cibmtr-genomics

name: cibmtr-genomics description: "Domain knowledge for Center for International Blood and Marrow Transplant Research (CIBMTR) work. Use when: analyzing HLA matching, stem cell transplant data, GVHD outcomes, donor selection, MMUD studies. Triggers: HLA, stem cell transplant, bone marrow, GVHD, donor matching, PBSC, CIBMTR."

CIBMTR Genomics & Transplant Domain Skill

Domain Terminology

HLA (Human Leukocyte Antigen)

Proteins found on most cells that help the immune system recognize self from non-self. HLA matching is crucial for finding a compatible stem cell donor.

Key HLA loci for matching:

• HLA-A, HLA-B, HLA-C (Class I)
• HLA-DRB1, HLA-DQB1 (Class II)

Matching levels:

• 10/10 match: All 5 loci matched at allele level
• 9/10 match: Single mismatch
• 8/10 match: Two mismatches (often MMUD threshold)

MMUD (Mismatched Unrelated Donor)

A stem cell donor who is not related to the patient and does not fully match the patient's HLA types. Often used in studies focusing on transplant access for diverse populations.

Clinical context:

• Used when matched unrelated donor (MUD) unavailable
• Higher GVHD risk requires careful management
• Critical for patients from underrepresented ethnic backgrounds with limited donor pool

PBSC (Peripheral Blood Stem Cells)

Stem cells collected from circulating blood (rather than bone marrow) for transplants.

Collection process:

• Donor receives G-CSF (growth factor) to mobilize stem cells
• Apheresis collects cells from blood
• Often preferred for adult patients due to faster engraftment

Comparison to bone marrow:

GVHD (Graft-versus-Host Disease)

Condition where transplanted immune cells (the graft) attack the recipient's body (the host).

Types:

• Acute GVHD: Occurs within 100 days post-transplant; affects skin, liver, GI tract
• Chronic GVHD: Occurs after 100 days; can affect multiple organ systems

Grading (acute):

• Grade I: Skin only, mild
• Grade II: Skin + mild liver/GI
• Grade III: Moderate multi-organ
• Grade IV: Severe, life-threatening

Risk factors:

• HLA mismatch degree
• Donor/recipient age and sex mismatch
• Stem cell source (PBSC vs bone marrow)
• Conditioning regimen intensity

Workflow

Step 1: Identify Analysis Type

Ask user what type of analysis:

1. HLA matching analysis
2. Donor selection optimization
3. GVHD outcome prediction
4. Transplant access/equity analysis

Step 2: Data Requirements

For HLA analysis:

• Patient HLA typing (high-resolution preferred)
• Donor registry data with HLA types
• Population frequencies if available

For outcomes analysis:

• Transplant date, conditioning regimen
• GVHD incidence and grade
• Survival/relapse data
• Donor characteristics (age, sex, CMV status)

Step 3: Connect to Genomic Data

Use Snowflake genomic tables:

-- Example: Find variants in HLA region (chr6: 28-34 Mb)
SELECT sample_id, chrom, pos, ref, allele1, allele2
FROM HEALTHCARE_DATABASE.DEFAULT_SCHEMA.GENOME_DATA_FILTERED
WHERE chrom = '6' AND pos BETWEEN 28000000 AND 34000000
LIMIT 100;

Join with clinical data:

-- Link genomic samples to patient records
SELECT g.sample_id, g.nhs_number, p.family_id
FROM HEALTHCARE_DATABASE.DEFAULT_SCHEMA.GENOME_DATA_FILTERED g
JOIN HEALTHCARE_DATABASE.DEFAULT_SCHEMA.PANEL p 
  ON g.sample_id = p.sample_id;

Output

Analysis results with:

• HLA matching summaries
• GVHD risk stratification
• Donor selection recommendations
• Population-level statistics for equity analysis

PubMed Search Criteria

Use these search strings to find CIBMTR-related research in PubMed.

Option 1: General CIBMTR Search (Broad)

Captures articles where CIBMTR is mentioned in title, abstract, author, or affiliation.

(CIBMTR[TW] OR "Center for International Blood and Marrow Transplant Research"[TW]) AND "last 5 years"[DP]

Option 2: Targeted Clinical Trials Search

Filters for clinical trials or comparative studies involving CIBMTR.

(CIBMTR[TW] OR "Center for International Blood and Marrow Transplant Research"[TW]) AND (Clinical Trial[PT] OR "Comparative Study"[PT]) AND "last 5 years"[DP]

Option 3: Funding/Grant Search (Highly Specific)

CIBMTR research is primarily supported by NCI and other agencies. Searching by core grant numbers finds official registry-supported studies.

(U24CA076518[GR] OR 75R60222C00011[GR] OR CIBMTR[AD]) AND "last 2 years"[DP]