scholarly journals Evaluation of the effi ciency of the activity of the register of potential donors of hematopoietic stem cells

2020 ◽  
Vol 65 (3) ◽  
pp. 291-298
Author(s):  
M. A. Loginova ◽  
N. A. Malysheva ◽  
N. V. Minaeva ◽  
I. V. Paramonov
Keyword(s):  
Cellular Material ◽  
Hla Typing ◽  
Activation Time ◽  
Hematopoietic Stem ◽  
Effective Work ◽  
Effi Ciency ◽  
Transplant Center ◽  
Interaction Scheme ◽  
Preliminary Activation ◽  
Activation Times

Introduction. One of the problems in providing Russian transplant clinics with unrelated hematopoietic steam cells (HSCs) is the lack of an interaction scheme “Registry — HSC collection center — Transplant center”. In order to ensure effective operation at the donor activation stage, registries need regulated and stable cooperation with the Collection center with a clear distribution of duties and responsibilities for both parties. Aim: to evaluate the effectiveness of the Kirov Registry.Materials and methods. Since 2009, the Kirov Registry has been systematically working with HSC donors (as of 25/11/2019, the total number of donors was 46,922, of which 43 % male, 57 % female; 49 % regular blood donors, 51 % volunteers from donor actions) since 2013. The Registry has its own Collection Center. The effectiveness of the Registry was evaluated by indicators: the number of donations, donor activation time, the number of refusals at the stages of preliminary activation and donation of cellular material. Results. As of 25/11/2019, more than 1,000 preliminary activations of potential HSC donors were performed, of which 175 were completed by collection of HSCs. The use of the created and validated activation model with the employment of the Registry and the Collection Center currently provides the following activation times: the period for sending a sample for confi rming HLA typing does not exceed 14 days; the total time to satisfy the transplant center request for cellular material does not exceed 2 months. A detailed analysis of the causes of refusals at the stages of preliminary activation and after receiving a request for the collection of cell material was carried out. Conclusion. Between 2009 and 2019 the Kirov registry has developed a model of effective work with the donors of the HSCs at all stages of the chain “Registry — HSC collection center — Transplant center”. The effectiveness of the work is confi rmed by the demand for donors, observance of the donor activation time, and a relatively low percentage of refusals from donations.

scholarly journals Bachmann bundle impairment following linear ablation of left anterior wall: impact on left atrial function

2020 ◽  
Author(s):  
Yanjuan Zhang ◽  
Fengming Wu ◽  
Yu Gao ◽  
Nan Wu ◽  
Gang Yang ◽  
...  
Keyword(s):  
Contractile Function ◽  
Anterior Wall ◽  
Activation Time ◽  
Linear Ablation ◽  
Measured Activation ◽  
Mechanical Remodeling ◽  
Activation Times ◽  
And Function ◽  
Bachmann Bundle

Background: We aimed to evaluate the effect of Bachmann bundle (BB) impairment on electrical and mechanical function of the left atrium (LA), as well as the long-term clinical impact of such impairment. Design: We measured activation time in the five LA walls in 56 patients with atrial fibrillation. LA reservoir, conduit, and contractile function were also evaluated. Patients were divided into two groups based on ablation strategy: the circumferential pulmonary vein isolation (CPVI) group and CPVI with anterior wall linear ablation (LAWA) group. Patients in the CPVI+LAWA group were divided into two sub-groups based on ECG differences following ablation: the BB impairment group and intact BB group. LA activation time and function were then compared between the ablation strategy groups and the CPVI+LAWA subgroups. Results: Patients in the CPVI+LAWA group exhibited longer activation times in the anterior and lateral walls of the LA, poorer LA synchrony, and reduced LA contractile and reservoir function when compared with those in the CPVI group. In the BB impairment subgroup, we observed a discrepancy between electrical/mechanical remodeling. Among five walls, activation time was longest in this region. BB impairment was also associated with reduced LA function. Conclusion: Significant changes in LA function and conductibility were observed in patients with anterior wall ablation, especially those with iatrogenic BB impairment.

