Table 1 Statements and results of the Delphi consensus process.
Statements | Level of agreement (%) | Rounds | Abstention rate % |
|---|---|---|---|
1. Sample procedure and tube collection | |||
1.1. Bone marrow Procedure: If large sample volumes are required (e.g., for multiple diagnostic tests), it is necessary to change the bone marrow aspiration site to avoid haemodilution | 95% (21/22) | R2 | 31% (10/32) |
1.2. The needle should be reinserted at different angles through the original puncture site | 82% (14/17) | R2 | 19% (4/21) |
1.3. For storage of viable cells, the preferred tube is: Sodium Heparin or EDTA or Acid Citrate Dextrose (ACD) | No consensus | R1A and R2 | 22% (7/32) |
1.4. The material should be taken in Coagulation/serum tubes or clot activator tubes for serum | No consensus | R1A and R2 | 48% (15/32) |
1.5. The type of collection tube should be noted | 91% (30/33) | R1A | 11% (4/37) |
1.6. Time between sampling and processing should be noted | 81% (29/36) | R1A | 3% (1/37) |
1.7. Storage and transport temperature till processing should be noted | 70% (23/33) | R1A | 11% (4/37) |
2. Biobanking of cells, DNA and RNA | |||
2.1. Biobanking of cells from preferably bone marrow (BM) and/or peripheral blood (PB) and/or infiltrated extramedullary samples should be done at diagnosis and relapse as critical time-points | 91% (32/35) | R1A | 5% (2/37) |
2.2. Biobanking of BM and/or PB cells should be done at the end of induction and at the end of consolidation | 81% (26/32) | R1A | 14% (5/37) |
2.3. There are no other desirable time-points with the current trial strategy | 71% (15/21) | R2 | 34% (11/32) |
2.4. Before storage, blast cells should be concentrated using density gradient centrifugation (e.g., Ficoll, Lymphoprep) | 85% (29/34) | R1A | 8% (3/37) |
2.5. If visible erythrocyte contamination persists in the cell pellet after density gradient centrifugation and separation, red cell lysis should be performed | No consensus | R1A and R2 | 28% (9/32) |
2.6. All remaining cells not used for diagnostics should be biobanked | 83% (30/36) | R1A | 3% (1/37) |
2.7. Viable cells should be stored using 5–50 million cells per vial | 72% (23/32) | R1A | 14% (5/37) |
2.8. Viable cells should be stored in liquid nitrogen | 87% (32/37) | R1A | 0/37 |
2.9. If there are less than 5 million cells after density gradient centrifugation and separation, this material should be stored as viable cells (DMSO), non-viable cells (dry pellet), DNA (direct extraction), or other | No consensus | R2 | 22% (7/32) |
2.10. Dry pellets should be stored at −80 °C | 87% (27/31) | R1A | 16% (6/37) |
2.11. The biobank should have information about DNA and RNA isolation and availability (even if the isolations are done in a Diagnostic Lab) | 81% (29/36) | R1A | 3% (1/37) |
2.12. If RNA isolation is not performed by the biobank, storage of viable cells should be prioritized | 77% (20/26) | R2 | 19% (6/32) |
2.13. If DNA isolation is not performed by the biobank, storage of viable cells should be prioritized | 73% (19/26) | R2 | 19% (6/32) |
2.14. Leukaemic cell percentage should be determined by flow cytometry or morphology after cell isolation | 79% (26/33) | R1A | 11% (4/37) |
2.15. Cell viability should be determined after cell isolation (by flow cytometry or morphology or trypan blue) | 91% (19/22) | R2 | 31% (10/32) |
2.16. The following procedural information for obtaining cells should be noted: Red cell lysis required, Cell viability, Time of cryopreservation, Type of cryopreservation solution, Date of cryopreservation solution preparation, Date/time of storage, Number of cells per tube, Blast percentage per tube | 74% (26/35) | R1A | 5% (2/37) |
2.17. A protocol for cryopreservation based on general consensus is recommended to harmonize cryopreservation procedures | 93% (31/33) | R1A | 11% (4/37) |
3. Biobanking of plasma | |||
3.1. Patients with Acute Lymphoblastic Leukaemia should have plasma biobanked | 68% (21/31) | R1B | 9% (3/34) |
3.2. Plasma should be stored at diagnosis and relapse (bone marrow (BM) and/or peripheral blood (PB) | 82% (23/28) | R1B | 7% (2/30) |
3.3. If BM and PB have been sent to the biobank, the plasma of both specimens should be stored | 77% (20/26) | R1B | 13% (4/30) |
3.4. BM and/or PB plasma should be stored at the end of induction (TP1) | 76% (19/25) | R1B | 17% (5/30) |
3.5. Plasma should be also stored at the end of consolidation (TP2) | 83% (10/12) | R2 | 63% (20/32) |
3.6. Plasma storage at other time-point is not required with the current trial strategy (other than diagnosis/Relapse/TP1/TP2) | 77% (10/13) | R2 | 59% (19/32) |
3.7. The type of collected material should be recorded by the biobank (BM/PB/etc.) | 96% (27/28) | R1B | 7% (2/30) |
