Stem Cell Therapeutic Outcomes Database (Product Form)

Instructions for Confirmation of HLA Typing (Form 2005)
This section of the CIBMTR Forms Instruction Manual is intended to be a
resource for completing the Confirmation of HLA Typing Form.
E-mail comments regarding the content of the CIBMTR Forms Instruction Manual
to: [email protected]. Comments will be considered
for future manual updates and revisions. For questions that require an immediate
response, please contact your transplant center’s CIBMTR CRC.

TABLE OF CONTENTS
Key Fields ............................................................................................................. 4
Donor/Cord Blood Unit Identification ..................................................................... 5
HLA Typing by DNA Technology .......................................................................... 7
Class I ................................................................................................................. 8
Class II ................................................................................................................ 8
Class II (Optional) ............................................................................................... 8
Antigens Defined by Serologic Typing .................................................................. 9
Optional Antigen Reporting ................................................................................. 10

Confirmation of HLA Typing Data
For transplants using an NMDP donor or cord blood unit, the donor’s HLA typing
is reported on NMDP Form 22 (Confirmation of Donor HLA Typing) and the
recipient’s HLA typing is reported on NMDP Form 117 (Final Recipient HLA
Typing).
In all other situations, the Confirmation of HLA Typing form (Form 2005) is used
to report HLA typing for both the donor and recipient on the Transplant Essential
Data (TED) and comprehensive report form (CRF) tracks. This includes:
Non-NMDP unrelated donor
Non-NMDP unrelated cord blood unit
Related cord blood unit
HLA matched relative donor
HLA mismatched relative donor
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Instructions for Confirmation of HLA Typing
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Recipient of any of the donor types listed above
A separate Form 2005 should be completed for each recipient, cord blood
unit, or non-NMDP donor; however, only the recipient form is required for
syngeneic transplants. Both maternal and paternal typing should be
submitted, if available, for all mismatched related donor transplants on the
CRF track. Additionally, cord blood maternal typing should be submitted, if
available, for all unrelated cord blood transplants on the CRF track.
The human immune system recognizes and defends against threats from
outside the body. An important component of the immune system is the
human leukocyte antigen (HLA) genes. These genes produce proteins,
some of which are expressed on the surface of cells. These surface proteins
allow cells to recognize self from non-self. Cells with matching proteins are
recognized as self and passed over. However, when the proteins do not
match between cells, one cell is identified as non-self, and an immune
reaction is triggered to destroy it.
If the HLA of a donor and a recipient do not match closely, the immune
response could result in the recipient’s body attacking the transplanted cells
(resulting in graft failure), or the transplanted cells attacking the recipient’s
body (graft-versus-host disease).
HLA genes are divided into three classes. The two classes that are important in
matching donors and recipients are class I (HLA-A, B, C) and class II (includes
HLA-DR, DQ). All HLA genes are encoded on an area of chromosome six known
as the Major Histocompatibility Complex (MHC).
Finding a good donor-recipient HLA match can be difficult because HLA is highly
polymorphic, or variable. It can be completely unique to an individual. Since DNA
is inherited from parents, the likelihood of a complete match is greater between
full biological siblings than two unrelated individuals. Each individual has two
copies of chromosome six (one from each parent). This means that each parent
will be a haploidentical (half) match. A full sibling will have a 25% chance of
being an identical HLA match, a 25% chance of being completely non-identical,
and a 50% chance of being a haploidentical match.
Figure 1. Example of single HLA-A locus inheritance

HLA-A*02

Biological
Father

HLA-A
Heredity

Biological Mother
HLA-A*01 HLA-A*03

01, 02

03, 02

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HLA-A*24

Instructions for Confirmation of HLA Typing
CIBMTR Form 2005

01, 24

03, 24

The nomenclature (naming system) of HLA is an ever-evolving field, with an
international committee dedicated to maintaining standards for identifying the
genes and their allele sequences. Allele names consist of 3 to 5 parts, depending
on what is known about that individual allele.
Figure 2. HLA nomenclature

Anthony Nolan Research Institute. (2010). HLA Nomenclature. Web. 04 April 2013.
http://hla.alleles.org/nomenclature/naming.html

