Cord Blood Unit Selection Advisory Panel...as a result of being secondary, less than CR or had mds...

Cord Blood Unit Selection Advisory Panel

Kay Poulton PhD FRCPath

http://bsbmt.org

http://www.bshi.org.uk

Members of the Panel • Kay Poulton, BSHI Chair (Panel Chair) • Sergio Querol, Chair of WMDA CBWG, Vice Chair • Rachael Hough, CBWG Co-Chair • Nigel Russell, CBWG Co-Chair • Vanderson Rocha, Medical Director BBMR/NHSCBB (invited) • Andrew Clarke, Glasgow Royal Infirmary • Irina Evseeva, Anthony Nolan • Colin Brown, Consultant Clinical Scientist, Colindale NHSBT & BBMR • Cristina Navarrete, Consultant Clinical Scientist, Colindale & BBMR • Paul Dunn, Consultant Clinical Scientist, Leicester General Hospital • Katy Latham, Consultant Clinical Scientist, Anthony Nolan. • Ann-Margaret Little, Consultant Clinical Scientist, Glasgow Royal Infirmary • Leigh Keen, Principal Clinical Scientist, Bristol NHSBT, Filton • Pat Taylor, Principal Clinical Scientist, H&I Laboratory, NHSBT, Birmingham • Mike Watts, UCLH (Director Wolfson Cellular Therapy Unit) • Ines Ushiro-Lumb (NHSBT Clinical Microbiology Lead for Organ Donation & Transplantation)

Membership Responsibilities

Members of the CBUSAP are expected to:

• Respond by email to advisory requests in as timely a manner as possible subject to other commitments.

• Ensure that potential conflicts of interest are identified, recorded and managed to ensure advice provided is independent.

Figure 1: Flow Diagram Summarising Cord Blood Unit Selection

UCB Search indicated (lack of conventional donor, urgency of transplant etc)

UCB search HLA-A, HLA-B, HLA-DRB1, HLA-C (if available)

Prioritise a) according to HLA match and b) cell dose within each level of match

Single unit Allelic HLA match 6-8/8

Cell dose ≥ 3x107 TNC/Kg

Single unit Allelic HLA match 5/8


Malignant disease Non-malignant disease

Single unit Allelic HLA match 5-8/8


Yes Select largest unit (TNC) for degree

of HLA match and consider bank accreditation, CD34 dose, ABO

match, HLA Ab, red cell depletion







No No No

Consider double unit graft if each unit is ≥ 4/6 matched with recipient (Antigen level match HLA-A, HLA-B, allelic level HLA-DRB1)

and TNC ≥1.5x107/Kg (total of both units 3.5x107 TNC/Kg) Prioritise a) according to HLA match and b) cell dose within each level of match

c) consider bank accreditation, CD34 dose, ABO match, HLA Ab, red cell depletion

Case Studies http://bsbmt.org

http://www.bshi.org.uk

Case 2

Rank CBU ID

Bank

*FACT

accredite

d

Year

TN

C

x1

07

/kg

CD3

4

x105

/kg

CFU

X106

Viability

%

RB

C

Vo

l

ml

AB

O &

RhD

HLA HLA Match

A* B* DRB1

* C*

DQB

1*

Low

/6

High

/8

Patient HLA type A+ 11:01, 31:01

35:01, 41:02

04:04, 13:03

04:01, 17:03

03;01, 03:02

DUCB23931 Germany* 2013 3.09

1.1 See

below 90 R 53 O+

11:01, 66:01

35:01, 41:02

04:04, 13:03

04:01, 17:03

03:01, 03:02

5 7

992222266

NMDP MD Anderson*

2009 2.09

1.1 1.1 97

D

25 B+ 31:01, 68:02

35:01, 41:02

04:04, 13:03

04:19, 17:01/3

5 6 ?

