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href="https://www.acco.org/awarenessmap/">Childhood Cancer Awareness Map</a></li> <li class="page_item page-item-226"><a href="https://www.acco.org/childhood-cancer-legislation/">Childhood Cancer Legislation</a></li> <li class="page_item page-item-4707"><a href="https://www.acco.org/childhood-cancer-statistics/">Childhood Cancer Statistics</a></li> <li class="page_item page-item-1328"><a href="https://www.acco.org/childhood-leukemias/">Childhood Leukemias</a></li> <li class="page_item page-item-1344"><a href="https://www.acco.org/childhood-lymphomas/">Childhood Lymphomas</a></li> <li class="page_item page-item-1972"><a href="https://www.acco.org/childrens-oncology-group-cog-new-cooperative-group-created/">Children’s Oncology Group (COG): New Cooperative Group Created</a></li> <li class="page_item page-item-6627"><a href="https://www.acco.org/cbp-gm-2016/">Christmas Boat Parade Grand Marshals 2016</a></li> <li class="page_item page-item-105"><a href="https://www.acco.org/clinical-trials/">Clinical Trials</a></li> <li class="page_item page-item-1975"><a href="https://www.acco.org/clinical-trials-part-i/">Clinical Trials Part I</a></li> <li class="page_item page-item-24025"><a href="https://www.acco.org/cloudsmovie/">Clouds Movie Raises Awareness for Osteosarcoma and Childhood Cancer</a></li> <li class="page_item page-item-89"><a href="https://www.acco.org/cog-treatment-centers/">COG Treatment Centers</a></li> <li class="page_item page-item-14084"><a href="https://www.acco.org/coltons-survivor-story/">Colton’s Survivor Story</a></li> <li class="page_item page-item-568"><a href="https://www.acco.org/comfort-kit/">Comfort Kit</a></li> <li class="page_item page-item-1758"><a href="https://www.acco.org/complementary-and-alternative-medicine/">Complementary and Alternative Medicine</a></li> <li class="page_item page-item-68"><a href="https://www.acco.org/contact/">Contact ACCO</a></li> <li class="page_item page-item-1979"><a href="https://www.acco.org/cord-blood-transplantation/">Cord Blood Transplantation</a></li> <li class="page_item page-item-13320"><a href="https://www.acco.org/coronavirus-links/">Coronavirus Links</a></li> <li class="page_item page-item-5407"><a href="https://www.acco.org/corporate-events/">Corporate Events</a></li> <li class="page_item page-item-13158"><a href="https://www.acco.org/corporate-partnerships/">Corporate Partnerships</a></li> <li class="page_item page-item-158"><a href="https://www.acco.org/cozy-cares-journal/">Cozy Cares Journal</a></li> <li class="page_item page-item-565"><a href="https://www.acco.org/cozy-cat/">Cozy Cat Stuffed Animal</a></li> <li class="page_item page-item-3733"><a href="https://www.acco.org/cozycoloring/">Cozy Coloring Contest</a></li> <li class="page_item page-item-13614"><a href="https://www.acco.org/cpap-bipap-donation/">CPAP/BiPAP Donation</a></li> <li class="page_item page-item-229"><a href="https://www.acco.org/ongoingadvocacy/">Current and 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Heaven- TX</a></li> <li class="page_item page-item-94"><a href="https://www.acco.org/education-issues/">Education Issues</a></li> <li class="page_item page-item-97"><a href="https://www.acco.org/education-scholarships/">Education Scholarships</a></li> <li class="page_item page-item-13662"><a href="https://www.acco.org/elises-isolation-story/">Elise’s Isolation Story</a></li> <li class="page_item page-item-14070"><a href="https://www.acco.org/emmas-survivor-story/">Emma’s Survivor Story</a></li> <li class="page_item page-item-13463"><a href="https://www.acco.org/emotional-communication-kit-online/">Emotional Communication Kit: Online!</a></li> <li class="page_item page-item-12771"><a href="https://www.acco.org/la-roche-posay/">Emotional Communication Kits</a></li> <li class="page_item page-item-5437"><a href="https://www.acco.org/event-registration/">Event Registration</a></li> <li class="page_item page-item-30880"><a href="https://www.acco.org/ewings-sarcoma/">Ewing’s Sarcoma</a></li> <li class="page_item page-item-34456"><a href="https://www.acco.org/family-resources/">Family Resources</a></li> <li class="page_item page-item-10889"><a href="https://www.acco.org/federal/">Federal</a></li> <li class="page_item page-item-8300 page_item_has_children"><a href="https://www.acco.org/financial/">Financial</a> <ul class='children'> <li class="page_item page-item-6218"><a href="https://www.acco.org/financial/social-security-disability/">Getting Social Security Benefits For a Child with Cancer</a></li> </ul> </li> <li class="page_item page-item-520"><a href="https://www.acco.org/for-families/">For Families</a></li> <li class="page_item page-item-191"><a href="https://www.acco.org/for-kids/">For Kids</a></li> <li class="page_item page-item-196"><a href="https://www.acco.org/for-siblings/">For Siblings</a></li> <li class="page_item page-item-194"><a href="https://www.acco.org/for-teens/">For Teens</a></li> <li class="page_item page-item-14395"><a href="https://www.acco.org/franciscos-survivor-story/">Francisco’s Survivor Story</a></li> <li class="page_item page-item-11647"><a href="https://www.acco.org/gavinfritts/">Gavin Fritts