In unrelated marrow transplantation, the benefit of matching class II HLA-DRB1 and DQB1 alleles of the donor and recipient is well documented. Little is known about the clinical relevance of matching for class I HLA-A, B, and C alleles. We used DNA-amplification methods to identify the HLA-A, B, and C alleles of 300 patients and their donors. The incidence of graft failure was correlated with multiple class I mismatching in the donor. The risk of grades III-IV acute graft-versus-host disease was highest with class II mismatching in the recipient. Mismatching for a single class I or class II allele had no effect on survival, but mortality was increased by mismatching for more than one class I allele and by simultaneous mismatching for class I and class II alleles. We conclude that matching HLA class I and class II alleles of the donor and recipient can improve outcome after unrelated marrow transplantation.

MARROW TRANSPLANTATION from an HLA-matched sibling has been well established as a curative therapy for a variety of malignant and nonmalignant diseases.1-6 The establishment of volunteer donor registries has facilitated transplantation from unrelated donors for patients who lack a suitably matched related donor.7-13 Current standards for HLA typing include serological methods for class I HLA-A, HLA-B, and HLA-C antigens and DNA-based typing for class II HLA-DRB1 and HLA-DQB1 alleles. Molecular analysis has disclosed that the same serologically defined class I antigen can be encoded by an entire family of alleles. Among the 24 HLA-A, 50 HLA-B, and 11 HLA-C antigens, more than 86 HLA-A, 185 HLA-B, and 45 HLA-C alleles have been described.14 With sibling pairs, there is no need to identify the HLA class I and II alleles of the donor and recipient because they have inherited identical HLA haplotypes. With unrelated pairs, typing of HLA alleles is needed to evaluate genetic disparity, and matching of HLA alleles provides the closest possible approximation of the compatibility that can be achieved with a related donor.

Donor-recipient identity for HLA-DRB1 and DQB1 alleles reduces the risk of acute graft-versus-host disease (GVHD) and improves survival after unrelated marrow transplantation.13 15 However, with matching for serologically defined HLA-A and B antigens and for HLA-DRB1 and DQB1 alleles, the risks of acute GVHD, graft failure, and mortality remain higher with unrelated donors than with HLA-identical sibling donors. In this study, we tested the hypothesis that the increased risk of complications after unrelated marrow transplantation could be caused by mismatching for HLA-A, B, and C alleles of the donor and recipient. We found that outcome after unrelated donor transplantation can be optimized by matching the HLA-A, B, C, DRB1, and DQB1 alleles of the donor and recipient. However, mismatching for a single allele was well-tolerated. We also present evidence that class I and class II antigens have biologically different functions in clinical marrow transplantation. Whereas class I determinants govern graft acceptance, class II determinants play a role in GVHD.

Study population.

Between May 1985 and March 1998, 439 patients received an unrelated marrow transplant for treatment of chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP), or blast phase in remission. In the interest of decreasing the heterogeneity of factors associated with the risk of acute GVHD, we restricted the study to patients who received T-cell–replete marrow16 with methotrexate and cyclosporine as GVHD prophylaxis17 (n = 402). Samples were sufficient for complete retrospective typing of HLA-A, B, and C alleles in 300 of the 402 pairs. The 102 pairs lacking DNA were similar to the 300 pairs with respect to demographic and clinical outcome.

Histocompatibility testing and donor selection criteria.

Before transplantation, HLA-A and HLA-B antigens of the donor and recipient were typed by the standard two-stage National Institutes of Health complement-dependent microcytotoxicity test, and HLA-DR and HLA-DQ antigens were typed by using Dynabead-purified B cells in a microcytotoxicity assay. Before 1991, donor selection was based on matching for HLA-A, B, DR, and Dw.18 A single HLA-Dw mismatch with serological matching for HLA-DR or a single HLA-A or HLA-B mismatch within a serological cross-reactive antigen group was allowed for patients younger than 36 years of age if an HLA-A, B, DR, Dw-matched donor could not be identified. After 1991, HLA-DRB1 allele typing19 superceded Dw typing, and a single HLA-DRB1 allele mismatch was allowed for patients younger than 36 years of age if an HLA-DRB1–matched donor could not be identified. In 1992, prospective HLA-DQB1 allele typing15 was introduced, and HLA-DQB1–matched donors were selected in preference to HLA-DQB1–mismatched donors. Beginning in 1996, HLA-C serological typing was used to select HLA-C–matched donors in preference to HLA-C–mismatched donors.20 Among the 300 pairs in this study, 20 were mismatched at HLA-A and 10 were mismatched at HLA-B by serologic testing.

