Predictors and GVL Effects of UCB Chimerism after Haplo-Cord Transplant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4385-4385
Author(s):  
Nebu Koshy ◽  
Sebastian A. Mayer ◽  
Adrienne Phillips ◽  
Rosanna Ferrante ◽  
Ronit Slotky ◽  
...  
Keyword(s):  
Prospective Study ◽  
Cord Blood ◽  
Relapse Rate ◽  
P Value ◽  
Inverse Association ◽  
Hla Matching ◽  
Cell Dose ◽  
Cd34 Cells

Abstract Haplo cord transplant combines an umbilical cord blood unit (CBU) graft with a CD34 selected adult haplo-identical graft for the purpose of establishing long term CBU chimerism, which occurs in most but not all cases. Previously we showed that excessive haplo CD34 doses impair CBU engraftment (Liu et al, Blood 2011). Since then we have utilized a fixed haplo CD34 dose of 5x106 CD34 cells/kg. We also conducted a prospective study of CBU threshold dose de-escalation and established a minimum CBU dose of 1.2 x106 TNC/kg as the threshold for further study (van Besien ASH 2014, 1093). Here- using the patients from our prospective study- we sought to identify additional predictors of CBU engraftment as measured by percentage of CBU chimerism in CD33 and CD3 lineages in patients engrafted and in remission by day 56. We focused on d56 chimerism because durable patterns of chimerism are established by then. 83 pts were enrolled, but 23 were excluded from analysis because of early death (6) relapse before day 60 (8), failure of both grafts with residual MDS (4), lost to follow up (1) and no chimerism measurements (3). 61 pts were analyzed with median age 62 (18-72 years), 41 AML/MDS, 12 NHL, 5 ALL and 4 others. 24 had ASBMT high risk, 13 intermediate and 23 low risk disease. Conditioning was Flu Mel ATG (n=46), Flu Mel TBI 400 ATG (n=14) and Flu Mel TBI 600 ATG (n=1). All pts received GVHD prophylaxis with tacrolimus until d 180 and mycophenolate until d 30. The haplo dose was fixed at 5 x 106 CD34 cells/kg. Donors targeted by recipient donor specific antibodies (DSA) were avoided if possible. CBU units were selected based on HLA matching in sequential cohorts of decreasing threshold cell dose. Coh 1(n=12), minimum 2.0 x106 TNC/kg, coh 2 min (n=14) 1.5 x106 TNC/kg, coh 3 (n=25) min 1.0 x106 TNC/kg. After min cell dose was established, further enrollment occurred with a min dose of 1.2 x106 TNC/kg (coh 4 n=10). Median CBU TNC across all cohorts was 2.27 x107/kg (1.0-8.3). CBU were matched (HR HLA) at 3/8 (n=1), 4/8 (n=7), 5/8 (n=18), 6/8 (n=14) 7/8 (n=16) and 8/8 (n=5). DSA against CBU were present in 7. Haplo graft was 4/8 (n=42), 5/8 (n=13), 6/8 (n=3) and 7/8 (n=3). DSA against haplo were present in 6. Median follow up for survivors is 16 mo (5 -34). Cord graft characteristics, matching, enrollment cohort, nor presence of DSA were associated with d56 CBU chimerism. There was a strong inverse association between degree of matching of the haplo donor and d56 CBU (Fig 1). 54 pts with ≤ 5/8 haplo HLA match had 68% d56CD33 UCB chimerism vs 14% for the six pts with 6/8 or 7/8 HLA match (p=0.004). There was also a significant association between use of TBI and cord blood engraftment. 15 pts who received TBI had 79% d56CD33 UCB chimerism vs 50% for the 46 pts without TBI (p=0.05). Decreasing d56UCB chimerism was strongly associated with cumulative relapse risk (Fig 2A). It was not associated with TRM. The associations were even stronger if only considering AML/MDS (Fig 2B). Best discrimination was with 40% CD33 and 80% CD3 (Table 1). Table 1. Relapse rate at one year Day 56 CD3 <80% (22) CD3>80% (39) p value CD33<40% (19) CD33>40% (42) p value All pts n= 61 47% 21% 0.006 52% 19% 0.0008 CD3 <80% (15) CD3>80% (26) p value CD33<40% (13) CD33>40% (28) p value AML/MDS n=41 60% 14% 0.0003 58% 16% 0.00007 Conclusions: The establishment of a durable cord blood graft is heavily influenced by HLA matching of the haplo-graft. 6/8 and 7/8 HLA-matched haplo-graft which occur by chance in about 10% of cases, should probably be avoided. More intensive conditioning with the addition of low dose TBI may further favor establishment of the cord blood graft. Cell dose or HLA matching of the cord blood graft has less effect on its long-term establishment. Increasing cord blood chimerism is associated with a much reduced risk of relapse despite- not shown here- very low rates of chronic GVHD). Low levels of cord blood chimerism are associated with very high rates of relapse. These data provide further support for the GVL effects of CBU grafts, particularly in AML/MDS. Figure 1. Relation between Haplo Graft Matching and d56 CD33 CBU chimerism Figure 1. Relation between Haplo Graft Matching and d56 CD33 CBU chimerism Figure 2. Relapse Rate in All patients (A) and AML/MDS (B) based on d56 CD33 chimerism ≥40% vs <40% Figure 2. Relapse Rate in All patients (A) and AML/MDS (B) based on d56 CD33 chimerism ≥40% vs <40% Disclosures van Besien: Miltenyi Biotec: Research Funding.

