Stem Cell Donor Matching for Stem Cell Donor Matching for Patients of Mixed RacePatients of Mixed RaceTed Bergstrom, UCSBRod Garratt, UCSBDamien Sheehan-Connor, Wesleyan UniversityASSA Winter MeetingsJanuary 8, 2011MotivationIf Nick Glasgow were white, he would have a nearly 90 percent chance of finding a matching bone marrow donor who could cure his leukemia. But because the 28-year-old bodybuilder is one-quarter Japanese, his doctor warned him the outlook was grim. Glasgow's background, he said, would make it impossible to find a match, because a match usually comes from a patient's own ethnic group. “The doctor didn't say it was slim-to-none. He didn't say it would be hard. He said `zero chance,’” Glasgow's mother,…, recalled.-Associated Press, 27 May 2009Motivation• Friends and family of Mr. Glasgow organized a web-based campaign to recruit potential donors• Focus of recruitment was on those of mixed European-Japanese background• The punch line:Found two matching potential donors within one monthQuestions Posed• Mr. Glasgow’s chances of finding a match were obviously not zero. What were they?• To what extent are individuals more likely to find a match within their “own” ethnic group? How do we define “own”?• Is there an economic case for aggressive recruitment of new potential donors of mixed race?Bone Marrow Transplants• Many diseases of the blood can be potentially cured by a hematopoietic stem cell (bone marrow) transplant• This involves destruction of the patient’s bone marrow and its replacement with bone marrow from a donor• The new bone marrow replenishes the blood with non-diseased cellsMatching Patients with Donors• In order to be successful, patient and donor must be adequately “matched”• In solid organ transplants:– Match blood type to prevent rejection of graft by recipient– Rarest blood type is in 7% of population• In hematopoietic stem cell transplants:– Match HLA type to prevent rejection of recipient by the graft (GVHD)Many HLA Types• More than 10 million distinct types, even at a relatively gross level of matching• Probability of matching a sibling is 25%– Approximately 30% of needy patients have a matching sibling• Approximately 4,000 patients per year in United States who could benefit from a transplant, but have no matching siblingMatching Probabilities by RaceCaucasianAfrican‐AmericanAsian HispanicCaucasian 1/8,000African‐American 1/133,000 1/127,000Asian 1/270,000 1/2,000,000 1/37,000Hispanic 1/45,000 1/370,000 1/370,000 1/39,000Note: Table entries give the probability that a randomly selected member of the row race matches a randomly selected member of the column race.Other Facts: • 50% of Caucasians belong to groups with a prevalence less than 1in 100,000• 20% of Caucasians belong to groups with a prevalence less than 1 in 1,000,000Marrow Donor Registries• To solve this matching problem, registries of willing donors have been established– Determine HLA type and store along with contact information• A needy patient’s type can be compared to those in the registry• A matching registrant will be asked to donateNMDP Registry, 2009Race or Ethnicity (Self-Identified) Number in RegistryAmerican Indian/Alaska Native 90,000Asian 550,000Black or African American 600,000Native Hawaiian or Other Pacific Islander 11,000White 6,000,000Multiple Race 250,000Hispanic or Latino800,000Total 8,301,000Source: 2009 NMDP Facts and Figures, accessed at http://www.marrow.org/NEWS/MEDIA/Facts_and_Figures/2009 Facts and Figures Final 20031210.pdfNMDP Registry Imputations• Best available HLA data (from NMDP) divided into the following categories:– Caucasian– African-American–Asian– Hispanic• Need to impute number of registrants for each of these groups, plus each mixed-race combinationNMDP Registry Imputations• Caucasian:– White, AI/AN• African-American– Black or African American•Asian– Asian, Native Hawaiian or Other Pacific Islander• Hispanic– Hispanic or LatinoNMDP Registry Imputations• The “multiple race” category was divided among the six biracial combinations in proportion to their 2000 US Census numbersImputed NMDP RegistryRacial Group Imputed Number in RegistryWhite6,090,000African-American600,000Asian-American561,000Hispanic800,000African-American, White43,700Asian-American, White50,900Hispanic, White92,500African-Amer., Asian-Amer.8,000African-American, Hispanic44,600Asian-American, Hispanic10,400Imputed NMDP RegistryRacial GroupImputed NumberProbability AvailableEffective NumberWhite6,090,000 0.57 3,471,300African-American600,000 0.27 162,000Asian-American561,000 0.35 196,350Hispanic800,000 0.34 272,000African-American, White43,700 0.42 18,400Asian-American, White50,900 0.46 23,400Hispanic, White92,500 0.46 42,100African-Amer., Asian-Amer.8,000 0.31 2,500African-American, Hispanic44,600 0.30 13,600Asian-American, Hispanic10,400 0.34 3,600Total8,301,000 4,205,250Matching Patients and Donors: Haplotypes and Phenotypes•A haplotype describes the combination of alleles on a particular chromosome• Each individual has two haplotypes, one from each parent• Patient-donor compatibility depends upon the phenotype, which is the union of the two haplotypesPhenotype MatchingA4B10DR1A1B3DR6A4B3DR1A1B10DR6Phenotype:A1,A4,B3,B10,DR1,DR6Phenotype:A1,A4,B3,B10,DR1,DR6These two individuals are of matching phenotype, but do not share the same haplotypes.Probability of having no match• Let pixbe fraction of the population of racial group x that is type i.– We estimate these values using recent data on haplotype distributions from Kollman, et al. (2007) • Probability that a person of type i has no match in the registry is • Probability that a randomly selected person ofracial group yhas no match in the registry is xRxiixpp 100iiyippMatch ProbabilitiesRacial GroupProbability of Match in RegistryWhite0.93African-American0.58Asian-American0.77Hispanic0.82African-American, White0.71Asian-American, White0.80Hispanic, White0.87African-Amer., Asian-Amer.0.50African-American, Hispanic0.65Asian-American, Hispanic0.72Match ProbabilitiesRacial GroupProbability of Match in RegistryWhite0.93African-American0.58Asian-American0.77Hispanic0.82African-American, White0.71Asian-American, White0.80Hispanic, White0.87African-Amer., Asian-Amer.0.50African-American, Hispanic0.65Asian-American, Hispanic0.72CompareMatch ProbabilitiesRacial GroupProbability of Match