant phenotype. Blood flow cytometric analysis detected 77% pathologic T-lymphocytes (TL) with SS phenotype and positive T-cell receptor (TCR) ϒ gene rearrangement. Lymph node biopsy showed SS infiltration. She was diagnosed with stage IVA1 SS (T4N1M0B2). Due to disease progression after treatment with bexarotene, mogamulizumab was started following the usual protocol. Patient achieved complete clinical response (CR) since the 2nd infusion in skin, blood and lymph nodes. She presented grade IV neutropenia after the 6th infusion which resolved with filgastrim, and a grade II lymphopenia after the 5th infusion which resolved with posology spaced to every 6 weeks. Patient continues disease-free after 12 months of treatment. <h3>Case 2:</h3> A 66-year-old woman presented with a 1-year history of erythroderma. Skin biopsies were consistent with MF. Blood flow cytometric analysis detected 59.2% of pathological TL with SS phenotype and positive TCR ϒ gene rearrangement. Lymph node biopsy showed SS infiltration. Diagnosis of stage IVA2 SS (T4N3M0B2) was stablished. She was treated with extracorporeal photopheresis, interferon α-2B, bexarotene and gemcitabine with partial response. Treatment with mogamulizumab was started with complete CR after the 4th infusion in skin, lymph nodes, and blood with good tolerability. She received an allogeneic bone marrow transplant after the 5th cycle and continues disease-free after 100 days post-transplant. CASE 3 A 36-year-old man presented with follicular infiltrated papules and alopecia affecting most of the body surface. Blood flow cytometric analysis showed 93% of pathological TL and positive TCR ϒ gene rearrangement. Skin biopsy was consistent with MF. Lymph nodes showed SS infiltration. Patient was diagnosed with Stage IVA2 SS (T2N3M0B2). He was treated with bexarotene and brentuximab with initial CR but disease progression after 10 cycles. Treatment with mogamulizumab was started with initial improvement but failure after 6 months. Mogamulizumab is a monoclonal antibody that selectively binds to CCR4 present on atypical TL. To date, only a series of 13 patients with CTCL treated with mogamulizumab in clinical practice has been reported, with good tolerability and CR in blood and skin. In our series 2 out of 3 patients presented an impressive CR in all aspects of the disease. One patient developed neutropenia and lymphopenia in relation to mogamulizumab, which resolved after specific treatment. This series supports the use of mogamulizumab in patients with refractory SS. Larger series are needed to evaluate the use mogamulizumab for CTCL in routine clinical practice.

NKp46 Is a Useful Diagnostic Biomarker in Gastrointestinal T-Cell Lymphoproliferative Diseases and Constitutes a Therapeutic Target. a Celac Network Study

