scholarly journals Human Leukocyte Antigen Matched Unrelated Donors for Patients with Sickle Cell Disease According to Geographic Origin: Results of International Donor Searches

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1021-1021 ◽  
Author(s):  
Karina Tozatto-Maio ◽  
Margareth Afonso Torres ◽  
Neifi Hassan Saloum Degaide ◽  
Juliana Fernandes Cardoso ◽  
Fernanda Volt ◽  
...  
Keyword(s):  
African American ◽  
Stem Cell ◽  
Ethnic Groups ◽  
Human Leukocyte ◽  
Haplotype Frequency ◽  
P Value ◽  
Unrelated Donor ◽  
International Donor ◽  
Hla Haplotypes ◽  
Brazilian Cohort

Background: Hematopoietic stem cell transplantation (HSCT), the only available curative therapy for sickle cell disease (SCD), remains hampered by the lack of histocompatible stem cell donors. Most patients will not have a suitable human leukocyte antigen(HLA) matched sibling donor. In addition, SCD affects ethnic groups that are underrepresented in stem cell donor registries worldwide. Objective: to assess the probability of having a potential allelic HLA matched unrelated donor(MUD) for HLA-A,B and DRB1 loci (6/6) in international donor registries for patients with SCD. Methods: 185 patients with SCD were included, 116 from Brazil, of whom 23 underwent HSCT, and 69 patients who underwent HSCT in centers reporting to the European Society for Blood and Marrow Transplantation (EBMT). All patients had HLA typing available at intermediate or high resolution. For intermediate resolution, using the National Marrow Donor Program (NMDP) code, we assigned alleles based on allele frequencies.We performed HLA haplotype estimation using the HaploStats website, which describes HLA haplotype frequency from the NMDP registry for the following ethnic groups: Caucasian, African-American, Asian, Hispanic and Native American. Because Hispanic is not a primary ethnicity, we did not consider this group in our analyses. Based on haplotype frequency of each ethnic group, we defined the most likely ethnicity for each estimated haplotype; those with frequency >1:1000 in all ethnic groups were named common. Unrelated donor search was done using the World Marrow Donor Association (WMDA) algorithm, which is based on haplotype matching. A potential allelic donor was defined as a full match high resolution 6/6 donor. Because it is described that testing at least 5 potential allelic donors simultaneously increases the chances of having a real donor, we assessed the probability of finding at least 1 and at least 5 potential allelic donors. Patients who received HSCT from MUD were excluded from donor searches (n=10).Comparisons of probabilities of having potential allelic donors between Brazilian and EBMT cohorts were performed by chi-square. Results: In the Brazilian cohort, from 181 HLA haplotypes, 45% were classified as African-American, 18% common, 12% Caucasian, 9% Amerindian and 16% could not be classified. In the EBMT cohort, from 116 HLA haplotypes, 70% were classified as African-American, 8% common, 6% Caucasian, 3% Amerindian and 13% were not classified. Although Brazilians showed greater genetic admixture, chances of finding at least one potential allelic MUD were 47% in both groups (p-value not significant) and chances of having at least 5 potential allelic MUD were 24% for Brazilians and 15% for EBMT (p-value not significant). Overall, most potential allelic MUD were found in the NMDP registry, followed by the Brazilian registry (REDOME) and by the German registry (ZKMD); for the Brazilian cohort, most potential allelic MUD were found in REDOME. Discussion: Migration from Africa to Brazil started at the colonial period, and interethnic admixture have been occurring since then, explaining the higher diversity observed in the Brazilian cohort. Despite differences in ethnic composition, chances of having at least one potential allelic MUD are identical, probably because carrying at least one African or Amerindian haplotype decreases the chances of a full HLA matching. Although we demonstrated higher probabilities of finding a potential allelic MUD in SCD than previous studies, the chances are still low, therefore further strategies are required to increase donor representativeness for SCD. In this setting, alternative sources, such as haploidentical HSCT and cord blood, should be considered. Also, our study might help to predict the probabilities of finding a MUD for patients with SCD. This is important because given that HSCT in SCD has better results if performed at earlier age, knowing which patients are less likely to find a MUD might influence therapy management. Disclosures No relevant conflicts of interest to declare.

