Clinical studies of chimerism after DCBT
| Number of patients . | Conditioning (no of patients) . | Timing of chimerism (sample used for analysis) . | Key findings . | Predictor of predominant unit . | Exclusions . | Reference . |
|---|---|---|---|---|---|---|
| 23 | MAC – Cy/TBI +/−Flu +/− ATG | Day 21, 60, 100, 180, 360, 720 (PB, BM) | At day 21 single unit chimerism in 76% At day 100 single unit chimerism in 100% | CD3 dose | Unevaluable at day 21 (n = 2) Early death (relapse in 2, TRM in 2) | 5 |
| 110 | RIC – Flu/Cy/TBI | Day 21, 100, 180, 365 (BM) | At day 21: 2 units present in 43% At day 100: 2 units present in 9% At day 180: 2 units present in 3% At day 365: 2 units present in 0% | No significant predictor on multivariate analysis | Graft failure (n = 7) | 4 |
| 21 | RIC – Flu/Mel/ATG | Weeks 2,4,6,8,10,12 Months 6,12,24 (PB whole blood, where possible CD3 and CD33) | 3 groups: 10 patients: single unit chimerism at week 6 + 12 4 patients: both units present at week 6 but one dominant at week 12 3 patients: recipient + 1 unit present at week 12 | At 3 mo, predominant unit was the first infused in 76% patients | Graft failure (n = 2) Early death (n = 2) | 10 |
| 61 | MAC (57) RIC (4) | Month 1, 3, 6 and 12 | Persistence of 2 units in 1 patient Single unit chimerism in 49 patients | CFU-GM | Graft failure (n = 5) Autologous recovery (n = 5) Early TRM (n = 1) | 22 |
| 60 | MAC – Flu/Cy or Treo/TBI (46) RIC – Flu/Cy/TBI (14) | PB–day 7, 14, 21, 28, 56 and 80 BM–day 28, 56 and 80 | MAC Single unit chimerism at a median of 14 d (range 14-21 d) in all but 1 patient who had persistent mixed unit chimerism (HLA match 6/6) RIC At day 28 single unit dominance in 4 patients At day 80 single unit dominance in 10 patients, persistence of 2 units in 3 patients | CD3 dose Naïve CD8+ cell dose | Graft failure and early death (n = not given) | 6 |
| 262 | MAC (102) – Cy/Flu/TBI 13.2G NMA (109) – Cy/Flu/TBI 2G NMA (51) - Cy/Flu/TBI 2G/ATG | Day 21, 100, 180, 360, 720 (whole BM) | At day 21, a predominant unit (>70%) was observed in 81% patients undergoing MAC transplant and 61% after NMA transplant By day 100 and later time points, a predominant unit was observed in 97% MAC and 95% NMA patients | MAC–CD3 dose NMA–CD3 dose + HLA match | Graft failure (n = 29) Dual chimerism (n = 6) Unavailable (n = 2) | 8 |
| 29 | TBI/Cy/Ara-C/BCNU (19) Bu/Cy/BCNU/ATG (4) Bu/Flu/TBI/ATG (6) | Day 7,14,21,30 (PB, whole blood) | 24 patients engrafted: 1 had dual chimerism and 23 had full donor chimerism of one unit Suggestion that primary graft failure may be predicted by lack of detectable cord blood by PCR at day 14 | No significant predictor on multivariate analysis | Graft failure (n = 2) Dual chimerism (n = 1) Early death (n = 3) | 40 |
| 36 | RIC - Flu/Cy/TBI | Day 30, 60, 100 (PB CD3) | 29 patients achieved full donor chimerism (at least 95%) of 1 unit within 100 d, 7 patients had mixed chimerism (14-94% contribution by 1 unit) Attainment of full donor chimerism within 100 d was significantly associated with a lower relapse risk | No significant predictor of predominant unit | — | 9 |
| 38 | RIC – Flu/Mel/ATG | Day 30, 60, 100 (PB, whole blood) | At day 100, 66% patients had hematopoiesis derived from single unit. Persistent dual chimerism beyond 1 y observed in 2 patients | First unit infused predicted dominant unit | 11 | |