Introduction:Primary gastrointestinal (GI) T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which diagnoses and therapeutic options remain to be standardized. Beside aggressive lymphoma, such as enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), the indolent T-cell lymphoproliferative disease (indolent T-LPD) has been recently described. A differential diagnosis to consider is type II refractory coeliac disease (RCDII) that may complicate CD. Intraepithelial lymphocytes (IEL) from RCDII are dependent for survival on IL-15, which reprograms T-lymphocytes towards a cytotoxic NK phenotype. We previously showed that NKp46 is a new biomarker for both diagnosis and prognosis in GI T-LPD (ICML-2017 Lugano, unpublished).Patients and Methods:The expression of NK receptors was assessed on CD/RCD by flow-cytometry. The number of NKp46 positive IEL per 100 epithelial cells (NKp46+ IEL/100 EC) was studied by immunohistochemistry (IHC) on 195 biopsies from 84 CD/RCD, 44 GI T-cell lymphoma, and on a blinded confirmatory cohort of 48 CD/RCD.8B6A-PBD is an anti-NKp46 monoclonal antibody conjugated (ADC) to a potent cytotoxic drug, pyrrolobenzodiazepine (PBD). For in vivo assessment, tumor-bearing NOD-SCID mice were randomly assigned to PBS, isotype-matched irrelevant Ig-PBD controls, or 8B6A-PBD treatment groups. For ex vivo cytotoxicity assays, isolated cells from fresh small bowel biopsies of RCDII patients were incubated with 8B6A-PBD, Ig-PBD, anti-NKp46 deglycosylated or PBD alone.Results:NKp46 was the only NK receptor that differs between RCDII and CD or RCDI. By doing ROC analysis, a number of NKp46+ IEL/100 EC above 25 clearly discriminated RCDII from CD and RCDI, with excellent positive and negative predictive values of 100 and 95% respectively. Among CD and RCD patients, the survival was shorter if this count is above 25 (OS-5years 72.8% vs. 96.4%, P=0.0004). NKp46 was expressed in EATL (n=20/25) and MEITL (n=4/4) but was never expressed in indolent T-LPD (n=0/15). Positive NKp46 GI T-cell lymphoma had a shorter survival compared to negative NKp46 cases (OS-5years 5.4% vs. 50.5%, P=0.0011).In vivo the anti-NKp46-PBD promoted tumor regression (Fig. B) and prolonged survival (Fig. A) of NOD-SCID mice injected by human NKp46-transfected Raji tumors embedded in matrigel. Ex vivo and as a proof of concept, the anti-NKp46-PBD was highly potent (Fig. D) and selective (Fig. C) against NKp46 positive primary sorted IEL (n=5).Conclusion:NKp46 provides a new biomarker for both diagnosis and prognosis in GI T-LPD. We propose a diagnostic algorithm for GI T-LPD based on the NKp46 expression, which is adapted to immediate, individual patient management. Overall, our results demonstrate for the first time that anti-NKp46 ADC may serve as an effective therapy for RCDII, EATL and MEITL and provide strong preclinical rationale for evaluation of 8B6A-PBD in clinical studies. [Display omitted] DisclosuresCheminant:Innate Pharma: Research Funding. Bruneau:Innate Pharma: Research Funding. Malamut:Cellimmune: Research Funding. Pouyet:MI-mAbs: Employment. Lhospice:Innate Pharma: Employment. Molina:Merck Serono: Honoraria; Takeda: Other: travel support to the ASH meeting; Novartis: Honoraria. Cellier:Cellimmune: Research Funding. Cerf-Bensussan:Cellimmune: Research Funding. Hermine:Novartis: Research Funding; Celgene: Research Funding; AB Science: Equity Ownership, Honoraria, Patents & Royalties, Research Funding; Hybrigenics: Research Funding; INatherys: Equity Ownership, Research Funding.

Clinico-Hematological Profile and Copy Number Abnormalities in a Cohort of STIL-TAL1 and NUP214-ABL1 Positive Pediatric T-Cell Acute Lymphoblastic Leukemia.

T cell acute lymphoblastic leukaemia (T-ALL) is a genetically heterogeneous and aggressive form of malignancy. Although a number of recurrent fusion genes are reported in T-ALL, their involvement in disease stratification and therapeutic intervention is still controversial. Considering the prognostic value of STIL-TAL1 fusion and tyrosine kinase inhibitor (TKI) based therapeutic potential of NUP214-ABL1, the present study aimed to investigate their frequency and clinical correlation in pediatric T-ALL cases. Our cohort consisted of 48T-ALL pediatric cases (age ≤ 12years) with a median age of 6years and male to female ratio of 20.5:1. The median TLC of the study group was noted to be 220,000/ cu mm with a range from 26,810/cu mm to 785,430/cumm. By MLPA and RT-PCR analysis we observed that 11/48 cases (23%) showed STIL-TAL1 fusion and 4/48 cases (8.3%) had NUP214-ABL1 fusion gene. Both of the fusion genes did not show any significant correlation with any of the clinico-hematological or treatment outcome parameters. However, upon analysis of copy number variations (CNVs) with other clinically relevant genes, we found significant correlation between LEF1 (p = 0.024) and PTEN (p = 0.049) gene deletions with STIL/TAL1 fusion in T-ALL patients. NUP214-ABL1 fusion gene did not reveal any association with either CNVs or with survival. Although limited with the small cohort size and follow up, our study supports the similar frequency of these fusions as compared to other Asian and Western studies and also highlights utility of MLPA technique as a good diagnostic modality to screen for both STIL-TAL1 and NUP214-ABL1 fusions in a single assay with additional data on secondary copy number changes.

Dissociation of humoral and cellular immune responses in kidney transplant recipients with EBV mucocutaneous ulcer

EBV-positive mucocutaneous ulcer (EBV-MCU) is a rare EBV-positive B-cell lymphoproliferative disorder occurring in immunocompromised patients such as patients with solid organ or hematopoietic stem cells transplantation. EBV-MCU often consists of an isolated and circumscribed cutaneous or mucosal ulcerative lesion with a self-limited growth potential and a high regression rate upon immunosuppressive treatment withdrawal or rituximab therapy. Nevertheless, the pathophysiology of this latent infection leading to clonal lymphoproliferation is not well established. We report here two cases of EBV-MCU in kidney transplant recipients with a dissociated immune response to EBV with the absence of EBV-related antibodies and a positive T-cell response to EBV suggesting a potential specific oncogenic mechanism in this lymphoproliferative disorder.