Shining Star – NC</a></li> <li class="page_item page-item-14174"><a href="https://www.acco.org/gavins-survivor-story/">Gavin’s Survivor Story</a></li> <li class="page_item page-item-1982"><a href="https://www.acco.org/genetic-changes-in-cancer-second-of-three-parts/">Genetic Changes in Cancer: Second of Three Parts</a></li> <li class="page_item page-item-1984 current_page_item"><a href="https://www.acco.org/genetics-and-anti-leukemia-therapy-the-tpmt-story/" aria-current="page">Genetics and Anti-Leukemia Therapy: The TPMT Story</a></li> <li class="page_item page-item-524"><a href="https://www.acco.org/get-help-from-a-local-division/">Get Help from a Local Division</a></li> <li class="page_item page-item-414"><a href="https://www.acco.org/get-involved/">Get Involved</a></li> <li class="page_item page-item-7728"><a href="https://www.acco.org/maylea/">Giggles of Gold Project</a></li> <li class="page_item page-item-6360"><a href="https://www.acco.org/givingtuesday/">Giving Tuesday</a></li> <li class="page_item page-item-4254"><a href="https://www.acco.org/global-childhood-cancer-event/">Global Childhood Cancer Event</a></li> <li class="page_item page-item-253"><a href="https://www.acco.org/gogold/">Go Gold For Kids With Cancer®</a></li> <li class="page_item page-item-35569"><a href="https://www.acco.org/go-gold-gala/">GO GOLD® Gala</a></li> <li class="page_item page-item-34042"><a href="https://www.acco.org/go-gold-the-run/">GO GOLD® THE RUN</a></li> <li class="page_item page-item-3297"><a href="https://www.acco.org/gold-ribbon-awareness/">Gold Ribbon Awareness</a></li> <li class="page_item page-item-65"><a href="https://www.acco.org/gold-ribbon-heroes/">Gold Ribbon Heroes</a></li> <li class="page_item page-item-13817"><a href="https://www.acco.org/gold-wall-of-gratitude/">Gold Wall of Gratitude</a></li> <li class="page_item page-item-4631"><a href="https://www.acco.org/goldenangels/">Golden Angels – Puerto Rico (PR)</a></li> <li class="page_item page-item-12853"><a href="https://www.acco.org/golden-warriors-of-maine-me/">Golden Warriors of Maine – ME</a></li> <li class="page_item page-item-14066"><a href="https://www.acco.org/graces-survivor-story/">Grace’s Survivor Story</a></li> <li class="page_item page-item-6538"><a href="https://www.acco.org/green-family/">Green Family</a></li> <li class="page_item page-item-23"><a href="https://www.acco.org/groups/">Groups</a></li> <li class="page_item page-item-14098"><a href="https://www.acco.org/hannahs-survivor-story/">Hannah’s Survivor Story</a></li> <li class="page_item page-item-1831"><a href="https://www.acco.org/health-related-outcomes-for-hodgkin-disease-survivors/">Health-Related Outcomes for Hodgkin Disease Survivors</a></li> <li class="page_item page-item-31010"><a href="https://www.acco.org/hepatoblastoma-cancer-de-higado/">Hepatoblastoma (Cáncer de Hígado)</a></li> <li class="page_item page-item-1339"><a href="https://www.acco.org/hepatoblastoma/">Hepatoblastoma (Liver Cancer)</a></li> <li class="page_item page-item-170"><a href="https://www.acco.org/hero-beads/">Hero Beads®</a></li> <li class="page_item page-item-37"><a href="https://www.acco.org/history/">History of ACCO</a></li> <li class="page_item page-item-551"><a href="https://www.acco.org/history-timeline/">History Timeline</a></li> <li class="page_item page-item-2"><a href="https://www.acco.org/">Home</a></li> <li class="page_item page-item-1407"><a href="https://www.acco.org/home-2/">Home</a></li> <li class="page_item page-item-3235"><a href="https://www.acco.org/hope4heroes/">Hope 4 Heroes – CO</a></li> <li class="page_item page-item-34438"><a href="https://www.acco.org/hope-amidst-sorrow/">Hope Amidst Sorrow: A Seminar for Bereaved Parents</a></li> <li class="page_item page-item-5188"><a href="https://www.acco.org/hope4ccf/">Hope4CCF – LA</a></li> <li class="page_item page-item-34720"><a href="https://www.acco.org/hospital-organization-resources/">Hospital & Organization Resources</a></li> <li class="page_item page-item-11769"><a href="https://www.acco.org/hospitalnetwork/">Hospital Network Program</a></li> <li class="page_item page-item-1760"><a href="https://www.acco.org/hydrocephalus-shunts-and-gamma-knife/">Hydrocephalus, Shunts, and Gamma Knife</a></li> <li class="page_item page-item-13521"><a href="https://www.acco.org/i-feel-afraid/">I feel afraid.</a></li> <li class="page_item page-item-13503"><a href="https://www.acco.org/i-feel-angry/">I feel angry.</a></li> <li class="page_item page-item-13509"><a href="https://www.acco.org/i-feel-bored/">I feel bored.</a></li> <li class="page_item page-item-13525"><a href="https://www.acco.org/i-feel-disgusted/">I feel disgusted.</a></li> <li class="page_item page-item-13490"><a href="https://www.acco.org/i-feel-happy/">I feel happy.</a></li> <li class="page_item page-item-13494"><a href="https://www.acco.org/i-feel-proud/">I feel proud.</a></li> <li class="page_item page-item-13472"><a href="https://www.acco.org/i-feel-sad/">I feel sad.</a></li> <li class="page_item page-item-13498"><a href="https://www.acco.org/i-feel-surprised/">I feel surprised.</a></li> <li class="page_item page-item-13519"><a href="https://www.acco.org/i-feel-tired/">I feel tired.