CY1134284D

CYCORD (Cyprus)

2010 2.04

0.3 Not

stated 95

D 26 O+

11:01, 02:01

35:01, 41:02

04:01, 13:03

04:01, 17:03

03:01, 03:02

4 6

73312

MDA

Israel* 2004

1.57

0.57 Not

stated

Not stated

D

25 O- 02:01,

31:01/2

35:02, 41:02

04:03, 13:03

04:01, 17:01/3

4 5 or 6

290196402 Sydney

Australia* 2014

3.22

0.92 Not

stated 100

D

60 O+ 24, 66:01 35:05, 41:02

04:04, 13:03

04

17

03:01, 03:02

4 6?

Additional Information

High resolution HLA typing is outstanding on Unit 290196402 (Australia) at all loci unless otherwise stated. DUCB23931 CFU-GM: 8.8 x105 and CFU:GEMM: 2.84x104

NMDP do not perform sequencing at exon 1 of HLA-C.

Date Dec 2015

Centre Clinical Contact Clinical contact email

H&I Contact H&I contact email

Patient Details:

Initials Case

#2 Unique

Identifier Age or DOB 38 Weight (Kg) 54

Proposed Transplant Date As soon as possible Diagnosis ALL

HLA-Specific Antibodies HLA specific antibody Negative on sample dated one week ago

Case 2 Clinical Follow Up

• Delayed / Failed Engraftment

TNC Post Cryo CD34 Post Cryo CFU-GM Post Viability 7 AAD Post Thaw

DUCB23931

CBB results 2.91 x 10*7/kg 1.0 x 10*5/kg 1.59 x 10*4/kg 98%

Transplant Centre Results 2.09 x 10*7/kg 0.46 x 10*5/kg 0.8 x 10*4/kg 36%

9922-2226-6

CBB results 1.97 x 10*7/kg 1.0 x 10*5/kg 0.82 x 10*4/kg 98%

Transplant Centre Results 1.57 x 10*7/kg 0.67 x 10*5/kg 1.02 x 10*4/kg 65%

Engraftment Neuts (N=0.5) day +34, Platelets(N=20) day +55 STR 100% DUCB23931 day +30

Case 3

Rank CBU ID

Bank

*FACT

accredit

ed

Year

TN

C

x107

/kg

CD3

4

x105

/kg

CFU

X106

Viabilit

y

%

RB

C

Vol

ml

ABO

&

RhD

HLA HLA

Match

A* B* DRB1* C* DQB1

*

Low

/6

H

i

g

h

/

8

Patient HLA type O 01:01

31:01

07:02

44:03

04:04

09:01

04:01

07:02

03:02

03:03

1

994026517

NMDP

*AABB

24/05/

2005

3.6

1

2.30 D

59

O+ 01:01

31:01

07:02

40:01

04:04

09:01

03:04

07:02

03:02

03:03

5

6

4

FRCBLI691336210

69

FCB

France

*N

24/06/

2013

3.5

6

0.88

D

25

A+ 01:01

23:01

07:02

44:03

03:01

09:01

04:01

07:02 NK

4

6

2

992229899

U1CB

NMDP

*Y

24/11/

2009

2.6

7

3.15

D

25

A+ 23:01

31:01

39:11

07:02

04:04

09:01

07:02

----

03:02

02:02

4

5

3

AU390077924

AUCB

Australia

*Y

15/02/

2007

2.1

3

0.71

D

48.

6

O- 03:01

31:01

07:02

39:01

04:04

09:01

07:02

12:03 NK

4

5

5

EN110555686D

(G180109195396G

)

BSCB

UK

*Y

29/06/

2009

1.5

8

1.18

D

25.

