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1.
Br J Haematol ; 201(6): 1159-1168, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36949601

RESUMEN

ABO incompatibility affects approximately 40% of allogeneic stem cell transplants in Caucasian patient populations. Because bone marrow (BM), the preferred graft from paediatric sibling donors and for non-malignant diseases, has a red blood cell (RBC) content similar to blood, anti-donor isoagglutinins must either be depleted from the recipient or RBCs removed from the graft. To achieve tolerability of unmanipulated BM grafts, we used controlled infusions of donor ABO-type RBC units to deplete isoagglutinins before the transplant. This retrospective study evaluates the outcomes of 52 ABO major incompatible BM transplants performed at our centre between 2007 and 2019. The use of donor-type RBC transfusions was well tolerated. They effectively reduced isoagglutinins levels, typically achieving target titres after one (60%) or two (29%) transfusions. The approach allowed for successful and uneventful infusions of unmanipulated BM which provided timely engraftment. The transplant outcomes were not inferior to those of a matched-pair control group of patients with ABO-identical donors.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Aplasia Pura de Células Rojas , Humanos , Niño , Médula Ósea , Transfusión de Eritrocitos/efectos adversos , Estudios Retrospectivos , Aplasia Pura de Células Rojas/etiología , Sistema del Grupo Sanguíneo ABO , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Médula Ósea/efectos adversos , Incompatibilidad de Grupos Sanguíneos
2.
Br J Haematol ; 200(5): 608-621, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36370064

RESUMEN

In a prospective, explorative study, the donor-source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft-versus-host disease (GVHD) in HF-HCT patients (49%, 7%, and 16% for HF-, MS- and UD-HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF-HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri-engraftment acute GVHD was not observed in MS-HCT or UD-HCT patients. Additionally, a significantly higher proportion of HF-HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF-, MS- and UD-HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non-relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG-containing conditioning, stronger donor-patient alloreactivity was observed in HF-HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Busulfano/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Donante no Emparentado , Hermanos , Estudios Prospectivos , Recurrencia Local de Neoplasia , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante
3.
Eur J Haematol ; 108(4): 327-335, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34962675

RESUMEN

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is increasingly used, but this treatment is complex and costly. As clinical outcomes of HSCT with matched unrelated donor (MUD) and haploidentical donors are similar, costs could influence donor choice. METHOD: We retrospectively compared resource utilisation and costs of HSCT using the three different donor types (matched related donor (MRD) (n = 32), haploidentical related (n = 30) and MUD (n = 60)) within the first year after transplantation. Costs were analysed through a bottom-up method. Non-parametric bootstrapping was applied to test for statistical differences in costs. Subgroup analyses were performed to identify predictors for costs. RESULTS: Cost pre-transplant for search and acquisition of the graft were significantly higher in MUD HSCT (€35 222) versus MRD and haploidentical HSCT (€15 356 and €16 097 respectively). The costs of haploidentical HSCT were the highest in the transplant phase. Main cost factors were inpatient days and medication. Overall, the costs for haploidentical and MUD HSCT were similar (€115 724 for MUD, €113 312 for haploidentical). CONCLUSION: Our study suggests no difference in total transplantation costs between allogeneic HSCT using a MUD or a haploidentical donor. Since clinical outcomes seem similar as well, the choice of donor type might be based on availability, speed and logistics.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Países Bajos/epidemiología , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Donante no Emparentado
4.
Transpl Int ; 35: 10199, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35185379

RESUMEN

Reduced estimated glomerular filtration rate (eGFR) at 12-months after kidney transplantation is associated with increased risk of allograft loss, but it is uncertain whether donor age and types modify this relationship. Using Australia and New Zealand registry data, multivariable Cox proportional modelling was used to examine the interactive effects between donor age, types and 12-month eGFR on overall allograft loss. We included 11,095 recipients (4,423 received live-donors). Recipients with lowest 12-month eGFR (<30 ml/min/1.73 m2) experienced the greatest risk of allograft loss, with adjusted HR [95% CI) of 2.65 [2.38-2.95] compared to eGFR of 30-60 ml/min/1.73 m2; whereas the adjusted HR for highest eGFR (>60 ml/min/1.73 m2) was 0.67 [0.62-0.74]. The association of 12-month eGFR and allograft loss was modified by donor age (but not donor types) where a higher risk of allograft loss in recipients with lower compared with higher 12-month eGFR being most pronounced in the younger donor age groups (p < 0.01). Recipients with eGFR <30 ml/min/1.73 m2 12-months after transplantation experienced ≥2.5-fold increased risk of overall allograft loss compared to those with eGFR of >60 ml/min/1.73 m2, and the magnitude of the increased risk is most marked among recipients with younger donors. Careful deliberation of other factors including donor age when considering eGFR as a surrogate for clinical endpoints is warranted.