Allele Level HLA Matching On Outcomes After Double Umbilical Cord Blood (dUCB) Transplantation for Hematological Malignancies: Stronger Graft Vs. Leukemia with HLA Mismatch

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1976-1976
Author(s):  
Claudio G Brunstein ◽  
Todd E. Defor ◽  
Harriet Noreen ◽  
David Maurer ◽  
Margaret L. MacMillan ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Treatment Failure ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hla Typing ◽  
P Value ◽  
Hla Matching ◽  
Transplant Outcomes

Abstract Abstract 1976 Multiple single center and registry reports have documented the critical impact of donor-recipient HLA match on engraftment, transplant-related mortality (TRM) and survival after umbilical cord blood (UCB) transplantation. However, nearly all reports have only considered HLA A and B at antigen level and HLA DRB1 at allele level typing without consideration of HLA C or DQ. Therefore, we retrospectively performed allele level HLA typing for HLA-A, B, C, DRB1, DQB1 for UCB donor-recipient pairs in order to assess the importance of high resolution HLA typing on transplant outcomes. After 2002, most patients received a dUCB transplant in order to achieve the desired cell doses of ≥3, ≥4 and ≥5 × 10e7 NC/kg for grafts that were HLA 6/6, 5/6 and 4/6 matched by original typing resolution, respectively. Therefore, the analysis was limited to 275 recipients of dUCBT for hematological malignancy and whom DNA from both units was available. The effect of HLA match was based on the HLA type of the predominant long term engrafting unit. The median recipient age and weight was 44 years (range, 0.6–69) and 76.9 kg (range, 7.1–148), respectively. Conditioning was myeloablative (40%) consisting of cyclophosphamide (CY) 120 mg/kg, fludarabine (FLU) 75 mg/m2 and total body irradiation (TBI) 1320 cGy, or non-myeloablative (60%) consisting of CY 50 mg/kg, FLU 200 mg/m2, TBI 200 cGy with 95% receiving cyclosporine A (CsA) and mycophenolate mofetil (MMF) immunosuppression. Patients had acute leukemia (62%), standard risk disease (62%), cytomegalovirus seropositive (59%), and received at least one UCB unit that was sex mismatched to the recipient (78%). Results reported are based on the long-term predominant UCB unit. Notably, survival was not adversely affected by HLA mismatch. The probability of survival at 5 years was 46% (95%CI, 33–58%), 47% (95%CI, 38–54%) and 29% (95%CI, 13–47%) in patients engrafting with a 3–5/10, 6–8/10 and 9–10/10 HLA-matched UCB grafts, respectively (p=.47). In multivariable analysis after adjusting for disease risk, CMV serostatus, and KPS, there was similar risk of overall mortality for all groups regardless of HLA matching level. All other transplant outcomes including the incidence of acute and chronic GVHD were similar for all HLA-matching groups (data not shown). In the subset with acute leukemia (n=174), however, greater HLA mismatch was associated with a significantly lower risk of relapse without a deleterious effect on risk of TRM, resulting in a benefit in LFS (inverse of treatment failure) as shown below. Transplant Outcome for Acute Leukemia HLA 3–5/10 match (n=84) RR (95%CI), p-value HLA 6–8/10 match (n=168) RR (95%CI), p-value HLA 9–10/10 match (n=34) RR (95%CI), p-value TRM at 2 years 1.0 1.1 (0.6–2.4)
 P=.73 1.1 (0.6–2.4)
 P=.73 Leukemia Relapse 1.0 1.9 (0.9–4.3)
 P=.11 3.5 (1.3–9.5)
 P=.01 Treatment failure 1.0 1.4 (0.8–2.4)
 P=.19 2.2 (1.1–4.2)
 P=.02 Together these data indicate that UCB units with greater HLA mismatch may confer greater GVL effect without greater TRM compared to HLA better-matched UCB grafts. These results suggest importance of evaluating allele level HLA typing in the setting of dUCB transplantation. If confirmed, these results could have major implications not only on graft selection (ie avoidance of HLA matched units), but also the target size of the international UCB banking inventory. Disclosures: No relevant conflicts of interest to declare.

