scholarly journals Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts

Blood ◽  
2011 ◽  
Vol 117 (12) ◽  
pp. 3277-3285 ◽  
Author(s):  
Sharon Avery ◽  
Weiji Shi ◽  
Marissa Lubin ◽  
Anne Marie Gonzales ◽  
Glenn Heller ◽  
...  

Abstract The influence of cell dose and human leukocyte antigen (HLA) match on double-unit cord blood (CB) engraftment is not established. Therefore, we analyzed the impact of cell dose and high-resolution HLA match on neutrophil engraftment in 84 double-unit CB transplant recipients. The 94% sustained engraftment rate was accounted for by 1 unit in nearly all patients. Higher CD3+ cell doses (P = .04) and percentage of CD34+ cell viability (P = .008) were associated with unit dominance. After myeloablative conditioning, higher dominant unit total nucleated cell (TNC), CD34+ cell, and colony-forming unit doses were associated with higher sustained engraftment and faster neutrophil recovery (P = .07, P = .0008, and P < .0001, respectively). Total infused TNC (P = .0007) and CD3+ cell doses (P = .001) also significantly influenced engraftment. At high-resolution extensive donor-recipient HLA disparity was frequent, but had no influence on engraftment (P = .66), or unit dominance (P = .13). Although the unit-unit HLA match also did not affect sustained engraftment (P = 1.0), recipients of units closely (7-10 to 10-10) HLA-matched to each other were more likely to demonstrate initial engraftment of both units (P < .0001). Our findings have important implications for unit selection and provide further insight into double-unit biology.

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1343-1347 ◽  
Author(s):  
Juliet N. Barker ◽  
Daniel J. Weisdorf ◽  
Todd E. DeFor ◽  
Bruce R. Blazar ◽  
Philip B. McGlave ◽  
...  

AbstractLimited umbilical cord blood (UCB) cell dose compromises the outcome of adult UCB transplantation. Therefore, to augment graft cell dose, we evaluated the safety of the combined transplantation of 2 partially human leukocyte antigen (HLA)–matched UCB units. Twenty-three patients with high-risk hematologic malignancy (median age, 24 years; range, 13-53 years) received 2 UCB units (median infused dose, 3.5 × 107 nucleated cell [NC]/kg; range, 1.1-6.3 × 107 NC/kg) after myeloablative conditioning. All evaluable patients (n = 21) engrafted at a median of 23 days (range, 15-41 days). At day 21, engraftment was derived from both donors in 24% of patients and a single donor in 76% of patients, with 1 unit predominating in all patients by day 100. Although neither nucleated or CD34+ cell doses nor HLA-match predicted which unit would predominate, the predominating unit had a significantly higher CD3+ dose (P &lt; .01). Incidences of grades II-IV and III-IV acute GVHD were 65% (95% confidence interval [CI], 42%-88%) and 13% (95% CI, 0%-26%), respectively. Disease-free survival was 57% (95% CI, 35%-79%) at 1 year, with 72% (95% CI, 49%-95%) of patients alive if they received transplants while in remission. Therefore, transplantation of 2 partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in many adults and adolescents.


2019 ◽  
Vol 20 (19) ◽  
pp. 4875 ◽  
Author(s):  
Vanegas ◽  
Galindo ◽  
Páez-Gutiérrez ◽  
González-Acero ◽  
Medina-Valderrama ◽  
...  

Hematopoietic progenitor cell (HPC) transplantation is a treatment option for malignant and nonmalignant diseases. Umbilical cord blood (UCB) is an important HPC source, mainly for pediatric patients. It has been demonstrated that human leukocyte antigen (HLA) matching and cell dose are the most important features impacting clinical outcomes. However, UCB matching is performed using low resolution HLA typing and it has been demonstrated that the unnoticed mismatches negatively impact the transplant. Since we found differences in CD34+ viability after thawing of UCB units matched for two different patients (p = 0.05), we presumed a possible association between CD34+ cell viability and HLA. We performed a multivariate linear model (n = 67), comprising pre-cryopreservation variables and high resolution HLA genotypes separately. We found that pre-cryopreservation red blood cells (RBC), granulocytes, and viable CD34+ cell count significantly impacted CD34+ viability after thawing, along with HLA-B or -C (R2 = 0.95, p = 0.01; R2 = 0.56, p = 0.007, respectively). Although HLA-B*40:02 may have a negative impact on CD34+ cell viability, RBC depletion significantly improves it.


Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2839-2846 ◽  
Author(s):  
Minoko Takanashi ◽  
Yoshiko Atsuta ◽  
Koki Fujiwara ◽  
Hideki Kodo ◽  
Shunro Kai ◽  
...  

Abstract The majority of cord blood transplantations (CBTs) have human leukocyte antigen (HLA) disparities. We investigated the impact that patients' pretransplantation anti-HLA antibodies have on the outcome of CBTs. Testing for anti-HLA antibody and its specificity was performed retrospectively at the Japanese Red Cross Tokyo Blood Center with sensitive solid-phase antibody detection assays. Among 386 CBTs, which were first myeloablative stem cell transplantations for malignancies and used a single unit of cord blood, 89 tested positive. Among the antibody-positive group, the cord blood did not have the corresponding HLA type for the antibody in 69 cases (ab-positive), while 20 cases had specificity against the cord blood HLA (positive-vs-CB). Cumulative incidence of neutrophil recovery 60 days after transplantation was 83% (95% confidence interval [CI], 79%-87%) for the antibody-negative group (ab-negative), 73% (95% CI, 61%-82%) for ab-positive, but only 32% (95% CI, 13%-53%) for the positive-vs-CB (P < .0001, Gray test). With multivariate analysis, the ab-positive showed significantly lower neutrophil recovery than the ab-negative (relative risk [RR] = 0.69, 95% CI, 0.49-0.96, p = .027). The positive-vs-CB had significantly lower neutrophil recovery (RR = 0.23, 95% CI, 0.09-0.56, P = .001) and platelet recovery (RR = 0.31, 95% CI, 0.12-0.81, P = .017) than the ab-negative. Patients' pretransplantation anti-HLA antibodies should be tested and considered in the selection of cord blood.


2017 ◽  
Author(s):  
Belinda T. Lee ◽  
Anil Chandraker ◽  
Jamil Azzi ◽  
Martina M McGrath

Kidney transplantation remains the optimal renal replacement therapy for patients with end-stage renal disease (ESRD). A timely referral to kidney transplantation and a thorough pretransplantation evaluation ensure improvement in the morbidity and mortality of ESRD patients. Basic knowledge of immune biology and an in-depth understanding of the different induction and maintenance therapies used post kidney transplantation are imperative for optimal patient management. In this review, we discuss the multidisciplinary process of pretransplantation evaluation of kidney transplant recipients. We also discuss state-of–the-art early management post kidney transplantation with the different immunosuppressive therapies currently available. This review contains 3 figures, 11 tables, and 106 references. Key words: crossmatch, donor-specific antibody, immunosuppression, human leukocyte antigen, immunosuppression, induction, maintenance, medical evaluation, transplantation


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