Abstract
56 adults with hematologic malignancies underwent blood cell allografts from A/B-DR-identical MSDs or A/B/C/DRB1/DQB1-allele-identical MUDs after 100 mg/m2 melphalan with (n=39; no prior autograft) or without (n=17; prior autograft) 50 mg/kg cyclophosphamide. GVHD prophylaxis comprised mycophenolate with cyclosporine (MSD) or tacrolimus (MUD). No growth factors were used. Supportive care was uniform. There were significant differences between groups (Table 1); most strikingly with respect to donor age.
| MSD (n=37) | MUD (n=19) | P | |
|---|---|---|---|
| Pt age | 53 (38–66) | 47 (27–62) | 0.085 |
| Pt age >55 | 32% | 32% | 0.95 |
| Donor age | 51 (31–69) | 33 (24–50) | <0.0001 |
| Donor age >45 | 76% | 16% | <0.0001 |
| Refractory disease | 49% | 68% | 0.16 |
| PS 2–3 | 22% | 32% | 0.42 |
| LDH | 172 (83–1298) | 237 (105–1919) | 0.082 |
| Abnormal LDH | 43% | 63% | 0.16 |
| CD34+ cell dose | 5.0 (3.0–7.6) | 6.0 (1.4–11.8) | 0.12 |
| CD34+ cell dose >6 | 11% | 47% | 0.002 |
| MSD (n=37) | MUD (n=19) | P | |
|---|---|---|---|
| Pt age | 53 (38–66) | 47 (27–62) | 0.085 |
| Pt age >55 | 32% | 32% | 0.95 |
| Donor age | 51 (31–69) | 33 (24–50) | <0.0001 |
| Donor age >45 | 76% | 16% | <0.0001 |
| Refractory disease | 49% | 68% | 0.16 |
| PS 2–3 | 22% | 32% | 0.42 |
| LDH | 172 (83–1298) | 237 (105–1919) | 0.082 |
| Abnormal LDH | 43% | 63% | 0.16 |
| CD34+ cell dose | 5.0 (3.0–7.6) | 6.0 (1.4–11.8) | 0.12 |
| CD34+ cell dose >6 | 11% | 47% | 0.002 |
10 patients experienced transplant-related mortality (TRM), and 29 relapsed (23 dead). The following factors were analyzed in a Cox model for effect on outcome: chemosensitive (n=25) vs refractory disease (n=31), patient age ≤55 (n=38) vs >55 (n=18), performance status (PS) 0–1 (n=42) vs 2–3 (n=14), normal (n=28) vs abnormal (n=28) LDH, prior autograft or not, CD34+ cell dose ≤6 (n=43) vs 6 (n=13) x 106/kg, MSD vs MUD, male (n=38) vs female (n=18) donor, and donor age ≤45 (n=25) vs >45 (n=31). Donor age was also analyzed as a continuous variable. Patient age >55 and PS 2–3 resulted in higher TRM. Refractory disease and abnormal LDH resulted in higher relapse, and lower disease-free (DFS) and overall (OS) survival. PS 2–3 resulted in lower DFS and OS. Patient age >55 and MSD resulted in lower OS. OS was reanalyzed after excluding donor type as a variable (*) because of its correlation with donor age. Table 2 shows the favorable effect of donor age ≤45 on relapse, DFS and OS.
| Outcome | RR (95% CI) | P |
|---|---|---|
| Relapse | 0.28 (0.12–0.64) | 0.003 |
| DFS | 0.27 (0.13–0.57) | 0.001 |
| OS* | 0.42 (0.19–0.94) | 0.035 |
| Outcome | RR (95% CI) | P |
|---|---|---|
| Relapse | 0.28 (0.12–0.64) | 0.003 |
| DFS | 0.27 (0.13–0.57) | 0.001 |
| OS* | 0.42 (0.19–0.94) | 0.035 |
When analyzed as a continuous variable, lower age resulted in lower relapse and higher OS with donor type in the model, and with higher DFS when donor type was excluded. Figures 1 and 2 show the effect of donor age on relapse and DFS in plots generated from the Cox model at the means of the covariates.
Figure
These data appear to suggest that a young MUD may be preferable to an older MSD. However, small numbers preclude obtaining an answer to the question of the age at which a sibling donor should be considered too old. Additionally, logistic issues involved in obtaining a MUD may reduce any benefit from having a young donor. We conclude that a younger donor should be chosen whenever possible. Further work is required to address the intrguing possibility of superiority of MUD over MSD based on age.
