Melphalan/TBI is not more carcinogenic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a ... View Full Text


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Article Info

DATE

2000-02-01

AUTHORS

S Kulkarni, R Powles, J Treleaven, S Singhal, C Horton, B Sirohi, N Bhagawati, D Tait, R Saso, S Killick, R Pinkerton, A Atra, S Meller, J Mehta

ABSTRACT

As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2–17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). the cumulative overall risk of developing a smn at 2, 5, 10 and 15 years post transplant was 0.4% (95% ci 0.1–2.6%), 1.7% (95% ci 0.6–4.4%), 6.4% (95% ci 2.8–10.8%) and 6.6% (95% ci 3.4–12.4%), respectively. even though age-adjusted rates were higher than the general population melphalan/tbi was not associated 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 vs4/363; 10 year risk 4.4%, 95% CI 1.8–10.6 vs 8.4%, 95% CI 2.9–22.9; P = NS). The risk was significantly higher with use of additional 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 incidence 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 for 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 was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI. Bone Marrow Transplantation (2000) 25, 365–370. More... »

PAGES

365-370

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bmt.1702148

DOI

http://dx.doi.org/10.1038/sj.bmt.1702148

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049972881

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10723578


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27 schema:description As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2–17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). the cumulative overall risk of developing a smn at 2, 5, 10 and 15 years post transplant was 0.4% (95% ci 0.1–2.6%), 1.7% (95% ci 0.6–4.4%), 6.4% (95% ci 2.8–10.8%) and 6.6% (95% ci 3.4–12.4%), respectively. even though age-adjusted rates were higher than the general population melphalan/tbi was not associated 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 vs4/363; 10 year risk 4.4%, 95% CI 1.8–10.6 vs 8.4%, 95% CI 2.9–22.9; P = NS). The risk was significantly higher with use of additional 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 incidence 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 for 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 was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI. Bone Marrow Transplantation (2000) 25, 365–370.
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35 TBI
36 acute lymphatic leukemia
37 additional cranial
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41 carcinogenic potential
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44 cranio-spinal irradiation
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