1

O- 01:01

02:22

07:02

44:03

01:02

04:05

04:01

07:02

03:02

05:01

3

5

R/D

R/D


Ranking based, in this order of ‘importance’: cell count + dose, DRB1 allele match, A/B allele match, A/B antigen match, C match

Date Nov 2015 Centre Clinical Contact Clinical contact email


Patient Details:

Initials Case 3 Unique

Identifier Age or DOB 63y Weight (Kg) 76.4kg

Proposed Transplant Date 3 weeks from submission of request Diagnosis AML

HLA-Specific Antibodies 1 week ago: Anti-A2, B8, B57, B75 ANT Reference No

Case 3 Panel response CBUSAP Recommended Choice:

Cord 1 994026517

Additional comments about this cord: Regarding the issue with the volume, I would say

that this cord has been processed a while ago (2005), when SEPAX or AXP were not well implemented at CBB, so probably a manual process was done. Another aspect to keep in mind for this unit is that as it’s older, probably virology tests were not done following current practices and CBB probably won’t have samples to perform them.

(St Louis Panel) In response to your questions above for CBU SL052660 / 9940-2651-7, currently reserved for RID 271-048-4 through the NMDP:

The initial collected volume was 145 ml with a preprocessing Hct of 37.7%. The product was then RBC/ Plasma reduced during processing

The post processing volume is 47ml + 11.75 ml DMSO/Dextran cocktail (58.75 ml) with a Hct of 40.6% of this more concentrated product, which is stored and frozen in two separate bags of 24 ml (+ 6ml DMSO/Dextran) and 23 ml (+ 5.75 ml DMSO/Dextran)

Case 3 Panel response Alternative Suggestions – Potential Double CBU combinations

992229899 & AU390077924 as a double CBU if Unit 1 is unsuitable due to volume/cell dose

If happy that unit 1 is red cell depleted I’d use 1 (994026517) and 2 FRCBLI69133621069 If not I’d use 2 and 3 992229899 I’d use a double graft as dose of 1 or 2 alone – while meeting the criteria- is borderline ( though would understand if single unit ultimately chosen). If this AML is high risk as a result of being secondary, less than CR or had mds preceeding then even more reason for maximising cell dose as failure to engraft increased.

• I completely agree with the rank already listed, favouring cell dose (especially CD34) and DRB1 match, in this high risk acute leukemia.

• Nothing to add nor comment.

• As above. Ranking based, in this order of ‘importance’: cell count + dose, DRB1 allele match, A/B allele match, A/B antigen match, C match

• Cord 1. 6/8 (and 8/10). Good cell dose and CD34 and ABO compatible. No relevant antibodies

• Having looked at the selected units I agree with the ranking as given. I may have selected different had the third ranked unit had a better CD34 count.


• red cell reduced cord. – Not washed.

– Single unit.