HLA-A, B, and C alleles were sequenced by using direct automated fluorescence methods.20 When improved methods for sequencing became available, HLA-A exons 1-5 were amplified with 5.IN/3.IN21 or A1/A2 primers (Lifecodes, Inc, Stamford, CT), and introns 1-3 of HLA-C were amplified with primer pair C1/C2 (Lifecodes, Inc). Amplified HLA-A and C templates were sequenced by using dye-labeled primers21,22 (HLA-A Sequencing Based Typing Kit; Applied Biosytems, Inc, Foster City, CA). In 133 typings, class I alleles were assigned by using oligonucleotide probe hybridization reagents (Lifecodes, Inc). Because most unrelated transplant pairs are HLA-DPB1 mismatched,23 24 no consideration was given to HLA-DPB1 matching in this study.

Transplant procedure.

All patients were prepared for transplantation with intravenous cyclophosphamide (60 mg/kg recipient body weight) administered on each of 2 successive days followed by total body irradiation (1,200 to 1,575 cGy in 6 to 12 fractions) from dual opposed 60Co sources. Prophylaxis for CMV, fungal, and Pneumocystis carinii infection was administered as described.25,26 All protocols were reviewed and approved by the Institutional Review Board of the Fred Hutchinson Cancer Research Center. Engraftment and the severity of acute GVHD were assessed according to criteria previously described.1 20 

Statistical methods.

The primary end point of this study was survival after transplantation. Grades III-IV acute GVHD and graft failure were secondary endpoints. Associations between type of donor and the hazard appropriate for survival and GVHD were examined by fitting multivariable proportional hazards regression models. Logistic regression was used to examine the probability of graft failure. Variables shown from previous studies to be associated with these end points were included in the multivariable models.13,20 27 Because the intention of this study was to assess associations between HLA allele matching and clinical outcome, parameters for age, gender, pretransplant therapy, stage of disease, body weight, and time interval from diagnosis to transplant are not displayed. Associations between these variables and clinical outcome have been reported elsewhere.

For analysis of each end point, donor and recipient pairs were categorized as follows: allele match at HLA-A, B, C, DRB1, and DQB1; mismatch involving only one class I allele; mismatch involving two or more class I alleles; mismatch involving only one class II allele; mismatch involving two or more class II alleles; and mismatch involving at least one class I allele and at least one class II allele. For analysis of GVHD, mismatching was defined as the presence of recipient alleles not shared by the donor (recipient disparity). For analysis of graft failure, mismatching was defined as the presence of donor alleles not shared by the recipient (donor disparity). For analysis of survival, mismatching included either type of disparity. The probability of GVHD was estimated as the cumulative incidence,28 with death, relapse, and graft failure without GVHD considered as competing risks. Kaplan-Meier estimates were used to describe survival.29 All P values resulting from regression models were derived from the Wald test and are two-sided. No adjustments were made for multiple comparisons.

HLA matching.

Of the 300 pairs in the study, 142 were matched for HLA-A, B, C, DRB1, DQB1 alleles. Among the 158 mismatched pairs, 83 were mismatched at only one HLA locus (21 HLA-A, 11 HLA-B, 26 HLA-C, 9 HLA-DRB1, and 16 HLA-DQB1) and 75 were mismatched at two or more loci. Eighty-three percent of the transplants were performed from a Caucasian donor for a Caucasian patient; the patient and donor were of the same race in 85% of the transplants.

Graft failure.

