Page 300 - Haematologica May 2020
P. 300

A. Radujkovic et al.
   sion of patients' general health status prior to alloSCT can- not be ruled out.
Currently, there is an ongoing “testosterone debate” in the field of cardiovascular medicine. Although the associ- ation between testosterone levels and cardiovascular mor- tality seems to be conclusive, prospective data on testos- terone treatment are scarce, and so far no prospective con- trolled study has been able to show that treatment with testosterone or normalization of testosterone levels can reduce cardiovascular events.30 On the contrary, results of a recently published prospective controlled study, which is one of seven co-ordinated National Institutes of Health (NIH)-supported trials of testosterone treatment in elderly men (“T Trials”),31 indicate that testosterone may even increase cardiovascular risk, as reflected by increasing coronary artery plaque volume following testosterone treatment.32 Thus, although of potential clinical value, any long-term health benefits of testosterone supplementation remain to be established.
As regards myeloid malignancies, testosterone among other sex steroids has been shown to exert cytostatic and
cytotoxic effects on several myeloid leukemia cell lines in vitro.33 However, although an early pilot study on AML patients using androgens as an adjunct in different first- line and maintenance treatment approaches showed an unexpectedly high rate of long-term survivors in a group of patients who achieved complete remission,10 larger ran- domized studies failed to show beneficial effects on over- all and disease-free survival.11 Only recently, a prospective controlled trial in elderly patients with AML suggested that maintenance therapy with low-dose oral norethandrolone, a synthetic androgen with similar ana- bolic activity to testosterone, significantly improves over- all, disease- and event-free survival,12 and this has renewed interest in this treatment approach. However, in this study, the beneficial effects of androgen maintenance ther- apy were observed only in patients with low disease bur- den at diagnosis and only in the absence of relapse during the first year of treatment.12 This might imply that andro- gen treatment has had some impact on disease-indepen- dent mortality. Interestingly, in the aforementioned trial, female patients were also treated, and the multivariable
Table 3. Multivariable analysis of the training cohort with the end points overall survival (OS), progression-free survival (PFS), non-relapse mor- tality (NRM), and relapse following allogeneic stem cell transplantation and OS and PFS after onset of acute graft-versus-host disease (GvHD) (complete case analysis).
         OS (n=175)
PFS NRM* Relapse* OS after acute (n=175) (n=175) (n=175) GvHD* (n=48)
PFS after acute GvHD* (n=45)
   HR95%CI
Covariate
Testosterone 1.11 (per 100 ng/dL decrease) (1.00-1.22) Disease stage†
Early Ref Intermediate 0.92
(0.46-1.86) Late 1.87
(1.03-3.36) Age (per 10-year increase) 1.26
P
0.045
0.822
0.038
0.029
HR95%CI P CHR95%CI P CHR95%CI P HR95%CI P HR95%CI P
1.11 1.25 (1.02-1.22) 0.022 (1.05-1.47)
Ref Ref
0.94 0.62 (0.50-1.78) 0.857 (0.19-1.95) 1.74 2.11 (1.04-3.08) 0.036 (1.00-4.45)
1.06 1.14 1.12
0.013 (0.95-1.19) 0.277 (0.95-1.35) 0.152 (0.95-1.33) 0.171
Ref Ref Ref
1.14 3.65 3.35
0.411 (0.55-2.36) 0.720(1.26-10.61) 0.017 (1.13-9.88) 0.029 2.17 2.98 4.59
0.050 (1.25-3.76) 0.006 (1.16-7.64) 0.023 (1.80-11.68) 0.001
      1.28 1.13 1.28 1.11 1.13
 Conditioning
(1.02-1.54)
(1.06-1.55) 0.010 (0.84-1.52)
0.415 (1.01-1.61) 0.040 (0.78-1.59) 0.564 (0.80-1.59) 0.498
MAC Ref Ref --------
  RIC 0.70 (0.41-1.21) 0.203 0.69 (0.41-1.15) 0.152 Donor
Relateddonor Ref Ref -------- Unrelated Donor 1.36 1.35
(0.82-2.26) 0.233 (0.84-2.15) 0.214
Recipient - donor sex match
Donor source
BM 1.60 1.24
(0.62-4.13) 0.333 (0.49-3.15) 0.652
Number of events: OS, n=87; PFS, n=102; NRM, n=35; relapse, n=67; OS after acute GvHD, n=30; PFS after acute GvHD, n=32. *Slim model. †According to Gratwohl et al.13 BM: bone marrow; CHR: cause-specific hazard ratio; CI: confidence interval; HR: hazard ratio; MAC: myeloablative conditioning; PB: peripheral blood; RIC: reduced intensity conditioning.
 Matched Ref Ref -------- Male recipient / 0.77 0.89
female donor (0.46-1.31) 0.341 (0.55-1.43) 0.630
   PB Ref Ref --------
  1460
  haematologica | 2020; 105(5)
  

















































   298   299   300   301   302