Secondary Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Allogeneic stem cell transplantation is a curative therapeutical option for patients (pts) with hematological diseases. As result of long term survival, late complications such as secondary malignancies are emerging.

Methods: Here we present a retrospective analysis of 589 pts (median age at transplantation 41 years, range 16–75, male 339, female 250) who underwent allogeneic stem cell transplantation in our institution between 1995 and 2007 (siblings n= 285, unrelated donors n= 304). Pts suffered from acute leukemia (n= 257), chronic myeloproliferative disorders (n= 120), myelodysplastic syndrome (n= 39), non-hodgkin-lymphomas (n= 41) and others (n= 132). Pts received conditioning with (n= 436) or without (n=152) 12 Gy total body irradiation (TBI).

Results: Up to 2007, 283 of 589 pts (48%) died of relapse or transplant related mortality (n=135 relapse, n= 84 infection, n= 36 graft-vs-host-disease (GVHD), n= 8 organ toxicity, n= 20 others or unknown). 305 out of 589 pts (52%) had survived with a median follow-up of 40 months (range 1–144 months). 21 out of 305 pts (6,9%) developed secondary malignancies at a mean of 5,1 years (range 1–10 years) after allogeneic stem cell transplantation. Localizations of secondary malignancies were skin (n= 11 basalioma, n= 2 melanoma), gut (n= 2 adenocarcinoma of the small intestine, n= 1 coloncarcinoma), oral cavity (n= 1 squamous cell cancer) and 3 lymphomas. 17/21 pts (81%) received a myeloablative conditioning with 12 Gy TBI, 4/21 pts (19%) a reduced intensity conditioning. Acute GVHD > grade 2 and chronic GVHD extensive disease appeared in 48% and 67% respectively. Thus, these pts must be treated with prolonged immunosupressive therapy. 2/21 (9,5%) died of secondary malignancies (carcinoma of small intestine and colon) and one pts of accidential infection.

Conclusion: Long term surviver of allogeneic stem cell transplantation are at increased risk of a secondary malignancies. Most of the pts received TBI-based conditioning and suffered from chronic GvHD extensive disease with consecutive immunosupressive therapy. Life-long follow-up will be needed to detect secondary malignancies in early stage of disease which might offer curative therapeutical options. Therefore, in our institution all pts undergo annual skin screening program and are sensitized for possibility of secondary malignancies late after transplantation.