Asunto(s)
Trasplante de Riñón , Aloinjertos , Niño , Tasa de Filtración Glomerular , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Estudios Retrospectivos , Resultado del Tratamiento
5.
Pediatr Transplant ; 26(7): e14368, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35869899

RESUMEN

BACKGROUND: There are conflicting data on long-term outcomes of pediatric LURD renal Txs compared to Txs of kidneys from other donor sources. METHODS: An analysis of the OPTN database was conducted in children (<18 years) who had received their 1st kidney-only Tx between January 1, 2000, and September 30, 2021. The primary outcome measure was time to graft failure or death. Cox event history regression model for time to primary outcome, categorized by donor source and adjusting for confounders was performed. RESULTS: Of the 12 089 subjects, 327 (2.7%) received kidneys from LURDs, 4349 (36%) from LRDs and 7413 (61%) from DD. One year graft failure rate was 3.56%. On regression analyses, compared to LRD kidney recipients, LURD recipients had comparable graft survival (graft failure AHR 1.15, 95th percentile confidence interval 0.87-1.51; p .31) and DD recipients had lower graft survival (graft failure hazard ratio 1.26, 95th percentile confidence interval 1.10-1.43; p < .001). When using living unrelated kidney recipients as the reference group, DD kidney recipients had comparable graft survival, with a wide confidence interval (hazard ratio for graft failure 1.09; 0.83-1.43, p .53). CONCLUSIONS: Pediatric LURD kidney recipients have comparable graft survival to LRD kidney recipients; DD kidney recipients had the poorest survival. Our study, the largest to date, should encourage centers to embrace non-commercial living-unrelated transplantation as a viable option for children, preferable to DD kidneys.


Asunto(s)
Trasplante de Riñón , Obtención de Tejidos y Órganos , Niño , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Donadores Vivos , Donante no Emparentado
6.
Nano Lett ; 21(7): 2840-2847, 2021 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-33784810

RESUMEN

Development of biocompatible fluorophores with small size, bright fluorescence, and narrow spectrum translate directly into major advances in fluorescence imaging and related techniques. Here, we discover that a small donor-acceptor-donor-type organic molecule consisting of a carbazole (Cz) donor and benzothiazole (BT) acceptor (CzBTCz) assembles into quasi-crystalline J-aggregates upon a formation of ultrasmall nanoparticles. The 3.5 nm CzBTCz Jdots show a narrow absorption spectrum (fwhm = 27 nm), near-unity fluorescence quantum yield (ϕfl = 0.95), and enhanced peak molar extinction coefficient. The superior spectroscopic characteristics of the CzBTCz Jdots result in two orders of magnitude brighter photoluminescence of the Jdots compared with semiconductor quantum dots, which enables continuous single-Jdots imaging over a 1 h period. Comparison with structurally similar CzBT nanoparticles demonstrates a critical role played by the shape of CzBTCz on the formation of the Jdots. Our findings open an avenue for the development of a new class of fluorescent nanoparticles based on J-aggregates.

