S. Kulkarni et al., Melphalan/TBI is not more carcinogeneic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years, BONE MAR TR, 25(4), 2000, pp. 365-370
Hematology,"Medical Research Diagnosis & Treatment
As there is concern regarding the high carcinogenic potential of melphalan
(Mel), 725 patients with haematological malignancies who received allogenei
c (n = 714) or syngeneic (n = 11) transplants over the last 26 years were f
ollowed-up to evaluate if melphalan was more likely to result in secondary
malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ni
nety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients de
veloped non-haematological SMN. Median time to develop a SMN was 7 years (r
ange 2-17 years). Age-adjusted rate was significantly higher than in the ge
neral population (observed 12 expected 1.2, risk 10; P < 0.0001). The cumul
ative overall risk of developing a SMN at 2, 5, 10 and 15 years post transp
lant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-1
0.8%) and 6.6% (95% CI3.4-12.4%), respectively. Even though age-adjusted ra
tes were higher than the general population melphalan/TBI was not associate
d with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P
= NS). The cumulative overall risk of SMNs was not different with CY/TBI or
Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% C
I 2.9-22.9; P = NS). The risk was significantly higher with use of addition
al cranial or cranio-spinal irradiation (17.5 % vs 2.7% at 10 years; P = 0.
0241). Transplants for acute lymphatic leukaemia resulted in a higher incid
ence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.
3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN f
or patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.
5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor w
as associated with independently increased risk in multivariate analysis. U
se of melphalan and TBI for transplant conditioning does not appear to be a
ssociated with higher risk of second malignant neoplasms than cyclophospham
ide and TBI.