</a></li> <li class="page_item page-item-1986"><a href="https://www.acco.org/improving-informed-consent-in-childhood-cancer-trials/">Improving Informed Consent in Childhood Cancer Trials</a></li> <li class="page_item page-item-10881"><a href="https://www.acco.org/international/">International Advocacy</a></li> <li class="page_item page-item-33565"><a href="https://www.acco.org/iccd-2024/">International Childhood Cancer Day – 2024</a></li> <li class="page_item page-item-4711"><a href="https://www.acco.org/international-statistics/">International Statistics</a></li> <li class="page_item page-item-14265"><a href="https://www.acco.org/irenes-survivor-story/">Irene’s Survivor Story</a></li> <li class="page_item page-item-1977"><a href="https://www.acco.org/its-only-a-phase-clinical-trials-part-ii/">It’s only a Phase! Clinical Trials Part II</a></li> <li class="page_item page-item-10615"><a href="https://www.acco.org/jake/">Jake’s Dragon Foundation – PA</a></li> <li class="page_item page-item-14329"><a href="https://www.acco.org/jeffs-survivor-story/">Jeff’s Survivor Story</a></li> <li class="page_item page-item-241"><a href="https://www.acco.org/jelsert/">Jel Sert</a></li> <li class="page_item page-item-14399"><a href="https://www.acco.org/jennifers-survivor-story/">Jennifer’s Survivor Story</a></li> <li class="page_item page-item-14176"><a href="https://www.acco.org/jensens-survivor-story/">Jensen’s Survivor Story</a></li> <li class="page_item page-item-14283"><a href="https://www.acco.org/jillians-survivor-story/">Jillian’s Survivor Story</a></li> <li class="page_item page-item-14286"><a href="https://www.acco.org/juanitas-survivor-story/">Juanita’s Survivor Story</a></li> <li class="page_item page-item-2370"><a href="https://www.acco.org/karis-cause/">Karis’ Cause – OH</a></li> <li class="page_item page-item-13446"><a href="https://www.acco.org/kartersisolation/">Karter’s Isolation Story</a></li> <li class="page_item page-item-14109"><a href="https://www.acco.org/karters-survivor-story/">Karter’s Survivor Story</a></li> <li class="page_item page-item-14178"><a href="https://www.acco.org/kaydences-survivor-story/">Kaydence’s Survivor Story</a></li> <li class="page_item page-item-554"><a href="https://www.acco.org/kemper/">Kemper Foods International</a></li> <li class="page_item page-item-36077"><a href="https://www.acco.org/ks-acco/">Kendra Scott Supports Kids with Cancer</a></li> <li class="page_item page-item-6560"><a href="https://www.acco.org/kovach-family/">Kovach Family</a></li> <li class="page_item page-item-11687"><a href="https://www.acco.org/laborinlovebuildinginhope/">Labor in Love: Building in Hope – OR</a></li> <li class="page_item page-item-99"><a href="https://www.acco.org/late-effects/">Late Effects</a></li> <li class="page_item page-item-30421"><a href="https://www.acco.org/leucemias-infantiles/">Leucemias Infantiles</a></li> <li class="page_item page-item-14427"><a href="https://www.acco.org/lilys-survivor-story/">Lily’s Survivor Story</a></li> <li class="page_item page-item-31268"><a href="https://www.acco.org/linfomas-infantiles/">Linfomas Infantiles</a></li> <li class="page_item page-item-4490"><a href="https://www.acco.org/live-newsfeed/">Live Newsfeed</a></li> <li class="page_item page-item-36912"><a href="https://www.acco.org/lived-experience-of-cancer-a-who-study/">Lived Experience of Cancer: A WHO Study</a></li> <li class="page_item page-item-290"><a href="https://www.acco.org/local-groups/">Local Groups</a></li> <li class="page_item page-item-14401"><a href="https://www.acco.org/logans-survivor-story/">Logan’s Survivor Story</a></li> <li class="page_item page-item-2408"><a href="https://www.acco.org/love-for-zac/">Love for Zac – CA</a></li> <li class="page_item page-item-36370"><a href="https://www.acco.org/make-it-cute/">Make It Cute</a></li> <li class="page_item page-item-13433"><a href="https://www.acco.org/masonsisolation/">Mason’s Isolation Story</a></li> <li class="page_item page-item-24088"><a href="https://www.acco.org/matilda-jane/">Matilda Jane</a></li> <li class="page_item page-item-518"><a href="https://www.acco.org/medical-play-kit/">Medical Play Kit</a></li> <li class="page_item page-item-14243"><a href="https://www.acco.org/mias-isolation-story/">Mia’s Isolation Story</a></li> <li class="page_item page-item-7021"><a href="https://www.acco.org/microsoft/">Microsoft</a></li> <li class="page_item page-item-7085"><a href="https://www.acco.org/mission-of-hope/">Mission of Hope – Sean Swarner Cancer Climber</a></li> <li class="page_item page-item-32"><a href="https://www.acco.org/mission-statement-2/">Mission Statement</a></li> <li class="page_item page-item-14383"><a href="https://www.acco.org/mollys-survivor-story/">Molly’s Survivor Story</a></li> <li class="page_item page-item-36393"><a href="https://www.acco.org/name-shirts-are-back-in-2024/">Name Shirts are Back in 2024!