Faculty Opinions recommendation of The impact of anti-HLA antibodies on unrelated cord blood transplantations.

Author(s):  
Jacob Rowe ◽  
Tsila Zuckerman
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.


Transfusion ◽  
2008 ◽  
Vol 48 (4) ◽  
pp. 791-793 ◽  
Author(s):  
Minoko Takanashi ◽  
Koki Fujiwara ◽  
Hidenori Tanaka ◽  
Masahiro Satake ◽  
Kazunori Nakajima

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4384-4384
Author(s):  
Kristin M Page ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Gerard Michel ◽  
Cristina Diaz de Heredia ◽  
...  

Abstract Relapse remains a major barrier to the long-term overall survival (OS) of pediatric patients with acute lymphoblastic leukemia (ALL). Allogeneic HSCT is a potentially curative option for these patients and its mechanism relies on graft-versus-leukemia (GvL) and delivery of high-dose chemotherapy. However, the mechanism and degree of GvL in curing ALL is not fully understood. Unrelated cord blood (CB) is an attractive donor option for these patients due to rapid procurement and lenient HLA matching without increased graft-versus-host disease (GvHD). Despite less GvHD, relapse is not increased when compared to other donor sources. Therefore, through collaboration between Eurocord, PDWP-EBMT and Duke University, we performed a retrospective analysis to identify risk factors associated with relapse, and the role of GvHD (as time dependent co-variate) in preventing relapse after unrelated CB transplantation (CBT) for children with ALL. We analyzed 640 children (<18 years (y)) with ALL in complete remission (CR) who received a single-unit CBT in either first (n=257, 40%) or second (n=383, 60%) CR from 2000-2012. Most patients were diagnosed with B-cell (79%) or T-cell (18%) lineage ALL and had no CNS involvement (92%). Cytogenetic data was available for 411 patients (CR1=171, CR2=240), and 37% were considered intermediate risk and 36% poor risk. Pre-transplant, 49% of patients were CMV seropositive. All patients received myeloablative regimens and most received anti-thymocyte globulin (88%). Regimens included total body irradiation (TBI; 69%) with either cyclophosphamide (Cy)+Fludarabine (Flu; 10%) or other agents (59%), Busulfan (Bu)+ Cy (16%), or Thiotepa+Bu+Flu (8%). Most patients received HLA mismatched CBs at 1 (50%) or 2+ (34%) loci. GvHD prophylaxis included cyclosporine with either steroids (72%) or mycophenolate mofetil (21%), or other agents (6%). Considering CR1 patients only, the median age at CBT was 5.3 y. Most were diagnosed with B-cell ALL (75%) and approximately half of those with known cytogenetics were considered poor risk. The median duration from diagnosis to CBT was 6.7 months and median follow up was 47 months. Estimated OS and LFS at 5 y for CR1 patients was 59% and 52%, respectively. Improved OS and LFS were associated with TBI-containing regimens and younger age at time of CBT (Table 1). The CI of relapse at 5 y was 23% for CR1 patients. In a multivariate analysis (MVA) the presence of acute GvHD (grade II-IV) and TBI-containing regimens were both protective of relapse (Table 1). No impact of GvHD was observed on OS, LFS or NRM. In CR2 patients, the median age at CBT was 6.9 y. Disease was primarily B-lineage ALL (82%) with intermediate or poor risk cytogenetics in 40% and 28% of patients, respectively. Median time from diagnosis to CBT was 36 months and median follow up was 54 months. Estimated OS and LFS in CR2 patients were 46% and 44%, respectively. In MVA, younger age and longer duration from diagnosis to CBT (>30 months) was associated with improved OS and LFS (Table 2). Conversely, the use of ATG was associated with lower OS. In CR2 patients, the CI of relapse was 28%. In MVA, longer duration from diagnosis to CBT (>30 months) and receiving TBI were both associated with less relapse. Importantly, receiving a fully matched HLA CB graft was a strong risk factor for increased relapse compared to mismatched CB recipients. Acute GvHD (II-IV) in this cohort was associated with higher mortality but not with relapse. In this large retrospective collaborative study, we investigated the impact of GvHD as a marker of GvL in pediatric ALL patients after CBT. In CR1 patients, acute GvHD and use of TBI were protective of relapse. However in CR2 patients, use of TBI, longer duration from diagnosis to CBT and HLA mismatched grafts were associated with decreased incidence of relapse but not with the presence of GvHD. These results showed that the impact of GvHD as a GvL marker is more evident in CR1 patients than CR2. Whereas, the impact of HLA mismatch CB on relapse is more important in CR2 patients. Decreasing immunosuppression more rapidly for CR1 patients or avoiding HLA identical CB for CR2 patients should be further investigated. In both cohorts, TBI has shown to be an important protective factor for relapse. Disclosures Bader: Riemser: Other: Institutional grants; Neovii: Other: Institutional grants; Medac: Other: Institutional grants; Amgen: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 154-154
Author(s):  
Sachiko Seo ◽  
Junya Kanda ◽  
Yoshiko Atsuta ◽  
Naoyuki Uchida ◽  
Kazuteru Ohashi ◽  
...  

