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  • This slide shows graphically what happens. A single mismatch which is compensated by a single NIMA match, results in a TRM which is near identical to a zero mismatch. Two HLA mismatches compensated by a single NIMA match results in a TRM identical to a single mismatch.

Jeremy Chapman - Australia - Tuesday 29 - Hematopoietic Stem Cells Jeremy Chapman - Australia - Tuesday 29 - Hematopoietic Stem Cells Presentation Transcript

  • Research Trends andRegulation in Haematopetic Stem Cell Transplantation Jeremy Chapman
  • Clinical Problem:Allogeneic Graft Availability Leukemia Patients Needing BMT 8/10 2/10 No Compatible Compatible Sibling Family Donor Donor Only 15-20% minority patients receive BMT via adult registry
  • Impact of Disease Stage and HLA Matching on Unrelated HCT Outcomes Low Risk Intermediate Risk High Risk
  • Impact of Single HLA Mismatch in Unrelated HCT for Low-risk Disease
  • LFS after Cord Blood or Bone MarrowTransplant from Unrelated Donors in Adult Leukemia Patients Rocha et al, N Engl J Med 2004;351:2276-85.
  • UnrelatedHaematpoetic Stem cell donations: Bone Marrow PBSC Cord Blood
  • Bone Marrow or Peripheral Blood Stem Cells? Stem Cell Trialists Collaborative Group, JCO 2005
  • Pioneers in Cord Blood TransplantationEliane Gluckman Paris Pablo Rubenstein New York John Wagner Minneapolis
  • Survival after 0-3 Mismatched Unrelated UCB & 6/6 HLA-matched BMT in children 1.0 1.0 Proportion Surviving 0.8 0.8 0.6 BMT-TCD 0.6 UCBT 56%Proportion 53%Surviving 0.4 41% 0.4 UCBT 52% BMT-MTX 0.2 0.2 p = .40 p > .80 0.0 0.0 0 6 12 18 24 0 6 12 18 24 Months Months Patient analyses with match for age, diagnosis, and disease stage. Barker et al, Blood. 2001 May 15;97(10):2957-61.
  • Probability of Neutrophil Recovery by UCB Graft Cell Dose 1.0 cell dose < 1.87*107/kg (n=23) cell dose (1.87, 2.41) (n=21) Probability of neutrophil recovery 0.8 cell dose > 2.41*107/kg (n=24) 0.6 p-value = 0.003 0.4 0.2 0.0 0 10 20 30 40 50 60 days after transplantation No. at Risk: 68 66 53 26 6 1 Laughlin, MJ., et al., N Engl J Med 2001;344:1815-22
  • DFS for Acute Leukemia in CR Single vs. Double UCBT CY60/TBI1320 1.0 I I I ICumulative Proportion 0.8 double I I I 0.6 I I I I single 0.4 Double: Adults + 0.2 Adolescents Single: Children 0.0 0 2 4 6 8 10 12 Months
  • PROBABILITY OF SURVIVAL Impact of Cell dose and HLA mismatch 1.0 0.8 CB matchedPROBABILITY 0.6 CB 1 agmm (>2.5) 0.4 CB 2 agmm (>2.5) 0.2 CB 1 agmm (<2.5) CB 2 agmm (<2.5) 0.0 0 1 2 3 YEARS
  • Mary Horowitz CIBMTR University of Wisconsin ... .. ............... . .. . .... .......... . .......... . . . . .. . .... .. . . .. . ......... ... .......... . .. . .. . . . .. .. . . . .. ... .. . .. . . . .. .... . . .... ... . ..135 staff including, 6 PhD statisticians, 14 MS statisticians, 11 MD-MS faculty;Active program of statistical methodology research specifically focused ontransplant outcomes in addition to supporting clinical studies
  • Overall Survival Pediatric Study 100 CB matched (n=36) 62%Adjusted Probability, % BM matched (n=116) 45% 80 CB 1-Ag MM high (n=157) 45% 60 40 20 CB 1-Ag MM low (n=44) 36% CB 2-Ag MM (n=267) 33% 0 0 12 24 36 48 60 Months Mjz06_13.ppt
  • Neutrophil Recovery Pediatric Study 100 BM (n=492), 97% CB matched (n=35), 86% 80 CB MM high dose (n=362), 79%Probability, % CB MM low dose (n=97), 64% 60 40 20 0 0 20 40 60 80 100 Days CAL05_13.ppt
  • Acute Grade 2-4 GVHD Pediatric Study 100 80 BM MM (n=123), 70%Probability, % 60 BM matched (n=368), 50% 40 CB MM (n=454), 40% 20 CB matched (n=35), 20% 0 0 20 40 60 80 100 Days CAL05_15.ppt
  • Chronic GVHD Pediatric Study 100 80Probability, % 60 BM MM (n=123), 35% 40 BM matched (n=369), 33% 20 CB matched/MM (n=466), 17% 0 0 6 12 18 24 30 36 Months CAL05_16.ppt