Graft failure occurred most frequently with donors who were mismatched for more than one class I allele (Table 1). Graft failure did not occur with donors who were mismatched only at HLA-DRB1, DQB1, or both. After adjusting for marrow cell dose, the odds of graft failure was much higher with donors who were mismatched only for class I alleles than with matched donors (odds ratio, 10.5; 95% confidence interval, 2.2 to 49.8; P = .003). The odds of graft failure were also higher with donors who were mismatched both for class I and class II alleles than with matched donors (odds ratio, 10.0; 95% confidence interval, 1.7 to 58.4; P = .01). These results indicate that graft failure was caused primarily by class I disparities in the donor. We could not evaluate the role of individual class I loci, because the number of patients with graft failure was too small.

Acute GVHD.

The risk of grades III-IV acute GVHD was influenced by the number and class of mismatched alleles in the recipient (Table 2 and Fig 1). Recipients with a single class I mismatch did not have an increased hazard of grades III-IV acute GVHD compared with matched recipients. Those with multiple class I mismatches appeared to have a higher hazard of severe GVHD than matched recipients, but the difference was not statistically significant. Recipients with both class I and class II mismatches had a significantly increased hazard compared with matched recipients. Recipients with a single class II mismatch also appeared to have a higher hazard than matched recipients. Although this difference was not statistically significant, the trend was suggestive, especially considering the relatively small number of patients. With respect to the development of grades III-IV acute GVHD, class II mismatches caused more difficulty than class I mismatches.

Fig. 1.

Cumulative incidence estimates of grades III-IV acute GVHD according to recipient disparity.

Fig. 1.

Cumulative incidence estimates of grades III-IV acute GVHD according to recipient disparity.

Close modal
Survival.

Patients with more than one class I mismatch and patients with both class I and class II mismatches had significantly lower survival than matched patients (Table 3 and Fig 2). In contrast, the survival of patients with a single class I or class II allele mismatch was similar to that of matched patients. Three of the seven patients mismatched for multiple class II alleles died before day 100. The other four remain alive from 3 to 8 years after transplant. These data demonstrate that a single class I or class II mismatch is well tolerated, but multiple class I allele mismatches and simultaneous class I and class II mismatches should be avoided.

Fig. 2.

Kaplan-Meier estimates of overall survival according to donor or recipient disparity. Tick marks indicate patients alive at the time of last contact. Some patients remain alive more than 8 years after the transplant, but no deaths have occurred past this time.

Fig. 2.

Kaplan-Meier estimates of overall survival according to donor or recipient disparity. Tick marks indicate patients alive at the time of last contact. Some patients remain alive more than 8 years after the transplant, but no deaths have occurred past this time.

Close modal

The results of this study demonstrate that survival after transplantation can be improved by matching HLA-A, B, C, DRB1, DQB1 alleles of the donor and recipient. The presence of multiple class I disparities in the donor was associated with an increased risk of graft failure, and the presence of class II disparities in the recipient was associated with an increased risk of GVHD. Disparity for a single class I or II allele did not appear to compromise survival. A parallel study of allele matching in a transplant population has been examined by the Japanese Marrow Donor Program.30 

The presence of HLA class I disparity had important effects on the risk of graft failure, especially when two or more class I mismatches were present in the donor. The high risk of graft failure explains the reduced survival observed in this group of patients. The assessment of possible qualitative differences between class I loci must await a larger transplant experience because the numbers of donors with a single HLA-A, B, or C mismatch were too small for meaningful comparisons (21 HLA-A, 11 HLA-B, and 26 HLA-C).

The differences between class I and class II disparity in conferring risks of graft failure and acute GVHD reflect the distinct biologic functions of class I molecules and class II molecules.31,32Class I molecules present peptides derived primarily from endogenously synthesized proteins, and the responding T cells express CD8. Class II molecules present peptides derived primarily from exogenously synthesized proteins, and the responding T cells express CD4. The peptides that bind respectively to class I and class II molecules differ in length and sequence.33 HLA class I molecules are further distinguished from class II molecules by their complex interaction with natural killer (NK) cells.34 

Although complete allele matching is desirable, the presence of a single class I or II allele mismatch had little demonstrable effect on survival. These results are encouraging particularly for Africans, Asians, Hispanics, Native Americans, and other ethnic groups who have a low probability of finding a fully matched donor.35Increased registry size and recruitment of specific ethnic populations can only partially alleviate this problem. Allowance for a single class I or II disparity offers access to marrow transplantation for patients who lack an HLA-A, B, C, DRB1, DQB1 allele-matched donor.

