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Clinical Trial
. 2017 Aug;23(8):1327-1334.
doi: 10.1016/j.bbmt.2017.04.017. Epub 2017 Apr 28.

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

Lynda M Vrooman  1 , Heather R Millard  2 , Ruta Brazauskas  3 , Navneet S Majhail  4 , Minoo Battiwalla  5 , Mary E Flowers  6 , Bipin N Savani  7 , Görgün Akpek  8 , Mahmoud Aljurf  9 , Rajinder Bajwa  10 , K Scott Baker  6 , Amer Beitinjaneh  11 , Menachem Bitan  12 , David Buchbinder  13 , Eric Chow  6 , Christopher Dandoy  14 , Andrew C Dietz  15 , Lisa Diller  16 , Robert Peter Gale  17 , Shahrukh K Hashmi  18 , Robert J Hayashi  19 , Peiman Hematti  20 , Rammurti T Kamble  21 , Kimberly A Kasow  22 , Morris Kletzel  23 , Hillard M Lazarus  24 , Adriana K Malone  25 , David I Marks  26 , Tracey A O'Brien  27 , Richard F Olsson  28 , Olle Ringden  29 , Sachiko Seo  30 , Amir Steinberg  25 , Lolie C Yu  31 , Anne Warwick  32 , Bronwen Shaw  2 , Christine Duncan  16
Affiliations
Clinical Trial

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

Lynda M Vrooman et al. Biol Blood Marrow Transplant. 2017 Aug.

Abstract

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.

Keywords: Graft-versus-host disease; Hematologic malignancy; Hematopoietic cell transplantation (HCT); Infants; Late effects; Pediatric; Relapse; Survival; Total body irradiation.

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Figures

Figure 1
Figure 1
Summary of patient selection and exclusions.
Figure 2
Figure 2
Overall (A) and relapse-free (B) survival among patients who survived, relapse-free at least one year following HCT for hematologic malignancy (performed at less than 3 years of age.)
See this image and copyright information in PMC

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