7.
Ann Hematol ; 100(8): 2071-2078, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34148110

RESUMEN

ABO incompatibility is not a barrier to allogeneic stem cell transplant but may result in acute hemolytic reactions. As stem cell product manipulation is cumbersome, we are reporting the effectiveness and safety of donor-type red cell infusion as a method of reducing acute hemolytic reaction while using marrow as stem cell source. In major ABO-mismatched bone marrow transplants, manipulation of marrow product requires expertise and expensive equipment, which may not be readily available to transplant centers in low- and middle-income regions. The aim behind our study is to report a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants. We retrospectively analyzed 303 consecutive allogeneic bone marrow transplants (BMTs) for beta thalassemia major, between August 2015 and March 2020, with either major (n = 41) or bidirectional (n = 14) mismatches. When isohemagglutinin titers were 1:32 or higher, donor-type packed red blood cell was divided into 4 aliquots, irradiated and administered over 4 days at incremental volumes. Patients were observed for hemolytic reaction, and if no reaction, bone marrow was infused without manipulation. Out of 55 patients, 20 received donor-type blood infusion. Twelve patients showed evidence of mild hemolysis. None developed severe hemolytic or anaphylactic reaction. Titers were rechecked in 14 patients and all had reduction in titers, except for one. Our experience demonstrated that donor-type PRBC infusion is safe and effective in preventing acute hemolysis in major ABO-mismatched stem cell transplants even with bone marrow as graft source.


Asunto(s)
Sistema del Grupo Sanguíneo ABO/sangre , Incompatibilidad de Grupos Sanguíneos/sangre , Trasplante de Médula Ósea/métodos , Transfusión de Eritrocitos/métodos , Hemaglutininas/sangre , Adolescente , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Femenino , Hemólisis , Humanos , Masculino , Estudios Retrospectivos , Donantes de Tejidos , Trasplante Homólogo
8.
J Postgrad Med ; 67(4): 235-237, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34121669

RESUMEN

Donor-type aplasia (DTA) is a condition where an individual continues to be aplastic even after a successful engraftment of a hematopoeitic stem cell transplant with a majority of donor type cells in the bone marrow. This entity has been seen with varying frequency around the world, especially in Southeast Asia. However, its incidence in the Indian subcontinent remains fairly low. Here is a case of a 17-year-old child with DTA who had a 89% population of donor cells after a successful transplant and presented with recurrent severe aplastic anemia later. The patient eventually succumbed to his condition before a second transplant could be performed. The awareness about the seriousness of this relatively rare condition, therefore, needs to be emphasized.


Asunto(s)
Anemia Aplásica , Trasplante de Células Madre Hematopoyéticas , Adolescente , Anemia Aplásica/terapia , Trasplante de Médula Ósea , Humanos , Incidencia
9.
Biol Blood Marrow Transplant ; 26(3): 480-485, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31733299

RESUMEN

There have been sporadic reports of the development of delayed disease recurrence after bone marrow transplantation for severe aplastic anemia despite sustained majority or full donor chimerism. This is termed "donor-type aplasia" (DTA). We describe the management and outcome of 11 pediatric patients from 8 institutions in Europe, the United States, and the Middle East who developed DTA at a mean of 35 months post-transplant. These patients were initially transplanted at a mean age of 10.0 years (range, 5.8 to 16.0 years), 9 from matched sibling donors and 2 from matched unrelated donors. Attempts to treat DTA with varying combinations of additional immunosuppression (including intravenous immunoglobulin, donor lymphocyte infusions, stem cell boosts, and other therapies) failed. Ten patients have received a conditioned second transplant, 9 from the same donor and 1 from a new matched unrelated donor. Aplasia has resolved in the remaining patient in response to ongoing eltrombopag therapy. All patients were alive at a mean of 92 months (range, 26 to 195) after a second transplant; 6 are in complete remission, but 4 suffered from second/recurrent DTA at 16 to 129 months after retransplant and required further transplant therapy.


Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adolescente , Anemia Aplásica/terapia , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Quimerismo , Europa (Continente) , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Recurrencia
10.
Biol Blood Marrow Transplant ; 26(9): 1747-1756, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32464284