The HLA prefix will precede the specific HLA locus (gene), which will be
separated from allele-specific information by an asterisk. The first field will refer
to a broad group of alleles (otherwise known as the “allele family”); this
designation will be separated from the next field by a colon. The second field will
refer to the specific allele, which yields a specific HLA protein. Third and fourth
fields may be specified, but are considered less important since they represent
differences at a DNA level, rather than at a level of protein expression, due to a
synonymous coding region (exon) or substitution in the non-coding region of the
gene (intron). The name may be followed by a letter, which can alter the meaning
of the preceding nomenclature. For example, the letter “N” signifies a null allele
that does not test serologically.
DNA testing is done at low, intermediate, or high resolution.
Low-resolution testing is equivalent to serologic testing that identifies the allele
group as represented by the first field of an HLA name (e.g., HLA-A*02).
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Intermediate-resolution testing is molecular testing that may have remaining
ambiguities. It reports allele groups that may contain 2 to 100 or more alleles.
The nomenclature for these ambiguities is not internationally standardized; it is
defined by the reporting lab or organization. NMDP reports frequently include
letter sets that refer to possible genotypes within an allele group. Other
laboratories may list all possible genotypes (e.g., DRB1*01:01 or 01:02,
DRB1*01:01/01:02), where each specified allele is possible at a single locus.
High-resolution testing, or testing at the molecular level, provides further
information about the gene itself, including what specific proteins will be
expressed by the cells and even differences in sequence that do not impact
protein expression. For cellular transplant, matching at the high resolution level is
critically important.
Complete this form specifying the recipient or donor HLA at the level it was
typed.
For a glossary of terms used in this section of the manual, see Appendix B.

Key Fields
Accuracy of the Key Fields is essential for ensuring that:
Data are being reported for the correct recipient.
Outcomes data accurately reflects appropriate transplant type and product
for each transplant center.
Data are being shared with the correct donor center, cord blood bank,
cooperative registry, or other agency.
The Key Fields precede the form body and are automatically populated in the
FormsNet3SM application based on information provided on the CRID
Assignment Form 2804. If errors are noted in the key fields, correct Form 2804
and then review it for accuracy. After Form 2804 has been corrected, verify data
has been updated on all completed forms. If the data has not been updated
automatically, centers will need to reprocess the completed forms to correct the
key field data. If errors are noted in key fields for second or subsequent
transplants, contact your CRC to make any necessary corrections to the
transplant or product type. Transplant and product type will not be automatically
populated on product or donor specific forms (Forms 2004, 2005, and 2006) and
will need to be manually reported.

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Donor/Cord Blood Unit Identification
Question 1: Specify the person for whom this typing is being done
Indicate whether the reported HLA typing is the final recipient typing, from a
related donor (biological mother, biological father, or other biological relative), an
unrelated donor with product procured from a source other than the NMDP, a
non-NMDP cord blood unit, or maternal HLA typing for a cord blood unit with
product procured from a source other than the NMDP. The HLA typing must be
reported for a non-NMDP cord blood unit; maternal typing is optional. Report
related or autologous cord blood units as non-NMDP cord blood units.
If the reported HLA typing is for:
The recipient, go to question 13.
The recipient’s biological relative, go to question 5.
PBSC or bone marrow donor not related to the recipient, go to question 2.
Cord blood unit with typing sample taken from the cord blood unit or infant,
go to question 3.
Maternal HLA typing, go to question 3.
Question 2: Non-NMDP unrelated donor ID
Specify the unrelated donor identification number used by the donor registry to
identify and track the peripheral blood stem cell or bone marrow donor. Continue
with question 7.
Question 3: Non-NMDP cord blood unit ID
Specify the cord blood unit identification number used by the cord blood bank to
identify and track the unit. If reporting confirmatory typing on the cord blood unit,
continue with question 4. If reporting maternal HLA typing, continue with question
12.
Question 4: Is cord blood unit maternal HLA typing available?
Maternal HLA that is not inherited by the fetus, or non-inherited maternal
antigens (NIMAs), may be used to select between comparable mismatched cord
blood units. Studies have found that NIMA-matched cord blood transplantation
may be associated with improved outcomes when compared to equivalent NIMAmismatched cord blood transplantation.
Indicate if the maternal HLA typing is available and continue with question 7; if
yes, also complete Form 2005 reporting maternal HLA typing.

