La biologia delle CSE. Raccolta, confezionamento e

Il procurement e trasporto di CSE da donatore non
consanguineo adulto o da unità di sangue cordonale
Genova 29 Settembre 2010
La biologia delle CSE. Raccolta, confezionamento e
trasporto dei prodotti donati da donatore adulto
T. Lamparelli
Lamparelli,, CT Ospedale San Martino, Genova
GL Ubezio S.I.T –E-O Ospedali Galliera, Genova
1
DONOR
• Idoneita’ HLA
• Edotto dei rischi legati alla
donazione
• Disponibilita’ alla donazione
• Idoneita’ fisica alla donazione
• Scelta modalita’ donazione
• Firma consensi
RACCOLTA
CSE
BM
PATIENT
Clereance
donatore
PBSC
•
•
•
•
•
Elegibilita’ ricerca
Attivazione ricerca
Identificazione donatore
Elegibilita’ al trapianto
Edotto dei rischi legati a trapianto
allogenico
• Firma consensi
CONDIZIONAMENTO
( CHEMIO+/- RADIOTERAPIA)
2
Pick up (1)
WMDA 8.05
The documentation and label, at a minimum, must include:
•information on the number of cells collected
• the donor’s unique identification code
•donor ABO group
• identification of the patient
• date and time of collection
•any processing details
•and name and contact information of the Transplant Center
Labeling of the product must ensure the identity of the
product.
CT
CP
3
CP
CP
II donazione :
- CSE
- LINFOCITI
4
Pick up (2)
WMDA 8.06
Packaging must comply with national and international regulations.
FACT-JACIE STANDARD (IV):
D10.2 Procedures for transportation and shipping of cellular therapy products
shall be designed to protect the integrity of the product and the health and safety of
individuals in the immediate area and shall follow the applicable laws and
regulations.
D10.2.1 The primary product container for non-frozen products shall be placed in a
secondary container and sealed to prevent leakage.
D10.3 Cellular therapy products that require a temperature-controlled environment
and that are transported or shipped over an extended period of time shall be
transported or shipped in a container validated to maintain the appropriate
temperature range.
placed in a secondary container and sealed
to prevent leakage.
5
Pick up (3)
FACT-JACIE STANDARD (IV):
D10.4 Cellular therapy products that are shipped to another facility shall be
packaged in an outer shipping container.
D10.4.1 Shipping conditions shall be established and maintained to preserve the
integrity and safety of cellular therapy products during shipment.
D10.4.2 The outer shipping container shall conform to the applicable regulations
regarding the mode of transportation or shipping.
D10.4.3 The outer shipping container shall be made of material adequate to withstand
leakage of contents, shocks, pressure changes, and other conditions incident to ordinary
handling during shipping.
D10.4.3.1 The temperature of shipping containers bearing cryopreserved products shall be
continuously monitored during shipping.
D10.4.3.2 The shipping facility shall maintain a record of the temperature over
the period of travel.
FACT-JACIE STANDARD (IV):METHOD OF
TRANSPORTATION AND SHIPPING
D10.5.1 The transit time should be minimized.
D10.5.2 If the intended recipient has received highdose therapy, the cellular therapy product shall be
transported by a qualified courier.
D10.5.3 There shall be plans for alternative means
of transport in an emergency.
D10.5.4 The cellular therapy products should not
be passed through X-Ray irradiation devices
designed to detect metal objects. If inspection is
necessary, the contents of the container should be
inspected manually.
6
Allegato T (V1 1/2 apr. 2007)
Specifiche tecniche per il trasporto di Cellule Staminali Ematopoietiche
allogeniche da non consanguineo a scopo trapianto
Il corriere è una persona fisica che è integralmente responsabile del trasporto,
ovvero è responsabile:
1.
2.
3.
dell'accuratezza del trasporto nonché della sicurezza, conservazione e preservazione delle CSE
dal e/o emocomponente dal momento in cui riceve il materiale dal Centro Prelievi sino alla
sua consegna al Centro Trapianti
della scelta dei mezzi più idonei;
della scelta dei percorsi migliori per effettuare la consegna delle CSE dal e/o emocomponente nel
rispetto dei tempi indicati.