RESUMEN

Allogeneic hematopoietic stem cell transplantation (alloHCT) may be associated with significant morbidity and mortality, resulting in increased healthcare utilization (HCU). To date, no multicenter comparative cost analyses have specifically evaluated alloHCT in children with acute leukemia. In this retrospective cohort study, we examined the relationship between survival and HCU while investigating the hypothesis that matched sibling donor (MSD) alloHCT has significantly lower inpatient HCU with unrelated donor (URD) alloHCT, and that among URDs, umbilical cord blood (UCB) alloHCT will have higher initial utilization but lower long-term utilization. Clinical and transplantation outcomes data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were merged with inpatient cost data from the Pediatric Health Information System (PHIS) database using a probabilistic merge methodology. The merged dataset comprised US patients age 1 to 21 years who underwent alloHCT for acute leukemia between 2004 and 2011 with comprehensive CIBMTR data at a PHIS hospital. AlloHCT was analyzed by donor type, with specific analysis of utilization and costs using PHIS claims data. The primary outcomes of overall survival (OS), leukemia-free survival (LFS), and inpatient costs were evaluated using Kaplan-Meier curves and Cox and Poisson models. A total of 632 patients were identified in both the CIBMTR and PHIS data. The 5-year LFS was 60% for MSD alloHCT, 47% for well-matched matched unrelated donor bone marrow (MUD) alloHCT, 48% for mismatched unrelated donor alloHCT, and 45% for UCB alloHCT (P = .09). Total adjusted costs were significantly lower for MSD alloHCT versus MUD alloHCT by day 100 (adjusted cost ratio [ACR], .73; 95% confidence interval [CI], .62 to .86; P < .001), and higher for UCB alloHCT versus MUD alloHCT (ACR, 1.27; 95% CI, 1.11 to 1.45; P < .001). By 2 years, total adjusted costs remained significantly lower for MSD alloHCT compared with MUD alloHCT (ACR, .67; 95% CI, .56 to .81; P < .001) and higher for UCB alloHCT compared with MUD alloHCT (ACR, 1.25; 95% CI, 1.02 to 1.52; P = .0280). Our data show that UCB and MUD alloHCT provide similar survival outcomes; however, MUD alloHCT has a significant advantage in cost by day 100 and 2 years. More research is needed to determine whether the cost difference among URD alloHCT approaches remains significant with a larger sample size and/or beyond 2 years post-alloHCT.


Asunto(s)
Sistemas de Información en Salud , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Estudios Retrospectivos , Donante no Emparentado , Adulto Joven
11.
Br J Haematol ; 188(5): 745-756, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31498883

RESUMEN

Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post-transplant cyclophosphamide. Median follow-up of alive patients was 32 months. On multivariate analysis, acute graft-versus-host disease (GVHD) grade 2-4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression-free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor.


Asunto(s)
Ciclofosfamida/administración & dosificación , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfoma , Acondicionamiento Pretrasplante , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Linfoma/mortalidad , Linfoma/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Tasa de Supervivencia , Trasplante Haploidéntico
12.
BMC Nephrol ; 21(1): 422, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33008322

RESUMEN

BACKGROUND: Early kidney transplantation (KT) is the best option for patients with end-stage kidney disease, but little is known about dialysis access strategy in this context. We studied practice patterns of dialysis access and how they relate with outcomes in adults wait-listed early for KT according to the intended donor source. METHODS: This study from the REIN registry (2002-2014) included 9331 incident dialysis patients (age 18-69) wait-listed for KT before or by 6 months after starting dialysis: 8342 candidates for deceased-donor KT and 989 for living-donor KT. Subdistribution hazard ratios (SHR) of KT and death associated with hemodialysis by catheter or peritoneal dialysis compared with arteriovenous (AV) access were estimated with Fine and Gray models. RESULTS: Living-donor candidates used pretransplant peritoneal dialysis at rates similar to deceased-donor KT candidates, but had significantly more frequent catheter than AV access for hemodialysis (adjusted OR 1.25; 95%CI 1.09-1.43). Over a median follow-up of 43 (IQR: 23-67) months, 6063 patients received transplants and 305 died before KT. Median duration of pretransplant dialysis was 15 (7-27) months for deceased-donor recipients and 9 (5-15) for living-donor recipients. Catheter use in deceased-donor candidates was associated with a lower SHR for KT (0.88, 95%CI 0.82-0.94) and a higher SHR for death (1.53, 95%CI 1.14-2.04). Only five deaths occurred in living-donor candidates, three of them with catheter use. CONCLUSIONS: Pretransplant dialysis duration may be quite long even when planned with a living donor. Advantages from protecting these patients from AV fistula creation must be carefully evaluated against catheter-related risks.


