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Multicenter Study
. 2019 May 1;173(5):e190081.
doi: 10.1001/jamapediatrics.2019.0081. Epub 2019 May 6.

Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant

Suhag H Parikh  1 , Prakash Satwani  2 , Kwang Woo Ahn  3 , Natasha A Sahr  4 , Caitrin Fretham  5 , Allistair A Abraham  6 , Vaibhav Agrawal  7 , Jeffery J Auletta  8 , Hisham Abdel-Azim  9 , Edward Copelan  10 , Miguel-Angel Diaz  11 , Christopher C Dvorak  12 , Haydar A Frangoul  13   14 , Cesar O Freytes  15 , Shahinaz M Gadalla  16   17 , Robert Peter Gale  18 , Biju George  19 , Usama Gergis  20 , Shahrukh Hashmi  21 , Peiman Hematti  22 , Gerhard C Hildebrandt  23 , Amy K Keating  24   25 , Hillard M Lazarus  26 , Kasiani C Myers  27   28 , Richard F Olsson  29 , Timothy Prestidge  30 , Seth J Rotz  31 , Bipin N Savani  32 , Evan B Shereck  33   34 , Kirsten M Williams  6 , Baldeep Wirk  35 , Marcelo C Pasquini  3 , Alison W Loren  36
Affiliations
Multicenter Study

Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant

Suhag H Parikh et al. JAMA Pediatr. .

Abstract

Importance: Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants.

Objective: To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant.

Design, setting, and participants: In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018.

Exposures: Allogeneic hematopoietic cell transplant.

Main outcomes and measures: Survival trends, disease relapse, and toxicity.

Results: A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P = .007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P = .01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes.

Conclusions and relevance: Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Abraham reports personal fees from Sangamo Therapeutics outside the submitted work. Dr Hashmi reports other from Mallinckrodt outside the submitted work. Dr Hidebrandt reports grants from Takeda, grants from Jazz and Pharmacyclics; personal fees from Jazz, INcyte, Kite, and Pfizer, outside the submitted work; stocks in AbbVie, Aetna, Axim, Bluebird, Cardinal Health, Celgene, Cellectis, Clovis Oncology, Crisper, CVS Health, Endocyte, GW Pharmaceuticals, Idexx Labs, Immunomedics, Insys Therapeutics, Johnson & Johnson, Juno Therapeutics, Kite Pharma, Novartis, Pfizer, Procter and Gamble, Sangamo Bioscience, and Vertex Pharmaceuticals; and travel accommodation and expenses from Kite Pharma, Incyte, Pfizer, Jazz Pharmaceuticals, and Astellas. Dr Myers reports personal fees from Novartis and Bellicum outside the submitted work. Dr Olsson reports personal fees from AstraZeneca outside the submitted work. Dr Pasquini reports personal fees from Medigene and Pfizer, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Forest Plot of Multivariable Models Showing Time Trend
RR indicates relative risk.
Figure 2.
Figure 2.. Adjusted Survival Curves by Period and Transplant Indication
Figure 3.
Figure 3.. Adjusted Survival Curves for the Nonmalignant Cohort by Graft Source and Donor Type
See this image and copyright information in PMC

References

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