</a></li> <li class="page_item page-item-13167"><a href="https://www.acco.org/national-pajama-day/">National Pajama Day</a></li> <li class="page_item page-item-1349"><a href="https://www.acco.org/neuroblastoma/">Neuroblastoma</a></li> <li class="page_item page-item-32359"><a href="https://www.acco.org/neuroblastoma-2/">Neuroblastoma</a></li> <li class="page_item page-item-1988"><a href="https://www.acco.org/neuropsychological-testing-an-excerpt-from-educating-the-child/">Neuropsychological Testing: An Excerpt from Educating the Child</a></li> <li class="page_item page-item-1990"><a href="https://www.acco.org/new-approaches-for-resistant-brain-tumors/">New Approaches for Resistant Brain Tumors</a></li> <li class="page_item page-item-40"><a href="https://www.acco.org/news-and-press/">News and Press</a></li> <li class="page_item page-item-4365"><a href="https://www.acco.org/newsfeed-test/">Newsfeed Test</a></li> <li class="page_item page-item-11391"><a href="https://www.acco.org/nickys-heart-of-gold-pa/">Nicky’s Heart of Gold – PA</a></li> <li class="page_item page-item-13438"><a href="https://www.acco.org/noahsisolation/">Noah’s Isolation Story</a></li> <li class="page_item page-item-11076"><a href="https://www.acco.org/orangeribbon/">Orange Ribbon Foundation</a></li> <li class="page_item page-item-1746"><a href="https://www.acco.org/osteonecrosis-a-source-of-bone-pain-and-loss-of-function/">Osteonecrosis: A Source of Bone Pain and Loss of Function</a></li> <li class="page_item page-item-7340"><a href="https://www.acco.org/goodwillchill/">Otter Pop Vibes Tour #GoodWillChill</a></li> <li class="page_item page-item-186"><a href="https://www.acco.org/outside-resources/">Outside Resources</a></li> <li class="page_item page-item-1992"><a href="https://www.acco.org/palliative-or-hospice-care-does-my-child-need-this-service/">Palliative or Hospice Care: Does my child need this service?</a></li> <li class="page_item page-item-246"><a href="https://www.acco.org/palmco/">Palmco</a></li> <li class="page_item page-item-10142"><a href="https://www.acco.org/pwap/">Paranormal With a Purpose – FL</a></li> <li class="page_item page-item-2438"><a href="https://www.acco.org/paulandthedragon/">Paul and the Dragon</a></li> <li class="page_item page-item-166"><a href="https://www.acco.org/paul-and-the-dragon-dvd/">Paul and the Dragon Video</a></li> <li class="page_item page-item-13424"><a href="https://www.acco.org/paxtonsisolation/">Paxton’s Isolation Story</a></li> <li class="page_item page-item-34857"><a href="https://www.acco.org/pediatric-cancer-teaching-resources-for-professionals-educators/">Pediatric Cancer Teaching Resources For Professionals & Educators</a></li> <li class="page_item page-item-396"><a href="https://www.acco.org/pjammin/">PJammin® For Kids with Cancer</a></li> <li class="page_item page-item-7315"><a href="https://www.acco.org/pjamminfaq/">PJammin® Frequently Asked Questions</a></li> <li class="page_item page-item-1764"><a href="https://www.acco.org/ports-and-central-lines/">Ports and Central Lines</a></li> <li class="page_item page-item-1994"><a href="https://www.acco.org/practical-genetics-in-cancer-the-human-genetic-code/">Practical Genetics in Cancer: The Human Genetic Code</a></li> <li class="page_item page-item-35046"><a href="https://www.acco.org/preventing-hearing-loss-from-chemo/">Preventing Hearing Loss from Chemo</a></li> <li class="page_item page-item-13222"><a href="https://www.acco.org/print-at-home-coloring-pages/">Print-at-Home Coloring Pages</a></li> <li class="page_item page-item-10883"><a href="https://www.acco.org/proclamations/">Proclamation Language</a></li> <li class="page_item page-item-14447"><a href="https://www.acco.org/quick-links/">Quick Links</a></li> <li class="page_item page-item-404"><a href="https://www.acco.org/raise-awareness-2/">Raise Awareness</a></li> <li class="page_item page-item-1141"><a href="https://www.acco.org/raise-awareness/">Raise Awareness</a></li> <li class="page_item page-item-530"><a href="https://www.acco.org/read-about-it-acco-publications/">Read About It: ACCO Publications</a></li> <li class="page_item page-item-13870"><a href="https://www.acco.org/read-alongs-with-acco/">Read Alongs with ACCO</a></li> <li class="page_item page-item-1996"><a href="https://www.acco.org/relapsed-all-chemotherapy-vs-transplant/">Relapsed ALL: Chemotherapy vs Transplant</a></li> <li class="page_item page-item-1998"><a href="https://www.acco.org/relapsed-all-questions-for-parents-to-ask/">Relapsed ALL: Questions for Parents to Ask</a></li> <li class="page_item page-item-10"><a href="https://www.acco.org/research/">Research</a></li> <li class="page_item page-item-208"><a href="https://www.acco.org/research-articles/">Research Articles</a></li> <li class="page_item page-item-1766"><a href="https://www.acco.org/researching-the-medical-literature/">Researching the Medical Literature</a></li> <li class="page_item page-item-1352"><a href="https://www.acco.org/retinoblastoma/">Retinoblastoma</a></li> <li class="page_item page-item-1355"><a href="https://www.acco.org/rhabdoid-tumors/">Rhabdoid Tumors</a></li> <li class="page_item page-item-5985"><a href="https://www.acco.org/ribbons-of-gold/">Ribbons of Gold – WI</a></li> <li class="page_item page-item-6423"><a href="https://www.acco.org/rock-bottom/">Rock Bottom</a></li> <li class="page_item page-item-6566"><a href="https://www.acco.org/rbfamilies2016/">Rock Bottom Holiday Families</a></li> <li class="page_item page-item-1406"><a