• Engrafted neuts 0.5 day +11

• Day 30 engraftment: PBL 98.6% donor; CD3+ 100% donor

• Day 60 engraftment: PBL 100% donor; CD3+ 100% donor



Rank CBU ID

Bank

*FACT

accredited

Year

TNC

x107

/kg

CD34

x105

/kg

CFU

X106

Viability

%

RBC Vol

ml

ABO &

RhD

HLA HLA Match

A* B* DRB1* C* DQB1* Low

/6

High

/8

Patient HLA type A+

03:01

33:03

35:01

53:01

13:03:01

08:06

04:01

16:01

^1 G180114109748G *NHSBT 25.1.14 4.15 0.86 D 27.3 B+ 03:01

33:03

35:01

53:01

04:04

13:03

04:01

04:01

7/8

hvg

2 G180112110827G *NHSBT 27.5.12 2.0 0.55 D 24.7 B+ 03:01

33:01/03

35:01

53:01

11:04

13:03

04:01

04:01 6/8 gvhd

3 9843-3781-7 *MD Anderson 3.1.14 3.35 1.84 D 25 O+ 02:05

33:03

35:01

53:01

03:02

13:03

04:01

04:01

7/8

hvg

4 IT15RC001813 Calabria 1.7.15 4.56 1.9 D 100 A+ 03:01

33:03

35:01

58:01

11:04

13:03

03:02

04:01 6/8 gvhd

$5 G221211102668 *ANT 10.5.11 2.02 0.64 D 115.21 O- 30:01

33:03

35:01

53:01

13:03

14:01

04:01

07:01

6/8

6 G1801131208999 *NHSBT 1.7.13 1.75 0.58 D 23.7 O+ 03:01

33:03

44:02

53:01

04:01

13:03

04:01

05:01

5/8

7 S003110900083 National Swedish

10.2.10 3.5 0.96 D 25 A- 03

68

35

53

04:05

13:03

5/8

8 9944-0089-4 *St Louis 28.6.12 3.9 1.13 D 03:01

30:02

35:01

53:01

08:06

11:01

04:01

04:01

5/8

9 9809-3970-7 *New York 8.3.09 2.75 1.33 D 25 O+ 23:01

33:03

15:03

53:01

08:06

13:03 4/6


^ DRB1 high res to be confirmed

$ Cord is sickle trait

Case 4 Date Jan 2015 Centre Clinical Contact Clinical contact email


Patient Details:


Identifier Age or DOB Weight (Kg) 52

Proposed Transplant Date 1 month from submission of request Diagnosis Hepatosplenic Non-Hodgkins Lymphoma

HLA-Specific Antibodies Currently negative ANT Reference No


We received responses or comments from 8 panel members . There were no NIMA matches identified. There is consensus that the panel would recommend a double CBU donation. Pending HLA-specific antibody testing results to eliminate the presence of donor-directed antibody the panel had a preference for

The combined donor pair with the closest HLA match:

I. G180114109748G (Ref 1) NHSBT (5/6 (7/8 [6/8 gvh]) CD34:= 0.865/Kg

with

I. G180112110827G (Ref 2) NHSBT (5/6 (7/8 [6/8 gvh]) CD34: 0.555/Kg

Aggregated cell dose with G180114109748G (Ref 1) 1.415/Kg

Case 4 Panel response

Acceptable alternative combinations are listed below:

I. 9944-0089-4 (Ref 8) St Louis (5/6 (6/8 or [5/8gvh]) CD34: 1.95/Kg

This cord is an HLA-A locus antigen match with the patient

Aggregated cell dose with G180112110827G (Ref 2) = 2.455/Kg

II. 9944-0089-4 (Ref 8) St Louis (5/6 (6/8 or [5/8gvh]) CD34: 1.95/Kg Aggregated cell dose with G180114109748G (Ref 1) = 2.765/Kg


Or

III. 9843-3781-7 (Ref 3) MD Anderson (4/6 (6/8)) CD34: 1.845/Kg



Case 4 Clinical Follow Up Day of Transplant -7 Urgent communication from Registry:

Rank CBU ID

Bank

*FACT

accredit

ed

Year

TN

C

x1

07

/kg

CD3

4

x105

/kg

CFU

X106

Viabili

ty

%

RB

C

Vol

ml

AB

O &

RhD

HLA HLA

Match

A* B* DRB1* C* DQB1

*

Low

/6

H

i

g

h

/

8

Patient HLA type 33:03,

68:02

42:01,

44:03

07:01,

15:03

07:01,

17:01

02:02,

06:02

U1CB 9924-1801-3 * NMDP 2012 2.4 2.3 98 D 25 O+ 29:02,

33:03

44:03,

49:01

07:01,

15:03

07:01,

16:01

02:02,

06:02 4 5

G221214126592 AN 2014 2.5 0.5 90-98 D 26 O+ 02:02,

33:03

44:03,

-

07:01,

15:03

04:01,

07:01

02:02,

06:02

4 or

5

5

o

r

6

G1801121043862 BBMR 2012 3.1 0.8 93 D 25 O+ 29:02+,

33:03+

42:01P,

44:03+

01:02,

07:01G

16:01+,

17:01G

02:02,

05:01 4 5

FRCBPL

00000008304P France 2012 1.7 0.7 96 D 25 B+

33:01,

68:02

44:03,

53:01

07:01,

15:03

04:01,

-

02:02,

06:02 5 4



Case 6 is DPB1*01:01, 14:01 *U1CB 9924-1801-3 is DPB1*11:01, 18:01; DSA present: DPB1*18:01 mfi: 14-18,000 (latest sample)