Umbilical Cord Blood (UCB) Banking: Is Performing the Quality Controls on a Thawed Cryovial Representative of the UCB Graft?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3643-3643
Author(s):  
Laura Salvaneschi ◽  
Cesare Perotti ◽  
Paola Bergamaschi ◽  
Claudia Del Fante ◽  
Gianluca Viarengo ◽  
...  
Keyword(s):  
Clinical Use ◽  
Growing Up ◽  
Hematopoietic Stem ◽  
Quality Controls ◽  
Inhibiting Factor ◽  
Transplant Center ◽  
Cd34 Cells ◽  
Gentle Agitation ◽  
Automated Cell Counter ◽  
Cell Counter

Abstract Introduction: Nowadays UCB represents an established source of hematopoietic stem cells for unrelated transplants in children and the employ in adults is quickly growing up. Nucleated cells (NCs) content is one of the main predictors to evaluate UCB for clinical use; however, other indicators of the hematopoietic potential, such as CD34+ cell and colony-forming cells (CFUs), have recently showed similar correlations. According to Netcord-FACT standards, it is recommended to test all the above mentioned parameters before releasing UCB to the transplant center; a segmented tubing of the UCB bag should be used but a satellite cryotube is more often available. We preliminarily report the results of quality controls performed on thawed cryovials corresponding to each of 15 units delivered by our UCB Bank. Material and methods: in our policy, all UCBs are stored accompanied by 3 satellite cryovials, treated under the same conditions of the unit. For each of the 15 UCBs released for transplantation, one cryotube was thawed in a 37°C water bath with a gentle agitation, without washing out DMSO. NCs and mononucleated cells (MNCs) were estimated with an automated cell counter. Viability and CD34+ cell count were evaluated by flow cytometry, with a no-wash, single-platform technique and 7-aminoactinomycin D. CFU assay was performed using commercial reagents (Methocult GF H4434, StemCell Technologies) and colonies were classified after a 14 days incubation. The same parameters referring to fresh UCBs (before cryopreservation) were always available. Results: the UCB characteristics measured after thawing a cryovial were compared with those of the fresh cord and are detailed in the table below. fresh UCB before cryopreservation UCB cryovial after thawing Yield (%) NC (x106) 1491.3 (148–2262) 1354.2 (167.4–2119.9) 92 (83–113) MNC (x106) 662.7 (96.5–900.3) 638.8 (295–1238.7) 95 (63–159) CD 34+ cells (x106) 3.47 (0.38–10.87) 3.19 (0.4–9.27) 85 (37–118) Viability (%) 96 (88–100) 62 (39–77) Viability of CD34+ cells (%) 92 (71–99) CFU-GM (x104) 838.5 (57.2–3581.2) 424.11 (65.29–917.64) 69 (16–184) BFU-E (x104) 1709.61 (159.84–5116) 473.34 (39.69–1204.14) 41 (5–139) total CFU (x104) 2565.17 (217.04–8953) 911.68 (164.43–2075.22) 57 (9–160) Excellent yields were found for NCs, MNCs and CD34+ cells. Despite of the decrease in the overall viability, the viable CD34+ cells as percentage was always highly satisfactory. The colonies growth was found lower in the thawed sample in comparison with fresh UCB before cryopreservation. Conclusion: in our experience, highly satisfactory evaluations of UCB content could be obtained using thawed cryotubes with regard to NC, MNC and also CD34+ cell. However, concerning the latter, the different methods employed on fresh UCBs, such as CD34+ cells detection without beads, may be advocated to explain some discrepancies in the yield range. The results of CFU assay confirmed to be poorly useful, essentially because affected by a subjective interpretation even if the reduced cell growth may be also related to the presence of DMSO as inhibiting factor.