href="https://www.acco.org/sample-page-2/">Sample Page</a></li> <li class="page_item page-item-14530"><a href="https://www.acco.org/sarcoma-awareness-month/">Sarcoma Awareness Month</a></li> <li class="page_item page-item-1358"><a href="https://www.acco.org/sarcomas/">Sarcomas</a></li> <li class="page_item page-item-32674"><a href="https://www.acco.org/sarcomas-2/">Sarcomas</a></li> <li class="page_item page-item-6585"><a href="https://www.acco.org/scherff-family/">Scherff Family</a></li> <li class="page_item page-item-13384"><a href="https://www.acco.org/sew-to-save-lives/">Sew to Save Lives</a></li> <li class="page_item page-item-14250"><a href="https://www.acco.org/sing-along-with-acco/">Sing Along with ACCO</a></li> <li class="page_item page-item-391"><a href="https://www.acco.org/sitemap/">Sitemap</a></li> <li class="page_item page-item-13309"><a href="https://www.acco.org/social-isolation-stories/">Social Isolation Stories</a></li> <li class="page_item page-item-13045"><a href="https://www.acco.org/stamp/">Stamp Out Childhood Cancer</a></li> <li class="page_item page-item-123"><a href="https://www.acco.org/start-a-division/">Start a Division or Group</a></li> <li class="page_item page-item-7261"><a href="https://www.acco.org/state/">State</a></li> <li class="page_item page-item-12073"><a href="https://www.acco.org/state-comprehensive-cancer-control-plan/">State Comprehensive Cancer Control Plan</a></li> <li class="page_item page-item-13667"><a href="https://www.acco.org/stevens-isolation-story/">Steven’s Isolation Story</a></li> <li class="page_item page-item-1730"><a href="https://www.acco.org/stories-from-adult-and-child-survivors/">Stories from Adult and Child Survivors</a></li> <li class="page_item page-item-7210"><a href="https://www.acco.org/kobie/">Strength to Survive Childhood Cancer Foundation – HI</a></li> <li class="page_item page-item-1725"><a href="https://www.acco.org/suicidal-thoughts-and-attempts-in-adult-survivors/">Suicidal Thoughts and Attempts in Adult Survivors</a></li> <li class="page_item page-item-6552"><a href="https://www.acco.org/sullivan-family/">Sullivan Family</a></li> <li class="page_item page-item-13972"><a href="https://www.acco.org/survivor-stories/">Survivor Stories</a></li> <li class="page_item page-item-30176"><a href="https://www.acco.org/survivor-stories-alec/">Survivor Stories: Alec</a></li> <li class="page_item page-item-30156"><a href="https://www.acco.org/survivor-stories-alex/">Survivor Stories: Alex</a></li> <li class="page_item page-item-30124"><a href="https://www.acco.org/survivor-stories-ashley/">Survivor Stories: Ashley</a></li> <li class="page_item page-item-30164"><a href="https://www.acco.org/survivor-stories-cara/">Survivor Stories: Cara</a></li> <li class="page_item page-item-30168"><a href="https://www.acco.org/survivor-stories-jordan/">Survivor Stories: Jordan</a></li> <li class="page_item page-item-30239"><a href="https://www.acco.org/survivor-stories-meg/">Survivor Stories: Meg</a></li> <li class="page_item page-item-30679"><a href="https://www.acco.org/survivor-stories-payal/">Survivor Stories: Payal</a></li> <li class="page_item page-item-30161"><a href="https://www.acco.org/survivor-stories-ronald/">Survivor Stories: Ronald</a></li> <li class="page_item page-item-30174"><a href="https://www.acco.org/survivor-stories-taylor/">Survivor Stories: Taylor</a></li> <li class="page_item page-item-30127"><a href="https://www.acco.org/survivor-stories-tj/">Survivor Stories: TJ</a></li> <li class="page_item page-item-30171"><a href="https://www.acco.org/survivor-stories-victoria/">Survivor Stories: Victoria</a></li> <li class="page_item page-item-198"><a href="https://www.acco.org/targeted-therapeutics/">Targeted Therapeutics</a></li> <li class="page_item page-item-2000"><a href="https://www.acco.org/targeted-therapeutics-workshop-at-international-cancer-congress/">Targeted Therapeutics Workshop at International Cancer Congress</a></li> <li class="page_item page-item-2002"><a href="https://www.acco.org/targeting-cancer-in-the-21st-century/">Targeting Cancer In The 21st Century</a></li> <li class="page_item page-item-5405"><a href="https://www.acco.org/team-go-gold/">Team Go Gold</a></li> <li class="page_item page-item-526"><a href="https://www.acco.org/teen-journal/">Teen Journal</a></li> <li class="page_item page-item-6357"><a href="https://www.acco.org/thank-you/">Thank you</a></li> <li class="page_item page-item-1852"><a href="https://www.acco.org/thank-you-for-ordering/">Thank You For Ordering</a></li> <li class="page_item page-item-16373"><a href="https://www.acco.org/brain-tumor-charter-of-rights/">The Brain Tumour Patients’ Charter of Rights</a></li> <li class="page_item page-item-4129"><a href="https://www.acco.org/madison/">The Miracle of Madison – MD</a></li> <li class="page_item page-item-1732"><a href="https://www.acco.org/the-problem-of-pain-in-childhood-cancer-survivors/">The Problem of Pain in Childhood Cancer Survivors</a></li> <li class="page_item page-item-5922"><a href="https://www.acco.org/xen/">Through Xen – CT</a></li> <li class="page_item page-item-1582"><a href="https://www.acco.org/timeline/">Timeline</a></li> <li class="page_item page-item-27985"><a href="https://www.acco.org/tipos-de-cancer-infantil/">Tipos de Cáncer Infantil</a></li> <li class="page_item page-item-2004"><a href="https://www.acco.org/treating-high-risk-neuroblastoma-at-the-turn-of-the-century/">Treating High-Risk Neuroblastoma at the Turn of the Century</a></li> <li class="page_item page-item-1770"><a href="https://www.acco.org/treatment-centers-for-childhood-cancers/">Treatment Centers for Childhood Cancers</a></li> <li class="page_item page-item-86"><a href="https://www.acco.org/treatment-2/">Treatment Options</a></li> <li class="page_item page-item-2745"><a href="https://www.acco.org/triderma/">TriDerma Supports ACCO!