| 53 | RIC - Flu/Cy/TBI 4Gy | Day 11, 18, 25, 32 (PB, whole blood and T cells, CD3, CD4, NK, Monocytes, granulocytes) Day 32 (unseparated BM) | Single unit dominance observed in 94% patients 1 patient experienced graft failure Unit predominance observed by day 11 and dominant unit predicted by CD4, CD8 and NK cell chimerism at day 11 | Higher TNC viability predicted dominant unit | 17,41 | |
| 8 | Various | 3-4 d intervals from day 7 until neutrophil recovery, then weekly until 3 mo (PB, whole blood) | Dominance of 1 unit by day of engraftment. All patients had contribution of dominant unit > 90% at day 28 | 42 | ||
| 35 | MAC Flu/Cy/TBI Flu/Treo/TBI | Day 7, 14, 21, 28, 42, 56, 80, 180, 365, 730 (PB T cells, granulocytes, monocytes, NK cells) | Single donor dominance in 38% at day 14 and additional 47% at day 28. T cell chimerism at day 7 predicted dominant unit. Too few granulocytes, monocytes and NK cells at day to be predictive. Persistent contribution of both units observed in 3 patients | No significant predictor | Primary graft failure (n = 2) Early relapse (n = 2) Early mortality (n = 1) | 43 |
| 56 | MAC | Day 21 (BM total chimerism) | 3 patients had graft failure Donor haemopoiesis was from 1 unit in 49 patients and 2 in 7 patients. Higher donor chimerism at day 21 correlated with speed of neutrophil engraftment and likelihood of platelet recovery by day 180 | — | — | 44 |
| 20 | MAC – Flu/Bu/TLI | Day 30, 60, 100, 180, 365 (BM or PB) | All evaluable patients achieved sustained full donor chimerism from day 30 with single donor in all but 1 patient | No significant predictor | Graft failure Early relapse N = not given | 45 |
| Number of patients . | Conditioning (no of patients) . | Timing of chimerism (sample used for analysis) . | Key findings . | Predictor of predominant unit . | Exclusions . | Reference . |
|---|---|---|---|---|---|---|
| 23 | MAC – Cy/TBI +/−Flu +/− ATG | Day 21, 60, 100, 180, 360, 720 (PB, BM) | At day 21 single unit chimerism in 76% At day 100 single unit chimerism in 100% | CD3 dose | Unevaluable at day 21 (n = 2) Early death (relapse in 2, TRM in 2) | 5 |
| 110 | RIC – Flu/Cy/TBI | Day 21, 100, 180, 365 (BM) | At day 21: 2 units present in 43% At day 100: 2 units present in 9% At day 180: 2 units present in 3% At day 365: 2 units present in 0% | No significant predictor on multivariate analysis | Graft failure (n = 7) | 4 |
| 21 | RIC – Flu/Mel/ATG | Weeks 2,4,6,8,10,12 Months 6,12,24 (PB whole blood, where possible CD3 and CD33) | 3 groups: 10 patients: single unit chimerism at week 6 + 12 4 patients: both units present at week 6 but one dominant at week 12 3 patients: recipient + 1 unit present at week 12 | At 3 mo, predominant unit was the first infused in 76% patients | Graft failure (n = 2) Early death (n = 2) | 10 |
| 61 | MAC (57) RIC (4) | Month 1, 3, 6 and 12 | Persistence of 2 units in 1 patient Single unit chimerism in 49 patients | CFU-GM | Graft failure (n = 5) Autologous recovery (n = 5) Early TRM (n = 1) | 22 |
| 60 | MAC – Flu/Cy or Treo/TBI (46) RIC – Flu/Cy/TBI (14) | PB–day 7, 14, 21, 28, 56 and 80 BM–day 28, 56 and 80 | MAC Single unit chimerism at a median of 14 d (range 14-21 d) in all but 1 patient who had persistent mixed unit chimerism (HLA match 6/6) RIC At day 28 single unit dominance in 4 patients At day 80 single unit dominance in 10 patients, persistence of 2 units in 3 patients | CD3 dose Naïve CD8+ cell dose | Graft failure and early death (n = not given) | 6 |
