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Some aspects of stem cell collection and transplantation - a single centre experience

Some aspects of stem cell collection and transplantation - a single centre experience. Dept. of Haematology and Oncology Charles University Plzen, Czech Republic Daniel Lysak. Saint- Petersburg, 8 Jun 2004. TRANSPLANT CENTERS IN CZECH REP. Czech Republic. 10.2 million inhabitants

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Some aspects of stem cell collection and transplantation - a single centre experience

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  1. Some aspects of stem cell collection and transplantation- a single centre experience Dept. of Haematology and Oncology Charles University Plzen, Czech Republic Daniel Lysak Saint- Petersburg, 8 Jun 2004

  2. TRANSPLANT CENTERS IN CZECH REP. Czech Republic 10.2 million inhabitants 10 transplant centers

  3. TRANSPLANT RATES - EUROPE Total SCT per 10 million 0 or no report 1-50 51-200 201-400 > 400 Transplant rates in European countries 2001. A.Gratwohl, Leukemia, 2003

  4. TRANSPLANT RATES - CZECH REP.

  5. TRANSPLANT RATES - OUR CENTRE 1992- 4/2004: 445 autologous 289 allogeneic transplantations

  6. our centre Europe* diagnosis alo (%) auto (%) alo (%) auto (%) CML 36 0 21 1 AML 24 8 25 8 ALL 10 0 18 2 NHL/M.H. 15 49 10 42 MM 3 43 5 27 MDS 6 0 7 0.4 AA 6 0 5 0 INDICATIONS FOR SCT • indications for SCT are similar in comparison with other European countries • alo transplants: more CML x ALL • auto transplants: more MM x solid tumors *A. Gratwohl, Blood, 2002

  7. STEM CELL SOURCE allogeneic transplantations autologous transplantations

  8. PBSC COLLECTION 1993- 2003: 1444 procedures – 1219 autologous – 225 allogeneic

  9. AUTOLOGOUS COLLECTION - MOBILIZATION REGIMEN cyclophosphamide 2.5 – 5.0 g/m2 79 % pts HAM 5 % pts HD-ara-c 10 % pts other 6 % pts + G-CSF 10 ug/kg/day (splitted in two doses) • Monitoring before apheresis: • CBC measured daily from day +7 (CY regimen) • when WBC recovered to > 1 x 109/l – CD34+ in PB enumerated • apheresis started if CD34+ count reached > 10 (20) cells/ul • target dose: 4.0 x 106 (MM pts – double transplant) • 3.0 x 106 (other pts) CD34+ cells/kg bw per SCT

  10. all pts good mobilizers CD34+ > 20 /ul poor mobilizers CD34+ < 20 /ul median age 53 54 (20 – 72) 50 (20 – 64) ns diagnosis: MM 43 % 51 % 10 % NHL/M.H./CLL 49 % 44 % 67 % AML 8 % 5 % 23 % disease stage at dg. (stage 0-3/4) 26 % / 74 % 25 % / 75 % ns time from diagnosis (months) 5.3 (1 – 126) 8.4 (0.4 – 75) ns no. of prior chemotherapy cycles 4.0 (2 – 14) 4.5 (2 – 12) ns disease status: CR 42 % 37 % 61 % p=0.0168 PR/SD 58 % 63 % 39 % PLT count (x 109/l) 224 (57 - 774) 174 (53 – 418) p=0.0005 Hb level (g/l) 128 (79 – 174) 125 (92 – 161) ns AUTOLOGOUS COLLECTION - PATIENTS • groups comparable in majority parameters, only different variables: • premobilization PLT count • premobilization disease status • higher representation of AML and lymfoma pts in poor mobilizers group • ( stem cell toxicity of previous therapy: ara-c, FLU, ...)

  11. AUTOLOGOUS COLLECTIONS - RESULTS I. all pts good mobilizers poor mobilizers 1st collection day, median 10 (8 – 28) 10 12 total CD34+ cells x 106/kg 6.8 (1.3 – 35.8) 7.7 3.5* no. of aphereses per patient 2 (1 – 6) 1 (1 – 3) 2 ( 1 – 6) CD34+ cells x 106/kg per LP 3.1 (0.5 – 35.8) 4.3 1.3* failure of collection (< target) 7 % 2 % 29 % peak CD34+ count in PB (cells/ul) 45 (10 – 387) 64 16* *p<0.0001

  12. AUTOLOGOUS COLLECTIONS - RESULTS II. Variables predictive for successful mobilization and collection: a)premobilization variables PLT count Hb level (in myeloma patients) previous chemotherapy stem cell toxicity x age, sex, disease stage at dg., no of prior CHT: 0 correlation b) preapheresis variables CD34+ cells count in PB correlated with CD34+ yield (r2 = 0.8) x WBC, PLT count: 0 correlation yield prediction (linear. regression STEP – WISE): CD34+ (x106/kg) = 0.99 + 0.002* weight (kg) + 0.064* CD34+ (/ul)

  13. 40 35 30 2 /kg R = 0,8022 6 25 20 C34+ cells x 10 15 10 5 0 0 100 200 300 400 CD34+ cells/ul in PB Number of CD34+ cells in PB versus number of CD34+ cells obtained in a single apheresis on the same day

