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Ability of minority patients to find donors from an ethnically diverse cord blood bank
Abstracts
S5
1.02 3-OR
ABILITY OF MINORITY PATIENTS TO FIND DONORS FROM AN ETHNICALLY DIVERSE CORD BLOOD BANK L.A. Baxter-Lowe,1 Y. Kim,2 S. Carter,2 M. Fernandez-Vina,3 E. Wagner,4 L.A. Jensen,4 J. Fraser,5 N. Kernan,6 J. Kurtzberg.7 1UCSF, San Francisco, CA; 2EMMES Corp, Rockville, MD; 3NMRI, Bethesda, MD; 4NHLBI, Bethesda, MD; 5UCLA, Los Angeles, CA; 6MSKCC, New York, NY; 7Duke U, Durham, NC The Cord Blood Transplantation (COBLT) study is investigating the use of unrelated umbilical cord blood (UUCB) for hematopoietic stem cell transplantation. The ethnicity of the 8,038 units currently in the COBLT bank is 42% Caucasian (C), 22% Hispanic (H), 15% African American (AA), 9% Asian (A), and 12% other (O). In 335 active searches (59% non-Caucasian), 94% of patients had a unit matched for at least 4/6 HLA types using intermediate- resolution A and B and high-resolution DRB1 types (original typing). In this interim report of the first 207 patients transplanted with units from the COBLT bank, 36% of patients and 39% of donors were non-Caucasian. For the 133 C, 16 AA, and 6 A patients, the majority of the UUCBs were the same ethnicity (77%, 75%, and 100%, respectively). In contrast, for 34 H patients, only 35% of the units were from H donors. To date, 188 (91%) of the pairs have been retrospectively typed at a high-resolution level (final typing). Using high-resolution types, 6% of patients received a 6/6 HLA matched UUCB. Comparison of the original typing with the final typing shows that 65% of 4/6 matches, 61% of 5/6 matches and 69% of 6/6 matches were unchanged. The frequencies of mismatched pairs were 25% 5/6, 47% 4/6, 18% 3/6, and 4% 2/6. For ethnic groups, increased HLA disparity after final typing was highest for H (70%) and A (67%) patients, followed by AA (42%) and C (25%). These data illustrate the current usage of an ethnically diverse cord blood bank. Upon completion of the study, clinical outcomes will be analyzed to investigate the suitability of UUCB transplantation for an ethnically diverse patient population.
4.01 4-OR
HLA-CLASS I AMBIGUITY RESOLUTION IN THE NATIONAL MARROW DONOR PROGRAM威 DONOR/RECIPIENT PAIR PROJECT: WHEN IS ENOUGH ENOUGH? S. Spellman,1 R. Cullen,1 M. Maiers,1 M. Fernandez-Vina,2 T.M. Williams,3 L. Baxter-Lowe,4 C.K. Hurley.5 1Coordinating Center, National Marrow Donor Program, Minneapolis, MN; 2Oncology, C.W. Bill Young Marrow Donor Program, Kensington, MD; 3Pathology, University of New Mexico School of Medicine, Albuquerque, NM; 4Surgery, University of Califorinia, San Francisco, San Francisco, CA; 5Oncology, Georgetown University Medical Center, Washington, DC Allele level DNA based typing of the class I loci (HLA-A, B, C) is complicated by allele combinations that yield multiple possible pairs of alleles that cannot be distinguished without additional testing increasing the time and expense for typing. Availability of a reliable validated source of allele frequency and ambiguity resolution data could allow assignment of alleles with relative confidence without additional testing. The NMDP Donor/Recipient Pair Project has retrospectively typed ⬎4500 stem cell donors for HLA-A, B, C at the allele level resolving all known ambiguities. All data were validated and quality controlled. The relative frequency for each ambiguous combination of alleles was determined and a threshold set for discontinuing ambiguity resolution when the likelihood of one pair of alleles was at least 20,000-fold the likelihood of a second possible pair of alleles. An example is HLA-B0702/0801 vs. 0705/0807. The estimated frequencies of B0702/0801 and B0705/0807 are 0.014 and 3⫻10⫺6, respectively, with a ratio of 46,667:1. Thus, the typing B0702/0801 can be assigned with little risk of error. This approach will reduce the proportion of typings requiring ambiguity resolution from 29%, 33% and 4% to 4.6%, 9.9% and 0.7% for the HLA-A, B, C loci, respectively. Although the dataset is likely biased towards common HLA types, the described ambiguity resolution analysis is a valuable resource for laboratories performing allele level typing on similar populations in low risk situations. Statistical analysis of typing ambiguities can reduce the time and expense of allele level tests without sacrificing accuracy and consistency.