During the past decade, clinical laboratories have focused efforts on developing methods for prospective typing of HLA-DRB1 and DQB1 alleles in selecting donors for unrelated marrow transplantation.36,37 The results of our study provide further clinical rationale for efforts to develop methods for routine clinical typing of HLA class I alleles.38-42 The benefits of prospective class I allele typing will depend on the ability to identify optimally matched donors. Matching for HLA alleles may be more feasible for patients with CML than for patients with acute leukemia where progression of the disease might not allow an extended period of time for finding a donor. For patients with CML, results of transplantation are best when the time interval between diagnosis and transplantation is minimized,13 and a delay in transplantation introduced by a lengthy search for a donor could be detrimental.

Two further questions remain to be answered. First, we confined our current analysis to patients with CML, and the applicability of the results to patients with other diseases is unknown. For example, graft failure occurs very rarely in patients with acute leukemia and might not be associated with class I disparity. Second, the importance of matching for HLA-DPB1 alleles has not been defined. This question may be more answerable when the effects of class I disparity are better understood.

In unrelated marrow transplantation, efforts should be made to match HLA-A, B, and C alleles as well as HLA-DRB1 and DQB1 alleles of the donor and recipient. In patients with CML, the presence of a single HLA class I or class II disparity is well tolerated, but multiple disparities between the donor and recipient should be avoided wherever possible.

The authors are indebted to Dr Ji Pei and Leigh Ann Guthrie for sample procurement; Andrew Yamane, Mari Malkki, Mark Gatterman, and Brenda Nisperos for technical assistance; Amy Mellon for collection of clinical data; and Alison Sell for preparation of the manuscript.

Supported by Grants No. AI33484, CA18029, and CA72978 from the National Institutes of Health and the Friends of Allison, Inc.

The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. section 1734 solely to indicate this fact.