Abstract Background: Donor selection is one of key factors for better outcomes after hematopoietic stem cell transplantation (HSCT). It is shown that increased donor age is associated with high mortality. In the era of high-resolution typing of HLA and various methodological options in HSCT (e.g. conditioning regimens or cell source), however, the significance of donor age in the selection of donor or cell source is unclear. Here we examined the impact of donor age on clinical outcome after unrelated bone marrow transplantation (UBMT) and compared to the outcome after unrelated cord blood transplantation (UCBT). Patients and methods: For this retrospective cohort study, clinical data of donors and recipients were obtained from the registry data of the Japan Society of Hematopoietic Cell Transplantation (JSHCT). This study included 6035 adult patients 16 years of age or older with AML, MDS, ALL, or CML who received the first HSCT between 2000 and 2010. Among them, 3304 recipients received UBMT from 8/8 HLA-matched or 7/8 HLA-matched for HLA-A, -B, -C, and -DRB1 allele-level donor and 2731 recipients received single-unit UCBT from maximum 2-antigen (HLA-A, -B, -DR antigen-level) mismatched donor. Risk factors for overall mortality and other endpoints were analyzed using Cox proportional hazards models and Fine and Gray's proportional hazards models, respectively. Results: The median ages of UBMT and UCBT recipients were 42 years (range, 16-77) and 50 years (range, 16-82), respectively. The median age of UBMT donor was 34 years (range, 20-55). Among 3304 UBMT recipients, older donor age (≥40 years) was a significant risk factor for overall mortality (adjusted HR, 1.14; 95% CI, 1.03-1.27, p=0.015) and grades II-IV acute graft-versus-host disease (aGVHD) (adjusted HR, 1.27; 95% CI, 1.13-1.43, p<0.001) after adjusting for other significant factors in the multivariable model. Similar results were obtained using donor age as a continuous variable (overall mortality: adjusted HR, 1.01; 95% CI, 1.00-1.02, p=0.007, aGVHD: adjusted HR, 1.02; 95% CI, 1.01-1.03, p<0.001). The effect of donor age on overall mortality was strongly detected in patients with the standard risk disease (interaction p=0.058) or recipients from 7/8 HLA-matched donor (interaction p=0.078). Therefore, we compared outcomes of the five groups including UCBT by donor types (8/8 matched younger donor, 8/8 matched older donor, 7/8 matched younger donor, 7/8 matched older donor and cord blood) only among the standard risk group (Figure). Survival in recipients from 8/8 matched older donor was similar to that in recipients from 7/8 matched younger donor (adjusted HR, 1.03; 95% CI, 0.83-1.28, p=0.790). In recipients from 7/8 matched older donor, the survival was comparable to that in recipients of cord blood (adjusted HR, 0.91; 95% CI, 0.73-1.13, p=0.398). Conclusions: The outcome of HSCT recipients with older donor (≥40 years) was worse compared with that of recipients with younger donor, especially in the standard risk group or HLA-mismatched donors. A 7/8 matched younger donor is a viable option as well as an 8/8 matched older donor in the absence of an 8/8 matched younger donor. In addition, UCBT is a reasonable option in the absence of these donors. Intensive GVHD prophylaxis in recipients with older donor might improve outcome, but further studies are needed to test this hypothesis. Figure 1. Probability of overall survival by donor types among HCT recipients with standard risk. Figure 1. Probability of overall survival by donor types among HCT recipients with standard risk. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2586-2586
Author(s):  
Jiawei Yan ◽  
Guangyu Sun ◽  
Wen Yao ◽  
Lei Zhang ◽  
Xiang Wan ◽  
...  

