March 18, 2019
3 min read

Survival rates after HSCT have not improved among infants with malignant diseases

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Infants with malignant diseases who underwent allogeneic hematopoietic stem cell transplantation did not demonstrate improved survival rates over a 15-year period, according to results of a study in JAMA Pediatrics.

Survival rates among infants with nonmalignant diseases who received allogeneic HSCT improved only during the earlier part of the study period, results showed.

Past studies of survival outcomes following HSCT have not analyzed changes over time among infants, who may be at greater risk for toxicities and transplant-related complications, according to researchers.

“Overall survival outcomes after allogeneic [HSCT] have improved over time: patients who received transplants in 2003 through 2007 experienced a 41% reduction in the hazard of death from any cause and a 52% reduction in transplant-related mortality compared with those diagnosed in 1993 through 1997,” Suhag H. Parikh, MD, pediatric bone marrow transplant specialist at Duke University Hospital, and colleagues wrote. “A similar decrease in transplant-related mortality was noted in patients with acute myeloid leukemia who were younger than 50 years. However, these studies did not focus on infants, who receive a small portion of overall transplants performed annually.”

In the multicenter cohort study, Parikh and colleagues evaluated 2,498 infants aged 1 year and younger (median age, 7 months; 65.3% white) who received their first allogeneic HSCT at transplant centers involved with the Center for International Blood and Marrow Transplant Research, a working group of more than 450 transplant centers around the world. Researchers grouped infants according to whether they had a malignant diagnosis (n = 472) — such as acute lymphoblastic leukemia (n = 182) — or a nonmalignant condition (n = 2,026), such as severe combined immunodeficiency (n = 834). Infants with malignant diagnoses tended to be older (87% aged 6 to 12 months).

Using time-trend analysis, the researchers analyzed three 5-year time periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. They assessed data between July 2017 and December 2018.

The study’s main objectives included identifying survival trends and characteristics linked to survival in each group; analyzing incidence of disease relapse, transplant-related death and, among infants with malignant diseases, DFS; and evaluating incidence of and risk factors for two major organ toxicities — idiopathic pneumonia syndrome and sinusoidal obstruction syndrome.

Results showed improvements in survival among infants in the nonmalignant cohort over time, from a 3-year OS of 65% for 2000 to 2004, to 72% for 2005 to 2009, and 74% for 2010 to 2014 (P = .001).


Improvement in OS occurred in the second (HR = 0.77; 95% CI, 0.63-0.93) and third (HR = 0.74, 95%CI, 0.6-0.91) study periods compared with the first; however, there was no further improvements between the second and third periods (HR = 1.04; 95% CI, 0.85-1.27).

Infants with malignant diseases demonstrated worse survival rates than those in the nonmalignant cohort, with no improvements over time. Three-year OS was 54.8% in 2000 to 2004, 64.6% in 2005 to 2009, and 58.9% in 2010 to 2014.

Researchers observed increasing 3-year relapse rates among infants with malignant diseases, from 19% (95% CI, 14-25) in 2000 to 2004, to 23% (95% CI, 17-30) from 2005 to 2009, and 36% (95% CI, 27-46) from 2010 to 2014 (P = .01).

Multivariable analysis showed relapse risk was higher in the later than early period (HR = 2.34; 95% CI, 1.47-3.75) and for patients who underwent total body irradiation (HR = 1.9; 95% CI, 1.24-2.92), but it was lower for patients with myelodysplastic syndrome than patients with AML (HR = 0.36; 95% CI, 0.2-0.67).

Univariate analysis found no significant difference in DFS across the study time periods. Multivariable models showed disease type as the only variable that affected DFS; infants with ALL had higher rates of treatment failure than those with AML (HR = 1.51; 95% CI, 1.1 -2.06).

Thirty-two percent (95% CI, 22-42) of infants with malignant diseases developed sinusoidal obstruction syndrome vs. 13% (95% CI, 11-16) of infants in the nonmalignant cohort.

According to the researchers, the following factors may have contributed to improved OS from 2000-2004 to 2005-2009: improvements in supportive care; improved donor/graft selection; increased use of reduced-intensity/nonmyeloablative conditioning regimens; reduced use of total body irradiation; and practice changes in the diagnosis and treatment of disease subgroups.

“Although children and adults who receive [HSCT] are surviving longer than before, infants who need [HSCT] face unique challenges,” the researchers wrote. “Research to enhance survival should focus on optimizing donor selection, refining conditioning regimens, reducing toxicity and improving supportive care.” – by Jennifer Byrne

Disclosures: Parikh reports no relevant disclosures. Please see the study for all other authors’ relevant financial disclosures.