1
Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD: Bone-marrow transplantation. N Engl J Med 292:832, 895, 1975
2
Blume
KG
Beutler
E
Bross
KJ
Chillar
RK
Ellington
OB
Fahey
JL
Farbstein
MJ
Forman
SJ
Schmidt
GM
Scott
EP
Spruce
WE
Turner
MA
Wolf
JL
Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia.
N Engl J Med
302
1980
1041
3
Champlin
R
Ho
W
Arenson
E
Gale
RP
Allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic or accelerated phase.
Blood
60
1982
1038
4
Goldman
JM
Apperley
JF
Jones
L
Bone marrow transplantation for patients with chronic myeloid leukemia.
N Engl J Med
314
1986
202
5
Forman
SJ
Schmidt
GM
Nademanee
AP
Amylon
MD
Chao
NJ
Fahey
JL
Konrad
PN
Margolin
KA
Niland
JC
O’Donnell
MR
Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia.
J Clin Oncol
9
1991
1570
6
Gluckman
E
Horowitz
MM
Champlin
RE
Hows
JM
Bacigalupo
A
Biggs
JC
Camitta
BM
Gale
RP
Gordon-Smith
EC
Marmont
AM
Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome.
Blood
79
1992
269
7
Beatty
PG
Ash
R
Hows
JM
McGlave
PB
The use of unrelated bone marrow donors in the treatment of patients with chronic myelogenous leukemia: Experience of four marrow transplant centers.
Bone Marrow Transplant
4
1989
287
8
O’Reilly
RJ
Dupont
B
Pahwa
S
Grimes
E
Smithwick
EM
Pahwa
R
Schwartz
S
Hansen
JA
Siegal
FP
Sorell
M
Svejgaard
A
Jersild
C
Thomsen
M
Platz
P
Esperance
P
Good
RA
Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor.
N Engl J Med
297
1977
1311
9
Mackinnon
S
Hows
JM
Goldman
JM
Arthur
CK
Hughes
T
Apperley
JF
Jones
L
Batchelor
JR
Brookes
P
Catovsky
D
Bone marrow transplantation for chronic myeloid leukemia: The use of histocompatible unrelated volunteer donors.
Exp Hematol
18
1990
421
10
Kernan
NA
Bartsch
G
Ash
RC
Beatty
PG
Champlin
R
Filipovich
A
Gajewski
J
Hansen
JA
Henslee-Downey
J
McCullough
J
Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program.
N Engl J Med
328
1993
593
11
McGlave
P
Bartsch
G
Anasetti
C
Ash
R
Beatty
P
Gajewski
J
Kernan
NA
Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: Initial experience of the National Marrow Donor Program.
Blood
81
1993
543
12
Drobyski
WR
Ash
RC
Casper
JT
McAuliffe
T
Horowitz
MM
Lawton
C
Keever
C
Baxter-Lowe
LA
Camitta
B
Garbrecht
F
Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia.
Blood
83
1994
1980
13
Hansen
JA
Gooley
TA
Martin
PJ
Appelbaum
F
Chauncey
TR
Clift
RA
Petersdorf
EW
Radich
J
Sanders
JE
Storb
RF
Sullivan
KM
Anasetti
C
Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia.
N Engl J Med
338
1998
962
14
Mason
PM
Parham
P
HLA class I region sequences, 1998.
Tissue Antigens
51
1998
417
15
Petersdorf
EW
Longton
GM
Anasetti
C
Mickelson
EM
Smith
AG
Martin
PJ
Hansen
JA
Definition of HLA-DQ as a transplantation antigen.
Proc Natl Acad Sci USA
93
1996
15358
16
Martin
PJ
Hansen
JA
Buckner
CD
Sanders
JE
Deeg
HJ
Stewart
P
Appelbaum
FR
Clift
R
Fefer
A
Witherspoon
RP
Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts.
Blood
66
1985
664
17
Storb
R
Deeg
HJ
Whitehead
J
Appelbaum
F
Beatty
P
Bensinger
W
Buckner
CD
Clift
R
Doney
K
Farewell
V
Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia.
N Engl J Med
314
1986
729
18
Dupont
B
Braun
DW
Yunis
EJ
Carpenter
CB
HLA-D by cellular typing
Histocompatibility Testing 1980.
Terasaki
PI
1980
229
University of California
Los Angeles, CA
19
Petersdorf
EW
Smith
AG
Mickelson
EM
Martin
PJ
Hansen
JA
Ten HLA-DR4 alleles defined by sequence polymorphisms within the DRB1 first domain.
Immunogenetics
33
1991
267
20
Petersdorf
EW
Longton
GM
Anasetti
C
Mickelson
EM
McKinney
SK
Smith
AG
Martin
PJ
Hansen
JA
Association of HLA-C disparity with graft failure after marrow transplantation from unrelated donors.
Blood
89
1997
1818
21
Scheltinga
S
Van den Berg
T
Versluis
L
Avinens
O
Eliaou
JF
Hohnston-Dow
L
Tilanus
M
Subtyping of HLA-A2 by reversed dot blot and sequencing based typing: A comparative study
HLA: Genetic Diversity of HLA. Functional and Medical Implications, vol 2.
Charron
D
1998
375
EDK
Paris, France
22
Krausa
P
Stein
J
McGinnis
M
A sequencing based typing approach for high resolution definition of HLA-A locus alleles.
Eur J Immunogen
25
1998
46
23
Petersdorf
EW
Smith
AG
Mickelson
EM