  • Treatment-related Mortality Pediatric Study 100 80Probability, % CB 1-Ag MM low (n=44), 43% BM MM (n=123), 40% 60 CB 2-Ag MM (n=267), 47% 40 CB 1-Ag MM high (n=157), 29% 20 BM matched (n=369), 26% CB matched (n=35), 6% 0 0 12 24 36 48 60 Months CAL05_27.ppt
  • Leukemia-free survival Pediatric study 100 80Probability, % CB matched (n=35), 60% 60 CB 1-Ag MM high (n=157), 41% 40 BM matched (n=369), 40% 20 CB 1-Ag MM low (n=44), 36% CB 2-Ag MM (n=267), 33% BM MM (n=123), 30% 0 0 12 24 36 48 60 Months CAL05_17.ppt
  • Overall Survival Pediatric Study 100 80Probability, % CB matched (n=36), 62% 60 CB 1-Ag MM high (n=157), 45% 40 BM matched (n=369), 44% 20 BM MM (n=123), 40% CB 1-Ag MM low (n=44), 35% CB 2-Ag MM (n=267), 35% 0 0 12 24 36 48 60 Months CAL05_20.ppt
  • The IPA/NIMA effect - Jon Van Rood Mother Father NIMA = non inherited maternal antigensIMA/NIMA IPA/NIPA NIPA = non inherited paternal antigens IMA = inherited maternal antigens IPA = inherited paternal antigens The mother develops B and T cell immunity against the IPA of the fetus, which is controlled by T reg. Likewise, the fetus develop immunity and T reg against the NIMA. Immunity can be lifelong in both mother and child. Patient IMA/IPA
  • HSCT with a parental donor shows a differential effect of maternal versus paternal donors on survival. 1.0 0.8 0.6 Mother donor N=47 Event 0.4 Free Survival 0.2 Father donor N=71 0.0 p<0.0001 Years Follow-Up 0 1 2 3 4 5 # at risk: 118 38 29 28 28 28 M. Stern et al. Blood 2008
  • Identification of an acceptable mismatch with the help of NIMA van Rood et al. Pnas: 2009, 106, pp 19952Patient A1, A2 - B7, B44cord blood A1, A3 - B7, B44mother of CB A1, A2 - B7, B8 NIMA=A2 and B8 Combining the NIMA A2 and B8 with the CB phenotype can create for example the following Virtual CB phenotype: A1, A2 / B7, B44and 5 other Virtual Phenotypes (VP) if there is one substitution and12 when there are two.HLA typing of the mother created 16 different VPs!!
  • Transplant-Related Mortality (Patients ≥ 10 Years Old) 80% with TRM (Cum. Incid.) 2 MM, No NIMA Match Reference 290/488 60 2 MM, 1NIMA Match 1 MM, No NIMA Match Reference 40 1 MM, 1NIMA Match 20/41 RR=0.6, P= 0.012 20 0 Mismatch 4/22 RR=0.3 P = 0.011 0 0 1 2 3 Years Post-Transplant PNAS 2009 106 (47) p10952
  • Time to Absolute Neutrophil Count ≥ 500 100 (Cum. Incid) 0 Mismatch 80 1-2 MM, 1 NIMA Match 60% with ANC 500 1-2 MM, No NIMA Match 40 20 0 0 7 14 21 28 35 42 56 70 days after transplant Patients N RR p value 0 MM 15 3.8 <0.001 1-2 MM,1 NIMA Match 18 1.9 0.031 1-2 MM, No NIMA Match 219 reference
  • Relapse (Patients with Myeloid Diseases) HLA MM/ NIMA RR P 2 MM/No NIMA (n = 343) 0.7 0.075 1 MN/No NIMA (n =193) Reference 40% with Relapse (Cum. Incid.) 2 MM/NIMA Match (n = 31) 0.7 0.448 1 MM/NIMA Match (n = 13) 0.2 0.074 0 MM (n = 33) 0.7 0.306 1 MM, No NIMA Match 30 0 Mismatch 2 MM, NIMA Match 20 2 MM, No NIMA Match 10 1 MM, NIMA Match 0 0 1 2 3 Years Post-Transplant PNAS 2009, 106, pp 19952
  • Acknowledgements NYBC - NCBP Europdonor Foundation• Andromachi Scaradavou • Henk van der Zanden• Pablo Rubinstein • Machteld Oudshoorn• C. Carrier, C. Carpenter • Jack Bakker,Angelo Melis• NCBP Program Staff • Frans Claas• Transplant centers/ physicians/data managers/ patients• Donating Mothers • Eurotransplant Foundation • Jacqueline Smits• Cladd Stevens
  • Current Status Stem Cell Products provided for unrelated transplantation 18,000 16,000 2008 2009Number of donations 14,000 Bone Marrow 3,221 3,445 12,000 10,000 PBSC 7,260 8,162 8,000 Cord Blood Units 3,522 3,749 6,000 4,000 2,000 0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Year BM donations PBSC donations Cord Blood Units Provided
  • % Patients Transplanted in Relation to Searches RequestedRed: 0-10%Yellow: 10-30%Orange: 30-50%Green: > 50% Analyzed from WMDA Annual Report 2009
  • The ABMDR is the best place to search for Australian Patients These are the best registries to search for Australian patients Chance of finding a donor for an AUSTRALIAN patient