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Question 5: Specify recipient’s biological relative and typing
If confirmation of HLA typing is being reported on a donor who is biologically
related to the recipient, specify their relationship.
Mother: The HLA typing is being reported on a donor who is the recipient’s
biological mother.
Father: The HLA typing is being reported on a donor who is the recipient’s
biological father.
Sibling: The HLA typing is being reported on a donor who shares the
same biological mother and father.
Syngeneic twin: The HLA typing is being reported on a donor who is the
recipient’s monozygotic (identical) twin. Monozygotic twins arise from the
division of a single implanted egg, resulting in two embryos that share the
same chromosomal profile.
Fraternal twin: The HLA typing is being reported on a donor who is the
recipient’s dizygotic twin. Dizygotic twins arise from two eggs being
independently fertilized and implanted, resulting in two embryos that are
the same age but are unlikely to share the same chromosomal profile.
Child: The HLA typing is being reported on a donor who is the recipient’s
biological child.
Aunt: The HLA typing is being reported on a donor who is the recipient’s
biological parent’s sister.
Uncle: The HLA typing is being reported on a donor who is the recipient’s
biological parent’s brother.
Cousin: The HLA typing is being reported on a donor who is the child of
the recipient’s aunt or uncle.
Other biological relative: The HLA typing is being reported on a donor who
does not fit the definition of other biological relatives specified above.
Specify the other biological relative’s relationship to the recipient (do not
report the donor’s name) and if preliminary or confirmatory typing was
done in question 6.
Questions 7-8: Date of birth (donor/infant)
Indicate whether the donor’s or infant cord donor’s date of birth is “known” or
“unknown.” If “known,” report the date of birth in question 8. If the date of birth is
known, it is not necessary to complete questions 9-10 specifying the donor’s or
infant cord donor’s age. If “unknown,” continue with question 9.
Questions 9-10: Age (donor/infant)
Indicate whether the donor’s or infant cord donor’s age at the time of HLA typing
is “known” or “unknown.” If “known,” report the donor’s or infant cord donor’s age
in question 10. If the infant’s age is less than one year, report as months rounded
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to the nearest whole month. If the HLA typing was done at birth or prenatally,
report “0” months. If “unknown,” continue with question 11.
Question 11: Sex (donor/infant)
Indicate the biological sex of the donor or infant cord donor.
Question 12: Was the person for whom this typing is being done used as
the donor?
Indicate if the reported typing is for the individual selected as the donor.
Reporting typing done on family members not selected as donors is optional, but
may be beneficial for additional HLA studies.

HLA Typing by DNA Technology
Complete this section for all typing done by DNA based methods. Examples of
HLA typing by DNA technology may include: sequence-specific primer (SSP),
sequence-specific oligonucleotide probe (SSOP), and sequence-based typing
(SBT).
DNA technology can be used to type for a single allele, combinations of alleles
(allele strings), or a “generic” allele designation similar to a serologic typing
result. For this reason, the number of digits reported, as well as the number of
alleles, will vary.
Laboratories may use “ / ” , “ – ” or a combination of numbers and letters on the
typing report as a shorthand notation for the results. Transcribe the information
onto the form as directly as possible. The letters, called allele codes, will be 1 or
more characters in length and represent a combination of possible alleles at a
locus. The same allele combination may be reported several different ways (e.g.,
DRB1*01:01 or 01:02, DRB1*01:01/01:02, DRB1*01:01/02, or DRB1*01:AB).
There will be two alleles reported for each locus, unless the individual is
presumed homozygous (i.e., carries two copies of the same allele) at a locus.
Transcribe the first allele designation in the first box, and the second allele
designation in the second box. If the person is homozygous, leave the second
box blank.
Question 13: Was documentation submitted to the CIBMTR (e.g., lab
report)?
Indicate if a copy of the HLA typing report is attached. Use the Log of Appended
Documents (Form 2800) to attach a copy of the HLA typing laboratory report.
Attaching a copy of the laboratory report assists in confirming the reporting of
HLA typing and reduces the need for later data queries.

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Class I
Questions 14-15: Locus A
Indicate whether the allele designations at HLA-A are “known” or “unknown.” If
known, report the first A* allele and second A* allele designations in question 15;
report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 16. If question 14 is “unknown,” then
question 36 (“A” antigens defined by serologic typing) is required.
Questions 16-17: Locus B
Indicate whether the allele designations at HLA-B are “known” or “unknown.” If
known, report the first B* allele and second B* allele designations in question 17;
report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 18. If question 16 is “unknown,” then
question 39 (“B” antigens defined by serologic typing) is required.
Questions 18-19: Locus C
Indicate whether the allele designations at HLA-C are “known” or “unknown.” If
known, report the first C* allele and second C* allele designations in question 19;
report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 20.
Class II
Questions 20-21: Locus DRB1
Indicate whether the allele designations at HLA-DRB1 are “known” or “unknown.”
If known, report the first DRB1* allele and second DRB1* allele designations in
question 21; report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 22.
Class II (Optional)
Questions 22-23: Locus DRB3
Indicate whether the allele designations at HLA-DRB3 are “known” or “unknown.”
If known, report the first DRB3* allele and second DRB3* allele designations in
question 23; report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 24.
Questions 24-25: Locus DRB4
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Indicate whether the allele designations at HLA-DRB4 are “known” or “unknown.”
If known, report the first DRB4* allele and second DRB4* allele designations in
question 25; report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 26.
Questions 26-27: Locus DRB5
Indicate whether the allele designations at HLA-DRB5 are “known” or “unknown.”
If known, report the first DRB5* allele and second DRB5* allele designations in
question 27; report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 28.
Questions 28-29: Locus DQB1
Indicate whether the allele designations at HLA-DQB1 are “known” or “unknown.”
If known, report the first DQB1* allele and second DQB1* allele designations in
question 29; report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 30.
Questions 30-31: Locus DPB1
Indicate whether the allele designations at HLA-DPB1 are “known” or “unknown.”
If known, report the first DPB1* allele and second DPB1* allele designations in
question 31; report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 32.
Questions 32-33: Locus DQA1
Indicate whether the allele designations at HLA-DQA1 are “known” or “unknown.”
If known, report the first DQA1* allele and second DQA1* allele designations in
question 33; report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 34.
Questions 34-35: Locus DPA1
Indicate whether the allele designations at HLA-DPA1 are “known” or “unknown.”
If known, report the first DPA1* allele and second DPA1* allele designations in
question 35; report a single allele, a string of alleles, or an allele code.
If “unknown,” continue with question 36.