3.8. The total plasma volume per specimen should be stored in the biobank (no limitation of the number of aliquots) | 82% (22/27) | R1B | 10% (3/30) |
3.9. A minimum of 2 aliquots should be stored (0.5–2 mL) | 95% (20/21) | R2 | 34% (11/32) |
3.10. If the total plasma volume of the received sample is less than 0.5mL, the material should be stored | 86% (19/22) | R2 | 31% (10/32) |
3.11. −80 °C is the preferable method to store plasma aliquots | 96% (23/24) | R1B | 20% (6/30) |
4. Biobanking of serum | |||
4.1. Patients with Acute Lymphoblastic Leukaemia should have serum biobanked | 78% (21/27) | R1B | 21% (7/34) |
4.2. Serum should be stored at diagnosis and relapse? (bone marrow (BM) and/or peripheral blood (PB) | 83% (20/24) | R1B | 20% (6/30) |
4.3. If BM and PB are received, serum of both specimens should be stored | 74% (17/23) | R1B | 23% (7/30) |
4.4. BM and/or PB serum should be stored at the end of induction (TP1) | 82% (18/22) | R1B | 27% (8/30) |
4.5. BM and/or PB serum should be stored at the end of consolidation (TP2) | 67% (14/21) | R1B | 30% (9/30) |
4.6. Serum storage at other time-point is not required with the current trial strategy (other than diagnosis/Relapse/TP1/TP2) | 67% (8/12) | R2 | 63% (20/32) |
4.7. The type of collected material should be recorded by the biobank (BM/PB/etc.) | 96% (25/26) | R1B | 13% (4/30) |
4.8. The total serum volume per specimen should be stored in the biobank (no limitation of the number of aliquots) | 78% (18/23) | R1B | 23% (7/30) |
4.9. A minimum of 2 aliquots should be stored (0.5–2 mL) | 95% (18/19) | R2 | 41% (13/32) |
4.10. If the total serum volume of the received sample is less than 0.5mL, the material should be stored | 94% (16/17) | R2 | 47% (15/32) |
4.11. −80 °C is the preferable method to store serum aliquots | 90% (18/20) | R1B | 33% (10/30) |
5. Biobanking of Cerebro-Spinal Fluid (CSF) | |||
5.1. Patients with Acute Lymphoblastic Leukaemia should have CSF specimens biobanked | 82% (23/28) | R1B | 18% (6/34) |
5.2. Biobanking of CSF should be done for ALL patients at diagnosis and at relapse | 100% (24/24) | R1B | 17% (5/29) |
5.3. Biobanking of CSF should be done at follow-up time-points (regardless of infiltration at diagnosis) | 81% (13/16) | R1B | 45% (13/29) |
5.4. CSF specimens should be collected in a dry sterile tube | 72% (13/18) | R1B | 38% (11/29) |
5.5. CSF should be centrifuged for separate storage of supernatant and pellet | 83% (15/18) | R1B | 38% (11/29) |
5.6. Both supernatant and pellet should be stored after sample centrifugation | 73% (16/22) | R2 | 31% (10/32) |
5.7. The total volume of CSF specimens should be stored in the Biobank (no limitation of the number of aliquots) | 83% (19/23) | R1B | 21% (6/29) |
5.8. The supernatant should be stored in 0.5mL aliquots | 75% (12/16) | R2 | 50% (16/32) |
5.9. If the total CSF volume of the received sample is less than 0.5mL, the material should be stored | No consensus | R2 | 34% (11/32) |
5.10. The preferred storage method for CSF supernatant vials is: Liquid Nitrogen, −80 °C or −20 °C | 100% (21/21) | R2 | 31% (10/32) |
6. Biobanking of germline material | |||
6.1. Patients with Acute Lymphoblastic Leukaemia should have germline material biobanked | 94% (29/31) | R1B | 9% (3/34) |
6.2. Skin biopsy is the preferred option to obtain germline material | 77% (17/22) | R1B | 31% (10/32) |
6.3. If a skin biopsy is not possible, sample at remission (PB or BM with <1% blasts) is acceptable for germline material | 83% (20/24) | R1B | 25% (8/32) |
6.4. A buccal swab is only acceptable for germline material if a skin biopsy or a PB or BM sample at remission (<1% blasts) are not possible | 73% (16/22) | R1B | 31% (10/32) |
6.5. The preferred source of germline DNA material is: skin biopsy without fibroblast culture (direct extraction) or fibroblast culture from skin biopsy | No consensus | R2 | 25% (8/32) |
6.6. For transplanted patients, the DNA of the stem cell donor should be retrieved and stored in the biobank | 68% (15/22) | R1B | 31% (10/32) |
7. Quality monitoring and data | |||
7.1. Biobanks should be accredited (e.g: ISO 20387:2018) | 73% (22/30) | R1B | 12% (4/34) |
7.2. Biobanks should have an internal quality monitoring of biobanked material | 91% (30/33) | R1B | 3% (1/34) |
7.3. Biobanks should ask users for feedback on the quality of received biobank material | 97% (31/32) | R1B | 6% (2/34) |
7.4. Biobanks should have a standard form for collecting user feedback | 94% (30/32) | R1B | 6% (2/34) |
7.5. Biobanks should collect data on research performed using the released samples (assays performed, e.g. RNAsequencing) | 84% (27/32) | R1B | 6% (2/34) |