  • Singapore Chinese Patients
  • In 2009 18 Products a Day 6,461 Products crossed a Border Percentage of bone marrow/PBSC donations provided for national and international patients 75 65 69.7 69.4 69.1 67.1 66.3 67.5 65.6 64.7 61.1 61.2Percentage (%) 55 58.0 56.2 55.1 45 43.8 44.9 35 38.8 42.0 38.9 34.4 35.3 32.9 33.7 32.5 30.3 30.6 30.9 25 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Year Donations to international recipients Donations to national recipients
  • In 2010, 149 cord blood banks participated worldwide Number of CBUs provided for unrelated transplantation 4,500 2010 2009 4,000Number of cord blood units CBUs provided 4,054 3,792 3,500 3,000 2,500 2,000 1,500 1,000 500 0 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Year No information provided Units provided for adults Units provided for children
  • Degree of matching of the cord blood units provided for children (N=1,286 units) 0 mismatched 664 1 mismatched 600 2 mismatchedNumber of cord blood units 3 or more 500 not specified 400 299 245 300 204 200 100 6 0 Degree of matching of the cord blood units provided for adults (N=2,768 units) 0 mismatched 1,213 1 mismatched 1,200 2 mismatchedNumber of cord blood units 3 or more 1,000 830 not specified 771 800 600 400 245 200 20 0
  • International exchange of cord blood products is increasing Number of cord blood units provided for national and international patients 3,000 2,726 2,537 2,321 2,500Number of Cord Blood Units 2,207 2,000 1,862 1,710 1,368 1,255 1,328 1,500 1,235 1,213 1,098 1,000 829 625 652 510 500 346 372 387 284 146 192 175 129 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Year Provided Internationally Provided NationallyIn 2010: 3.63 cord blood products passing an international border a day
  • NATIONAL MARROW DONOR PROGRAM® 36Entrusted to operate the C.W. Bill Young Cell Transplantation Program, including the Be The Match Registry®
  • AUSCORD 29% OF RELEASES FROM 3% OF INVENTORY
  • Over 70% of the CBUs shipped for adult patients have a TNC >150 Cord blood shipments by TNC for adult patients100%90%80%70%60%50%40%30%20%10% 0% 2004 2005 2006 2007 2008 2009 2010 <90 90-119 120-149 150-199 200-249 250-300 >300
  • 2010 Inventory and shipments TNC of BMDW inventory as of January 1, 2011 1% 2% 0.002% 6% 10% 12% 36% 33% TNC of the CBU products shipped in 2010 2% 0.003 6% <50 50-89 90-124 125-149 8% 14% 150-199 200-249 250-300 >300 20% 18%76% of the shipments camefrom 25% of the available 32%inventory <50 50-89 90-124 125-149 150-199 200-249 250-300 >300
  • Shipping rate of the units listed in BMDW based on TNC (units shipped/units available)TNC Percentage(%)< 50 0.0350-89 0.0990-124 0.3125-149 1.0150-199 2.3200-249 6.3250-300 10.5>300 17.0
  • NATIONAL MARROW DONOR PROGRAM® 41Entrusted to operate the C.W. Bill Young Cell Transplantation Program, including the Be The Match Registry®
  • 2010 WHO Guiding Principles on Human Cell, Tissue and Organ Transplantation World Health Assembly - 22 May 2010 1. 1. Consentfor deceased donors donation Consent for deceased donors donation 2. 2. No conflictfor death determination No conflict for death determination 3. 3. Deceasedbut also consenting live donors Deceased but also consenting live donors 4. 4. Protectionof minors and incompetent persons Protection of minors and incompetent persons 5. 5. No sale or purchase No sale or purchase 6. 6. Promotionof donation nono advertisingbrokering Promotion of donation advertising nor nor brokering 7. 7. Responsibility on origintransplant Responsibility on origin of of transplant 8. 8. Justifiable professional fees Justifiable professional fees 9. Allocationrules 9. Allocation rules 10. Quality safety efficacy of procedures and transplants 10. Quality safety efficacy of procedures and transplants 11. Transparency and confidentiality 11. Transparency and confidentiality