Case 6 Date April 2016 Centre Clinical Contact Clinical contact email


Patient Details:


Identifier Age or DOB 52 y Weight (Kg) 70Kg

Proposed Transplant Date asap Diagnosis FLT3 ITD+ AML

HLA-Specific Antibodies

All antibodies >2000 MFI from serum sample two weeks ago: B57,DR4,DR8,DR10,DR11,DR12,DR13,DR14,DR17,DR18,DR52,allelicDQB1*02:01,DQ4,allelicDQB1*06:03/09,DQ7,DQ8,DQ9,DP2,DPB1*04:02,DP10,DP18,DP28

ANT Reference No


We received responses or comments from 5 panel members. The blood group of the patient is not stated. Based upon the information provided to the panel, there is consensus that the panel would recommend a double CBU donation.

The cord with the best match which has the highest CD34 dose is U1CB 9924-1801-3 (Rank 4), which carries HLA-DPB1*18:01. The patient has donor-directed HLA-specific antibodies to HLA_DPB1*18:01 present at high MFIs (range 14 000 – 18 000). This cord has been disregarded by the panel due to the presence of the patient’s HLA specific antibody, but there is limited information available concerning the distribution of HLA-DPB1 on CD34 positive cells. CD34 positive cells express HLA-DR, with much weaker expression of HLA-DQ (see ref below). Anecdotally, a transplant was recently carried out across a high titre HLA-DP antibody (MFI 20,000) with no adverse effects at all upon engraftment, although the donor was a volunteer unrelated adult donor rather than UCB. If this cord is regarded as a preferred option by the referring team, it may be worth investigating the antibody titre further, perhaps with apheresis for antibody reduction if the patient could tolerate it.

There were no NIMA matches identified in the BBMR cord G1801121043862.

Case 6 Panel response

Of the remaining cords the panel recommends the following potential combinations based upon match and CD34 dose:

G221214126592 (Rank 1) AN (4 or 5/6 (5 or 6/8) CD34:= 0.5 5/Kg

with

G1801121043862 (Rank 2) BBMR (4/6 (5/8) CD34: 0.85/Kg

Aggregated CD34 dose with G221214126592 (Rank 1) 1.35/Kg

G221214126592 has a low CD34 count but may be acceptable for use once the CFU data are available. It has been ranked in this position as it is the best matched of the remaining units

Case 6 Panel response Acceptable alternative combinations are listed below:

G1801121043862 (Rank 2) BBMR (4/6 (5/8) CD34: 0.85/Kg

With

FRCBPL 0000000830P (Rank 3) France (5/6 (4/8) CD34: 0.75/Kg

Aggregated CD34 dose with G1801121043862 (Rank 2) = 1.55/Kg

FRCBPL 0000000830P has an allele level mismatch at HLA-A with the patient. HLA-A*33:01 differs from A*33:03 by only two amino acids at positions 171 and 186. 171 lies in the A pocket and may affect peptide binding; 186 lies beyond this and may not exhibit any clinical relevance.


• Not available yet

CBUSAP – Where next? • Now on BSHI Website:

– http://www.bshi.org.uk/html/cord_page.html

• Terms Of Reference

• Form for submission (Word)

• Case Studies (Members Only Area)

• Documents shared with BSBMT for publication

• Panel needs constant revision to ensure sufficient members are available for comment

http://www.bshi.org.uk/html/cord_page.html




Cord Blood Unit Selection Advisory Panel...as a result of being secondary, less than CR or had mds...

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Transcript of Cord Blood Unit Selection Advisory Panel...as a result of being secondary, less than CR or had mds...