A Case of ALK-Negative Anaplastic Large Cell Lymphoma Presenting as a Solitary Cutaneous Nodule

Anaplastic large cell lymphomas (ALCLs) are a group of CD30 positive T-cell non-Hodgkin lymphomas, accounting for only 3% of all non-Hodgkin lymphomas. As per the 2017 World Health Organization updated classification, there are four variants of ALCL: anaplastic lymphoma kinase (ALK) positive, ALK negative, primary cutaneous, and breast-implant associated. The different variants of ALCL share overlapping clinical presentations and pathologic features, creating a diagnostic challenge. A 71-year-old woman with a past history of T-cell lymphoma presented with a progressively growing nodule on her back for approximately 3 months. Physical exam demonstrated a 8.0 x 8.0 cm pink nodular indurated plaque located on her left upper back. A punch biopsy of the lesion revealed medium to large mononuclear cells with nuclear pleomorphism, hyperchromasia, and scattered mitotic figures. Immunohistochemistry demonstrated cells that were positive for CD30 and negative for ALK. Based on clinical and histopathologic findings, a diagnosis of ALCL was rendered. Differential diagnosis included primary cutaneous ALCL and cutaneous involvement by systemic ALK(-) ALCL. This case demonstrates the importance of clinicopathologic correlation in diagnosing ALCL and guiding therapy.

Intrafamilial Exposure to SARS-CoV-2 Associated with Cellular Immune Response without Seroconversion, France.

We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibodies and T-cell responses against SARS-CoV-2 and human coronavirus (HCoV) 229E and OC43 in 11 SARS-CoV-2 serodiscordant couples in Strasbourg, France, in which 1 partner had evidence of mild coronavirus disease (COVID-19) and in 10 unexposed healthy controls. Patients with confirmed COVID-19 were considered index patients and their partners close contacts. All index patients displayed positive SARS-CoV-2–specific antibody and T-cell responses that lasted up to 102 days after symptom onset. All contacts remained seronegative for SARS-CoV-2; however, 6 reported COVID-19 symptoms within a median of 7 days after their partners, and 4 of those showed a positive SARS-CoV-2–specific T-cell response against 3 or 4 SARS-CoV-2 antigens that lasted up to 93 days after symptom onset. The 11 couples and controls displayed positive T-cell responses against HCoV-229E or HCoV-OC43. These data suggest that exposure to SARS-CoV-2 can induce virus-specific T-cell responses without seroconversion.

Increased Risk of for Cytomegalovirus Reactivation after Allogeneic HSCT in T-Cell Depleted Patients

Background: Reactivation of Cytomegalovirus (CMV) is frequent after allogeneic hematopoietic stem cell transplantation (HSCT), occurring in approximately 70% of CMV seropositive patients. CMV reactivation is associated with higher non-relapse mortality (NRM) and worse overall survival (OS), but data in patients from Latin American countries, in which seroprevalence of CMV is higher, are lacking. Objectives: We analyzed the potential risk factors for CMV reactivation and the possible impact of CMV reactivation or primo-infection on HSCT outcomes. Patients and Methods: We performed an observational, retrospective study in 262 consecutive adult patients who underwent HSCT between April 2007 and April 2020 in two centers. The median follow-up was 30 months. Results: The median age was 50 years (range 18 to 83), most patients (58%) were male, had acute leukemia (acute myeloid leukemia in 40%, and acute lymphoblastic leukemia in 19%), and received transplants from alternative donors (matched unrelated in 32% and haploidentical in 36%). Most transplants were from peripheral blood stem cells (73%), with reduced-intensity conditioning regimens (76%). T-cell depletion was performed in 71% (post-transplant cyclophosphamide in 40%, antithymocyte globulin - ATG in 29%, and alemtuzumab in 2%). Pre-HSCT CMV IgG serostatus of donor (D) and recipient (R) was as follows: D+/R+ in 64%, D-/R+ in 22%, D+/R- in 8%, and D-/R- in 6% only. No patient received primary CMV prophylaxis. CMV reactivations were observed in 164 patients (63%), and all received preemptive therapy at the discretion of the treating physician. The CI for CMV reactivation at 100 days (CICMV) was 74% in D-/R+, 65% in D+/R+, 30% in D+/R-, and 0% in D-/R-, p&amp;lt;0.01, Figure 1). The CICMV was higher in patients receiving transplants with T-cell depletion (67% vs. 47% without T-cell depletion, p&amp;lt;0.01), and in patients with acute graft-versus-host disease (GVHD, 91% vs. 53% without GVHD, p=0.01). By multivariate analyses, all three factors remained associated with the CMV reactivation: pre-HSCT positive CMV serostatus (Hazard Ratio - HR: 6.06; 95% Confidence Interval - 95%CI 2.76.-13.35), T-cell depletion (HR 1.65, 95%CI 1.20-2.27), and acute GVHD (HR 1.67, 95%CI 1.31-2.14). By multivariate analysis, there was no significant association between CMV reactivation and the risk of acute GVHD, chronic GVHD, mortality, relapse, or survival. Conclusion: An increased frequency of CMV reactivation was observed in recipients with positive CMV serostatus, T-cell depletion, and acute GVHD. CMV reactivation had no significant impact on HSCT outcomes. Our findings may help to identify a group of patients who could benefit from closer monitoring and possibly primary prophylaxis with novel agents, such as letermovir. Disclosures No relevant conflicts of interest to declare.