  • 2010 WHO Guiding Principles on Human Cell, Tissue and Organ Transplantation GP 5 Free donation and no purchase of human transplant as such, but cost & expenditures recovery GP 6 GP 7 GP 8 GP 3 Promoting Responsibility Justifiable fees Maximizing DD No advertising for transplant origin Protecting LD GP 2 GP 4 GP 9 Death Δγ Protecting the Equitable allocation No conflict incompetent GP 1Consent DD Donor Process Recipient GP 10 Monitoring long term outcomes. Quality & safety of procedures & products GP 11 Transparency, openness to scrutiny, anonymity
  • WHO Guiding Principles on2010 Human Cell, Tissue Long term Short and and Organ Transplantation Donor Outcomes 2010 World Health Assembly - 22 May Recipient OutcomesGuiding Principle 10 Quality systems Traceability Vigilance Adverse event reporting
  • WHO Guiding Principles on2010 Human Cell, Tissue and Organ Transplantation World Health Assembly - 22 May 2010 Transparency Open to Scrutiny Maintaining privacy of Donors and Recipients
  • Clinical JASN 2011 on line
  • The blood safety paradigm doesn’t translate to Organs & Cells. What is the problem?Volume of activity Scarcity of DonorsBlood donations are in the Blood donors can bemillions in many countries replacedOrgan donations are in the Organ donors are verythousands in only a very scarcefew countries Hemopoetic stem cellHemopoetic stem cell donors are usually uniquedonations are even fewer for each recipient Mortality rates on organ transplant waiting lists are substantial Unavoidable mortality rates from transplantation are substantial Risks from transmission of disease are very small under standard procedures Regulation risk: causing more deaths than saved
  • The effect of putting the Barriers up +++ 500 400In Country 300 National Import 200 Export 100 0Out of Country -100 -200 -300 -400 -500 +
  • The effect of putting the Barriers up +++ 500 400In Country 300 Import National 200 Export 100 0Out of Country -100 -200 -300 -400 -500 +
  • Collateral damage by regulators ISUnacceptable
  • What happened?
  • Analyze: where are CBUs used for transplantation? Number of Cord Blood Units shipped to each continent over time 1,600Number of CBUs provided 1,400 1,200 1,000 800 600 400 200 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Year Asia Australia Europe North America South America Africa 35% of the CBUs shipped are shipped to North America 33% of the CBUs shipped are shipped to Asia
  • Guidance for Industry Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research October 2009 1 This guidance applies to HPC-Cs manufactured by U.S. cord blood establishments and non- U.S. cord blood establishments that distribute cord blood in the U.S. However, some non-U.S. cord blood establishments that participate in international registries may not apply for licensureImportation and use of unlicensed placental/umbilical cord of their products. Importation and use of unlicensed placental/umbilical cord stem/progenitor cell products from non-U.S. cord blood establishments would be acceptable under anstem/progenitor cell products from non-U.S. cord bloodan affiliated Investigational New Drug (IND) application held by the non-U.S. establishment,establishments the U.S. transplant center, or a registry. Also, certain HPC-Cs U.S. establishment, would be acceptable under an Investigational New manufactured in the U.S. may not be licensed but could be listed in registries and madeDrug (IND) applicationan IND. Additional non-U.S. establishment, anof available for clinical use under held by the recommendations regarding submissionaffiliated U.S. establishment, provided in the companion draft guidanceor a INDs for certain unlicensed HPC-Cs are the U.S. transplant center, entitled “Guidance for Industry and FDA Staff: Investigational New Drug Applications (INDs) forregistry. Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Minimally Hematopoietic Reconstitution for Specified Indications).”
