Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.
Introduction Graft-versus-host disease (GvHD) causes morbidity and mortality in recipients of allogeneic hematopoietic stem cell transplantation (ASCT). This study assessed the distribution of GvHD in gastrointestinal (GI) biopsies from the upper and lower GI tract in all patients who had undergone ASCT in our institution between 2005 to 2013 and evaluated the correlation between biopsy of upper and lower GI, possible relation with CMV Infection in GI biopsy and Blood sample, GvHD GI grade and extra-intestinal manifestations of GvHD Methods We performed a retrospective pathology records review for all patients diagnosed with positive GI GvHD biopsy, who underwent both upper and lower endoscopy. We also reviewed pathology and clinical reports to determine which biopsy sites were diagnostic of GvHD and to evaluate for the possible presence of extra-intestinal manifestations GvHD at the time of biopsy, CMV Status on the biopsy findings and blood sample. Results One hundred eighty nine patients (78 children and 111 adults) received ASCT transplant between 2005 to 2013. Twenty eight patients ( 14,8%) had undergone both upper and lower positive biopsy for acute GvHD diagnosis. Seventeen ( 60,7%) were male. The median age was 28 (1.50- 63.6) years old. Eleven patients had AML (39%), 6 had benign diseases (21.4%); five had ALL (17.9%); 2 lymphomas; 02 (7.1%) CML and 01 (3.1%) MDS. Main stem cell source was bone marrow 14 (50%), followed by PSCB in 7 (25%) and SCUP in 7 (25%). ATG was used in 16 (57, 1%) patients. Extra- intestinal manifestation of GVHD was: skin in 19 (67, 9%); liver in 6 (21,4%) patients. Five (17,9%) had the 3 organ involvement. The GI GvHD grade was: grade I in 7 ( 25%) , grade II in 4 ( 14,3%), grade III in 9 ( 32.1% ) and grade IV in 8 ( 28,6%). Regarding the concordance between the biopsy findings, there is agreement only between Ileum Biopsy Negative plus ileum and Rectum, because both have a higher percentage of positive GvHD. The stomach has a higher percentage of negative GvHD, and therefore there is no agreement with Colon plus ileum and Rectum. The frequency and correlation between involvement of different parts of GI-GVHD are presented in Tables 1,2 and 3. Just 2 ( 11.1%) patients had negative rectal biopsy and positive colon + ileum. Nine (32, 1%) had blood CMV detected. Five ( 17.9%) had positive Biopsy for CMV ( one in stomach, 3 in Colum and on in rectum), and just one patients had both positive. There is no association between clinical grade of GI-GVHD and the presence of CMV in biopsy and blood (CMV positive X GvHD grade, p=0.885; and biopsy CMV positive X GvHD grade, p= 0.859). It has no association between clinical grade of GI- GVHD and conditioning (p= 0.070) and use of ATG (p=0.867). HLA disparity was related with higher grades of GI-GVHD (p=0.029). All patients with Grade I are Fullmatch, whereas patients with Grade III and IV had highest percentage of mismatch [grade III= 5 (55.6%); and grade IV= 4 (57.15%) patients]. The median follow up was 7.2 (1.8-90.6) month. Overall survival (OS) was 40% in 60 month and patients with grade IV GVHD had worst OS ( P= 0.004). Conclusion Use of sigmoid biopsy for GvHD diagnosis is effective, safe, and less expensive compared to other endoscopic interventions, because it was most frequent site of lower GI-GVHD and only 11% of biopsies were discordant. CMV infection may be underdiagnosted with this approach, where colonocospy study should be considered as most of CMV positivity in biopsy was in Colum. Disclosures: No relevant conflicts of interest to declare.
Cell dose is a major criterion for cord blood unit (CBU) selection for allogeneic stem cell transplantation (allo-SCT). The aim of this study was the characterization of CBU cellular composition after thaw, and comparison with corresponding values at cryopreservation as reported by cord blood (CB) banks. The study included 87 CBUs, that were thawed for infusion in the context of single (n¼3) or dual-unit (n¼42) allo-SCT in adults with hematologic malignancies, from 8/2006 to 6/2013. Upon thawing, the cryoprotective solution (DMSO 10%) was either removed by centrifugation/washing (38 CBUs) or diluted in a less hypertonic solution of Dextran 40/Human Albumin 2.5% (49 CBUs). Total nucleated cells (TNC) were measured with a hematology analyzer, while enumeration of CD34+ stem cells was performed by singleplatform flow cytometry, according to ISHAGE guidelines. In 49 units, TNC and CD34+ cell viability was evaluated by addition of 7-AAD dye and sequential Boolean gating strategy. TNC counts after thawing were lower compared to their values at freezing (Wilcoxon test, p <10-4), and the difference was more pronounced in the units that were washed prior to infusion (Tables 1 and 2). Total cell viability was low (mean value, 42.6%), but this was mainly due to neutrophils. Regarding CD34+ cells, there was a significant difference between absolute counts at cryopreservation and at thaw (p<10-4). Despite reduction postthaw, the counts of both TNC and CD34+ cells did correlate with the corresponding values at cryopreservation by Spearman's analysis. Of note, washing seemed slightly advantageous in terms of CD34+ recovery (Tables 1 and 2). CD34+ cells retained high viability after thaw, with 90% of CBUs (44 out of 49 tested) demonstrating CD34+ viability !80%. Viability of <50% was noticed in only one CBU that failed to engraft. In conclusion, CB cellular content and especially the CD34+ cell count is frequently shown to be inferior at thaw compared to cryopreservation. This probably reflects both the lack of standardization of CD34+ cell measurement and the effect of thawing procedure. Therefore, CD34+ cell viability may be a more meaningful marker for determining CBU quality.