The Role of Race on Survival after Alternative Donor Hematopoietic Progenitor Cell Transplant for Pediatric Acute Leukemia: Provocative Single Center Data.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5323-5323
Author(s):  
David A. Margolis ◽  
Mary Eapen ◽  
Jeanette Carreras ◽  
Julie-An Talano ◽  
Meghen Browning ◽  
...  
Keyword(s):  
Risk Factors ◽  
African American ◽  
African Americans ◽  
Acute Leukemia ◽  
Children And Adolescents ◽  
Ethnic Groups ◽  
Hematopoietic Progenitor Cell ◽  
Unrelated Donor ◽  
Alternative Donor ◽  
Related Donor

Abstract Allogeneic blood or bone marrow transplant (BMT) can be a curative treatment for many children and adolescents with acute leukemia. With advances in unrelated donor transplant, others and we have shown that unrelated donor BMT can have similar survival to matched sibling BMT. There are several reports describing outcomes after matched related donor transplantation among various ethnic groups. Thus far, there are no published studies comparing outcomes among ethnic groups after alternative donor transplantation. Anecdotally, however, there have been concerns regarding outcomes among racial and ethnic groups, especially African-Americans. In order to address this question, we utilized our institutional database to analyze survival among children and adolescents receiving an alternative donor BMT at Children’s Hospital of Wisconsin from 1988-present. We compared survival in Caucasians and African-Americans undergoing unrelated donor and mismatched related donor transplantation (including haploidentical donors). One hundred and twenty four Caucasians underwent matched and mismatched unrelated donor transplantation compared to 11 African Americans. The 2-year probabilities of overall survival were significantly better for Caucasians at 53% (95% CI 44–62) than for African Americans, 18% (95% CI 2–45), p=0.01. Fifty-four Caucasians and 9 African Americans received mismatched family donor transplantation. Corresponding probabilities of overall 2-year survival were 38% (95% CI 25–51) and 30% (95% CI 5–64), respectively. Interestingly, our data show no statistically significant difference in survival after mismatched related donor transplantation between the Caucasian and African-American cohorts. Our data should be interpreted cautiously as the number of African Americans transplanted at our institution is few. Additionally, our analysis is limited by our inability to adjust for disease status at transplantation, HLA disparity and other known risk factors that may impact survival. Nevertheless these observations from a single institution cannot be ignored and warrant further analysis in a larger cohort such that outcomes after transplantation may be adjusted appropriately for relevant risk factors. We believe that a national database/registry study will have the numbers necessary to answer the questions that need to be asked regarding outcomes with alternative donor transplantation in the African-American population. We also believe that as cell processing and supportive care technologies improve mismatched family member transplantation outcomes, these advances could have a significant impact in improving leukemia-free survival for African-American children and adolescents.

Influence of Human Leukocyte Antigen Haplotypes on Acute Graft Versus Host Disease Incidence after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2887-2887
Author(s):  
Sameer Gupta ◽  
Charu Aggarwal ◽  
Philip L. McCarthy ◽  
Swaminathan Padmanabhan ◽  
Minoo Battiwalla ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
Graft Versus Host ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Hla Haplotypes