Asunto(s)
Cateterismo/métodos , Fallo Renal Crónico/terapia , Trasplante de Riñón , Diálisis Renal , Adulto , Derivación Arteriovenosa Quirúrgica , Catéteres Venosos Centrales , Femenino , Humanos , Donadores Vivos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Donantes de Tejidos , Listas de Espera
13.
J Korean Med Sci ; 35(7): e46, 2020 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-32080987

RESUMEN

BACKGROUND: This study aimed to assess the outcome of stem cell transplantation (SCT), including overall survival (OS), failure-free survival (FFS) and graft-versus-host disease (GvHD)-free/failure-free survival (GFFS), and to analyze prognostic factors in children with aplastic anemia (AA). METHODS: From 1991 to 2018, 43 allogeneic SCT recipients were enrolled in the study to investigate the demographic characteristics, survival outcomes and prognostic factors. RESULTS: With the median follow-up of 7.1 years, the estimated 10-year OS, FFS, GFFS were 86.0%, 60.5%, and 51.2%, respectively. Matched related donors (MRD, n = 28) showed better 10-year OS than unrelated donors (n = 15) (96.4% vs. 66.7%; P = 0.006). Engraftment failure was seen in 13 patients (30.2%). Donor-type aplasia was seen in 13.8% (4/29) after fludarabine (Flu)-based conditioning (Flu-group), while in 42.6% (6/14) after cyclophosphamide (Cy)-based regimen (Cy-group) (P = 0.035). Six patients died. The 10-year OS in Cy-group was 92.9% (n = 14, all MRD), while that of Flu-group was 82.1% (n = 29; P = 0.367). But Flu-group tended to have better FFS and GFFS than Cy-group, although Flu-group had less MRDs (41.4% vs. 100%; P = 0.019), and higher proportion of previous immunosuppressive treatment (IST; 62% vs. 21.4%, P = 0.012). In MRD transplants, OS was similar between Flu-group (100%, n = 14) and Cy-group (92.9%, n = 14), while FFS (100.0% vs. 42.9%; P = 0.001) and GFFS (85.7% vs. 35.7%; P = 0.006) were significantly better in Flu-group. Stem cell sources, irradiation in the conditioning, and method of GvHD prophylaxis did not significantly influence the outcome. CONCLUSION: This study reviewed SCT outcomes for pediatric AA with changes of transplant strategies over the last 25 years. The FFS and GFFS were higher in Flu-group than in Cy-group, especially in matched related transplantation. Graft failure including donor-type aplasia remains troublesome even with Flu-based conditioning. Further refinement of transplant strategies to ensure better quality-of-life should be pursued.


Asunto(s)
Anemia Aplásica , Inhibidores Enzimáticos , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Vidarabina/análogos & derivados , Adolescente , Anemia Aplásica/terapia , Niño , Supervivencia sin Enfermedad , Inhibidores Enzimáticos/uso terapéutico , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Masculino , Estudios Retrospectivos , Trasplante Homólogo , Vidarabina/uso terapéutico
14.
J Lesbian Stud ; 24(1): 41-55, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31218934

RESUMEN

Until 2004, Dutch women seeking donor insemination through medical facilities could opt for open-identity or anonymous donors. Since then, Dutch law only permits open-identity donation. The present study compared the well-being of adolescents conceived before 2004 through known, open-identity, and anonymous donors, and born into planned lesbian parent families (i.e., the mothers identified as lesbian before the children were conceived). The sixty-seven participating adolescents (Mage = 16.04 years) completed the Rosenberg Self-Esteem Scale and the Youth Self-Report, and answered questions about their donor. Thirty-three were conceived through known, twenty-two through open-identity, and twelve through anonymous donors. No significant associations were found between donor type and self-esteem or problem behavior. Likewise, no significant differences were found on these two variables for adolescents with known donors who did or did not play important roles in their lives. For adolescents conceived with sperm from as-yet unknown donors (open-identity or anonymous), feeling uncomfortable about not knowing the donor was associated with lower self-esteem and more externalizing problem behavior. That donor type was found to have no bearing on adolescent self-esteem or problem behavior may be useful to prospective lesbian parents.