Il corriere identificato deve essere in grado di offrire, per ogni singola tratta, un
servizio che sia conforme a quanto stabilito:
•
•
•
dalla normativa nazionale ed internazionale vigente relativa al trasporto di emocomponenti, cellule e
tessuti a scopo trapianto;
dal Manuale Operativo IBMDR, con particolare riguardo al paragrafo 12.3.5;
dal Capitolo 8 degli Standard Operativi WMDA;
RAPID TRANSPORT AND INFUSION OF HEMATOPOIETIC CELLS IS
ASSOCIATED WITH IMPROVED OUTCOME AFTER MYELOABLATIVE
THERAPY AND UNRELATED DONOR TRANSPLANT.
Lazarus H.M. et all, BIOL BLOOD MARROW TRANSPLANT
2009 May;15(5):589-96.
INCLUSION CRITERIA : 2000-Æ 2004
938 BM; 507 PBSC
disease : ALL, AML, MDS, CML (I-II CR, CP)
myeloablative conditioning regimen
GRAFT TRANSPORT:
Bags containing BM or PBPC were placed in an outer bag to prevent leakage. Collection bag(s)
were enclosed in a rigid container with temperature insulating properties.
All products were non-cryopreserved and transported at the temperature specified by the
transplant center or the NMDP. NMDP guidelines recommend transportation at ambient
temperature for BM and refrigerated for PBPC; transport temperature (ambient or refrigerated
for either graft) could also be requested by the transplant center. No product had direct
contact with wet ice or frozen gel packs. The temperature at which the grafts were transported
was not monitored. All products were hand carried by a courier. The NMDP ensures
transportation arrangements for the courier minimizes transit time from collection to
transplant centers. Ninety-three percent of BM grafts
were transported at ambient
temperature and 7% refrigerated at the request of the transplant center; 98% of PBPC grafts
were transported refrigerated and 2% at ambient temperature.
7
RAPID TRANSPORT AND INFUSION OF HEMATOPOIETIC CELLS IS
ASSOCIATED WITH IMPROVED OUTCOME AFTER MYELOABLATIVE
THERAPY AND UNRELATED DONOR TRANSPLANT.
Lazarus H.M. et all, BIOL BLOOD MARROW TRANSPLANT
2009 May;15(5):589-96.
ENDPOINT : neutrophil and platelet recovery
aGVHD, cGVHD
early (day 100) mortality
overal mortality
Bone Marrow
Peripheral Blood
Variables
Number (%)
Number (%)
Total number
938
507
<18 years
284 (30)
80 (16)
≥18 years
654 (70)
427 (84)
Recipient age
Disease status
early
534 (57)
312 (62)
adv
404 (43)
195 (38)
Domestic
877 (93)
466 (92)
International
61 ( 7)
41 ( 8)
Collection center
Time from end of collection to receipt at transplant center
<5 hours
69 ( 7)
31 ( 6)
5-9 hours
470 (50)
206 (41)
10-19 hours
345 (37)
205 (40)
≥20 hours
54 ( 6)
65 (13)
Lazarus H.M. et all, BIOL BLOOD MARROW TRANSPLANT
2009 May;15(5):589-96
8
BM
PBSC
Temperature of graft during shipping
Ambient
874 (93)
10 ( 2)
Refrigerated
64 ( 7)
496 (98)
<3 × 108/kg
291 (31)
20 (4)
≥ 3 x 108/kg
641 (68)
446 (88)
Unknown
6 (<1)
41 ( 8)
Total nucleated cell dose at receipt at transplant center
Time from receipt at transplant center to infusion into patient
<3 hours
421 (45)
269 (53)
3-5 hours
283 (30)
102 (20)
6-9 hours
55 ( 6)
26 ( 5)
≥10 hours
179 (19)
110 (22)
Total transport time, median (range) hours
14 (3-51)
15 (2-55)
Donor age
18-30 years
344 (37)
163 (32)
31-40 years
342 (36)
189 (37)