Excellent Engraftment and Long-Term Survival in Patients with Severe Aplastic Anemia (SAA) Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Haplo-Identical CD34+ Cells Combined with a Single Umbilical Cord Blood Unit

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5516-5516
Author(s):  
Enkhtsetseg Purev ◽  
Georg Aue ◽  
Ritesh Kotecha ◽  
Jennifer Wilder ◽  
Hahn M. Khuu ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Severe Neutropenia ◽  
Hla Matching ◽  
Term Survival ◽  
Long Term Survival ◽  
Hla Alleles ◽  
Cd34 Cells ◽  
Matched Donor

Abstract For SAA patients (pts) lacking an HLA identical donor, outcomes of HSCT using single or dual unrelated cord blood (UCB) transplants or haplo-identical donors have been associated with high graft failure rates and poor survival. We investigated whether co-infusion of a single UCB unit with CD34+ selected cells from a haplo-identical relative following a highly immunosuppressive conditioning could improve transplant outcome for this high-risk population. Methods: Eligible pts for HSCT were required to be between the ages of 4-55, have a diagnosis of SAA or SAA evolved to MDS, be unresponsive to immunosuppressive therapy, have severe neutropenia (ANC<500 cells/µL), lack an HLA-matched donor, have an available haploidentical family member, and at least one ≥ 4/6 HLA-matched UCB unit with a minimum TNC dose ≥1.5x107 cells/kg. Pts received conditioning with cyclophosphamide (120 mg/kg), fludarabine (125 mg/m2), equine-ATG (160 mg/kg) and 200 cGy of total body irradiation. On Day 0, pts received a CD34-selected (Miltenyi CliniMacs) G-CSF mobilized haplo-donor allograft combined with a single UCB. Tacrolimus and MMF were used for GVHD prophylaxis. Results: 21 pts (median age: 19.6 yrs, range: 4.5-48.6) including 14 with SAA and 7 with SAA that evolved to early stage MDS (< 5% blasts) underwent haplo-cord transplant. 14 pts received 4/6, and seven pts received a 5/6 HLA-matched UCB unit. UCB units contained a median 3.77x107 TNCs/kg (range: 1.96-6.93), a median 1.54x105 CD34+ cells/kg (range 0.46-3.45), and the haplo-graft contained a median 3.2x106 CD34+ cells/kg (range: 3.0-4.1) and a median 0.95x103 CD3+ cells/kg (range 0.3-5.04). All 21 pts engrafted, which was sustained and associated with transfusion independence in 20/21 pts. At a median follow-up of 3 yrs (1116 days, range: 226-2572), 19/21 pts survive for an overall survival rate of 90%. 2 pts died at day 414 and 402 post-HSCT from viral related complications (CMV pneumonitis and limbic encephalopathy). Neutrophil and platelet recovery occurred at a median 10 (range: 9-22), and 30 (range: 16-129) days respectively. Cord myeloid engraftment (cord ANC>500 cells/µl, calculated from chimerism data) occurred in 18/21 pts at a median 42 days while 3/21 did not achieve a cord ANC>500 but had haplo-donor engraftment which was sustained in 2 cases. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 28.6%, with only 1 pt (4.8%) developing grade III and no cases of grade IV or steroid refractory aGVHD. The cumulative incidence of chronic GVHD (cGVHD) was 47.8%, with 37% mild, 11% moderate, and no severe cGVHD. Engraftment profiles showed 16 achieved full cord chimerism in all cell lineages, 2 remained mixed haplo-cord chimeras, and 2 failed to have UCB engraftment but had sustained 100% haplo-donor myeloid chimerism. Higher degrees of HLA matching between recipient and UCB unit were associated with faster rates of cord engraftment (P=0.012) and the achievement of full cord chimerism (P= 0.004). Among the 16 pts who had lower degrees of HLA matching (≤5/8 HLA alleles) between the recipient and UCB unit, 9 received grafts with KIR ligand incompatibility in the haplo vs. cord direction ( defined as the presence of a KIR ligand in the haplo-donor graft that was absent in the UCB unit at HLA epitopes Bw4, HLA-C Groups 1 & 2, HLA-A3, and HLA-A11); KIR ligand incompatibility had a negative impact on cord myeloid engraftment as 6/9 (67%) of these pts failed to achieve full cord myeloid chimerism by day 400 and 5/9 (56%) pts failed to achieve a cord ANC>500 by day 250 post-HSCT. In contrast, cord myeloid engraftment occurred quicker in the 12 pts who did not have haplo vs. cord KIR ligand incompatibility including 7 pts with lower degrees of HLA matching (≤5/8 HLA alleles between the recipient and UCB) and 5 pts with higher degrees of HLA matching, where the median times to achieve a cord ANC>500 and full cord myeloid chimerism was 42 days (range: 28-58) and 60 days (range: 14-230) respectively ( both P<0.01 compared to the pts that received grafts with KIR ligand incompatibility). Conclusion: Transplantation of haplo-identical CD34+ cells with a single UCB unit in neutropenic pts with SAA and SAA evolved to MDS was associated with rapid neutrophil recovery, durable donor engraftment and excellent long-term survival. These results suggest that haplo-cord HSCT is an effective treatment option associated with excellent survival in pts with SAA who lack an HLA-matched donor. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Transplanted CD34+ Cell Dose Is Associated with Long-Term Platelet Count Following Autologous Hematopoietic Stem Cell Transplant in Patients with Non-Hodgkin’s Lymphoma and Multiple Myeloma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2175-2175
Author(s):  
Patrick J. Stiff ◽  
Ivana NM Micallef ◽  
Auayporn P. Nademanee ◽  
Edward A. Stadtmauer ◽  
Richard Thomas Maziarz ◽  
...  
Keyword(s):  
Platelet Count ◽  
Ad Hoc ◽  
Linear Trend ◽  
Autologous Transplantation ◽  
P Value ◽  
Safety And Efficacy ◽  
Cell Dose ◽  
Cd34 Cells ◽  
The Mean

