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Bone Marrow Registries

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Bone Marrow Registries and Donor MotivesTed Bergstrom, Rod Garratt,Damien Sheehan-ConnorUCSBBackground• Bone marrow transplants dramatically improve survival prospects of leukemia patients.• For transplants to work, donor must be a genetic match for recipient. • Only 30% of patients have matching sibling.• U.S. bone marrow registry started in 1986• Similar registries in other countries (Canada, 1989).Background• Bone Marrow Registry contains 6 million people in US and roughly 12 million worldwide• These people have promised to undergo a painful, somewhat risky procedure to help save a strangers life if asked• Why do people join the registry?– There is an episode of the HBO show "Curb Your Enthusiasm" in which the comedian Richard Lewis needs a kidney transplant and Larry David (the creator of Seinfeld) vows to donate his, thinking he won't be a match. Larry is horrified to learn he actually is a match, and goes to ridiculous lengths to get out of it by trying to find Richard a "better" match. Larry was clearly a pledge donor.• Is the registry the “right” size? the “right” composition?Some Genetics• Individuals “type” is controlled by 6 alleles, located in three loci, called HLA-A, HLA-B and HLA-DR.– HLA = Human Leukocyte Antigen• You inherit a string of 3 from Mom and another string of 3 from Pop. • Diploid reproduction, each parent has two strings, randomly picks one to give to you.• String inherited from a single parent called a haplotype.Possible combinations• There are about 30 possible alleles that could go in each of the first two loci, and about 10 possibilities for the third.• All that matters is what 6 alleles you have (phenotype), not who you got them from.• Matching phenotypes easier than matching genotypesYour most likely match• Probability that two full siblings match is about 1/4. They must receive same string from Mom and also same string from Pop. Chance of this is 1/2x1/2=1/4.• Note that chance of a match with a parent is very small. Same for uncles and aunts and cousins, etc.Matching a Stranger• Not all gene combinations on chromosome are equally likely• Makes estimating match probabilities difficult• Biologists used phenotype data from the bone marrow registry (included sample of about 400,000 “fully” typed people).• Biologists observed phenotypes, but not full genotypes. That is, they see what 6 genes each person has, but don’t know how they were linked on parental chromosomes.Clever statistics• The sample is not big enough to give good estimates of frequency of rare phenotypes.• They do a clever trick. They use phenotype distribution and maximum likelihood techniques to estimate distribution of haplotypes. • With estimated haplotype distribution and assumption of random mating w.r.t HLA type, we can estimate distribution of phenotypes.How many types? • About 9 million different relevant types• Probability that two random people match– Both US Caucasian : 1/11,000– Both Afr-American: 1/98,000– Both Asian-American: 1/29,000– Afr Am and Caucasian : 1/113,000• In contrast to blood transfusions.Distribution of type size is very nonuniform• About half the Caucasian population are in groups smaller than 1/100,000 of population. • About 20 per cent are in groups smaller than 1/1,000,000 of population.Social benefits from an additional donor:Behind the Veil of Ignorance• Every person in society faces some small probability of needing a life-saving transplant.• Adding a donor increases the probability of a match for any person.• We numerically calculate effect of an extra registrant on lives saved and value this increment at the “value of a statistical life” .• VSL estimated to be about $6.5 million (Viscusi-Aldy)Probability of having no match• Let pixbe fraction of the population of race x that is of HLA type i.• Probability that a person of type i has no match in the registry is • Probability that a randomly selected person of race x has no match in the registry is xRxixp )1(xRxiixixpp )1(Some Differences by RaceRace Number in RegistryFraction AvailableEffective No. in RegistryProb. of no MatchCaucasian 4,444,335 .65 2,888,818 .08Afr-Am 485,791 .34 165,169 .38Asian-Am 432,293 .44 190,209 .21Hispanic 594,801 .47 279,556 .16Nat. Am. 70,781 .48. 33,975 .11Gain from extra registrant of race x• Calculate the derivative with respect to Rxof the probability of no match.– Derivative applies to each search.• Multiply this by the number of people seeking matches to find the expected annual number of additional matches resulting from one more registrant.• Multiply number of additional matches by .21 to get expected number of lives saved.Expected Annual Lives Saved by 1,000 More RegistrantsCaucasian Afr-AmAsian-Am Hisp Nat AmLives Saved 0.009 0.035 0.015 0.016 0.01Race of New RegistrantTwo things going on here: 1. Gain in match probability for black from adding additional black registrant is over 20 times gain for Caucasian of adding an additional Caucasian because additional black is far less likely to be redundant.2. However, many more Caucasian searches (2,500) than black searches (200).Annual flow• A registrant can remain in registry until age 61. • Median age of registrants is 35.• We assume that registrants remain in registry for 25 years, on average.• We discount benefits appearing in later years.Present Value of Lives Saved by Additional RegistrantPresent value to this groupCaucasianAfr- Am Asian -Am Hispanic Nat AmCaucasian $1,012 $961 $664 $1,028 $928Afr-Am $71 $3,155 $81 $285 $150Asian-Am $27 $44 $1,063 $60 $59Hispanic $91 $341 $132 $701 $190Nat Am $5 $10 $8 $11 $37Total Value $1,206 $4,512 $1,947 $2,085 $1,364Race of Additional RegistrantCosts • Cost of tests and maintaining records about $105 per registrant. • Physician and hospital costs of transplants is around $166,000.Effective Registry• Need to register more than one person to make one effective registrant• Varies by race (Kollman et al.) – 1.6 Caucasians– 2.9 Afr. Am.• Inflates costs differently across races• Also number of transplants resulting from registrant differs across raceBenefit Cost Comparison:Present values of new registrantCaucasian Afr- Am Asian- Am Hispanic Nat AmBenefit $1,206 $4,512 $1,947 $2,078 $1,364Cost $297 $800 $446 $455 $359B/C Ratio 4.1 5.6 4.4 4.6 3.8Costs include typing and storage, but also these numbers are multiplied


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