| 262 | MAC (102) – Cy/Flu/TBI 13.2G NMA (109) – Cy/Flu/TBI 2G NMA (51) - Cy/Flu/TBI 2G/ATG | Day 21, 100, 180, 360, 720 (whole BM) | At day 21, a predominant unit (>70%) was observed in 81% patients undergoing MAC transplant and 61% after NMA transplant By day 100 and later time points, a predominant unit was observed in 97% MAC and 95% NMA patients | MAC–CD3 dose NMA–CD3 dose + HLA match | Graft failure (n = 29) Dual chimerism (n = 6) Unavailable (n = 2) | 8 |
| 29 | TBI/Cy/Ara-C/BCNU (19) Bu/Cy/BCNU/ATG (4) Bu/Flu/TBI/ATG (6) | Day 7,14,21,30 (PB, whole blood) | 24 patients engrafted: 1 had dual chimerism and 23 had full donor chimerism of one unit Suggestion that primary graft failure may be predicted by lack of detectable cord blood by PCR at day 14 | No significant predictor on multivariate analysis | Graft failure (n = 2) Dual chimerism (n = 1) Early death (n = 3) | 40 |
| 36 | RIC - Flu/Cy/TBI | Day 30, 60, 100 (PB CD3) | 29 patients achieved full donor chimerism (at least 95%) of 1 unit within 100 d, 7 patients had mixed chimerism (14-94% contribution by 1 unit) Attainment of full donor chimerism within 100 d was significantly associated with a lower relapse risk | No significant predictor of predominant unit | — | 9 |
| 38 | RIC – Flu/Mel/ATG | Day 30, 60, 100 (PB, whole blood) | At day 100, 66% patients had hematopoiesis derived from single unit. Persistent dual chimerism beyond 1 y observed in 2 patients | First unit infused predicted dominant unit | 11 | |
| 53 | RIC - Flu/Cy/TBI 4Gy | Day 11, 18, 25, 32 (PB, whole blood and T cells, CD3, CD4, NK, Monocytes, granulocytes) Day 32 (unseparated BM) | Single unit dominance observed in 94% patients 1 patient experienced graft failure Unit predominance observed by day 11 and dominant unit predicted by CD4, CD8 and NK cell chimerism at day 11 | Higher TNC viability predicted dominant unit | 17,41 | |
| 8 | Various | 3-4 d intervals from day 7 until neutrophil recovery, then weekly until 3 mo (PB, whole blood) | Dominance of 1 unit by day of engraftment. All patients had contribution of dominant unit > 90% at day 28 | 42 | ||
| 35 | MAC Flu/Cy/TBI Flu/Treo/TBI | Day 7, 14, 21, 28, 42, 56, 80, 180, 365, 730 (PB T cells, granulocytes, monocytes, NK cells) | Single donor dominance in 38% at day 14 and additional 47% at day 28. T cell chimerism at day 7 predicted dominant unit. Too few granulocytes, monocytes and NK cells at day to be predictive. Persistent contribution of both units observed in 3 patients | No significant predictor | Primary graft failure (n = 2) Early relapse (n = 2) Early mortality (n = 1) | 43 |
| 56 | MAC | Day 21 (BM total chimerism) | 3 patients had graft failure Donor haemopoiesis was from 1 unit in 49 patients and 2 in 7 patients. Higher donor chimerism at day 21 correlated with speed of neutrophil engraftment and likelihood of platelet recovery by day 180 | — | — | 44 |
| 20 | MAC – Flu/Bu/TLI | Day 30, 60, 100, 180, 365 (BM or PB) | All evaluable patients achieved sustained full donor chimerism from day 30 with single donor in all but 1 patient | No significant predictor | Graft failure Early relapse N = not given | 45 |