Abstract There is increasing evidence that the Human Leukocyte Antigen (HLA) alleles may influence the incidence of acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT). Differential presentation of recipient antigens to donor-derived T-cells by the respective HLA molecules may be a responsible factor. We have reported a decreased rate of aGVHD in HLA DR15 positive patients (pt) undergoing alloHSCT for myeloid malignancies (Blood, 2006; 107:1970). We investigated the influence of different HLA alleles and the three most common HLA haplotypes in US Caucasians on grade 2–4 acute GVHD (graded using published criteria) in HLA matched alloHSCT. We conducted a retrospective review of 195 related and 70 unrelated consecutive first myeloablative alloHSCT pt treated from 01/1992 to 4/2005 at our center. HLA typing was determined by either molecular (n=176) or serologic (n=89) methods. Pt characteristics included: AML (n=84), CML (n=62), NHL (n=47), ALL (n=41), MDS (n=20), HD (n=7) and CLL (n=4); median age 39 years (range 6–66), < 40 years (n=130); Male (n=168), Female (n=97); Caucasian (>95%); Donor-Recipient Sex Mismatch (n=112); Total Body Irradiation (TBI) conditioning regimens (n=205); Etoposide/Cyclophosphamide(Cy)/TBI (n=122), Busulfan(Bu)/Cy (n=28), Bu/TBI (n=27), Thiotepa/TBI (n=23), Cy/TBI (n=22), Fludarabine/Melphalan (n=8), Thiotepa/Carboplatin (n=8) or other combinations (n=27) and peripheral blood stem cell source (n= 35). HLA Haplotypes analyzed for their effect on aGVHD were A1B8DR3 (n=25), A3B7DR15 (n=20) and A2B44DR4 (n=13). There was no significant difference in the pt characteristics (donor relation, conditioning regimen, donor-recipient sex match, diagnosis, age, gender, performance status, disease status at transplant, stem cell source and GVHD prophylaxis) by each of the three haplotypes. We analyzed prior published HLA alleles that were associated with an increased or decreased risk of aGVHD and pt characteristics for their effect on grade 2–4 aGVHD incidence. By univariate analysis, donor relation (unrelated vs. related, 52% vs. 38%, p=0.0002), HLA A2 (44% vs. 33%, p=0.05) and HLA B8 were associated with increased aGVHD (61% vs. 37%, p=0.005) whereas HLA B18 was associated with decreased aGVHD (19% vs. 43%, p=0.017) in contrast to prior reports using serological typing only. By multivariate analysis, HLA A2 (RR=1.5, 95%CI: 1.0 to 2.2, p=0.04), HLA B8 (RR=1.9, 95%CI: 1.1 to 3.0, p=0.01) and unrelated donor (RR= 1.9, 95%CI: 1.3 to 2.9, p=0.001) were associated with increased aGVHD. HLA haplotype multivariate analysis demonstrated increased risk of aGVHD with haplotypes A1B8DR3 and A2B44DR4 (A1B8DR3: 64% vs. 32%, RR 2.6, 95% CI: 1.1 to 5.9, p=0.012 and A2B44DR4: 61% vs. 39%, RR 3.5, 95% CI: 1.7 to 7.5, p=0.04) whereas haplotype A3B7DR15 had less aGVHD compared to others (18% vs. 42%, RR 0.31, 95%CI: 0.098 to 0.98, p=0.049). This is the first published report of the effect of HLA haplotypes on aGVHD incidence. Results of our haplotype analysis substantiate our findings of single allele effects of HLA A2, HLA B8 and HLA DR15 suggesting a differential effect on aGVHD incidence. The ability to predict aGVHD after alloHSCT using HLA haplotypes may improve outcomes by allowing for individualized GVHD prophylaxis regimens.

The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated Donor Over Chemotherapy As Post-Remission Treatment for Patients with High-Risk Acute Lymphoblastic Leukemia in First Remission

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1986-1986
Author(s):  
Jiong Hu ◽  
han-Bo Dou ◽  
Ling Wang ◽  
Wei Tang
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Relapse Rate ◽  
Lymphoblastic Leukemia ◽  
P Value ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Chemotherapy Group

