hematopoietic stem cells from cord blood: - costless but too expensive? Dr. Vincent Kindler Geneva Cord Blood Bank HUG vincent.kindler@hcuge.

Transcription

1 hematopoietic stem cells from cord blood: - costless but too expensive? Dr. Vincent Kindler Geneva Cord Blood Bank HUG vincent.kindler@hcuge.ch

2 Spring water: Manufactured by nature COSTLESS Cord Blood: Manufactured by nature COSTLESS! PROCESSING & CONDITIONING PROCESSING & CONDITIONING COSTLY END PRODUCT (VERY) COSTLY END PRODUCT

3 - brief recall about the need of banking - CBU processing scheme - where Switzerland stands - really more expensive than PBSC? - what future?

4 Hematopoietic stem cell graft banking and donor indexing: An unavoidable requirement resulting from the complexity of the human leukocyte antigen (HLA) locus, which determines the compatibility between the graft and the recipient

5 Mother Father chr.1 chr.2 chr.1 chr.2 25% to find a compatible donor within the same sibling

6 Most often an unrelated donor is required => need of an index or a bank

7 -Two main registries of HSC graft under the regulation of the World Marrow Donor Association (WMDA). -Live adult donors registry 47 countries for 17.8 millions of donors ( ) donations (or 0.5% of the pool) This number, though impressive represents only 0.26% of the human population (6.85x10 9 individuals, Aug 2011) and does not cover the entire HLA diversity.

8 Cord blood registry units (WMDA, August 2011) Of these, have been used for transplantation (or 4.2% of the pool), that is almost 10 times more than live adult donors.

9 HUMAN LEUKOCYTE ANTIGENS (HLA) (mo: inherited from the mother; fa: inherited from the father) A mo A fa C mo B mo DR mo DQ mo DP mo C fa B fa DR fa DQ fa DP fa Class I Class II

10 Compatibility requirements PERIPHERAL BLOOD STEM CELLS full match 9-10/10 A mo A fa C mo B mo DR mo DQ mo DP mo C fa B fa DR fa DQ fa DP fa CORD BLOOD match 4-6/6 A mo A fa C mo B mo DR mo DQ mo DP mo C fa B fa DR fa DQ fa DP fa Cord blood requires less stringency to reach «therapeutic» compatibility compared to PBSC

11 Post natal life of cord blood

12 Recruitment:

13 Collection:

14 Processing:

15 Quality control: Side scatter CD %

16 cryopreservation

17 Cryopreservation: Addition of dimethylsulfoxide (DMSO) to protect cells from microcristals, controlled temperature decrease to avoid overheat when DMSO freezes

18 shipping:

19 shipping: temperature [ C] Delivery to the consignee -150 Custom Check? time [hours]

20 % units banked # recruited mothers From recruitment to banking # consent given % banked/consent (a) At collection 20 Volume* TNC 0 MNC CD34C Absolute value 84 ± 27 ml [n=1553] 1.5 ± 0.55 x 10 9 [n=1553] 0.68 ± 0.38 x 10 9 [n=934] 4.8 ± 3.4 x 10 6 [n=1041] 20-25% of the recruitments lead to banking Post processing Absolute value PEf Volume 25± 7.0 ml [n=1510] 20 ± 6.9 % [n=1510] TNC 1.2 ± 0.44 x 10 9 [n=1486] 77 ± 10 % [n=1486] MNC 0.60 ± 0.23 x 10 9 [n=848] 85 ± 11 % [n=848] CD34C 4.3 ± 3.8 x 10 6 [n=965] 79 ± 12 % [n=436]

21 Who collects and banks CBU in Switzerland?

22 -2 processing and banking centers: - Basel & Geneva - several collecting centers: Basel, Liestal, Bern, Tessin, Geneva.