Abstract Introduction: The impact of transplanted CD34+ cell dose on clinical outcomes remains controversial. The purpose of this study was to examine the relationship between CD34+ cell dose transplanted and platelet, neutrophil, and lymphocyte counts at 100 days, 6, and 12 months following autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). Methods: Data were obtained from two phase 3 clinical studies that compared the safety and efficacy of plerixafor and G-CSF with placebo and G-CSF in mobilization of hematopoietic blood stem cells for autologous transplantation in NHL patients and in MM patients. The details of the study designs and preliminary safety and efficacy outcomes have been reported (DiPersio, ASH 2007). The following data were obtained from the two clinical study databases: number of CD34+ cells transplanted (first transplant only) as determined by a central laboratory, absolute neutrophil, platelet, red blood cell, and lymphocyte counts at 100 days, 6, and 12 months post-transplant. The proportions of patients who had platelet ≥150 x 109/L or neutrophil ≥2.5 x 109/L or lymphocyte ≥0.5 x 109/L at 100 days, 6, and 12 months were compared among these transplanted CD34+ cell dose categories regardless of mobilization treatment: 2–4 x 106 cells/kg, &gt;4–6 x 106 cells/ kg, and &gt; 6 x 106 cells/kg. Two separate analyses were performed, one for NHL patients and one for MM patients. Results: For the NHL study, 135/150 (90.0%) patients in the plerixafor group underwent transplantation after initial mobilization compared with 82/148 (55.4%) patients in the placebo group, p&lt;0.001. The mean number of CD34+ cells transplanted was 6.06 ± 2.98 x 106 (median 5.41, range 1.79–17.6) for the plerixafor-treated patients and 4.09 ± 1.56 x 106 (median 3.85, range 1.98–8.7) for the placebo-treated patients, p&lt;0.001. For the MM study, 142/148 (95.9%) patients in the plerixafor group and 136/154 (88.3%) patients in the placebo group underwent transplantation. The mean number of CD34+ cells transplanted was 5.84 ± 2.64 x 106 (median 5.34, range 1.9 to 16.7) for the plerixafor-treated patients and 4.37 ± 2.01 x 106 (median 3.98, range 1.8 to 16.9) CD34+ cells/kg for the placebo- treated patients. A significant linear trend with increasing proportion of patients with platelet count ≥150 x 109/L with increasing transplanted cell dose categories was observed at 100 days, 6, and 12 months for NHL patients and at 100 days for MM patients (Table 1). There were no apparent significant relationships between transplanted cell dose categories and other hematopoietic parameters. Table 1: Analysis of percentage of patients reaching a platelet count of ≥ 150 x 109/L by transplanted cell dose categories Transplant Cell Dose (CD34+ cells/kg) 2–4 x 106 ≥ 4–6 x 106 ≥ 6 x 106 P value* NHL Patients N=76 N=75 N=66 100 days 28 (48.3%) 42 (66.7%) 45 (81.8%) &lt;0.001 6 months 31 (56.4%) 36 (66.7%) 42 (76.4%) 0.026 12 months 18 (56.3%) 21 (80.8%) 24 (82.8%) 0.020 MM Patients N=75 N=82 N=64 100 days 41 (68.3%) 57 (90.5%) 47 (88.7%) 0.004 6 months 48 (78.7%) 61 (89.7%) 51 (87.9%) 0.147 12 months 25 (73.5%) 33 (82.5%) 26 (81.3%) 0.435 For all transplanted cell dose categories, the proportions of patients are based on the number of patients with available data at each time point.*p-value for testing linear trend using Mantel-Haenszel Chi-square test Conclusions: Results from these ad hoc analyses confirm previous reports that transplanted cell dose may be associated with better long-term platelet recovery. Due to the small sample size in each transplanted cell dose category and the nature of ad hoc analyses, further studies are warranted to determine if the introduction of plerixafor will allow the mobilization and transplantation of higher quantity of CD34+ cells, which may positively influence long-term hematopoietic recovery.