41-60 years
252 (27)
155 (31)
Lazarus H.M. et all, BIOL BLOOD MARROW TRANSPLANT
2009 May;15(5):589-96
BM
PBSC
Well matched
516 (55)
334 (66)
Partially matched
297 (32)
119 (23)
Mismatched
125 (13)
54 (11)
Cyclophosphamide + TBI
694 (74)
333 (66)
Cyclophosphamide + busulfan
193 (21)
126 (25)
Busulfan + fludarabine +antithymocyte globulin
21 ( 2)
12 ( 2)
Tacrolimus ± other
378 (40)
246 (49)
Cyclosporine ± other
560 (60)
261 (51)
2000-2002
606 (65)
202 (40)
2003-2004
332 (35)
305 (60)
Follow up of surviving patients, median (range) months
48 (6-85)
36 (3-76)
Donor –recipient HLA match
Conditioning regimen
Graft-versus-host disease prophylaxis
Year of transplant
Lazarus H.M. et all, BIOL BLOOD MARROW TRANSPLANT
2009 May;15(5):589-96
9
BM
PBSC
USA
93
89
international
14
COLLECTION CENTER
2 COLLECTION
8
58%
INTERNATIONAL TRANSPORT
12%
12%
domestic
9 h (<1- 47)
10 ( (<1-32)
international
19 h (9-40)
32 (7-45)
3 h (<1- 45)
3 h (<1-39)
60
19
CC
3.8 ( <1- 35)
7.5 (<1- 68)
TC
3.6 (<1- 28)
7.5 (<1-53)
MEDIAN TIME TRANSPORT CC-->TC (range)
MEDIAN TIME FROM RECEIPT TO INFUTION
MANIPULATION %
MEDIAN CELLS DOSE x10^8/kg (range)
Lazarus H.M. et all, BIOL BLOOD MARROW TRANSPLANT
2009 May;15(5):589-96
Probability of Platelet Recovery at 60 Days after BM Transplants
Variables
N
Odds Ratio for Recovery (95% Confidence
Interval)
PValue
Time from end of collection to receipt, hours
<20
883
1.00
≥20
54
0.47 (0.26-0.83)
.010
Time from receipt to infusion, hours
<6
703
1.00
≥6
234
0.57 (0.41-0.80)
.001
Performance score
90-100
705
1.00
<.001*
<90
139
0.42 (0.28-0.62)
<.001
Unknow
n
93
0.72 (0.43-1.22)
.221
Year of transplant
20032004
331
1.00
20002002
606
0.57 (0.40-0.79)
<.001
Lazarus H.M. et all, BIOL BLOOD MARROW TRANSPLANT
2009 May;15(5):589-96
10
OVERAL SURVIVAL 1 YEAR
N patient
BM
PBSC
431/938
290/507
58%
57%
probability
Lazarus H.M. et all, BIOL BLOOD MARROW TRANSPLANT
2009 May;15(5):589-96
Risk factors for Overall Mortality after BM Transplants
Variables
N
Relative Risk (95% Confidence Interval)
<6
704
1.00
≥6
234
1.18 (0.97-1.44)
P-Value
Time from receipt to infusion, hours
.107
Donor recipient HLA disparity and time from collection to receipt, hours*
Well matched, <20 hours
494
1.00
Well matched, ≥20 hours
22
2.67 (1.64-4.35)
Partially matched/mismatched, <20 hours
390
1.00
Partially matched/mismatched, ≥20 hours
32
0.88 (0.55-1.43)
CML first chronic phase
223
1.00
AML frist clinical remission
153
2.06 (1.54-2.76)
<.001
ALL first clinical remission
125
1.58 (1.15-2.18)
.005
.033
<.001
.611
Disease and disease status*
MDS refractory anemia
33
1.75 (1.05-2.92)
CML second chronic phase
58
1.00
AML second clinical remission
162
0.72 (0.50-1.05)
.091
ALL second clinical remission
184
0.81 (0.56-1.16)
.245
2003-2004
332
1.00
2000-2002
606
1.51 (1.23-1.84)
Year of transplant
<.001
11
RISULTATI 1
Sorgente BM
- durata trasporto > =20 ore
(n 54)
- intervallo arrivo/infusione >= 6 ore (n 234)
RECUPERO PIASTRINICO
RISULTATI 2
Sorgente BM
durata trasporto > = 20 ore
(n 22)
OVERAL MORTALITY
HLA MATCH PAIR
RR 2.67 p<.001
12
RISULTATI 2
Sorgente BM
intervallo fine prelievo / infusione
>=26 ore (n 125)
OVERAL MORTALITY
RR 0.66 p<.001
REQUISITI
CORRIERE
13
14