Title: Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma with Cutaneous Presentation: A Biomarker Phase Ib/IIa Study (NCT03192202)

Introduction: Natural Killer cells (NK) play an important role in tumor immune-surveillance. The innate cell engager AFM13 is a CD30/CD16A targeting high affinity bispecific tetravalent antibody that engages and activates NK. This study evaluates AFM13's clinical and immunological activity. It examines the immunologic changes in the tumor and in peripheral blood (PB) as a function of the dose and method of administration of AFM13. Methods: Subjects with relapsed or refractory CD30 expressing lymphoma with cutaneous involvement were recruited into 4 cohorts: 1.5 mg/kg IV weekly, 7 mg/kg IV weekly, 7 mg/kg continuous intravenous infusion (CIVI) over 5 days weekly and 200mg IV weekly. Each cohort consisted of 3 subjects with 3 additional subjects in cohort 4. Subjects received 8 weeks of therapy for up to 2 cycles. Response assessment was performed on week 11 of each cycle by mSWAT, photography, PET imaging and PB flow cytometry. A second cycle was administered if there was no progression. Subjects underwent skin biopsies and PB immunologic studies as follows: pretreatment, day 5, week 4 and week 8 of therapy. Biopsies were analyzed and evaluated by a pathologist and IHC image analyzer. PB samples were analyzed by flow cytometry. Results: Fourteen subjects were accrued. The median number of prior therapies was 4 (1-11) and 4 subjects had progressed on brentuximab vedotin. The disease etiologies, treatment emergent toxicities and response by cohort are presented in Table 1. An objective response rate of 40% was observed in the study. In the PB, flow cytometry revealed a decrease in circulating NK (CD16/56+ CD3- CD19- lymphocytes) during therapy with post therapy recovery. The activation marker CD69 on NK increased in responders (R) compared to non-responders (NR). Similarly, tumor biopsies in R showed increased infiltration and activation of CD56+ NK as opposed to NR (Figure 1). NK cytotoxicity through the expression of Granzyme B was seen in R vs. NR. Flow quantitation of circulating CD4+ CD25+ T cells (Tregs) showed a decrease in R vs. NR. Conclusions: AFM13 demonstrated a high ORR of 40% among a population of heavily pretreated subjects with CD30 positive lymphoproliferative T-cell malignancies. AFM13 exhibited activity post brentuximab vedotin failure. In addition, biological changes in NK infiltration and activation in the PB and tissue biopsy correlated with response. These data are the first to demonstrate that innate cell engagers modulate NK and T cell populations in the peripheral blood and tumor from patients and to determine that such changes are associated with patient benefit. Disclosures Sawas: Roche: Current equity holder in publicly-traded company; Affimed: Research Funding; Daiichi Sankyo: Speakers Bureau; Seattle Genetics: Speakers Bureau; Gilead: Speakers Bureau; Flatiron Health: Current Employment. Chen:Affimed: Research Funding. Lipschitz:Affimed: Research Funding. Rodig:Bristol Myers Squibb: Research Funding; Merck: Research Funding; Affimed: Research Funding; KITE/Gilead: Research Funding; Immunitas: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees.

