Stem Cell Therapeutic Outcomes Database (Product Form)

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Forms Instruction Manual - 1

2005: Confirmation of HLA Typing
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
• 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 and HLA identical siblings. 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).

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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 Heredity

Biological Mother

Biological Father HLA-A*01 HLA-A*03
HLA-A*02

01, 02

03, 02

HLA-A*24

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 Nomenclature1

1

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

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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).
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.
Q1-12: Donor/Cord Blood Unit Identification
Q13-35: HLA Typing by DNA Technology
Q36-41: Antigens Defined by Serologic Typing
Q42-58: Optional Antigen Reporting
Manual Updates:
Sections of the Forms Instruction Manual are frequently updated. The most recent updates to the manual
can be found below. For additional information, select the manual section and review the updated text.
If you need to reference the historical Manual Change History for this form, please click here or reference
the retired manual section on the Retired Forms Manuals webpage.

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Add/
Remove/ Description
Modify

Date

Manual
Section

12/
3/15

2005:
Confirmation
Add
of HLA
Typing

Added the following text to question 4:
Indicate if the maternal HLA typing is available and continue with question 7; if
yes, also complete Form 2005 reporting maternal HLA typing.The form will not
come due on its own, so must be added by the data manager.

Q1-12: 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?

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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. The form will not come due on its own, so must be added by the data
manager.

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)

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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 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

Q13-35: 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

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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
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

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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.

Q36-41: 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.
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.

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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.

Q42-58: 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 “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?

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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.

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