Abstract Abstract 1986 For adult patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donor (MSD) is recommended for standard and high-risk patients. The role of unrelated donor transplantation (URD) is not fully determined. In this single-center retrospective analysis, we included all consecutive adult patients with high-risk ALL in 1st complete remission (CR) without sibling donor between Jan 2007 to June 2012. Overall, 74 patients were included in the analysis in which 32 patients received URD allo-HSCT during 1st CR with busulfan-cyclophophamide preparation regimen and in vivo T cell depletion with anti-T-lymphoglobulin (ATG). The median time from remission to transplantation was 4.5 months (3∼13). Forty-two patients in the chemotherapy group with 1st CR more than 6 months received consolidation chemotherapy alone either due to lack of suitable URD (n=21), refuse to URD search (n=14), unwillingness to undergo transplantation with available URD (n=5) and donor refuse to donate (n=2). Salvage allo-HSCT was allowed after relapse and actually 5 patients in the chemotherapy group received transplantation from URD donor (n=2) or haplo-identical donor (n=2) in the subsequent remission. The clinical characteristics such age, sex, initial WBC, and Philadelphia chromosome are all distributed equally in the two groups. With a median follow-up of 18 months for the whole group, 30 patients relapsed with estimated 3-year relapse rate (RR) at 58.1±8.5%. The 3-year event-free survival (LFS), non-relapse mortality (NRM) and overall survival (OS) were 38.0±7.9%, 11.1±4.4% and 46.0±9.0% respectively. In the URD allo-HSCT group, RR was 30.6±11.4% which was significantly lower than chemotherapy group (80.5±10.1%, p<0.001) while NRM was higher (16.4±6.7% vs. 0, p=0.028). Overall, 3-year LFS was superior in URD allo-HSCT group compared to chemotherapy (57.8±10.6% vs. 19.5±10.5%; median not reached vs. 13 months, p=0.002) and 3-year OS was also improved in URD allo-HSCT group (63.5±13.3%, median not reached versus 31.6±10.6%, median 24 months, p=0.016). Based on our data, URD allo-HSCT significantly reduced the relapse rate in high-risk ALL and the benefit translated into improvement in both LFS and OS. Prospective randomized study based on availability of HLA matched URD is warranted to confirm the exact role of URD transplantation in adult ALL. Table 1. Patient's characteristics Chemotherapy URD-allo-HSCT P value No of patients N=42 N=32 Median Follow-up (months) 15 (7.7∼48) 22 (8.2∼49) Sex (M/F) 19/23 21/11 0.08 Age 24.5 (16∼60) 25 (16∼57) 0.10     >35 14 9 0.61     <=35 28 23 Initial WBC (×109/L) 80.3 (15.3∼97.9) 61.5 (3.2∼98.4) 0.12 Cytogenetics     Ph+ 8 10 0.33     Ph− 33 22 Table 2. Clinical outcome in different treatment strategies Chemotherapy URD-allo-HSCT P value No of patients N=42 N=32 OS 31.6 ± 10.6% 63.5 ± 13.3% 0.016     median 24.9 months not reached LFS 19.5 ± 10.5% 57.8 ± 10.6% 0.002     median 13.2 months not reached Relapse rate 80.5 ± 10.1% 30.6 ± 11.4% <0.001 NRM 0% 16.4 ± 6.7% 0.028 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Use of alternative donors for allogeneic stem cell transplantation

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 220-224 ◽  
Author(s):  
Claudio Anasetti
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Human Leukocyte ◽  
Unrelated Donor ◽  
Factors Affecting ◽  
Blood Transplantation ◽  
Cell Sources

Abstract For patients without a human leukocyte antigen (HLA)-matched sibling or unrelated donor, options include transplantation from HLA-mismatched related donors, HLA-mismatched unrelated donors, or unrelated cord blood units. Graft failure remains a problem in 10%-20% of cord blood transplants that contain a limited number of hematopoietic cells. Many approaches are tested in clinical trials to offset the risk of graft failure after cord blood transplantation. GVHD remains a hurdle with any HLA mismatched graft. The use of post-transplant cyclophosphamide holds the promise to overcome the HLA barrier and prevent GVHD despite donor mismatch for a full HLA haplotype. Priority should be given to enrolling patients onto transplant protocols addressing the fundamental problems of engraftment, GVHD, relapse or treatment-related mortality tested with one or more of the alternative stem cell sources. Principles for prioritization of alternative stem cell sources are discussed separately for children and adults who cannot be enrolled on clinical trials. It is difficult ranking currently available sources in the face of multiple factors affecting outcomes, rapidly changing transplant technology and without results from comparative trials.

scholarly journals Unrelated Donor Selection for Stem Cell Transplants using Predictive Modelling

2018 ◽  
Author(s):  
Adarsh Sivasankaran ◽  
Eric Williams ◽  
Martin Maiers ◽  
Vladimir Cherkassky
Keyword(s):  
Stem Cell ◽  
Human Leukocyte ◽  
Predictive Modelling ◽  
Donor Selection ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Multi Stage ◽  
Cell Transplants ◽  
Selection For

AbstractUnrelated Donor selection for a Hematopoietic Stem Cell Transplant is a complex multi-stage process. Choosing the most suitable donor from a list of Human Leukocyte Antigen (HLA) matched donors can be challenging to even the most experienced physicians and search coordinators. The process involves experts sifting through potentially thousands of genetically compatible donors based on multiple factors. We propose a Machine Learning approach to donor selection based on historical searches performed and selections made for these searches. We describe the process of building a computational model to mimic the donor selection decision process and show benefits of using the proposed model in this study.