The association of artificial intelligence-enabled electrocardiogram-derived age (physiologic age) with atherosclerotic cardiovascular events in the community

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Medina-Inojosa ◽  
A Ladejobi ◽  
Z Attia ◽  
M Shelly-Cohen ◽  
B Gersh ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Bypass Graft ◽  
P Value ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Age Gap ◽  
Predicted Risk ◽  
Age And Sex

Abstract Background We have demonstrated that artificial intelligence interpretation of ECGs (AI-ECG) can estimate an individual's physiologic age and that the gap between AI-ECG and chronologic age (Age-Gap) is associated with increased mortality. We hypothesized that Age-Gap would predict long-term atherosclerotic cardiovascular disease (ASCVD) and that Age-Gap would refine the ACC/AHA Pooled Cohort Equations' (PCE) predictive abilities. Methods Using the Rochester Epidemiology Project (REP) we evaluated a community-based cohort of consecutive patients seeking primary care between 1998–2000 and followed through March 2016. Inclusion criteria were age 40–79 and complete data to calculate PCE. We excluded those with known ASCVD, AF, HF or an event within 30 days of baseline.A neural network, trained, validated, and tested in an independent cohort of ∼ 500,000 independent patients, using 10-second digital samples of raw, 12 lead ECGs. PCE was categorized as low&lt;5%, intermediate 5–9.9%, high 10–19.9%, and very high≥20%. The primary endpoint was ASCVD and included fatal and non-fatal myocardial infarction and ischemic stroke; the secondary endpoint also included coronary revascularization [Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft (CABG)], TIA and Cardiovascular mortality. Events were validated in duplicate. Follow-up was truncated at 10 years for PCE analysis. The association between Age-Gap with ASCVD and expanded ASCVD was assessed with cox proportional hazard models that adjusted for chronological age, sex and risk factors. Models were stratified by PCE risk categories to evaluate the effect of PCE predicted risk. Results We included 24,793 patients (54% women, 95% Caucasian) with mean follow up of 12.6±5.1 years. 2,366 (9.5%) developed ASCVD events and 3,401 (13.7%) the expanded ASCVD. Mean chronologic age was 53.6±11.6 years and the AI-ECG age was 54.5±10.9 years, R2=0.7865, p&lt;0.0001. The mean Age-Gap was 0.87±7.38 years. After adjusting for age and sex, those considered older by ECG, compared to their chronologic age had a higher risk for ASCVD when compared to those with &lt;−2 SD age gap (considered younger by ECG). (Figure 1A), with similar results when using the expanded definition of ASCVD (data not shown). Furthermore, Age-Gap enhanced predicted capabilities of the PCE among those with low 10-year predicted risk (&lt;5%): Age and sex adjusted HR 4.73, 95% CI 1.42–15.74, p-value=0.01 and among those with high predicted risk (&gt;20%) age and sex adjusted HR 6.90, 95% CI 1.98–24.08, p-value=0.0006, when comparing those older to younger by ECG respectively (Figure 1B). Conclusion The difference between physiologic AI-ECG age and chronologic age is associated with long-term ASCVD, and enhances current risk calculators (PCE) ability to identify high and low risk individuals. This may help identify individuals who should or should not be treated with newer, expensive risk-reducing therapies. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic

scholarly journals High Integrity and Fidelity of Long-Term Cryopreserved Umbilical Cord Blood for Transplantation

2021 ◽  
Vol 10 (2) ◽  
pp. 293
Author(s):  
Gee-Hye Kim ◽  
Jihye Kwak ◽  
Sung Hee Kim ◽  
Hee Jung Kim ◽  
Hye Kyung Hong ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Clinical Applications ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Hsc Transplantation