</a></li> <li class="page_item page-item-32712"><a href="https://www.acco.org/tumor-de-wilms-y-otros-tumores-renales-infantiles/">Tumor de Wilms y Otros Tumores Renales Infantiles</a></li> <li class="page_item page-item-32701"><a href="https://www.acco.org/tumores-de-la-medula-espinal/">Tumores de la Médula Espinal</a></li> <li class="page_item page-item-32667"><a href="https://www.acco.org/tumores-rabdoides/">Tumores Rabdoides</a></li> <li class="page_item page-item-73"><a href="https://www.acco.org/types-of-childhood-cancer/">Types of Childhood Cancer</a></li> <li class="page_item page-item-77"><a href="https://www.acco.org/us-childhood-cancer-statistics/">US Childhood Cancer Statistics</a></li> <li class="page_item page-item-14635"><a href="https://www.acco.org/virtual-advocacy/">Virtual Advocacy</a></li> <li class="page_item page-item-36325"><a href="https://www.acco.org/voyageur-outward-bound-school/">Voyageur Outward Bound School</a></li> <li class="page_item page-item-21662"><a href="https://www.acco.org/wacco/">WACCO</a></li> <li class="page_item page-item-6544"><a href="https://www.acco.org/walsh-family/">Walsh Family</a></li> <li class="page_item page-item-27552"><a 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class="col col-6 links"> <div id="flex-item" class="w-100 d-block"> <a href="https://www.acco.org">Current Specials </a> <a href="https://www.acco.org">Get Directions </a> <a href="https://www.acco.org/photo-gallery/">Photo Gallery </a> </div> </div>  </div> </div>  <div class="container-fluid"> <div class="row"> <div class="bg-container" style="background-image: url(https://www.acco.org/wp-content/themes/acco-new/img/bg-slider.png)"><div class="bg-overlay"><div class="container"><h1 class="entry-title">Genetics and Anti-Leukemia Therapy: The TPMT Story</h1></div></div></div> </div> </div> <div id="one-column"> <div class="container"> <div class="row"> <div id="primary" class="col-md-12"> <div class="content-wrapper"> <article id="post-1984" class="post-1984 page type-page status-publish hentry"> <div class="entry-content"> <h4><strong>GENETICS AND ANTI-LEUKEMIA THERAPY: THE TPMT STORY</strong></h4> <p><em>by Mary Relling MD</em> Source: Fall 2003 CCCF Newsletter</p> <p>There is lots of variability among patients in medication effects. All patients differ from each other in the way that their bodies absorb, metabolize and excrete all medications. For example, if the same dosage of a medication is given to 100 children, even though the dosage is exactly the same for all children (based on body size), there can be more than a 10-fold variation in the amount of medicine that circulates in the blood. Then drugs have to get from blood to their target in tissue – for example, into tumor cells. The tumor cells can vary 10-fold in their level of responsiveness to the anticancer drugs.</p> <p>For many medicines there is a wide therapeutic range. That is, the dosage that is required to achieve efficacy in a large percentage of patients is much lower than the dosage that is expected to produce adverse effects in a large percentage of patients. This means that it is possible to give all patients a dosage of a medicine that is high enough to achieve its therapeutic effects without causing many to be at risk for side effects. Medicines such as penicillin and ibuprofen are examples of medications that have a wide therapeutic range. Anticancer medicines are examples of medicines that have a very narrow therapeutic range. That is, the dosage that is required to achieve anticancer efficacy is not very much lower than the dosage that may result in life-threatening toxicity or adverse effects. Because of the large inter-patient variability in the amount of drug in the blood, and the variability in tumor responsiveness, it’s difficult to determine an average dose that will work in a high percentage of patients without causing a high percentage to have side effects. This is why adverse effects are so common for anticancer agents.</p> <p>Medication dosing is further complicated, because many anticancer medications require metabolism (a chemical change caused by enzymes in the body) by proteins to be activated as anticancer agents, and most require a different type of metabolism to be detoxified and excreted.</p> <p>All of this variability makes it easy to understand why the same dosages given to 100 different children may have very different effects, both desirable and undesirable, in different children.