INTRODUCTION Transplant-associated thrombotic microangiopathy (TMA) is a severe complication after allogeneic stem cell transplantation (ASCT) due to endothelial injury caused by many factors such Calcineurin-inhibitors. In most severe cases, TMA could affect different organs. Intestinal TMA could be fatal and missdiagnosed in many patients. Clinical and pathological criteria to differentiate from intestinal GVHD are needed in order to distinguish both entities with different therapeutical approach. The aim of this study was to review pathological TMA features in patients diagnosed of systemic TMA . PATIENTS AND METHODS We analyzed the incidence of TMA in 527 pts who underwent ASCT in our institution between jan-2010 and apr-2018. Patients were identified if they had TMA according to probable TMA criteria by Ho. We do a pathological review in 96 samples from 18 of 42 patients in whom an endoscopy have been performed after the diagnosis of the TMA; endoscopy have been performed between 30 days before and 60 days after diagnosis of TMA for initial clinical diagnosis of GVHD. Review was performed by a pathologist expert. He examined the biopsies in search of features of GVHD, TMA or viral infection. Diagnosis of GVHD was stablished according to Mcdonald and Sales criteria, intestinal TMA diagnosis was perfomed by the 8 criteria summarized by Warren et al (perivascular mucosal hemorrhage, endothelial cell swelling, endothelial cell separation, intraluminal schistocytes, fibrin or microthrombi, loss of glands and mucosal denudation). RESULTS Baseline/transplant characteristics of patients with TMA are shown in table 1, TMA data in 2 and review hystological features of biopsies in 3. 45 (8.5%) were diagnosed of TMA with a median time from transplant of 75 days. Median age was 49 (19-69). Prophylaxis of GVHD was: Calcineurin inhibitor-MTX in 16 (35.5%), Tacrolimus-Sirolimus in 21 (46.6%), Tacrólimus-MMF and Cyclophosphamide in 8 (17.6%). 42 (93%) had prior or simultaneous acute GVHD, half of them grade III-IV, and 80% with gastrointestinal GVHD. 42% had elevated levels of tacrolimus and 13.6% elevated levels of sirolimus, one week before the diagnosis of TMA. Gastrointestinal MAT have been reported only in 5 patients (28%) at diagnosis whereas when review based on Warren criteria was performed, in 16 patients (89%) the pathologist found at least 1 of the criteria of endothelial damage and 50 % of the patients met 3 or more Warren criteria. The most frequent features were endothelial cell swelling (13 patients, 73 %) and perivascular mucosal hemorrhage (12 patients, 66.7%). In 3 biopsies which we perfomed the inmunochemistry of C4d, an activation of classic way of complement biomarker, it was positive. 4 of the 18 patients (22.2%) presented refractory-hypertension and 3 of them (26.6%) more than 30 mg/d Lof proteinuria, both suggested of poor prognosis. Regarding GVHD, it was founded in 72% at diagnosis and in all patients (18) at pathological review. 13 had grade I, 1 grade II, 1 grade III and 3 histological grade IV). With a median follow-up of 5 months (2-25) 25 of the 45 (56%) are dead. 6 of the deaths (24%) were related to TMA (1 due to TMA, 3 due to TMA+GVHD, 2 due to TMA+infection). Other causes of death were progression (4), GVHD+Infection (7), GVHD (3), infection (2), sinusoidal obstruction síndrome (1) and other causes (2). CONCLUSION TMA is a frequent complication, related with GVHD and underdiagnosed frequently. Only 5 of 18 patients were diagnosed of gastrointestinal TMA. In our study, we found that most of our patients had endotelial damage in the gastrointestinal biopsy pathological reviews. Although histological criteria of GVHD were present at review, in most of them it was only grade I; it contrasts with the severe clinical features. That lack of correlation would suggest that TMA and not GVHD is the main feature. Management of TMA and GVHD are different. To stress an appropiate diagnosis in gastrointestinal TMA is needed in order to offer the patients the best approach. REFERENCES Warren et al. A Complete Histologic Approach to Gastrointestinal Biopsy From Hematopoietic Stem Cell Transplant Patients With Evidence of Transplant-Associated Gastrointestinal Thrombotic Microangiopathy. Arch Pathol Lab Med.2017 Nov;141(11):1558-1566. Jodele S et al. A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev. 2015;29(3):191-204. Disclosures No relevant conflicts of interest to declare.