Abstract Few reports have focused on the impact of ABO incompatibility on the clinical outcomes, after unrelated cord blood transplantation (UCBT). Therefore, we retrospectively analyzed the impact of ABO mismatching on the clinical outcomes of 177 patients with hematologic malignancies, which underwent single UCBT in Anhui Provincial Hospital from May 2008 to April 2014. The study patients included 86 ABO-identical, 52 minor, 32 major, and 11 bidirectional ABO-incompatible recipients. All of them received a homogeneous intensified myeloablative pre-transplantation conditioning regimen of total body irradiation (TBI)cyclophosphamide (CY) [TBI (total,12 Gy; four fractions) and CY (60 mg/kg daily for 2 days)] (age≥14 years) or BuCY2 [busulfan (0.8 mg/kg every 6 h for 4 days) and CY]. Medians of 3.85×107/kg (range, 1.03-10.43) total nucleated cell (TNC) and 2.0×105/kg (range, 0.45-6.88) CD34+cells were transfused. Of the 177 patients who underwent UCBT, 169 achieved successful neutrophil engraftment. In patients receiving ABO-identical, minor, major, and bidirectional ABO-incompatible UCBT, the cumulative incidences of neutrophil engraftment were 92.7%, 100%, 96.9% and 90.9%, respectively (P=0.509). The median days to achieve neutrophil engraftment were 17, 18, 17, and 20, respectively (P=0.409). The cumulative incidences of platelet engraftment were 81.7%, 86.5% , 87.5% and 63.6%, respectively(P=0.436) .And the median days to achieve platelet engraftment for the 4 groups were 36, 40, 36, and 38, respectively; (P=0.545). All of the data did not show any significant difference among the 4 groups. Neutrophil engraftment(cumulative incidence, 95.5% versus 95.3% , P=0.861; median day, 17 versus 18, P=0.717) also did not differ significantly between the ABO-identical/minor ABO-incompatible and major/bidirectional ABO-incompatible recipients (HR1.08, P=0.680). And platelet engraftment (83.6% versus 81.4%, P=0.964; median day, 38 versus 37, P=0.699) reached the similar result (HR1.104, P=0.621). We investigated the results from a 169-patient population with neutrophil engraftment, the average units of platelets (Plts) and red blood cells (RBCs) transfused during the hospitalization after the UCBT were 0.204 units/kg(range, 0.03-1.45)and 0.159 units/kg (range, 0-1.56).In patients with ABO-identical, minor, major, and bidirectional ABO-incompatible UCBT, the average units of Plts transfused after UCBT were 0.221, 0.202, 0.169, and 0.195 units/kg(P=0.53), respectively, and the average units of RBCs transfused were 0.151, 0.156, 0.163, and 0.221 units/kg (P=0.847), respectively. No significant differences in the transfusion requirements among the 4 groups were noted, so did the comparison between the ABO-identical/minor ABO-incompatible and major/bidirectional ABO-incompatible recipients. With a median follow-up of 12 months (range, 3-74 months), the disease-free survival (DFS) rates among the ABO-identical, minor, major, and bidirectional ABO-incompatible groups were 67.1%, 57.7%, 62.5 % and 54.5%, respectively (P=0.804), and the overall survival (OS) also did not differ significantly among the four groups (68.3%, 61.5%, 65.6%, and 63.6%, respectively; P=0.929). When it came to the comparison between the ABO identical/minor incompatible group and the ABO major/bidirectional incompatible group, the DFS (63.4% versus 60.5%; P=0.995) and OS estimates (65.7% versus 65.1%; P=0.820) were not significantly different, either. What’s more, none of the patients clinical developed severe immune hemolysis or pure red-cell aplasia after transplantation. In summary, the results above indicated that :1) ABO incompatibility did not seem to have a significant impact on clinical outcomes after UCBT, such as engraftment, transfusion requirements and survival. 2) No patients developed pure red-cell aplasia after UCBT. 3) In addition, we also compared the outcomes between the ABO-identical and bidirectional ABO-incompatible groups, even it did not show any significant difference, the former did better on platelet engraftment (81.7% versus 63.6%) and DFS (67.1 versus 54.5%). The reason led to this result may be the lack of bidirectional ABO-incompatible recipients. Therefore, we’d better avoid selecting bidirectional ABO-incompatible in UCBT to improve the patients’ recovery and survival time. Disclosures No relevant conflicts of interest to declare.


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