Longton
GM
Anasetti
C
Choo
SY
Martin
PJ
Hansen
JA
The role of HLA-DPB1 disparity in the development of acute graft-versus-host disease following unrelated donor marrow transplantation.
Blood
81
1993
1923
24
Santamaria
P
Reinsmoen
NL
Lindstrom
AL
Boyce-Jacino
MT
Barbosa
JJ
Faras
AJ
McGlave
PB
Rich
SS
Frequent HLA class I and DP sequence mismatches in serologically (HLA-A, HLA-B, HLA-DR) and molecularly (HLA-DRB1, HLA-DQA1, HLA-DQB1) HLA-identical unrelated bone marrow transplant pairs.
Blood
83
1994
280
25
Goodrich
JM
Bowden
RA
Fisher
L
Keller
C
Schoch
G
Meyers
JD
Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant.
Ann Intern Med
118
1993
173
26
Slavin
MA
Osborne
B
Adams
R
Levenstein
MJ
Schoch
HG
Feldman
AR
Meyers
JD
Bowden
RA
Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation—A prospective, randomized, double-blind study.
J Infect Dis
171
1995
1545
27
Morton
AJ
Gooley
T
Hansen
JA
Appelbaum
FR
Bjerke
JW
Clift
R
Martin
PJ
Petersdorf
EW
Sanders
JE
Storb
R
Sullivan
KM
Woolfrey
A
Anasetti
C
Association between pre-transplant interferon-alpha and outcome after unrelated donor marrow transplantation for chronic myelogenous leukemia in chronic phase.
Blood
92
1998
394
28
Pepe
MS
Longton
G
Pettinger
M
Mori
M
Fisher
LD
Storb
R
Summarizing data on survival, relapse, and chronic graft-versus-host disease after bone marrow transplantation: Motivation for and description of new methods.
Br J Haematol
83
1993
602
29
Kaplan
EL
Meier
P
Nonparametric estimation from incomplete observations.
J Am Stat Assoc
53
1958
457
30
Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H, Yoshida T, Kimura A, Akaza T, Kamikawaji N, Kodera Y, Takaku F: Importance of HLA class I allele matching for clinical outcome after unrelated donor hematopoietic stem cell transplantation. N Engl J Med (in press)
31
Rosenberg
AS
Singer
A
Cellular basis of skin allograft rejection: An in vivo model of immune-mediated tissue destruction.
Annu Rev Immunol
10
1992
333
32
Simpson
E
Scott
D
Chandler
P
The male-specific histocompatibility antigen, H-Y: A history of transplantation, immune response genes, sex determination and expression cloning.
Annu Rev Immunol
15
1997
39
33
Rammensee
H.-G
Friede
T
Stevanovic
S
MHC ligands and peptide motifs: First listing.
Immunogenetics
41
1995
178
34
Lanier
LL
Gumperz
JE
Parham
P
Melero
I
Lopez-Botet
M
Phillips
JH
The NKB1 and HP-3E4 NK cells receptors are structurally distinct glycoproteins and independently recognize polymorphic HLA-B and HLA-C molecules.
J Immunol
154
1995
3320
35
Beatty
PG
Mori
M
Milford
E
Impact of racial genetic polymorphism on the probability of finding an HLA-matched donor.
Transplantation
60
1995
778
36
Scharf
SJ
Griffith
RL
Erlich
HA
Rapid typing of DNA sequence polymorphism at the HLA-DRB1 locus using the polymerase chain reaction and non-radioactive oligonucleotide probes.
Hum Immunol
30
1991
190
37
Molkentin
J
Gorski
J
Baxter-Lowe
LA
Detection of 14 HLA-DQB1 alleles by oligotyping.
Hum Immunol
31
1991
114
38
Browning
MJ
Krausa
P
Rowan
A
Bicknell
DC
Bodmer
JG
Bodmer
WF
Tissue typing the HLA-A locus from genomic DNA by sequence-specific PCR: Comparison of HLA genotype and surface expression on colorectal tumor cell lines.
Proc Natl Acad Sci USA
90
1993
2842
39
Levine
JE
Yang
SY
SSOP typing of the Tenth International Histocompatibility Workshop reference cell lines for HLA-C alleles.
Tissue Antigens
44
1994
174
40
Fernandez-Vina
M
Lazaro
AM
Sun
Y
Miller
S
Forero
L
Stastny
P
Population diversity of B-locus alleles observed by high-resolution DNA typing.
Tissue Antigens
45
1995
153
41
Arguello
R
Avakian
H
Goldman
JM
Madrigal
JA
A novel method for simultaneous high resolution identification of HLA-A, HLA-B and HLA-Cw alleles.
Proc Natl Acad Sci USA
93
1996
10961
42
Inamdar
A
Sintasath
DM
Husted
L
Henson
V
Ng
J
Hartzman
RJ
Hurley
CK
Typing the HLA-B locus by a nested primer approach and oligonucleotide hybridization.
Tissue Antigens
47
1996
519

Author notes

Address reprint requests to Effie W. Petersdorf, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, PO Box 19024, Seattle, WA 98109-1024.

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