Secondary malignancies after allogeneic stem-cell transplantation in the era of reduced-intensity conditioning; the incidence is not reduced.
Secondary malignancies are well established complication in long-term survivors after allogeneic stem-cell transplantation (SCT) with myeloablative conditioning (MAC). Fludarabine-based reduced-intensity (RIC) and reduced-toxicity conditioning (RTC) regimens are increasingly used in the last decade; however, due to limited long-term follow-up, there is no data on secondary malignancies in this setting. The records of 931 consecutive patients given allogeneic SCT with MAC (n=257), RIC (n=449) or RTC (n=225), in a single institution over a 13-year period, were reviewed. Twenty-seven patients had secondary malignancy, diagnosed a median of 43 months (7 months-11.5 years) after SCT. The 10-year cumulative incidence was 5.6% (95% confidence interval (CI), 3.6-8.7), twice the expected rate in matched normal population. The incidence was 1.7, 7.4 and 5.7% after MAC, RIC and RTC, respectively (P=0.02). Multivariate analysis identified fludarabine-based conditioning (hazard ratio (HR) 3.5, P=0.05), moderate-severe chronic graft-versus-host disease (HR 2.8, P=0.01) and diagnosis of chronic myeloproliferative or non-malignant disease (HR 0.2, P=0.04) as risk-factors for secondary malignancy. The related 10-year mortality rate was 2.4% (95% CI, 1.0-5.4). In conclusion, the risk of secondary malignancies is not reduced and is even possibly increased in the era of fludarabine-based RIC/RTC. Patients and physicians should be aware of this association and life-long cancer screening is required for all transplant survivors.
Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel. ashimoni@sheba.health.gov.il
A
A
Shimoni
N
N
Shem-Tov
A
A
Chetrit
Y
Y
Volchek
E
E
Tallis
A
A
Avigdor
S
S
Sadetzki
R
R
Yerushalmi
A
A
Nagler
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult