Cardiac and Pulmonary Function Late Effects after Bone Marrow Transplantation in Childhood: Prospective Study on Behalf of EBMT LEWP Group.

BACKGROUND

Patients (pts) undergoing bone marrow transplantation (BMT) for hematological childhood disorders might present long-term cardiac and pulmonary function (CPF) complications. The current study assessed incidence and risk factors of CPF late sequelae by a multicenter study.

METHODS

From March 1994 to December 1997 we enrolled 220 consecutive children (130 males, median age at BMT 9,5 yrs) who underwent BMT (162 allogeneic and 58 autologous) for malignant (193) and non malignant (27) diseases in 9 EBMT centers. Total body irradiation (TBI) based conditioning regimen was used in 120/220 pts. A total of 165/220 pts were alive at the end of the study with a reliable CPF assessment which consisted of pulmonary function tests (PFTs) and M-Mode echocardiography performed at pre-BMT phase, at 1^st year post-BMT and yearly. Statistical analysis to evaluate the difference between pre-BMT and post-BMT CPF was performed by paired t-test, while the assessment of risk factors was based on univariate and multivariate analysis.

RESULTS

Median follow-up of evaluable pts was 5 yrs (range 4–8 yrs). Fifty-five of 220 patients deceased, none for late CPF abnormalities. The 5-year cumulative incidence of lung and cardiac impairment was 35% (hazard rate=0,07) and 23% (hazard rate =0,04) respectively. Patients presenting abnormal PFTs and shortening fraction (SF) at last follow-up were 15% and 12% respectively, even if asymptomatic. Chronic GVHD was a major risk factor in reducing lung function at both univariate (P=0.02) and multivariate analysis (P=0,006). Patients undergoing TBI based conditioning regimen showed a SF impairment at multivariate analysis (P=0,03). Gender, age, diagnosis, pre-BMT anthracyclines, BMT type, non-TBI based conditioning, malignant or non malignant diseases at BMT were not significantly related to pulmonary and cardiac late effects. No difference was ascertained in the cumulative incidence of non relapse mortality in a competing risk setting which suggests that BMT can also be successful for those children who experienced both abnormal PFTs and SF. At the end of the study all surviving pts had a median Lansky index >90.

CONCLUSIONS

Our study focused on low incidence of only asymptomatic CPF late effects in children transplanted for hematological disorders. TBI for cardiac function and C-GVHD for pulmonary function are the most important risk factors. Despite most of the alive pts remains in the normal range both for CPF complications from the beginning of BMT up to 5^th year of median follow-up, a continue surveillance at least in adolescent age is recommended.