  • Europe Reliant upon each national competent authority.....EUROPEAN DIRECTIVE 2004/23/EC; article 9Import/export of human tissues and cellsMember States and tissue establishments that receive suchimports from third countries shall ensure that they meetstandards of quality and safety.
  • Legislation to enact European Directive on HSC August 2011Not standardisedLegislatedNot Legislated
  • Global Quality Standards
  • Quality, efficacy and safety International Standards Accreditation and Audit Data collection and analysis Donor safety - SEAR Product safety - SPEAR Recipient safety – Outcome databasesThis will not be enough – but it will
  • 2009 – 9 events reported to the WMDA (to date) • 2009 – 7 events reported to the WMDA (to date). All except 1 prior to – 8 incidents from donations before 2009, 1 in 2009 2009 (4 - 2008, 1 - 2006, 1 - 1996): (3 - 2008, 3 - 2006, 1 - 2003, 1-1997): – Donor blood group incorrect on label (all other identifiers • 5 cancers correct) – Breast/ brain (benign)/NHL post BM – Incorrect product collected by courier (2 harvested on same day). – Lung/ hepatoma post PBSC (hepatoma had 3 doses of Identified and rectified before courier left airport GCSF - not collected due to patient factors) – Cord unit arrived partially thawed. 28% viability in segment. Not • 1 cauda equina syndrome post BM infused • 1 severe groin bruising post groin line for DLI – Clots in apheresis bag - engrafted • 1 faint following tubing rupture during PBSC (target dose – Rupture of tubing on cell separator. Collection abandoned. Target collected on second day) achieved on day 2 • 1 fat embolism post GA and BM harvest - full recovery – 2 donor derived malignancies • Patient with MDS (Tx 04/06) diagnosed with CML in 11/08. Donor diagnosed with CML 05/08 • Patient with CML (Tx 06/96) diagnosed with mantle cell lymphoma in 05/08. Donor diagnosed with MCL 098/08
  • Clinical Working Group (S(P)EAR committee)Chair: Bronwen ShawVice-chair: Jeff Szer
  • S(P)EAR committee• 175 S(P)EAR reported in 2011 thus far (26 october) – 44 SPEAR (product related) – 131 SEAR (donor related)
  • SPEAR• 10 BM – 4 bacterial contamination of product – 3 Quality • Clot/haemolysed/incorrect recipient name on product – 2 transfer of donor disease • Hepatitis B (possible) • B-CLL (definite) – 1 hypertension post infusion. PRES (probably not)
  • SPEAR• 11 PBSC – 2 ‘suboptimal product’ • 2 failed mobilisation – 1 patient received BM – 3 cryopreserved – poor viability on thaw (2 engrafted/1 PGF – probable) – 1 transport delay/low viability – PGF (possible) – 1 different cell counts and volume at HC and TC – 2 TRALI (both possible) – 1 Donor XXY on chimerism – 1 fever post infusion (bacillus in patient, not in product)• 1 DLI – unable to collect (whole blood collected)
  • SPEAR• 22 CBU – 17 Quality • 6 Damage • 4 Thawed • 4 Other transport (e.g. Xrayed/temperature loggers/bacterial contamination) • 2 Data incorrect • 1 poor cell recovery (engrafted) – 2 Non-engraftment • 1 Low viability (probable) • 1 positive bacterial culture (possible) – 1 Donor derived MDS in engrafting cord (probable) – 1 ‘shocked heart’ (possible) – 1 infusion/washing issue – ARF (probable)
  • SEAR• 22 BM – 6 malignancies (1 haem: CLL) – 2 osteomyelitis – 1 laryngospasm required retubing (definite) – 1 low sats in recovery – observation only (possible) – 2 thrombophlebitis (cannulae) (definite) – 1 sacral haematoma (surgery) (definite) – 3 prolonged back pain (definite) – 2 tendon/nerve injury (1 definite/1 probable) – 1 allogeneic blood for symptomatic anaemia – 1 cardiac arrythmia 6/52 post (possible) – 1 prolonged orthostatic dysregulation (definite) – 1 donor collapse 10 hours post harvest. Successful CPR. 2 allo units (definite)• 2 DLI – anaphylaxis to apheresis set (definite) – Trigeminal neuralgia 21 days post (possible)
