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Background:
AHCT remains the only curative option for MM despite improved survival with novel agents. We analyzed our single center experience of AHCT in MM over the past decade and examined factors associated with outcomes.
Methods:
The outcomes of 77 consecutive MM patients receiving allotransplants from matched sibling (n=69) or unrelated donors (n =8) between 2002 and 2013 at our institution were analyzed. The primary objectives were to compare overall survival (OS), progression free survival, (PFS), and non-relapse mortality (NRM) in patients based on biologic disease risk and conditioning regimen intensity. 60 pts. received allotransplant after non-myeloablative regimens (regimen 1) – low dose 200-cGy total body irradiation (TBI) +/-Fludarabine (n = 52) or Cyclophosphamide + Fludarabine (n=8) while 17 received higher intensity conditioning (regimen 2) consisting of Fludarabine + Melphalan 140 mg/2 (11) or Cyclophosphamide + TBI (6).
Results:
Patient, disease and transplant related characteristics are given in Table 1. Median follow up of survivors was 49.4 months. 27 (35.1%) had high-risk cytogenetics – t (4:14), 17p deletion, Chr 1 abnormality, or t (14:16). 96% had prior auto transplant with 17(22%) relapsing after auto transplant.
On multivariate analysis, older age (HR 1.06 95% CI 1.015, 1.120, p=0.0112), lack of a complete remission (CR) at allotransplant (HR 0.15 95% CI 0.046, 0.485, p=. 0015 in CR), longer interval from autologous transplant to AHCT (6.0 m vs. 5.2 m) (HR 1.04, 95%CI 1.008, 1.072, p=0.01) and CMV reactivation (HR 3.2, 95% CI 1.41, 7.52,p=0.005) were significant for higher mortality. CR at the transplant was associated with superior PFS (HR for treatment failure 0.332, p=0.041). Increasing age (HR, 1.07 p= 0.047) and non-CR status at transplant (HR for CR - 0.164, 95% CI .035, .770, p=0.021) were associated with higher NRM. High- risk disease and conditioning intensity were not associated with outcomes (Fig 1, 2).
Conclusions:
The adverse effect of high-risk genetics may be overcome by the allogeneic effect irrespective of conditioning intensity. Allotransplant benefited younger patients and those in CR at the time of transplant and with short intervals from prior auto-grafts. No plateau in survival was demonstrated.
Table 1.
Variables
| Total, N=77
| Regimen 1,N= 60
| Regimen 2, N=17(%)
| P value
| |||||||||
Age, years median (range)
| 52(23-69)
| 52.5(32-69)
| 52(23-61)
| 0.40
| |||||||||
Female, n (%)
| 28(36.4)
| 26(43.3)
| 2(11.8)
| 0.017
| |||||||||
FISH risk ,n(%) Low High
| 50(64.9) 27(35.1)
| 40(66.7) 20(33.3)
| 10(58.8) 7(41.2)
| 0.55
| |||||||||
Time from auto to AHCT, months median (range)
| 5.2(3.3-75.2)
| 5.0(3.0-47.1)
| 6.3(4.1-75.2)
| 0.02
| |||||||||
Response status at transplant, n(%) CR PR SD
|
|
|
| 0.21
| |||||||||
CMV reactivation, n(%) | 14 (18.2)
| 9 (15.0)
| 5 (29.4)
| 0.28
|
Fig 1. Overall survival by conditioning regimen intensity
Fig 2. Progression free survival by FISH risk