Brentuximab Vedotin As Single Agent in the Treatment of Relapsed/Refractory CD30 Positive Peripheral T-Cell Lymphoma Patients: A Phase 2 Study of the Fondazione Italiana Linfomi

Brentuximab Vedotin As Single Agent in the Treatment of Relapsed/Refractory CD30 Positive Peripheral T-Cell Lymphoma Patients: A Phase 2 Study of the Fondazione Italiana Linfomi

Identification of LAG3+ T Cell Populations in the Tumor Microenvironment of Classical Hodgkin Lymphoma and B-Cell Non-Hodgkin Lymphoma

Identification of LAG3+ T Cell Populations in the Tumor Microenvironment of Classical Hodgkin Lymphoma and B-Cell Non-Hodgkin Lymphoma

How our specialty can contribute and benefit from COVID‐19 research

How our specialty can contribute and benefit from COVID‐19 research

Intrathymic Selection and Defects in the Thymic Epithelial Cell Development.

Intimate interactions between thymic epithelial cells (TECs) and thymocytes (T) have been repeatedly reported as essential for performing intrathymic T-cell education. Nevertheless, it has been described that animals exhibiting defects in these interactions were capable of a proper positive and negative T-cell selection. In the current review, we first examined distinct types of TECs and their possible role in the immune surveillance. However, EphB-deficient thymi that exhibit profound thymic epithelial (TE) alterations do not exhibit important immunological defects. Eph and their ligands, the ephrins, are implicated in cell attachment/detachment and govern, therefore, TEC–T interactions. On this basis, we hypothesized that a few normal TE areas could be enough for a proper phenotypical and functional maturation of T lymphocytes. Then, we evaluated in vivo how many TECs would be necessary for supporting a normal T-cell differentiation, concluding that a significantly low number of TEC are still capable of supporting normal T lymphocyte maturation, whereas with fewer numbers, T-cell maturation is not possible.

Hydroa Vacciniforme-Like Lymphoproliferative Disorder in an Adult Patient With Chronic Lymphocytic Leukemia

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorder (LPD) which primarily affects children from Latin America and Asia. Typical features include vesicles and ulceration in sun-exposed areas which may be accompanied by systemic symptoms such as fever, lymphadenopathy and hepatosplenomegaly. We report a 73-year-old man diagnosed with HV-LPD in the context of zanubrutinib (oral Bruton tyrosine kinase (BTK)-inhibitor) treatment for chronic lymphocytic leukemia (CLL). The patient presented with slowly progressive peri-orbital edema and erythema non-responsive to topical therapies which eventually progressed to focal crusting and erosion. Prednisolone was subsequently introduced, which led to a good response in the patient’s symptoms. J Med Cases. 2020;11(11):366-369 doi: https://doi.org/10.14740/jmc3576

Evaluation of Positive B- and T-Cell Gene Rearrangement Studies in Patients With Negative Morphology, Flow Cytometry, and Immunohistochemistry

The significance of positive immunoglobulin (IG) or T-cell receptor (TCR) gene rearrangement studies in the context of otherwise normal ancillary findings is unknown. To examine long-term hematologic outcomes of individuals with positive gene rearrangement studies with otherwise unremarkable blood or bone marrow studies in parallel. Data from patients who underwent IG or TCR gene rearrangement testing at the authors' affiliated Veterans Affairs Hospital January 1, 2013 to July 6, 2018 were extracted from medical records. Date of testing, specimen source, and morphologic, flow cytometric, immunohistochemical, and cytogenetic characterization of the tissue source were recorded. Gene rearrangement results were categorized as test positive/phenotype positive (T+/P+), test positive/phenotype negative (T+/P-), test negative/phenotype negative (T-/P-), or test negative/phenotype positive (T-/P+) based on comparison to other studies and/or final diagnosis. Patient records were reviewed for subsequent diagnosis of hematologic malignancy for patients with positive gene rearrangements but no other evidence for a disease process. A total of 136 patients with 203 gene rearrangement studies were analyzed. For TCR studies, there were 2 T+/P- and 1 T-/P+ results in 47 peripheral blood assays, as well as 7 T+/P- and 1 T-/P+ results in 54 bone marrow assays. Regarding IG studies, 3 T+/P- and 12 T-/P+ results in 99 bone marrow studies were identified. None of the 12 patients with T+/P- TCR or IG gene rearrangement studies later developed a lymphoproliferative disorder. Positive IG/TCR gene rearrangement studies in the context of otherwise negative bone marrow or peripheral blood findings are not predictive of lymphoproliferative disorders.

A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-celllymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis.