  • SEAR• 107 PBSC – 1 donor death – CVC related (Definite) Mobilisation – 1 microscopic haematuria (probable) – 1 pain (hospitalised) (definite) – 1 severe headache-admission and CT (normal) (possible) – 1 intractable vomiting (hospitalised) (definite) – 1 elevated LFT (probable) – 1 erythema of legs D3 (hospitalised - steroids) (probable) – 1 collapse after 1st dose (went ahead) (probable) – 1 dysphagia ? Stress (probable) – 1 acute gout ankle on D3 – no pmh (definite) – 1 epidydimitis/urethritis needing antibiotics (probably not) – 1 severe breathlessness (?stress) G stopped. No collection (probable)
  • SEAR• 107 PBSC Collection – 2 failed collections (citrate toxicity, BM instead; no peripheral access, donor refused CVC) – 1 limited collection (access problems – false aneurysm after femoral CVC, arterial puncture, 43% collected) – 1 chest tightness – 1 tetany – 1 abdo pain, normal ultrasound, admitted later ?cholecystitis – 1 allergic urticaria and hives, continued for 6 months requiring steroids (definite) – 1 herpes zoster (second apheresis)
  • SEAR• 107 PBSC Within 1 month – 3 thrombophlebitis – 1 nerve damage to hand (definite) – 1 abnormal LFT ? Cause (probably not) – 1 MI (several risk factors) (probably not) – 1 anterior uveitis (3/7 post) (possible) – 1 intracranial haematoma 10/7 post, hospitalised, no intervention (possible) – 1 convulsions/palsy 1 mo post – brain bx, unknown cause (possible) – 1 hypertension and tiredness (possible) – 1 otitis media, pneumonia and renal insufficiency 2 /7(inpatient 16/7) (possible) – 1 pyogenic necrotising/haemorrhagic enteritis requiring surgery 3/7 (possible) – 1 atopic dermatitis of both hands 20/7 (possible) – 1 fever, abdo pain 2/7 post, 7/7 inpatient (possible) – 1 near syncope at home (probable) – 1 ITP 3/52 post - ?treatment (possible) – 1 paroxysmal AF 13/7, cardioversion (probably not) – 1 hyperthyroid (auto-immune) crisis with secondary cardiac failure at home 14/7. Second donation (first also PBSC 17 months prior) (probable)
  • SEAR• 107 PBSC – 1 pilonidal sinus 6/52 post (probably not) – 1 hypertonus 2/12, 8/12 thrombosis left eye with retinal detachment (probably not) – 1 retinal detachment 5/12 (probably not) – 1 basilar artery haemorrhage 3/12 (probably not) – 1 acute sarcoidosis 2/52 post. Resolved (possible) – 1 multiple liver haemangiomas and elevated LFT 6/12 (probably not) – 1 auto-immune hypothyroidism 2/12 (possible) – 1 fibromyalgia 6/12 (probably not) – 1 balanced chromosomal abnormality (18) – increased miscarriages – 1 severe disabling hip pain (>1 year) (possible) – 1 dilated cardiomyopathy 1yr (probably not) – 2 Crohns disease (18mo, 2yrs) (probably not) – 1 stroke 1yr (definitely not) – 1 neutropenia 1yr (N BM) (definitely not) – Joint swelling/raised LFT 1yr (probably not) – Transverse myelitis 3yr (probably not)
  • SEAR• 107 PBSC – 3 ulcerative colitis (5 weeks, 2 mo, 4 mo) (possible) – 3 Rheumatoid arthritis (6mo-years) (prob not) – 4 Multiple sclerosis/optic neuritis (prob not) – 1 Atypical athropathia psoriatica (prob not) – 2 alopecia (3 mo/18 mo) (possible) – 1 ankylosing spondylitis (10 mo) (prob not) – 1 wegeners (3 mo) (prob not) – 1 ITP (3 yrs) ((prob not) – 1 Hashimotos (6 mo) (possible) – 1 de quervians (3 mo) (prob not) – 1 chronic keratitis (prob not) – 25 malignancies (non-haematological) – 8 haematological (T-ALL/ALL/2 HD/CML/AML/malt lymphoma/MGUS)
  • Challenges1. Keeping open access for all recipients to allHSC’s2. Keeping the costs of HSC products down3. Ensuring individual patient risk benefitdecisions4. Maintaining small market share tests andproducts5. Maintaining rapid access search systems6. Working with regulators and governments torecognize the global nature of the issues but notbeing afraid to call them to task7. Establishing a coding and labelling system
  • Thank youJeremy_Chapman@wsahs.nsw.gov.au