Antigens Defined by Serologic Typing
Complete this section for all serologic typing. If serologic typing was not
performed, leave this section blank. Report broad antigens only when your
laboratory was not able to confirm typing for a known split antigen.
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Each HLA locus has a serologically defined “X” antigen specificity: AX, BX, CX,
DRX, DPX, and DQX. At this time, an “X” specificity is defined as “unknown but
known to be different from the other antigen at that locus.” This is different from a
blank specificity, which is assumed to be the same as the other antigen at that
locus.” When comparisons between recipient and donor antigens involve an “X”
or “blank” specificity, the “X” or “blank” is assumed to be homozygous for the
antigen reported at the locus. In other words, the search algorithm treats typing
containing “blank” or “X” antigens in the same manner as known homozygous
typing.
Questions 36-38: Number of A antigens provided
Indicate if one or two HLA-A antigens were tested. If one antigen was tested,
report the first antigen specificity in question 37 and continue with question 39.
If two antigens were tested, report the first antigen specificity in question 37 and
the second antigen specificity in question 38. Continue with question 39.
Questions 39-41: Number of B antigens provided
Indicate if one or two HLA-B antigens were tested. If one antigen was tested,
report the first antigen specificity in question 40 and continue with question 42.
If two antigens were tested, report the first antigen specificity in question 40 and
the second antigen specificity in question 41. Continue with question 42.

Optional Antigen Reporting
Questions 42-44: Number of C antigens provided
Indicate if one or two HLA-C antigens were tested. If one antigen was tested,
report the first antigen specificity in question 43 and continue with question 45.
If two antigens were tested, report the first antigen specificity in question 43 and
the second antigen specificity in question 44. Continue with question 45.
Question 45: Specificity Bw4 present?
Bw4 refers to an epitope expressed by HLA-B alleles; epitopes are presented on
the surface of the antigen and are recognized by the immune system. Bw4 and
Bw6 are mutually exclusive and may confer reactivity with lymphocytes. Select
“yes” if Bw4 specificity is present. Leave blank if specificity for Bw4 was not
tested.
Question 46: Specificity Bw6 present?
Bw6 refers to an epitope expressed by HLA-B alleles; epitopes are presented on
the surface of the antigen and are recognized by the immune system. Bw4 and
Bw6 are mutually exclusive and may confer reactivity with lymphocytes. Select
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“yes” if Bw6 specificity is present. Leave blank if specificity for Bw6 was not
tested.
Questions 47-49: Number of DR antigens provided
Indicate if one or two HLA-DR antigens were tested. If one antigen was tested,
report the first antigen specificity in question 48 and continue with question 50.
If two antigens were tested, report the first antigen specificity in question 48 and
the second antigen specificity in question 49. Continue with question 50.
Question 50: Specificity DR51 present?
HLA-DR51 is an HLA-DR variant that recognizes antigens from HLA-DRB5.
Select “yes” if DR51 specificity is present. Leave blank if specificity for DR51 was
not tested.
Question 51: Specificity DR52 present?
HLA-DR52 is an HLA-DR variant that recognizes antigens from HLA-DRB3.
Select “yes” if DR52 specificity is present. Leave blank if specificity for DR52 was
not tested.
Question 52: Specificity DR53 present?
HLA-DR53 is an HLA-DR variant that recognizes antigens from HLA-DRB4.
Select “yes” if DR53 specificity is present. Leave blank if specificity for DR53 was
not tested.
Questions 53-55: Number of DQ antigens provided
Indicate if one or two HLA-DQ antigens were tested. If one antigen was tested,
report the first antigen specificity in question 54 and continue with question 56.
If two antigens were tested, report the first antigen specificity in question 54 and
the second antigen specificity in question 55. Continue with question 56.
Questions 56-58: Number of DP antigens provided
Indicate if one or two HLA-DP antigens were tested. If one antigen was tested,
report the first antigen specificity in question 57 and continue with the signature
section.
If two antigens were tested, report the first antigen specificity in question 57 and
the second antigen specificity in question 58. Continue with the signature section.
Signature
The FormsNet3SM application will automatically populate the signature data
fields, including name and email address of person completing the form and date
upon submission of the form.
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