Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age

Vrooman, L. M.; Millard, H. R.; Brazauskas, R.; Majhail, N. S.; Battiwalla, M.; Flowers, M. E.; Savani, B. N.; Akpek, G.; Aljurf, M.; Bajwa, R.; Baker, K. S.; Beitinjaneh, A.; Bitan, M.; Buchbinder, D.; Chow, E.; Dandoy, C.; Dietz, A. C.; Diller, L.; Gale, R. P.; Hashmi, S. K.; Hayashi, R. J.; Hematti, P.; Kamble, R. T.; Kasow, K. A.; Kletzel, M.; Lazarus, H. M.; Malone, A. K.; Marks, D. I.; O'Brien, T. A.; Olsson, R. F.; Ringden, O.; Seo, S.; Steinberg, A.; Yu, L. C.; Warwick, A.; Shaw, B.; Duncan, C.

Biol Blood Marrow Transplant. 2017 May 4; 23(8):1327-1334


Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for >/=1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced >/=1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free >/=1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age.

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