scholarly journals The AML EBMT Cytogenetic Risk Score for Acute Myeloid Leukaemia (AML) Is Prognostic for Outcomes of Allogeneic Stem Cell (HSCT)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-20
Author(s):  
Yan Beauverd ◽  
Sarah Morin ◽  
Mitja Nabergoj ◽  
Caroline Stephan ◽  
Carmen De Ramon Ortiz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Risk Score ◽  
Prognostic Model ◽  
Multivariable Analysis ◽  
P Value ◽  
Unrelated Donor ◽  
Free Survival ◽  
Stem Cell Source ◽  
Karnofsky Index

Background: The AML EBMT Cytogenetic Risk score is a new prognostic model recently published (Canaani et al. Leukemia. 2019 Aug;33(8):1944-1952; Nagler el al. Am J Hematol. 2020 Jun 12) combining cytogenetics and FLT3ITD status for AML patients in complete remission (CR) at transplant time. The AML EBMT Cytogenetic Risk score is prognostic for leukemia-free survival (LFS), overall survival (OS), GVHD-free/relapse-free survival (GRFS) and cumulative incidence of relapse (CIR). In our centre, we frequently offer in-vitro partial T-cell depleted graft (pTDEP) for patient in CR to decrease morbidity and mortality associated with graft-versus-host disease (GvHD). Currently, The AML EBMT Cytogenetic Risk score has not been evaluated in this population. Aims: We investigate the impact of the AML EBMT Cytogenetic Risk score for 3 years OS, LFS, GRFS, CIR and NRM in a cohort with patients allografted with pTDEP graft. Methods: All consecutive ≥18 years patients who received a first allograft for AML between 2008 and 2018 with data available to determine The AML EBMT Cytogenetic Risk score in CR at transplant time were included. OS and LFS were investigated with the Kaplan-Meier method and we used the cumulative incidence estimator as defined by Fine and Gray to calculate CIR (with NRM as competing event), NRM (with relapse as competing event) and GvHD (with relapse as competing event). Results: 135 patients were included, median age at transplant time was 56 years (range: 19-74), 44% were female, median Karnofsky index was 90 (80-100). 21% of graft were from HLA identical, 57% from matched unrelated donor, 10% from mismatched unrelated donor and 12% from haploidentical donor. Stem cell source was peripheral blood in 89% and bone marrow in 11%. Partial in-vitro T-cell depletion (pTDEP) was performed in 40% of HSCT. Reduced-intensity (RIC) was performed in 62%. Median follow-up was 3.1 year (range 1.3-10 years) for living patients. Among the 135 patients, 4 (3%) were assigned in the favourable (Fav), 58 (43%) in the intermediate/FLT3wt (Int/FLT3wt), 36 (27%) in the intermediate/FLT3ITD (Int/FLT3ITD), and 37 (27%) in the adverse (adv) risk group. 3-years OS for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 75% (32-100%), 65% (52-77%), 60% (43-77%) and 28% (10-45%), respectively (p=0.033) (Fig 1A). 3-years LFS for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 75% (95%CI: 32-100%), 60% (47-73%), 49% (32-66%) and 25% (8-42%), respectively (p=0.028) (Fig 1B). 3-years GRFS for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 75% (32-100%), 45% (31-58%), 39% (22-55%) and 14% (0-27%), respectively (p=0.008) (Fig 1C). 3-years CIR for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 0%, 22% (11-33%), 31% (15-47%) and 56% (37-75%), respectively (p=0.02). 3-years NRM for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 25% (95%CI: 0-75%), 17% (7-28%), 21% (6-35%) and 17% (2-32%), respectively (p=0.92). 3-years grade 2-4 aGVHD for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 0%, 35% (22-47%), 19% (2-36%) and 42% (25-58%), respectively (p=0.46). 3-years cGVHD for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 25% (95%CI: 0-75%), 17% (6-27%), 22% (7-38%) and 21% (6-35%), respectively (p=0.9). In addition to The AML EBMT Cytogenetic Risk score, variables with a significance in univariate for OS with a p-value ≤0.1 (Karnofsky index [&lt;90 vs. ≥90]; stem cell source [PBSC vs. BM] and donor type [matched vs mismatched donor]) and pTDEP were included in the multivariable model. In multivariable analysis, only the Cytogenetic Risk Score (Fav + Int/FLT3wt: ref; Int/FLT3ITD + Adv: HR: 1.8 [95%CI: 1.1-3.1], p-value 0.03) and Karnofsky index (&lt;90: ref; ≥90: HR 1.8 [95%CI: 1.0-3.2], p-value 0.049] remain significant. Because of the low number of patients in pTDEP (53) and non-pTDEP (82), statistical analysis couldn't be performed specifically in these subgroups but pTDEP had no impact in multivariable analysis for OS. Conclusion: In the analysis of our retrospective cohort including 40% of pTDEP patients, we confirm that the AML EBMT cytogenetic risk is prognostic for relevant outcomes (OS, LFS, GRFS, CIR) of HSCT. Similarly with recently published data, we confirm this prognostic model can help physicians and patients in transplant choice and remains valid for patients undergoing HSCT with in-vitro graft manipulation. Disclosures No relevant conflicts of interest to declare.