Asunto(s)
Conducta del Adolescente/fisiología , Padres , Problema de Conducta/psicología , Psicología del Adolescente , Autoimagen , Minorías Sexuales y de Género , Donantes de Tejidos , Adolescente , Protección a la Infancia , Servicios de Planificación Familiar , Femenino , Homosexualidad Femenina , Humanos , Masculino , Madres , Países Bajos , Revelación de la Verdad
15.
Transplant Cell Ther ; 30(2): 245.e1-245.e8, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37977336

RESUMEN

The preferred donor (haploidentical donor [HID] versus matched unrelated donor [URD]) choice in patients with acquired severe aplastic anemia (SAA) who lack an HLA-matched sibling donor (MSD) and fail upfront immunosuppressive treatment (IST) therapy is unknown. We retrospectively investigated SAA patients (n = 58) who underwent allogeneic stem cell transplantation (allo-SCT) between January 2012 and October 2022. The 5-year overall survival (OS) and 5-year failure-free survival (FFS) were comparable among the URD (n = 8), HID (n = 25), and MSD (n = 25) cohorts (OS: mean, 87.5 ± 11.7% versus 98.0 ± 6.5% versus 83.3 ± 7.6% [P = .926]; FFS: mean, 60.0 ± 18.2% versus 87.0 ± 7.0% versus 78.3 ± 8.6% [P = .222]). Multivariate analysis revealed that primary engraftment failure independently predicted OS and secondary graft failure predicted FFS among SAA patients who underwent allo-SCT, but donor type and age were not predictive of these outcomes. An urgent second SCT for patients with engraftment failure may be an effective salvage treatment. Our findings show that an alternative donor SCT is indicated for eligible SAA patients without an MSD even if age ≥40 years.


Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Anemia Aplásica/terapia , Estudios Retrospectivos , Hermanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre
16.
Hematology ; 29(1): 2337160, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38597819

RESUMEN

Pathogenic variants in the genes SAMD9 (sterile a-motif domain containing protein - 9) and SAMD9L (SAMD9-like) cause bone marrow failure with characteristic syndromic features. We report a case of a previously healthy, 3-year-old boy with no dysmorphology, who presented with severe aplastic anemia and a novel variant in the SAMD9L gene. His father, elder brother and sister who harbored the same variant were completely healthy. In the absence of a matched unrelated donor, he underwent a stem cell transplant from his sister, a 10/10 match. Almost 2 years later he developed donor type aplasia and succumbed to an invasive fungal infection after a failed haplograft from his mother. This case highlights the pathogenicity of this previously undescribed germline variation of uncertain significance in the SAMD9L gene and the value of comprehensive genetic testing for inherited bone marrow failures even in the absence of a positive family history or characteristic congenital abnormalities.


Asunto(s)
Anemia Aplásica , Trasplante de Células Madre Hematopoyéticas , Pancitopenia , Masculino , Femenino , Niño , Humanos , Anciano , Preescolar , Médula Ósea , Anemia Aplásica/genética , Anemia Aplásica/terapia , Factores de Transcripción , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Péptidos y Proteínas de Señalización Intracelular/genética
17.
Transplant Cell Ther ; 29(9): 578.e1-578.e9, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37406882

RESUMEN

Allogeneic hematopoietic cell transplantation (alloHCT) provides cure for older patients with acute myeloid leukemia (AML); however, disease relapse remains a major concern. Based on recent data suggesting that younger donor age confers the greatest benefit for alloHCT with matched unrelated donors (MUDs), we attempted to answer a practical question: which donor type provides the best outcomes when an older patient with AML has a matched sibling donor (MSD, also older) versus the best MUD? This retrospective cohort registry study accessed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients with AML age ≥ 50 years undergoing alloHCT from older MSDs (age ≥ 50 years) or younger MUDs (age ≤ 35 years) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis. The primary outcome was relapse risk. Secondary outcomes included nonrelapse mortality (NRM), GVHD, disease-free survival (DFS), and overall survival. Among 4684 eligible patients, 1736 underwent alloHCT with an older MSD (median donor age, 60 years), and 2948 underwent alloHCT from a younger MUD (median donor age, 25 years). In multivariable analysis, compared to older MSDs, the use of younger MUDs conferred a decreased relapse risk (hazard ratio [HR], .86; P = .005) and a significantly lower adjusted 5-year cumulative incidence of relapse (35% versus 41%; P = .003), but was associated with an increased risk for chronic GVHD (HR, 1.18; 95% confidence interval [CI], 1.08 to 1.29; P = .0002) and greater NRM only in the earlier period of 2011 to 2015 (HR, 1.24; P = .016). The corresponding NRM rates were significantly lower in the more recent period of 2016 to 2018 (HR, .78; P = .017). The adjusted 5-year DFS probability was 44% (95% CI, 42% to 46%) with an alloHCT from younger MUDs compared to 41% (95% CI, 38% to 43%) with older MSDs (P = .04). In summary, for older patients with AML undergoing alloHCT, the use of younger MUDs is associated with decreased relapse risk and improved DFS compared with the use of older MSDs.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Anciano , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Leucemia Mieloide Aguda/terapia , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/prevención & control , Recurrencia
18.
Nanomaterials (Basel) ; 13(21)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37947743

