should the number of collected cd34+ cells be considered major criteria for ucb unit choice in...
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Should the number of collected CD34+ cells be considered major
criteria for UCB unit choice in adults?
Reunión anual GETH 2011
Madrid, 11 marzo 2011
Guillermo Sanz
Hospital Universitario La Fe, Valencia, Spain
Main prognostic factors after UCBTMain prognostic factors after UCBT
• Number of TNC infused
• Degree of HLA match
Gluckman E et al. Exp Haematol 2004; 32:397-407.
Guidelines for UCB unit choiceGuidelines for UCB unit choice Eurocord 2004 criteria
• At least 4/6 HLA match
• Collected TNC above 2.5 – 3.0 × 107/kg
Policy on cell dose for UCB unit choicePolicy on cell dose for UCB unit choice
• Most transplant centers use the number of collected TNC as the only cell dose criteria for unit choice
– Greater TNC dose threshold for higher degree of HLA mismatch
• 2.5 × 107/kg if 0 or 1 HLA mismatches
• 3.5 × 107/kg if 2 HLA mismatches
Is this cell dose criteria enough?
Should the number Should the number of collected CD34+ cells be considered an
additional major cell dose criteria in adults for guiding UCB unit choice? for guiding UCB unit choice?
Reasons for not including the number Reasons for not including the number of collected CD34+ cells among criteria of collected CD34+ cells among criteria
for guiding UCB unit choicefor guiding UCB unit choice
• Not enough data on impact of CD34+ cells (infused or collected)
• Measurement of CD34+ cells not well standardized– Great differences among CB banks could emerge
• TNC dose could be a good surrogate of CD34+ cells
• No available data on correlation between number of CD34+ cells collected and infused
• Number of collected CD34+ cells not available for 25 – 50% UCB units worldwide
Number of infused CD34+ cells is Number of infused CD34+ cells is relevant after UCB transplants relevant after UCB transplants
• Impact on engraftment (children and adults)
• Impact on survival (children and adults – some series)
Review by Rocha V & Gluckman E on behalf of Eurocord/EBMT. Br J Haematol 2009; 147:262-274.
Prognostic value of infused CD34+ cellsPrognostic value of infused CD34+ cells((× 10× 1055/kg) /kg) after myeloablative UCBT in adults after myeloablative UCBT in adults
with hematologic malignancieswith hematologic malignancies
1 N Engl J Med 2001;344:1815-22.2 Br J Haematol 2007;139:464-74.
3 Biol Blood Marrow Transplant 2008;14:1341-7.4 Biol Blood Marrow Transplant 2010;16:86-94.
5 Biol Blood Marrow Transplant 2010;16:1589-95.
Reference
PMN engraftment DFS
Cut-off point
Pvalue
Cut-off point
Pvalue
Laughlin, 20011 1.2 0.05NS
Van Heekeren, 20072 NSHigher 0.015
Ooi, 20083 NS1.0 < 0.0001
Sanz, 20104 NS1.5 0.009
Sanz, 20105 NS0.6 0.02
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 10 20 30 40 50 60
Days after transplant
Cum
ulat
ive
inci
denc
e
CD34+ > 1 x 105/kg(n = 111)CI: 94%
Median: 20 days
CD34+ ≤ 1 x 105/kg(n = 66 )CI: 89%
Median: 25 days
P = 0.0002
Myeloid engraftment after myeloablative single UCBT in adults with malignant
disorders (n = 177) by infused CD34+ cells
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 10 20 30 40 50 60
Days after transplant
Cum
ulat
ive
inci
denc
e
CD34+ > 1.5 x 105/kg(n = 92)CI: 96%
Median: 20 days
CD34+ ≤ 1.5 x 105/kg(n = 73)CI: 90%
Median: 23 days
P = 0.007
Myeloid engraftment after myeloablative single UCBT in adults with malignant
disorders (n = 165) by collected CD34+ cells
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 10 20 30 40 50 60
Days after transplant
Cum
ulat
ive
inci
denc
e
TNC ≤ 2.5 × 107/kg(n = 58)CI: 93%
Median: 22 days
TNC > 2.5 × 107/kg(n = 120)CI: 92%
Median: 22 days
P = 0.6
Myeloid engraftment after myeloablative single UCBT in adults with malignant disorders (n = 178) by collected TNC
Correlation between collected TNC and infused CD34+ cells after myeloablative single UCBT in
adults with malignant disorders (n = 164)
0
1
2
3
4
5
6
7
8
0 1 2 3 4 5 6 7 8