Results of Alternative Donor Search in Adult Patients with Severe Sickle Cell Disease (SCD) Eligible for Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2260-2260 ◽  
Author(s):  
Matthew M. Hsieh ◽  
Jennifer Wilder ◽  
Courtney Fitzhugh ◽  
Beth Link ◽  
John F. Tisdale
Keyword(s):  
Cord Blood ◽  
Great Majority ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Potential Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Sibling Donor ◽  
Alternative Donor ◽  
Matched Sibling

Abstract Supportive care has improved the outlook for patients with SCD, but life expectancy remains considerably shorter than those without SCD. The major causes of mortality are end-organ failure, stroke, pulmonary disease, and acute vaso-occlusive crises (VOC). Myeloablative allogeneic HSCT in children under age 16 is curative in the majority. However organ damage that meets severity criteria for HSCT may not become evident until adulthood, at which time conventional myeloablative transplant is no longer an option. Additionally, the great majority of SCD patients do not have a 6/6 HLA-matched sibling donor available. Reduced-intensity conditioning may extend this potentially curative treatment to adults with SCD. Since non-myeloablative transplants may result in mixed donor chimerism, major ABO-mismatch may lead to red cell aplasia, and therefore should be avoided. Finally, cell dose is likely an important parameter in non-myeloablative transplant regimens, potentially further limiting donor availability. We initiated an IRB approved non-myeloablative allogeneic HSCT program for adults with severe SCD for whom a matched sibling donor is available. For those without related donors, we devised a search strategy for alternative donors to establish the feasibility of matched unrelated donor (MUD) or umbilical cord blood (UCB) HSCT. HLA typing was performed for potential donors and patients who on initial screen met at least one the following criteria: stroke, pulmonary hypertension, sickle related nephropathy, or frequent VOC/ACS not improved by HU. Typing at the serologic level was performed for HLA-A,-B, and at the allele level for HLA-DR B1. For patients without matched sibling donors, searches in the National Marrow Donor Program for marrow and cord blood donors were initiated. Since 2003, we performed initial screening in >100 patients, typed 58 potential recipients and 85 donors, and identified 13 potential recipients (age ≥ 16 years) with matched sibling donors. Two were excluded because of major ABO incompatibility. Among the remaining 43, 10 patients who met all study criteria on full screening were selected for alternative donor searching. MUD search results identified a median of 2.5 (range 0–18) 6/6 HLA-matched donor available. Five individuals had 0, four had 4–6, and one had >15 potential donors. UCB search revealed no patient had a 6/6 HLA-matched, two had 15–16 5/6 HLA-matched, and five had 11–190 4/6 potential donor UCB units. The median UCB units containing ≥ 2 × 10e7 nucleated cells per kg were 0 for 6/6 HLA-matched (range 0–1), 0 for 5/6 HLA-matched (range 0–19), and 8.5 for 4/6 HLA-matched (range 0–190). When ethnic haplotype and allelic frequency, the available ABO status, the likelihood of requiring two UCB units for each adult recipient were considered, 5 had neither MUD nor UCB units available, 2 only had potential UCB units available, and 3 had both MUD and UCB units available. The majority of adults with severe SCD who are eligible for non-ablative allo-HSCT do not have matched sibling donors. Our search shows that the minority of African-American adults have potential alternative donors, 10% and 50% MUD and UCB, respectively. These numbers will likely be reduced when major ABO mismatches are excluded. Further, unlike pediatric patients, one cord blood unit may not provide sufficient cells to overcome the barrier of graft rejection in most adults. Given these limitations, the feasibility of haplo-identical family donor allo-HSCT should be investigated.