RESUMEN

Based on the PM6:Y6 binary system, a novel non-fullerene acceptor material, D18-Cl, was doped into the PM6:Y6 blend to fabricate the active layer. The effects of different doping ratios of D18-Cl on organic solar cells were investigated. The best-performing organic solar cell was achieved when the doping ratio of D18-Cl reached 20 wt%. It exhibited a short-circuit current of 28.13 mA/cm2, a fill factor of 70.25%, an open-circuit voltage (Voc) of 0.81 V, and a power conversion efficiency of 16.08%. The introduction of an appropriate amount of D18-Cl expanded the absorption spectrum of the active layer, improved the morphology of the active layer, reduced large molecular aggregation and defects, minimized bimolecular recombination, and optimized the collection efficiency of charge carriers. These results indicate the critical importance of selecting an appropriate third component in binary systems and optimizing the doping ratio to enhance the performance of ternary organic solar cells.

19.
Food Res Int ; 173(Pt 1): 113217, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37803537

RESUMEN

Cultivated meat produced with primary muscle satellite cells (SCs) will need a continuous supply of isolated cell material from relevant animal donors. Factors such as age, sex, and breed, along with the sustainability and availability of donor animals, could determine the most appropriate donor type for an efficient production. In this study, we focus on the proliferation and differentiation of bovine SCs isolated from bull calf and dairy cow muscle samples. The proliferative performance of bull calf SCs was significantly better than SCs from dairy cows, however a dynamic differentiation assay revealed that the degree of fusion and formation of myotubes were similar between donor types. Furthermore, the proliferation of SCs from both donor types was enhanced using an in-house developed serum-free media compared to 10% FBS, which also delayed myogenic differentiation and increased final cell population density. Using gene chip transcriptomics, we identified several differentially expressed genes between the two donor types, which could help explain the observed cellular differences. This data also revealed a high biological variance between the three replicate animals within donor type, which seemed to be decreased when using our in-house serum-free media. With the use of the powerful imaging modalities of Cytation 5, we developed a novel high contrast brightfield-enabled label-free myotube quantification method along with a more efficient end-point fusion analysis using Phalloidin-staining. The results give new insights into the bovine SC biology and potential use of bull calves and dairy cows as relevant donor animals for cultivated beef cell sourcing. The newly developed differentiation assays will further enhance future research within the field of cultivated meat and SC biology.


Asunto(s)
Células Satélite del Músculo Esquelético , Femenino , Animales , Bovinos , Masculino , Células Satélite del Músculo Esquelético/metabolismo , Medio de Cultivo Libre de Suero/metabolismo , Fibras Musculares Esqueléticas , Diferenciación Celular , Carne
20.
Transfus Clin Biol ; 29(1): 94-97, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34655817

RESUMEN

Dynamic monitoring ABO chimera including erythroid ABO antigen and anti-A/B is crucial to not only assess the status of erythroid engraftment but also achieve personalized safety transfusion in patients post ABO incompatible hematopoietic stem cell transplantation. Transfusion support for ABO incompatible (ABOi) HSCT patients after achieved complete alteration to donor origin still remains cautious because the instant hematopoietic status on these transplant patients possibly returned to patient origin derived from early disease relapse and graft loss or failure. We reported that reemergent anti-B in a female patients (donor/patient: B/O) at the early phase after achievement complete donor type were not effectively found from partial automatic ABO blood grouping systems, which directly resulted in differential judgement of transplantation stage for about 15 days and disturbed the optimal recommendation on transfusion support. Meanwhile, the solely alteration of ABO chimera was found and earlier than changes of other markers such as MRD diagnosis, chimerism analysis by STR-PCR and sex chromosome assays, which can be an available predictors for bad transplant outcomes such as graft failure.


Asunto(s)
Tipificación y Pruebas Cruzadas Sanguíneas , Trasplante de Células Madre Hematopoyéticas , Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Transfusión Sanguínea , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Trasplante Homólogo
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