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Chemosensitivity to Induction or High Dose Therapy, Pre/Post Transplant PET Negativity and Absence of Minimal Residual Disease within Mobilized Stem Cell Graft Predict Long Term Disease Free Survival in Multiple Myeloma
Despite the improvements in response rates in multiple myeloma during the last decade, relapses still remain as a problem. Aim of this study was to evaluate the factors associated with response and the length of progression free survival (PFS) following autologous hematopoietic cell transplantation (ASCT). Out of 113 consecutive patients with newly diagnosed MM, 43 % and 19% achieved Post-ASCT complete remission (CR) or very good partial remission (VGPR) respectively. Post-ASCT response status was significantly associated with female sex, light chain myeloma, β-2 microglobulin (≤3.5mg/L) and pre-ASCT response status. Multiparameter flow cytometry detected abnormal plasma cells (APC) in the harvests of 9.7% of patients. Higher proportion of patients who had contaminated harvests were at <VGPR status during mobilization compared to patients who did not have contamination (73% vs 53%; p=0.088). Presence of APC in the harvests compared to those lacking APC was significantly associated with progression at 12 months after ASCT (75% vs 36%; p=0.039). The median PFS was 13 (2-45) months after a median follow-up of 33 (7-148) months. Myeloma subtype, ISS, post-ASCT response and PET activity were significantly associated with PFS. Post-ASCT PET(-) CR had significantly longer PFS than patients with PET(+) CR (31.4 ± 9.9 vs 18.4 ± 3.5 months; p=0.029). In conclusion, having an ISS-3 stage myeloma, pre and post-ASCT response <VGPR had negative impact on PFS. Contamination of PBSC harvests with APC was associated with shorter PFS. Our results also demonstrate the importance of achieving PET negativity after transplantation. Thus, not only an immunological CR but also PET(-) CR should be achieved for long term PFS.
Table Factors Affecting the Post-transplant Progression Free Survival
| PFS (months) mean ±SD | 95% CI | P |
Sex Female Male | 26.1 ± 2.6 20.3 ± 2.2 | 21.0-31.2 16.0-24.5 | 0.135 |
Subtype Light chain Others | 30.6 ± 3.0 20.3 ± 1.9 | 24.7-36.5 16.5-24.1 | 0.008 |
International Staging System ISS1 ISS2 ISS3 |
27.2 ± 2.8 24.2 ± 2.9 15.9 ± 2.7 | 21.7-32.7 18.6-29.9 10.7-21.1 | 0.047 |
Cytogenetics del13q negative del13q positive |
24.0 ± 3.1 14.5 ± 2.5 |
18.1-30.0 9.4-19.5 | 0.101 |
β 2 microglobulin, mg/L ≤3.5 >3.5 |
25.7 ± 2.7 20.9 ± 2.2 |
20.5-30.9 16.5-25.2 | 0.230 |
Post-transplant PET Negative Positive | 30.1 ± 3.2 17.8 ± 2.6 | 23.9-36.3 12.7-22.8 | 0.008 |
APC in harvests Absent Present | 24.0 ± 1.9 14.4 ± 3.3 | 20.4-27.7 8.0-20.8 | 0.206 |
Pre-transplant response <PR PR VGPR CR | 14.8 ± 3.8 19.9 ± 2.5 28.2 ± 4.3 28.4 ± 2.8 | 7.3-22.2 15.0-24.8 19.8-36.7 22.8-33.9 | 0.021 |
Post-transplant response <PR PR VGPR CR | 3.2 ± 1.2 17.1 ± 2.8 30.9 ± 3.7 26.9 ± 1.8 | 0.85-5.55 11.6-22.6 23.7-38.0 19.8-26.7 | 0.001 |