Superior Outcomes with Matched Unrelated Donors Compared with One Human Leukocyte Antigen Mismatched Related Donors In Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 907-907
Author(s):  
Stefan O. Ciurea ◽  
Rima M. Saliba ◽  
Gabriela Rondon ◽  
Poliana A. Patah ◽  
Fleur Aung ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Resolution ◽  
Graft Failure ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Class I ◽  
Hematopoietic Stem ◽  
Leukocyte Antigen ◽  
Unrelated Donors ◽  
Related Donor

Abstract Abstract 907 Most candidates for hematopoietic stem cell transplantation lack a human leukocyte antigen (HLA)-identical sibling donor; however, many patients may have a related donor with whom they are mismatched at one antigen/allele. It is not known whether such a match is preferable to a matched unrelated donor (MUD). We hypothesized that, in transplantation using related donors, adding a single HLA antigen/allele mismatch, identified through high resolution HLA typing at HLA-A, -B, -C, -DRB1 and -DQB1, would be associated with worse outcomes than transplantation using matched unrelated donors. Patients and Methods: To test this hypothesis, we analyzed outcomes (survival, relapse, non-relapse mortality) of 367 patients who received transplants from either a 10/10 MUD (n=318) or a one-antigen/allele mismatched related donor (MRD) by 7/8 HLA typing (n=49) treated during the same period of time (1995-2009) at our institution. All patients had intermediate/high-resolution HLA typing at all 5 loci either prospectively or retrospectively, if treated after or before year 2002. Of the 49 patients treated with mismatched related donors, 28 patients (57%) had one antigen/allele mismatched at HLA class I or II loci (or 9/10), 18 patients (37%) had 2 alleles mismatched (or 8/10), and 3 patients (6%) had 3 alleles mismatched (or 7/10). From the 28 patients with a one-allele mismatch, 24 had class I mismatches at either HLA-A or -B loci, and 4 had class II mismatches at either HLA-DR or -DQ loci. Characteristics between the MUD group and 9/10 MRD group were similar [median age 53 vs. 47 years (p=0.08); AML/MDS diagnosis 84% vs. 82% (p=0.5); active disease at transplant 59% vs. 57% (p=0.9); myeloablatie conditioning 63% vs. 75% (p=0.2); bone marrow stem cells 58% vs. 70% (p=0.2); pentostatin use 14% vs. 11% (p=0.4); median year of transplant 2006 vs. 2004, respectively] except more patients in the MUD group received ATG (96% vs. 68%, p=0.02). Results: Outcomes at 3-years were analyzed for the 28 consecutive patients who had received a transplant from a 9/10 MRD based on 5-loci (including -DQB1) HLA typing. Graft failure was more common in patients treated from 9/10 related donors than from MUD. The incidences of primary and secondary graft failure for the 9/10 MRD were 7% and 14%, respectively, whereas none of the MUD transplant recipients had either primary or secondary graft failure (p= 0.02). Cumulative incidence of progression was 40% vs. 25% (p=0.02, HR 1.9, CI 1.1–3.9), non-relapse mortality 40% vs. 26% (p=0.05, HR 1.9, CI 1.0–3.6) and grade II-IV a GVHD was 27% vs. 38% (p=0.4, HR 0.7, CI 0.3–2.5) for the two groups, respectively. Median survival was 6 months for the 9/10 MRD vs. 18 months for the MUD group. The overall survival and progression-free survival rates were 19% and 45% (p=0.007, HR 1.8, CI 1.2–2.9) and 19% vs. 42% (p=0.006, HR1.8, CI 1.2–2.9), respectively. Outcomes for 9/10 MRD transplant patients with class I mismatches (n=24) were significantly worse than outcomes in those with MUD transplants (n=318). The 2-year actuarial OS rate was 27% for the 9/10 MRD and 48% for the MUD transplant group (HR 1.9; 95% CI 1.1 – 3.1; p=0.01). Conclusion: These results indicate that transplant outcomes for patients treated from a one-antigen/allele mismatch related donor are significantly worse than from a MUD, primarily due to increased non-relapse mortality. Patients receiving transplants form a 9/10 related donors, at least with a class I mismatch, should be treated on investigational protocols. Disclosures: No relevant conflicts of interest to declare.