</p> <p><strong>Some differences among patients are due to genetics:</strong> Many factors influence why patients differ so widely from each other in how they handle and respond to medications. Diet, kidney function, liver function, infections, are all factors that may cause patients to differ from one another in their response to medications. For example, drinking grapefruit juice along with prednisone, vincristine, and many other medicines may increase their side effects by interfering with their metabolism and excretion from the body. But all of these factors exert their influence on the background of the genetic constitution of the individual.</p> <p>Medications work by interacting with proteins, and all proteins are encoded by genes. The order of bases (A, C, G, and T) in DNA is what determines our genetic make-up. From the human genome project, we know that 1 in every 300-1000 bases can be variant from one individual to another. These genetic variations may not be substantial enough to cause disease, but they might be substantial enough to cause a slight alteration in the function of the proteins coded for by the genes. If those proteins are involved in the absorption, the metabolism, or the responsiveness of the body or of the tumor cells to medications, then those genetic variations may be part of the reason why individuals differ from one another in how they respond to a medicine. So, one lesson of the human genome project is that variation is much more common than we had previously thought. Currently, the field of <strong>pharmacogenetics</strong> is an active area of research, which is determining which, of the many thousands of genetic variations, are the most important causes of why patients differ in how they respond to medications.</p> <p><strong>TPMT metabolizes 6MP and 6TG:</strong> Thiopurine methyltransferase (TPMT) is a protein that metabolizes two of the medications that are often used to treat children with leukemia or lymphoma: 6- mercaptopurine (6MP) and 6-thioguanine (6TG). For acute lymphoblastic leukemia (ALL), the doses of 6MP and 6TG are often adjusted, along with other chemotherapy, to cause a moderate “target” degree of myelosuppression. By adjusting doses, the goal is to keep the blood counts within a certain range, from week to week. TPMT is also an enzyme that is responsible for inactivating both of these medications. The higher the TPMT activity, the less the drug is available to be activated to thioguanine nucleotide metabolites. The lower the TPMT activity, the greater the exposure of the child to active 6MP or 6TG metabolites. Therefore, the side effects from thiopurines are affected by the patient’s TPMT enzyme activity.</p> <p><strong>TPMT undergoes genetically regulated variation in activity:</strong> In the early 1980’s, it was demonstrated that this enzyme, TPMT, is genetically regulated. One in 300 individuals is completely deficient—homozygous deficient, in this enzyme activity. This means that the copy of the gene from the mother and the copy of the gene from the father both carry inactivating genetic variations. Ten percent of the population is heterozygous (one copy of the gene from one parent is “variant” and one is normal or “wild type”) and has intermediate activity. Ninety percent of the population has normal or high TPMT activity, meaning that both the maternal and paternal copies of the gene are “wild-type,” that is, do not carry any genetic variations and therefore activity is unimpeded by genetic variation. This genetic variation in TPMT activity translates into differences in the concentrations of active metabolites when patients are treated with normal dosages of 6-mercaptopurine, and to a lesser extent, 6-thioguanine. Genetic tests for TPMT can be used to determine each patient’s TPMT “genotype.”</p> <p>So, the starting doses for these medications are based upon the population average, which is heavily influenced by the 90 percent of the population that have normal high wild-type TPMT activity. However, the doses tolerated by the remaining 10% may be lower. For the 1 in 300 individuals who have deficient activity, the normal doses of these medications cause severe myelosuppression due to extremely high, more than 10-fold, concentrations of these active thioguanine nucleotide metabolites. This could result in sepsis, and theoretically, death from a serious infection. It has been demonstrated that by decreasing the dosage of 6-mercaptopurine approximately 10- fold in these rare children who are homozygous deficient, one can maintain the expected degree of myelosuppression and actually still maintain high levels of thioguanine nucleotides. By knowing which patients have low TPMT activity, it is possible to avoid decreasing the dosages of other myelosuppressive therapy that may be confounding the clinical picture of myelosuppression in any one individual patient. For the 10% of the population who are heterozygote, the case is not as dramatic. About one-third of children who are heterozygous for TPMT activity experience myelosuppression severe enough to warrant a dosage decrease. Nonetheless, in this one-third of patients who are identified as TPMT heterozygotes, it is reasonable to adjust the dose of 6-mercaptopurine alone and