The Impact of Rituximab in the Development of Acute Graft Versus Host Disease (GVHD) Following Allogeneic Stem Cell Transplantation (SCT) for Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1803-1803
Author(s):  
Partow Kebriaei ◽  
Rima M. Saliba ◽  
Carrie Ma ◽  
Cindy Ippoliti ◽  
Daniel R. Couriel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Control Group ◽  
P Value ◽  
Unrelated Donor ◽  
Study Group ◽  
Donor Characteristics ◽  
The Impact

Abstract We investigated the safety and efficacy of administering rituximab in combination with a standard myeloablative conditioning regimen of cyclophosphamide (Cy, 60 mg/kg daily x 2 doses) and total body irradiation (TBI, 12 Gy in four daily fractions) with allogeneic SCT in adult patients (pts) with ALL. Pts were eligible if their disease expressed CD20 in &gt;20% blasts by flow cytometry. Rituximab was administered at 375 mg/m2 on days 6, −1, +7 and +14 following stem cell infusion. 24 pts were entered on study. The results were retrospectively compared with those of a historical control group of 31 pts receiving the same preparative regimen without rituximab. The two treatment groups had similar numbers of matched sibling and unrelated donor grafts. Pt and donor characteristics are detailed in Table 1. GVHD prophylaxis consisted of tacrolimus and methotrexate for nearly all pts in both study and control groups; 4 pts in the control group and 1 pt in the study group received pentostatin in addition to tacrolimus and methotrexate. Preliminary data suggests that pentostatin reduces the incidence of acute GVHD (de Lima et al. Blood2004;104:727a). The cumulative incidence of non-relapse mortality (NRM) at 2 years was 18% for the study group and 33% for the controls. There was no delay in engraftment or increased incidence of infection in pts treated with rituximab. Despite the greater use of pentostatin in the control group, the incidence of grade II–IV acute GVHD tended to be lower in pts treated with rituximab as compared to controls: 17% vs. 39%, p=0.07. The incidence of chronic extensive GVHD was not significantly different between the two groups: 37% vs. 34%, p=0.7. OS at 2 years was 45% for the study group and 38% for the controls, p=0.5. PFS at 2 years was 31% for the study group and 38% for the control group, p=0.8. Treatment outcomes are summarized in Table 1. In conclusion, our results demonstrate that the addition of rituximab to standard Cy/TBI conditioning for allogeneic SCT in ALL is associated with a relatively low rate of acute GVHD and NRM. Differences in pt characteristics preclude direct comparison. However, there is no apparent benefit for the addition of rituximab on disease relapse. Table 1. Patient, Donor Characteristics, and Outcomes Cy/TBI/rituximab No. pts Cy/TBI No. pts P-value 1. Donor age missing for 1 pt in each treatment group. Total Pts 24 31 Median Recipient Age, yrs (range 30 (18–54) 35 (18–53) Median Pt Age, yrs (range)1 38 (15–53) 36 (14–54) Donor Type (%) Matched related 15 (62) 21 (68) Matched unrelated 9 (38) 10 (32) 0.7 Stem Cell Source (%) BM 9 (38) 17 (55) PB 15 (62) 14 (45) 0.2 Sex donor/pt mismatch (%) 8 (33) 12 (40) 0.7 CMV donor/pt mismatch (%) 10 (43) 12 (40) 0.8 ABO donor/pt mismatch (%) 14 (58) 10 (33) 0.05 Graft Composition, median (range) Total nucleated cells (x108/kg) 4 (1–14) 4 (1–9) 0.6 CD34+(x106/kg) 5 (1–9) 5 (2–8) 0.9 CD3+ (x106/kg) 110 (8–370) 37 (5–286) 0.2 Disease Status at SCT (%) CR1 6 (25) 17 (54) Remission, beyond CR1 13 (54) 7 (23) Not in Remission 5 (21) 7 (23) 0.03 Acute GVHD II–IV 17% 39% 0.07 Chronic Extensive GVHD 37% 34% 0.7 OS, 2 yrs 45% 37% 0.5 PFS, 2 yrs 31% 38% 0.8