A Population-Based Study In Acute Myeloid Leukemia (AML) Suggests Improved Overall Survival (OS) up to Age 80 with Intravenous Therapy: 2000–2007 Data From the Surveillance, Epidemiology, and End Results (SEER)-Medicare Registry In the United States (US),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3589-3589
Author(s):  
Betul Oran ◽  
Daniel J. Weisdorf ◽  
Beth Virnig
Keyword(s):  
Treatment Group ◽  
Age Groups ◽  
Human Leukocyte ◽  
The United States ◽  
Population Based ◽  
Older Age ◽  
Hla Typing ◽  
Hypomethylating Agents ◽  
Intravenous Therapy ◽  
Hematopoietic Stem

Abstract Abstract 3589 Background: AML is the most common leukemia among US adults with median age of 69. Earlier 1990s studies reported a median OS was 2.4 months among patients older than age 65. Considering the trends in older AML treatment might have changed during the last decade, we investigated clinical practice for older AML patients. Methods: Patients age ≥ 66 in the National Cancer Institute's (NCI) SEER cancer registry with a first, primary cancer of AML diagnosed between January 2000 and December 2007 were matched to their Medicare Part A and Part B claims for long-term follow-up. Diagnostic evaluation and treatment patterns with disease outcomes were assessed. There were 4633 AML patients identified, and 1791(38.6%) received intravenous leukemia therapy within 3 months of diagnosis (treatment group). Treated patients then were sub-grouped as receiving chemotherapy (chemo) (94.9%) and hypomethylating agents (hypo) (5.1%). Results: The median age of the study population was 78. Treatment group had similar demographics compared to the no treatment group except they were younger (median age, 74 vs. 80, p<0.01) and more were male (56.9 % vs. 48.8%, p<0.01). Median Charlson comorbidity score (CCS) were similar (median, 0) but less patients in treatment group had CCS ≥ 2 (13.0% vs. 20.1%, p<0.01). Patients in treatment group received more extensive diagnostic work-up including: flow cytometry (72.3% vs. 50.8%, p<0.01), cytogenetics (48% vs. 27.4%, p<0.01) and human leukocyte antigen (HLA) typing (6.8% vs. 0.6%, p<0.01). Median OS was 3 months, but superior in the treatment group (7 mo. vs. 2 mo, p<0.01). This benefit was demonstrable in all age groups with greatest improvements in age 66–69 (10 mo. vs. 4 mo, p<0.01) and 70–74 (8 mo. vs. 3 mo, p<0.01) (Figure 1). Older age and CCS ≥2 were also associated with decreased OS (HR=1.04 (for each year), p<0.01 and HR=1.3, p<0.01 respectively). Within the treatment group, 2-month mortality after treatment was 31.2 % with the lowest level in age groups 66–69 and 70–74 (19.8 % and 25.2 %). Logistic regression analyses revealed that older age and CCS ≥2 were significantly associated with higher 2-month mortality (HR=1.08 (for each year), p<0.01 and HR=1.3, p<0.01 respectively). Among treated patients, a subgroup analysis of 91 patients receiving hypo showed that they were older than chemo group (median age 78 vs. 74, p<0.01), but had similar CSS scores. Although OS with hypo was increased compared to chemo group (9 mo. vs. 6 mo.) in multivariate analysis this difference was not significant (HR=1.25, p=0.07). Hematopoietic stem cell transplantation (HCT) was performed only in 57 patients (1.2%) after AML diagnosis. Median time to HCT after AML diagnosis was 6 months. These patients were younger (median age 66 vs. 73 in other treated patients) and none had CSS scores >2 (0% vs. 6.1%). Their median OS from diagnosis was 25 months. Conclusion: Intravenous therapy improves OS in older AML patients and most patients up to 80 years of age should be considered for treatment based on their comorbidity status. New therapies including hypomethylating agents and allogeneic HCT are promising and must be compared with other chemotherapy in the appropriately selected population. Disclosures: Weisdorf: Genzyme: Consultancy, Research Funding.

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