R = 0.52P < .0001
CD34+ cells infused (× 105/kg)
TN
C c
olle
cted
(×
107 /
kg)
0
1
2
3
4
5
6
7
8
0 1 2 3 4 5 6 7 8
R = 0.52P < .0001
CD34+ cells infused (× 105/kg)
TN
C c
olle
cted
(×
107 /
kg)
Correlation between collected and infused CD34+ cells after myeloablative single UCBT in adults with
malignant disorders (n = 164)
R = 0.67P < .0001
CD34+ cells infused (× 105/kg)
CD
34+
ce
lls c
olle
cted
(×
105 /
kg)
0
1
2
3
4
5
6
7
8
0 1 2 3 4 5 6 7 8
CD34+ measurement is now CD34+ measurement is now almostalmost standardizedstandardized
• CD34+ quantification performed at NetCord CB banks according to a uniform protocol (ISHAGE)
• Quality control available and likely required for accreditation in near future
– i.e. Proficiency testing UKNEQAS
Capacity of collected TNC and CD34+ cells of Capacity of collected TNC and CD34+ cells of reaching a target number of infused CD34+ cells reaching a target number of infused CD34+ cells
(1 (1 × 10× 1055/kg)/kg) Experience in 164 UCB transplantsExperience in 164 UCB transplants
Number of cells collected
No. ofpatients
(%)
No. of patients (%) with infused CD34+ cells > 1 × 105/kg
> 2.5 × 107 TNC/kg 112 (68) 82 (73)
≤ 2.5 × 107 TNC/kg 52 (32) 23 (44)
> 1 × 105 CD34+ cells/kg 131 (80) 97 (74)
≤ 1 × 105 CD34+ cells/kg 33 (20) 8 (24)
Collected CD34+ cells perform better that TNC
Guidelines for UCB unit choiceGuidelines for UCB unit choice Eurocord 2009 criteria for malignant disorders
• UCB unit with 5/6 or 6/6 HLA match
– Collected TNC > 2.5 × 107/kg
– Collected/infused CD34+ cells > 1.2 × 105/kg
• UCB unit with 4/6 HLA match
– Collected TNC > 3.5 × 107/kg
– Collected/infused CD34+ cells > 1.7 × 105/kg
Rocha V & Gluckman E on behalf of Eurocord/EBMT. Br J Haematol 2009; 147:262-274.
Guidelines for UCB unit choiceGuidelines for UCB unit choice Eurocord 2009 criteria for malignant disorders
• UCB unit with 5/6 or 6/6 HLA match
– Collected TNC > 2.5 × 107/kg
– Collected/infused CD34+ cells > 1.2 × 105/kg
• UCB unit with 4/6 HLA match
– Collected TNC > 3.5 × 107/kg
– Collected/infused CD34+ cells > 1.7 × 105/kg
Rocha V & Gluckman E on behalf of Eurocord/EBMT. Br J Haematol 2009; 147:262-274.
These thresholds are difficult to achieve for many adults
Capacity of Eurocord 2009 criteria of reaching a Capacity of Eurocord 2009 criteria of reaching a target number of infused CD34+ cells (1 × 10target number of infused CD34+ cells (1 × 1055/kg)/kg)
Experience in 164 UCB transplantsExperience in 164 UCB transplants
Eurocord 2009 criteria
No. ofpatients
(%)
No. of patients (%) with infused CD34+ cells > 1 × 105/kg
Fulfilled 65 (40) 52 (80)
Absent 99 (60) 53 (54)
Thresholds may be excessive
Should it be possible to use a lower CN Should it be possible to use a lower CN and CD34+ threshold for UCB transplants and CD34+ threshold for UCB transplants
in adults with a single unit if BOTH cell in adults with a single unit if BOTH cell dose criteria are included in UCB unit dose criteria are included in UCB unit
choice?choice?
Capacity of current GETH/Hospital La Fe criteria* Capacity of current GETH/Hospital La Fe criteria* for CB unit choice of reaching a target number of for CB unit choice of reaching a target number of
infused CD34+ cells (1 × 10infused CD34+ cells (1 × 1055/kg)/kg)Experience in 164 UCB transplantsExperience in 164 UCB transplants
GETH/Hospital La Fe criteria*
No. ofpatients
(%)
No. of patients (%) with infused CD34+ cells > 1 × 105/kg
Fulfilled 129 (79) 52 (74)
Absent 35 (21) 10 (29)
* Collected TNC > 2 × 107/kg and collected CD34+ cells > 1 × 105/kg
Criteria almost as efficient as Eurocord 2009 criteria and accessible in a higher number of patients
Concluding remarksConcluding remarks
• The number of collected CD34+ cells must be included among the criteria for UCB unit choice
• Currently accepted thresholds for collected TNC and CD34+ cells in adults with hematologic malignancies need to be properly reviewed
• Additional criteria for accurately predicting the potency of the UCB graft are required