7/8 High-Resolution Unrelated Donor HLA Match Rate: Caucasian, African American, Hispanic, and Asian-Pacific Islander

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1998-1998
Author(s):  
Kelly Buck ◽  
Jason Dehn ◽  
Michelle Setterholm ◽  
Martin Maiers ◽  
Dennis L. Confer ◽  
...  
Keyword(s):  
African American ◽  
High Resolution ◽  
Ethnic Groups ◽  
Pacific Islander ◽  
The United States ◽  
Unrelated Donor ◽  
Match Rate ◽  
Asian Pacific Islander ◽  
Asian Pacific ◽  
Matched Donor

Abstract Aim Estimation of the National Marrow Donor Program's Be The Match Registry (BTMR) 8/8 (HLA-A, B, C, DRB1) high resolution (HR) unrelated donor (URD) match rate was determined in a 2009 study for each of the four most frequent patient race/ethnic groups in the United States- Caucasian (CAU), African American (AFA), Hispanic (HIS), and Asian Pacific Islander (API) (Dehn et al, ASBMT/CIBMTR abstract 2011). For patients without an 8/8 matched URD, a 7/8 match is often the minimum acceptable mismatch used by many transplant centers. A follow up to the 8/8 study was designed to determine the 7/8 or better match rate among the 4 major race/ethnic groups, using the same study cohort. Methods 1344 previously high resolution tested URD in the BTMR were randomly selected and treated as pseudopatients (PP) where HR testing was performed to identify an 8/8 matched URD. Following 8/8 potential URD testing, a search was performed on each PP to determine the 7/8 match rate, regardless of whether an 8/8 match was previously identified. The searches used a fixed BTMR file from January of 2012, composed of over 8.6 million URD. The BTMR race/ethnic diversity breakdown for 2012 was 65% CAU, 7% AFA, 10% HIS, 7% API, and 11% miscellaneous categories such as Multiple, Unknown, American Indian- Alaska Native, and Declined to answer. Search results from CAU (N=377), AFA (N=390), HIS (N=307), and API (N=270) PP were evaluated and classified as follow: 1) 7/8 HR matched donor exists on BTMR 2) Potential 7/8 HR donors exist on BTMR 3) No 7/8 potential donors exist on BTMR PP searches falling into category 2 had an HLA search strategy expert rank potential URD within BTMR in order of their matching likelihood. URD samples were HR HLA tested in order of ranking and evaluated to determine match status. Consecutive rounds of URD sample testing were performed until either a 7/8 matched URD was identified, no potential URD with stored samples remained, or a patient maximum number of URD testing was reached. Since many PP searches had greater than 100 potential 7/8 matched URD, it was not possible to type every URD. In these cases, up to 35 URD with sample were tested per patient. For analysis of the 7/8 match rate, PP with no 7/8 match identified after URD testing were considered as having no HR match. Results 98% of CAU and over 80% of the non-CAU race/ethnic groups- AFA, HIS, and API- had at least a 7/8 match identified (Table 1). For cases where an 8/8 matched donor had been previously identified, all but 8 PP also had a 7/8 match (CAU= 1, AFA= 3, API= 3, HIS= 1). Only three PP cases had no 7/8 potential donors on the search prior to URD testing. The range of donors tested for the cases resulting in a match was larger for the non-CAU race groups. The maximum number of URD tested before a 7/8 match was identified was 24 for AFA, 6 for HIS, and 10 for API, while for CAU the maximum number of URD tested was 2 (Table 2). A median of 1 URD was typed for cases resulting in a 7/8 match for each of the four race/ethnic groups. HLA expert review of cases where no 7/8 match was identified but additional 7/8 potential URD remained suggests that few additional cases would likely yield HR matches. Conclusions This study estimates a 7/8 or better HR match rate for the BTMR of over 80% for all four broad race/ethnic group categories. These results show that in the majority of cases, after first testing to identify an 8/8 matched URD, a 7/8 matched URD was identified after typing just one URD. However, particularly with non-CAU patients, testing additional URD may be needed to identify a 7/8 match. This study provides a baseline match rate that can be further supplemented using the additional worldwide URD inventory. Disclosures: No relevant conflicts of interest to declare.