Umbilical cord blood (UCB) is used as a source of donor cells for hematopoietic stem cell (HSC) transplantation. The success of transplantation is dependent on the quality of cord blood (CB) units for maximizing the chance of engraftment. Improved outcomes following transplantation are associated with certain factors of cryopreserved CB units: total volume and total nucleated cell (TNC) count, mononuclear cell (MNC) count, and CD34+ cell count. The role of the storage period of CB units in determining the viability and counts of cells is less clear and is related to the quality of cryopreserved CB units. Herein, we demonstrate the recovery of viable TNCs and CD34+ cells, as well as the MNC viability in 20-year-old cryopreserved CB units in a CB bank (MEDIPOST Co., Ltd., Seongnam-si, Gyeonggi-do, Korea). In addition, cell populations in CB units were evaluated for future clinical applications. The stable recovery rate of the viability of cryopreserved CB that had been stored for up to 20 years suggested the possibility of uses of the long-term cryopreservation of CB units. Similar relationships were observed in the recovery of TNCs and CD34+ cells in units of cryopreserved and fresh CB. The high-viability recovery of long-term cryopreserved CB suggests that successful hematopoietic stem cell (HSC) transplantation and other clinical applications, which are suitable for treating incurable diseases, may be performed regardless of long-term storage.

scholarly journals Predictors of adverse prognosis in patients with infective endocarditis in a surgical referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Scheggi ◽  
I Olivotto ◽  
N Ceschia ◽  
I Merilli ◽  
V Andrei ◽  
...  
Keyword(s):  
Renal Failure ◽  
Infective Endocarditis ◽  
Adverse Events ◽  
Ejection Fraction ◽  
Relapse Rate ◽  
Left Ventricular Ejection ◽  
All Cause Mortality ◽  
Fatal Adverse Events

Abstract Background Despite optimal medical and surgical treatment, mortality in infective endocarditis (IE) remains high. Aim of this study was to identify predictors of long term mortality for any cause, adverse event rate, relapse rate and valvular dysfunction at follow-up, in a high-volume surgical center. Methods We retrospectively analyzed 358 consecutive patients (127 women) admitted to our department with definite diagnosis of IE not device-related. IE occurred on native valves in 224 patients (63%); the infection involved the aortic valve in 192 (54%), mitral valve in 139 (39%) and tricuspid valve in 26 (7%). Overall 285 (80%) patients underwent surgery and 73 (20%) were treated conservatively, 38 due to absence of surgical indication and 35 due to refusal or prohibitive surgical risk. Long-term follow-up was obtained by structured telephone interviews. Primary endpoints were all-cause mortality, freedom from recurrent endocarditis, postoperative incidence of major adverse events (hospitalization for any cause, pace-maker implantation, new onset of atrial fibrillation, sternal dehiscence), worsening of left ventricular ejection fraction (LVEF) and valvular dysfunction. Results Mean age was 65 years (SD 15.2). Mean vegetation length was 8.9 mm (SD 7.6). Endocarditis was left-sided in 332 (93%). Average follow-up was 6 months. At univariable analysis, mortality was associated with female gender (p=0.031), age (p&lt;0.001), higher EuroSCORE 2 (p&lt;0.001), chronic renal failure (p&lt;0.001), diabetes (p=0.002), brain embolism on presentation (p=0.05), double valve infection (p=0.008), low ejection fraction (p&lt;0.001), paravalvular extension (p=0.031), prosthetic infection (p=0.018), exclusion from surgery if indicated (p&lt;0.001), high procalcitonin levels (p=0.035); factors associated with a significantly lower mortality were streptococcal infection (p=0.04; OR 0.34) and early surgery (p=0.009, OR 0.55). At multivariable analysis independent predictors of all-cause mortality were lower EF, EuroSCORE2, procalcitonin levels and diabetes. Non-fatal adverse events were associated with renal failure (p 0.035, OR 2.8). Relapse rate was associated with S aureus infection (p=0.005, OR 3.8), right-sided endocarditis (p&lt;0.001, OR 6.7) and drug abuse (p&lt;0.001, OR 9.4). Conclusions The present study shows that low EF, EuroSCORE2, procalcitonin levels and diabetes are independent predictors of death in patients with IE. Non-fatal adverse events are more frequent in patients with renal failure. Relapse rate is higher in drug abusers. These informations may help personalize follow-up strategies after acute admission for IE. Funding Acknowledgement Type of funding source: None

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