attempt to leave the doses of the other non-myelosuppressive treatments at the normal levels. On the other hand, the 90 percent of individuals who have normal, high TPMT activity are unlikely to experience acute myelosuppression from the normal dosages of thiopurines. In general, most leukemia treatment protocols include an algorithm for adjusting the dosages of other components of therapy with no particular emphasis or de-emphasis given to the thiopurine in patients with wild-type TPMT. More detailed information can be found:</p> <ul> <li><a href="http://www.ncbi.nlm.nih.gov/pubmed/10580024?dopt=Abstract">Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. </a>(http://www.ncbi.nlm.nih.gov/pubmed/10580024?dopt=Abstract)</li> <li><a href="http://www.ncbi.nlm.nih.gov/pubmed/10216075?dopt=Abstract">Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia.</a> (http://www.ncbi.nlm.nih.gov/pubmed/10216075?dopt=Abstract)</li> <li><a href="http://www.ncbi.nlm.nih.gov/pubmed/11259360?dopt=Abstract">Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase</a>. (http://www.ncbi.nlm.nih.gov/pubmed/11259360?dopt=Abstract)</li> </ul> <p><strong>Testing for TPMT:</strong> Until recently, TMPT testing was only available as a research test. However, there are now several laboratories conducting commercially available tests for TPMT activity, for TPMT genotype, and for the active thiopurine metabolites. The genotype is a genetic test performed using each patient’s DNA. Such DNA can be extracted from a small blood sample or even a swab of the inside of the mouth – a “buccal swab.” In addition, some laboratories offer tests that measure the actual levels of the thiopurine metabolites.These thiopurine tests, which costs approximately $400.00 can be useful not only for confirming the presence or absence of TPMT deficiency, but also for assessing the degree of compliance of patients with their thiopurine therapy. Measuring compliance can be especially useful for children who are responsible for taking their own dosages; if there are no detectable blood levels of metabolites, this can be a sign that the child is not taking his or her medicines.</p> <p><strong>Who should be tested and when:</strong> It has been controversial to decide which patients should be tested for TPMT status. Should all patients be tested for TPMT status before they receive their first dose of thiopurine? Some propose that such testing is unnecessary, and suggest that only those patients who experience acute myelosuppression during treatment should be tested for their TPMT status. Others propose that testing may be helpful prior to starting thiopurine therapy, in some situations. If a child is experiencing myelosuppression after thiopurine therapy, particularly early in therapy when they have only been exposed to 6-mercaptopurine or 6-thioguanine for a short time, it is possible that TPMT deficiency or low activity is the reason. You can talk to your child’s clinician about the possibility of testing for TPMT status.</p> <p>All treatment protocols for leukemia have contingencies and guidelines for adjusting the dosages of antileukemic medications. In treatment of acute lymphoblastic leukemia, decisions are often made on how to adjust the dosages of medications based on the blood counts. It is now clear that one of the factors that may have an influence on the dose of thiopurine that patients can tolerate is TPMT genetic variation. As more patients and clinicians become aware of the importance of pharmacogenetics, this and other genetic tests will work their way into the routine treatment of children with cancer.</p> <p>Mary V. Relling Pharmaceutical Sciences St. Jude Children’s Research Hospital 332 N. Lauderdale Room D-1052 Memphis, TN 38105 e-mail: mary.relling@stjude.org phone: 901 495 2348; fax: 901 525 6869</p> <p>Conflict of interest statement: “Dr. Relling is a faculty member of St. Jude Children’s Research Hospital and receives funding from the National Institutes of Health to study thiopurine pharmacology. St. Jude is the owner of patent rights based on the discovery of TPMT mutations that affect thiopurine metabolism. St. Jude has licensed these rights and receives a royalty based on sales of the genetic test for these TPMT mutations. This royalty is allocated to a St. Jude account, part of which is used to fund research in Dr. Relling’s department.”</p> <p> </p> </div> <footer class="entry-meta"> </footer> </article> <div id="comments"> </div> </div> </div> </div> </div> </div> </div> <footer id="footer"> <div id="footer-info"> <div class="bottom"> <div class="container wow fadeIn" data-wow-duration="1.75s" data-wow-offset="100"> <div class="row py-4"> <div id="footer-1" class="col-12 my-1 d-none d-md-block"> <div class="row"> <div class="col-md-2"> <img class="img-fluid d-block mx-auto" src="https://www.acco.org/wp-content/themes/acco-new/img/logo-footer.png" /> </div> <div class="col-md-10"> <p class="mt-4">The American Childhood Cancer Organization is a 501(c)(3) public charity, whose programs and services are funded entirely by private donations, foundation grants, and corporate contributions. 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