Thiotepa-Based Conditioning for Allogeneic Stem Cell Transplantation (allo-HSCT) in Acute Lymphoblastic Leukaemia (ALL) - a Survey from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4316-4316
Author(s):  
Sandra Eder ◽  
Eric Beohou ◽  
Myriam Labopin ◽  
Jaime Sanz ◽  
Jürgen Finke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Working Party ◽  
Disease Status ◽  
P Value ◽  
Unrelated Donor ◽  
Free Survival ◽  
One Year

Abstract Background Thiotepa is an alkylating compound with an effective antineoplastic activity that was used in the past mainly for solid tumors and lymphoma, partially due to its ability to penetrate the blood-brain-barrier. Moreover, beside its myelosupressive activities, thiotepa has immunosuppressive properties making it an attractive agent to be used in the conditioning pre-transplantation. In the current retrospective registry study, we analyzed thiotepa-based conditioning regimen for allo-HSCT in adult patients with ALL using the EBMT ALWP database. Methods Inclusion criteria were: adults with de novo or secondary ALL who underwent first allo-HSCT between 2000 and July 2014 with a thiotepa-based regimen. Donors were either HLA-matched siblings or matched unrelated donors. Haploidentical and cord blood transplantations were excluded as well as patients who received a previous allo-HSCT. Results A total of 323 patients with adult ALL were identified. Median age was 43 years (range, 18 - 76); 59% were males and 41% females. Disease status at allo-HSCT was CR1 in 48.9%, CR2 in 21.7%, CR3 in 6.2% and 23.2% of the patients had an active disease at time of transplant. Transplantation was performed from a HLA-matched sibling (49.8%) or a matched unrelated donor (51.2%). Sixty-five per cent of patients received a myeloablative and 35% a reduced-intensity conditioning regimen, respectively. Stem cell source was peripheral blood stem cells in 84% of the transplants, while 16% received bone marrow grafts. Neutrophil engraftment (defined as >0.5x109/L) was 98% with a median day of 15 (range, 2 - 41). Platelets engraftment (defined as >20x109/L) was 92% with a median day of 14 (range, 7 - 98). Incidence of acute GvHD (Grade> II) was 26.6%, while chronic GvHD occurred in 35.9% at one year (24.6% with extensive disease). With a median follow-up of 16.8 months, the non-relapse mortality was 12.4% and 25.3% at 100 days and one year, respectively. Relapse incidence at 1 year was 33.3%.The one-year leukemia-free survival and overall survival incidences were 57% and 66%. Table 1 shows the outcome according to donor and disease status at time of allo-HSCT. When looking for conditioning regimen more precisely, comparing thiotepa / busulfan ± melphalan (n=213) to thiotepa / other (n=110), higher relapse incidence at one year (34.9% vs 30.3%, p=0.016) and lower leukemia-free survival (38.8% vs 45.9%, p=0.0203), respectively were observed, without difference in non-relapse mortality (23.8% vs 26.3 %, n.s.) and overall-survival (59.6% vs 51.1%, p=0.109). Conclusion This large survey suggests that TTP-based conditioning therapy in adult ALL is feasible and effective, with main outcomes being comparable to literature published results achieved with other regimens. Table 1. Donor LFS,1 year p-value OS,1 year p-value Relapse,100 days Relapse,1 year p-value NRM,100 days NRM,1 year p-value HLA-matchedsibling 49% 0.0262 62% 0.0133 13.1% 31.9% 0.4641 8.7% 18.3% 0.0042 matchedunrelateddonor 33% 46% 15.2% 34.7% 16.2% 32.1% Table 2. Disease status at allo-HSCT LFS,1 year p-value OS,1 year p-value Relapse,100 days Relapse,1 year p-value NRM,100 days NRM,1 year p-value CR1 49% <0.0001 68% <0.0001 6.4% 27.5% 0.0028 7.6% 22.6% 0.1859 CR2+ 33% 40% 21.5% 39% 17% 27.8% Disclosures Mohty: Riemser: Honoraria, Research Funding.

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