Introduction It has been previously reported that increased fluid accumulation during peripheral blood hematopoietic stem cell (HSC) mobilization is associated with poor outcome in patients with amyloidosis who undergo autologous HSCT. It is unknown whether increased fluid accumulation during the early phases of HSCT is associated with poor survival in patients undergoing HSCT for other diseases. Objective To determine the impact of fluid accumulation during conditioning and in the first 10 days post HSC infusion on survival and risk of complications of patients who underwent both autologous and allogeneic HSCT. Methods We retrospectively reviewed the medical charts of 257 consecutive patients who underwent HSCT at our institution from January, 2007 until December, 2012. Information on patients' body weight (BW) was measured daily, starting at admission. The highest BW recorded until HSC infusion (D0) and until the first 10 days post-SCT (D+10) was used to calculate the BW increase in relation to the baseline BW. A ROC curve was built to determine the best cut-off point in BW increase that predicted for mortality. Information on the incidence of post-transplant complications was extracted from the time period that patients were admitted for transplant until discharge from the hospital. Endpoints analyzed included the presence or absence of respiratory failure, acute renal failure, sinusoidal obstruction syndrome (SOS), septic shock and requirement of diuretic use, hemodialysis, mechanical ventilation and ICU admission. Overall survival (OS) was estimated from the time of HSCT until death, and surviving patients were censored at last follow-up. Variables entered into the multivariate Cox analysis were those with a p-value<0.10 in the univariate analysis. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results Mean age was 39.4 years old (range <1 year-76 years) and 61% were male. HSC sources included autologous (47%), matched related donors (15%), matched unrelated donors (13%), cord blood units (19%) and mismatched related/unrelated donors (6%). Diagnosis included acute leukemia or chronic myeloid disorders (37%), lymphoma/multiple myeloma (42%) and non-malignant hematological disorders (21%).The results of the ROC curve defined the cut-point of 6% BW gain by D+10 as the best predictor for OS. A total of 69 patients (27%) had a BW increase ≥6% by D+10. This was associated with an increased risk of mortality, with a 100-days OS of 67% vs. 92% (HR 3.25, p<0.0001, 95% CI 2.04-5.18; Figure). A greater than 6% gain in BW by D+10 was also associated with an increased risk of developing SOS (31% vs. 6%; p<0.0001), septic shock (29% vs. 7%; p<0.0001), respiratory failure (35% vs. 9%; p<0.0001) and requiring diuretic use (91% vs. 71%; p<0.001), hemodialysis (13% vs. 4%, p=0.007), mechanical ventilation (33% vs. 9%; p<0.0001) and ICU admission (42% vs. 24%; p<0.0001). In a multivariate analysis considering age, diagnosis, type of SCT and sex, a ≥6% BW gain by D+10 was an independent variable associated with an increased risk of mortality (HR 3.28; p<0.0001; 95% CI 2.02-5.32). We next evaluated the prognostic impact of a ≥6% BW increase in the time period from admission until D0. Our results showed that it was similarly associated with an increased risk of mortality (HR 2.26; p=0.003; 95% CI 1.32-3.86), of developing SOS (32% vs. 9%; p<0.0001), respiratory failure (27%vs. 14%; p=0.04) and requiring hemodialysis (15% vs. 5%; p=0.01) and ICU admission (37% vs. 18%; p=0.008). After adjusting for age, sex, diagnosis and type of SCT, ≥6% BW gain by D0 was associated with an increased mortality (HR 1.94; p=0.026; 95% CI 1.08-3.48). Conclusion In our cohort of patients, fluid accumulation during the early stages of conditioning regimen and HSCT, reflected by a ≥6% increase in BW, was associated with an increased mortality and risk of developing severe complications. This may reflect the presence of increased endothelial damage, and further studies are needed to better clarify the mechanism behind weight gain during HSCT. Our results demonstrate that patients who have a ≥ 6% gain in BW by D0 and D+10 have an increased risk of complications, and more intensive monitoring of these patients is needed. Disclosures: No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.