Angioimmunoblastic T-cell lymphoma (AITL) is a uniquely aggressive mature T-cell neoplasm. In recent years, recurrent genetic mutations in ras homolog family member A (RHOA), tet methylcytosine dioxygenase 2 (TET2), DNA methyltransferase 3 alpha (DNMT3A) and isocitrate dehydrogenase [NADP(+)] 2 (IDH2) have been identified as associated with AITL. However, a deep molecular study assessing both DNA mutations and RNA expression profile combined with digital image analysis is lacking. The present study aimed to evaluate the significance of molecular and morphologic features by high resolution digital image analysis in several cases of AITL. To do so, a total of 18 separate tissues from 10 patients with AITL were collected and analyzed. The results identified recurrent mutations in RHOA, TET2, DNMT3A, and IDH2, and demonstrated increased DNA mutations in coding, promoter and CCCTC binding factor (CTCF) binding sites in RHOA mutated AITLs vs. RHOA non-mutated cases, as well as increased overall survival in RHOA mutated patients. In addition, single cell computational digital image analysis morphologically characterized RHOA mutated AITL cells as distinct from cells from RHOA mutation negative patients. Computational analysis of single cell morphological parameters revealed that RHOA mutated cells have decreased eccentricity (more circular) compared with RHOA non-mutated AITL cells. In conclusion, the results from the present study expand our understanding of AITL and demonstrate that there are specific cell biological and morphological manifestations of RHOA mutations in cases of AITL.

An HIV-infected patient with acute retinal necrosis as immune reconstitution inflammatory syndrome due to varicella-zoster virus.

An HIV-infected patient with acute retinal necrosis as immune reconstitution inflammatory syndrome due to varicella-zoster virus.

Clonal T-cell large granular lymphocyte proliferations in childhood and young adult immune dysregulation conditions.

Proliferation of large granular lymphocytes (LGL) and T-cell LGL (T-LGL) in peripheral blood along with demonstration of clonality are the hallmarks of a heterogeneous group of disorders, including T-LGL leukemia or T-LGL lymphocytosis. They are often associated with neutropenia and responsive to immunosuppression. The true nature of this entity is not well understood. Some cases are reported as reactive phenomena with very limited experience in pediatric population. Hematology/Oncology Flow Cytometry Laboratory database has been reviewed retrospectively. Patients with identifiable distinct CD5-dim T-cell population and positive clonal T-cell receptor rearrangement were included in the analysis. Clinical and laboratory data were then reviewed. Sixteen cases of children and young adults with increased peripheral blood clonal T-LGL population characterized by dim CD5 expression with wide range of underlying immune dysregulation/stimulation disorders were reviewed. Extended follow up with repeat testing suggested the reactive nature of persistent clonal T-LGL proliferations in this group. Our observations indicate that clonal T-LGL proliferations in children and young adults are reactive in nature and some can be persistent with an indolent course with unknown consequentiality. Clonal T-LGL cells could be targeting the most prominent immunogenic stressor(s) involved as a control mechanism.

TG01/GM-CSF and adjuvant gemcitabine in patients with resected RAS-mutant adenocarcinoma of the pancreas (CT TG01-01): a single-arm, phase 1/2 trial

BackgroundTG01 is the first cancer immunotherapy targeting KRAS oncogenic mutations. This study assessed the safety and efficacy of TG01/GM-CSF in patients with resected pancreatic adenocarcinoma.MethodsPatients with stage I or II pancreatic adenocarcinoma who had undergone surgical resection (R0 or R1) received adjuvant gemcitabine with TG01/GM-CSF using two schedules of vaccination. Immune response was defined as a positive delayed-type hypersensitivity (DTH) response and/or positive T-cell proliferation assay.ResultsThirty-two patients were enrolled between February 2013 and May 2016. Nineteen were treated with the high antigen burden, with four serious adverse reactions considered possibly related to TG01 treatment, including three allergic reactions. On this basis, a further 13 patients received a modified vaccination schedule with reduced antigen burden, with no serious adverse events related to TG01. Ninety-five percent patients in the main cohort and 92% in the modified cohort had a positive immune response. Median overall survival (OS) was 33.1 months, and median disease-free survival (DFS) was 13.9 months for the main cohort. For the modified cohort, the median OS was 34.3 months and median DFS was 19.5 months.ConclusionsTG01/GM-CSF with gemcitabine was well tolerated, with high levels of immune activation. OS and DFS compare favourably with published data for adjuvant gemcitabine.Clinical trial registrationThis clinical trial was registered at ClinicalTrials.gov (NCT02261714).