23 Units x 10-3 Delivered units From Blut Spende Dienst, CH, March 31, Registered units:1956/1245 = Delivered Cord Blood Units: Years Years

24 Switzerland and the world

25 CH FR UK BE IT AUS DE SP USA FR UK DE IT CH USA AUS SP BE absolute unit # unit/1000 inhab 1.0E+06 Registered units per country 1.8 Registered units per 1000 inhabitants 1.0E E E+03 0 Data Source: BMDW bmdw.org, accessed May 16, 2010, August 16, 2011

26 Switzerland is seen in the literature and is a recognized provider of CB units (2008 data)

27 - During the last 10 years, both Basel and Geneva CBB fulfilled their engagement toward the Swiss registry by banking CBU according to international standards. - Both banks collaborated with each other in an effort to uniformize the CBU processing. - This allowed Switzerland, despite of its small size to gain a good visibility at the international level in terms of CBU provider.

28 - CBU or PBSC, how costs compare?

29 CB against PBSC: flow chart Cord blood units: Processing fees 2000 CHF (if 200 units are banked/year) PBSC: Donor HLA typing 200 CHF UNIT BANKING Donor INDEXING Confirmatory HLA typing Confirmatory HLA typing Apheresis fees Shipment Shipment

30 CB against PBSC: flow chart Cord blood units: PBSC: Processing prior to banking Minimal analysis prior to banking ELEVATED BANKING COST per UNIT WORLD BANKING COST: 2x10 3 x 5x10 5 =1x10 9 CHF REDUCED INDEXING COST per UNIT WORLD INDEXING COST: 2x10 2 x 17x10 6 =3.5x10 8 CHF $ (2006) to bring the product to the bedside Biol Blood Marrow Transplant 15:564, (2009)] $ (2006) to bring the product to the bedside [Biol Blood Marrow Transplant 15:564, (2009)]

31 CBU/PBSC cost: after the transplant 100-day cost US$ (2006) cost/day survived 1 year-survival (%) 10 yearsurvival (%) PBSC(related) 137' Cord Blood 137' Data from: Biol Blood Marrow Transplant 15:564, 2009; Value Health 210:247, 2007 For a global approach see :ClinicoEconomics and Outcome Research 2:141, 2010

32 CBU/PBSC - CBUs represent a higher price for public health compared to PBSC, because they are banked as processed products, whereas only HLA data are banked for PBSC. - CBU, because it is processed before banking can be released rapidly, which is particularly welcomed for patients who failed to find a graft in the adult donor bank. -Thus, CBU and PBSC registries are complementary rather than antagonistic.

33 CBU transplantation: how to respond to the growing need? - In contrast with solid organ or peripheral blood donation, CB donors are plentiful. - We do not miss donors, but public infrastructures to store all the potential donations. - The paucity of public structures pushes misinformed mothers to choose depositing the unit under private supervision. - Increasing the size of the public registries requires the support of political authorities.

34 -Barcelona CBB policy : - observation in 2008: 50% of transplants were done with units 1.6x10 9 ; 16% with units =0.5x units with 2x10 9 cells at collection and 1.6x10 9 for banking. - Unit rejection rate is estimated at 90% (40 000units to collect in order to bank 4000). -Estimated cost: 15 million. - State of Madrid provides 10 million, 5 million to be found (May 2010). -In part covered by unit shipment on a long range.

35 Perspectives and development: Due to their rapid availability and their plasticity in terms of HLA compatibility, CBU are increasingly grafted in adult patients. This trend increases the pressure for the obtention of large units. However, CBU size has a biological limit.

36 Solutions? - Double unit infusion for adults is now a recognized therapy. - Multi-unit infusion (up to 7) has been investigated with success (Stem Cell Dev 16:177, 2007), which may open the possibility to rescue small units to be used either as such or after CD34+ cell purification. - Can in vitro amplification of a fraction of the unit help engraftment? -Can we valorize cord blood plasma and erythrocytes for a further application in transfusion therapies? -Can we increase the efficiency of unit processing?

37 Acknowlegments: All the people involved in cord blood banking: The Basel team (including all the collecting centers in and outside Basel) The Geneva team and the maternity The SBSC/BlutspendeDienst in Bern The LNRH/laboratoire national de référence d histocompatibilité in Geneva The José Carreras Fundation