Purpose The objective of this study was to investigate clinicopathologic features and prognostic factors of patients diagnosed with PTCL in 13 sites across Spain. Patients and Methods A multicenter, retrospective study was carried out between September 2015-November 2017.Medical charts of patients diagnosed with PTCLs between January 2008 and December 2013 that have signed the approved informed consent form were reviewed. PTCLs were then classified according to the 2016 revision of the WHO classification of lymphoid neoplasms. Clinical characteristics,history, standard immunohistochemistry (IHC) data, International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (TCL) (PIT) were also assessed. Medians (range), mean (standard deviation) and frequency as the number of patients (n) and percentages (%) with confidence intervals at 95% (CI95%) were calculated. Overall Survival (OS) and Progression Free Survival (PFS) were analyzed using the Kaplan Meier method. Results 175 (88.4%) patients were successfully analyzed, the male/female ratio was 1.7:1.0, and the median age was 67.2 years (range: 24.8 years -95.8 years). ECOG performance status >1 was reported for 31.9% patients. Ann Arbor stages were III and IV 27.4% and 45.7%, respectively, and LDH levels were elevated to 92 patients (52.6%). Those with B symptoms accounted for 39.4%, while soft tissue was the most frequent location (23,7%) among the 76 patient with extranodal disease; bone marrow infiltration was confirmed in 18.3% patients. Relevant clinical antecedents related to immunological aspects were also frequently reported, including previous neoplasia (18.9%), autoimmune disease (16%), immunosuppressive treatments (7.3%) and previous viral diseases (HIV, HBV or HCV, 5.7%, 4.6% and 7.4%, respectively). Most patients presented with angioimmunoblastic TCL (31.4%); similar proportions of patients were observed among nodal PTCL with TFH phenotype (13.1%, PTCL not otherwise specified (12.0%) and extranodal NK/TCL nasal type (11.4%). CD30 expression and staining pattern (ranged 1-4) allowed the stratification of patients according CD30 intensity (n= 121; weak: 35, moderate: 57, and intense: 29); Patients were also classified based on CD30 expression considering the median value of quantitative CD30 in our sample (15%) the cut-off point: n=132; Negative <15%: 64; Positive, ≥15%: 68). First-line treatment with a CHOP/CHOP-like regimen was the most common finding (69.7%). Best response was observed after a median of 4 months since the start of first-line treatment (range 0.0 months - 65.2 months). Overall response rate after first-line treatment was 66.9%, with 61/151 patients reaching complete response (CR). Median PFS (n=157) and OS (n=175) of this series were 7.87 months (CI95%: 4.98 months-10.75months) and 15.77 months (CI95%: 10.23 months -21.30 months), respectively. Overall, IPI and PIT scores influenced the PFS and OS (p<0.001). A higher number of adverse factors was associated with a shorter survival. Reaching a CR was associated with a better PFS (CR: 62.6m; CI95%: 20.2 months -105.1 months) than the rest of patients (3.97m: CI95%: 3.08 months -4.85m; p<0.001). Response was also associated with OS; patients with CR showed an average OS of 67.01 months (CI95%: 58.2 months -75.9 months) that were significantly longer than that of patients with No-CR (median: 7.34 months; CI95%: 5.85 months -8.83 months; p<0.001). Conclusion This is the largest series of T cell Lymphoma reported in Spain and has allowed the description of distribution of PTCL subtypes, analyzed through central hematopathologists reanalysis and reclassification of samples from 175 PTCL patients, according to the WHO 2016 classification of lymphoid neoplasms. Our data confirm the poor prognosis of these patients, as well as the impact of prognostic indexes and the response to first line treatment on their outcome. Disclosures Rodriguez-Pinilla: Takeda: Honoraria. Piris:Takeda: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Kura: Honoraria. Ruiz-Zorrilla:Takeda: Employment. Montoto:Takeda: Employment.
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