  14. ALLOGENEIC COLLECTION - MOBILIZATION REGIMEN • Mobilization regimen: • G-CSF 10 ug/kg/day (single dose) for 5- 6 days • Monitoring before apheresis: • CBC and CD34+ measured daily from day +4 • apheresis started on day +5 (or on day +4 if WBC • exceeds 50 x 109/l) • target dose: 5.0 x 106 CD 34+ cells/kg bw of the recipient • maximum of 2 aphereses performed • maximum WBC count: 70 x 109/l (or STOP G-CSF)

  15. all donors donors >= 50 years number of donors 105 32 sex (male/female) 64/41 10/22 median age 41 (16 – 75) 55 (50 – 75) HLA match. sibling/unrelated 64/41 31/1 weight (kg), median 76 (55 – 130) 86 (59 – 105) peripheral/central venous access 67 % / 33 % 54 % / 46 % blood volumes processed 3.2 (2.5 – 4.4) 3.0 (2.5 – 3.8) ALLOGENEIC COLLECTIONS - DONORS

  16. all donors donors >= 50 years CD34+ cells x 106/kg donor b.w per LP 2.2 (0.3 – 16.7) 1.9 (0.4 – 10.2) CD34+ cells x 106/kg recipient b.w. 5.0 (0.7 – 17.5) 4.4 (0.7 – 10.6) 1 LP to reach target 28 % 19 % failure of collection (< target) 45 % 56 % CD34+ count in PB (cells/ul) on day+5 64 (11 – 204) 56 (11 - 204) PLT count at day +6 (x109/l) 141 (77 – 257) 136 (77 – 257) CD3+ cells x 108/kg recipient b.w. 2.66 (0.71 – 5.54) 2.58 (1.16 – 4.44) side efects of G-CSF treatment 23 % 37 % complication of apheresis 20 % 22 % ALLOGENEIC COLLECTIONS - RESULTS I. differencies in all parameters not significant

  17. ALLOGENEIC COLLECTIONS - RESULTS II. • older donors compared to younger (> 50 vs < 30 years): • WBC and CD 34+ kinetics similar peaking at day +5 • CD 34+ count at day +5 significantly lower (56 vs 80 • cells/ul, p=0.048) • median number of CD34+ (x106/kg bw of the recipient) • significantly lower (4.4 vs 6.3, p = 0.0404) • 2 LP more frequently necessary • median number of CD 3+ (x108/kg bw of the recipient) • comparable (2.58 vs 2.54, ns)

  18. APHERESIS PROCEDURE COBE Spectra (from 1995), Fenwal CS3000 LVL: 3 – 4 x TBV ACD-A rate: 1.1 ml/l TBV/min ACD-A:PB ratio: 1:14 – 15 inlet flow: 60 – 90 ml/min depending on ACD:blood ratio and venous access patients: intpatient basis donors: int/outpatient basis (venous access) Ca prophylaxis: CaCl2 (2 amp) intermitent i.v. bolus Minimal precollection blood counts: PLT (x 109/l) hematocrit (%) patients: > 20 30 donors: > 100 (v.6), > 150 (v.4) NA

  19. Apheresis unit 2 collection rooms airconditioning/filtration

  20. MNC (v 4.7) autoPBSC (v 6) procedures 30 % 70 % inlet volume (l), median 17 (13 – 22) 17 (13 – 23) ns CD34+ cells x 106/kg bw/LP 3.3 (0.98 – 32.4) 3.4 (0.4 – 35.8) ns postLP PLT (% of preLP count) 57 (35 – 90) 75 (45 – 91) p< 0.0001 procedure time (min), median 209 240 time per one TBV (min), median 66 (51 – 126) 80 (64 – 108) p= 0.0003 PLT contamination (x109/l), med 1434 677 p< 0.0001 patient related CD34+ recov. (%) 101 (21 – 268) 94 (15 – 254) ns complication rate 10 % 9 % ns component CD34+ count x volume x 100 PR recovery = --------------------------------------------------------- patient CD34+ count x TBV MNC vs. AutoPBSC I.

  21. MNC vs. AutoPBSC II. MNC:AutoPBCS: PLT depletion: higher lower apheresis time: shorter longer (+ ~ 15 %) other parameters (CE, AE ..) not significantly different Advantages of AutoPBSC: 1. automated interface establishment and higher separation factor - increased stability of IF position - more consistent results 2. more of the operator attention to the patient or donor 3. reduced mistakes of staff members during collection AutoPBSC: pts/donors with: low PLT count lower CE related to interface instability MNC: pts/donors with: limited procedure toleration (time)

  22. QUALITY ASSURANCE OF THE GRAFT Before collection (pt/donor PB): ABO blood group infectious disease: HIV, HBV, HCV, syphilis After collection (apheresis product): volume (ml) WBC count (x 109/l) total NC (x 108/kg) CD34+ cells (%, ISHAGE based protocol, double platform) CD34+ yield (x 106/kg) CD3+ content (x 108/kg) – allogeneic collections cell viability (7-AAD exclusion on flow cytometry) sterility (Eu Pharmacopoeia approved method)

  23. SUMMARY 1. PBSC are increasingly used to support autologous or allogeneic transplantation. 2. Stem cell collection with apheresis is effective, safe and well tolerated method with low complication rate. 3. COBE Spectra is a gold standard for PBSC collection, providing comparable results among centers. 4. MNC and AutoPBSC have similar performance, version selection can be affected by precollection variables.

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