S5
1.02 3-OR
ABILITY OF MINORITY PATIENTS TO FIND DONORS FROM AN ETHNICALLY DIVERSE CORD BLOOD BANK L.A. Baxter-Lowe,1 Y. Kim,2 S. Carter,2 M. Fernandez-Vina,3 E. Wagner,4 L.A. Jensen,4 J. Fraser,5 N. Kernan,6 J. Kurtzberg.7 1UCSF, San Francisco, CA; 2EMMES Corp, Rockville, MD; 3NMRI, Bethesda, MD; 4NHLBI, Bethesda, MD; 5UCLA, Los Angeles, CA; 6MSKCC, New York, NY; 7Duke U, Durham, NC The Cord Blood Transplantation (COBLT) study is investigating the use of unrelated umbilical cord blood (UUCB) for hematopoietic stem cell transplantation. The ethnicity of the 8,038 units currently in the COBLT bank is 42% Caucasian (C), 22% Hispanic (H), 15% African American (AA), 9% Asian (A), and 12% other (O). In 335 active searches (59% non-Caucasian), 94% of patients had a unit matched for at least 4/6 HLA types using intermediate- resolution A and B and high-resolution DRB1 types (original typing). In this interim report of the first 207 patients transplanted with units from the COBLT bank, 36% of patients and 39% of donors were non-Caucasian. For the 133 C, 16 AA, and 6 A patients, the majority of the UUCBs were the same ethnicity (77%, 75%, and 100%, respectively). In contrast, for 34 H patients, only 35% of the units were from H donors. To date, 188 (91%) of the pairs have been retrospectively typed at a high-resolution level (final typing). Using high-resolution types, 6% of patients received a 6/6 HLA matched UUCB. Comparison of the original typing with the final typing shows that 65% of 4/6 matches, 61% of 5/6 matches and 69% of 6/6 matches were unchanged. The frequencies of mismatched pairs were 25% 5/6, 47% 4/6, 18% 3/6, and 4% 2/6. For ethnic groups, increased HLA disparity after final typing was highest for H (70%) and A (67%) patients, followed by AA (42%) and C (25%). These data illustrate the current usage of an ethnically diverse cord blood bank. Upon completion of the study, clinical outcomes will be analyzed to investigate the suitability of UUCB transplantation for an ethnically diverse patient population.
4.01 4-OR
HLA-CLASS I AMBIGUITY RESOLUTION IN THE NATIONAL MARROW DONOR PROGRAM威 DONOR/RECIPIENT PAIR PROJECT: WHEN IS ENOUGH ENOUGH? S. Spellman,1 R. Cullen,1 M. Maiers,1 M. Fernandez-Vina,2 T.M. Williams,3 L. Baxter-Lowe,4 C.K. Hurley.5 1Coordinating Center, National Marrow Donor Program, Minneapolis, MN; 2Oncology, C.W. Bill Young Marrow Donor Program, Kensington, MD; 3Pathology, University of New Mexico School of Medicine, Albuquerque, NM; 4Surgery, University of Califorinia, San Francisco, San Francisco, CA; 5Oncology, Georgetown University Medical Center, Washington, DC Allele level DNA based typing of the class I loci (HLA-A, B, C) is complicated by allele combinations that yield multiple possible pairs of alleles that cannot be distinguished without additional testing increasing the time and expense for typing. Availability of a reliable validated source of allele frequency and ambiguity resolution data could allow assignment of alleles with relative confidence without additional testing. The NMDP Donor/Recipient Pair Project has retrospectively typed ⬎4500 stem cell donors for HLA-A, B, C at the allele level resolving all known ambiguities. All data were validated and quality controlled. The relative frequency for each ambiguous combination of alleles was determined and a threshold set for discontinuing ambiguity resolution when the likelihood of one pair of alleles was at least 20,000-fold the likelihood of a second possible pair of alleles. An example is HLA-B0702/0801 vs. 0705/0807. The estimated frequencies of B0702/0801 and B0705/0807 are 0.014 and 3⫻10⫺6, respectively, with a ratio of 46,667:1. Thus, the typing B0702/0801 can be assigned with little risk of error. This approach will reduce the proportion of typings requiring ambiguity resolution from 29%, 33% and 4% to 4.6%, 9.9% and 0.7% for the HLA-A, B, C loci, respectively. Although the dataset is likely biased towards common HLA types, the described ambiguity resolution analysis is a valuable resource for laboratories performing allele level typing on similar populations in low risk situations. Statistical analysis of typing ambiguities can reduce the time and expense of allele level tests without sacrificing accuracy and consistency.