Symptomatic venous thrombotic events complicate outcomes in pediatric oncology patients

SAN DIEGO — Children with cancer had worse outcomes if they had symptomatic venous thrombotic events, according to results of a population-based study conducted in the Maritimes, Canada presented at the ASH Annual Meeting and Exposition.

Perspective from Julia Jaffray, MD

“There is a significant body of data published on symptomatic venous thrombotic events [sVTE], which are a well-recognized complication in pediatric cancer patients,” Ketan Kulkarni, MD, pediatric hematologist/oncologist at IWK Health Centre in Halifax, Nova Scotia, said during his presentation. “There are a lot of data on the incidence of sVTE and their risk factors. However, the association of sVTE with survival outcome in pediatric cancer patients is not well studied, and it’s not clear what the association is.”

Researchers used a database of patients treated at IWK Health Centre — which treats all pediatric oncology patients from Nova Scotia, New Brunswick and Prince Edward Island — to evaluate OS and EFS outcomes related to the incidence of sVTE in 936 children.

“All of the pediatric cancer patients in the Maritimes are diagnosed and treated at IWK Health Centre in a shared-care model of 25 regional and provincial hospitals,” Kulkarni said. “This is pretty much a population-based cohort of pediatric cancer patients, and that helps us significantly in terms of the strength of the data, because it is likely our data are representative of the total oncology population from the region.”

Researchers supplemented data from the hospital database with data from the Provincial Cancer in Young People registry, hospital health records and pharmaceutical databases to identify all patients with sVTE.

Forty-seven children (5.02 ± 0.01%) had sVTE, defined as radiographically documented VTE with at least one sign or symptom of VTE.

The mean age of diagnosis of children with sVTE was 10.1 years, and most were boys (ratio of boys to girls, 1.8:1). The most common cancers in these children were leukemia (n = 17; 36.2%), lymphoma (n = 9; 19.1%), sarcoma (n = 9; 19.1%), brain tumor (n = 1; 2.1%) or others (n = 11; 23.4%).

The most common location of sVTE was central veins (n = 34; 72.3%).

Seventeen of the patients with sVTE died, compared with 133 patients without sVTE (36.2% vs. 15%; P = .001).

Estimated mean OS was 133.1 ± 33.6 months in children with sVTE compared with 163.7 ± 4.8 months in those without sVTE (P < .0001). Researchers also estimated that patients with sVTE were significantly less likely to achieve 5-year OS (P = .007).

Estimated mean EFS also was inferior in patients with sVTE (112.7 ± 31 months vs. 148.7 ± 5.9 months; P < .001).

“We think that patients possibly at higher risk for death are more likely to be diagnosed with VTE,” Kulkarni said. “None of these deaths were directly related to VTE; we looked at survival from a standpoint of cancer, and not VTE–associated mortality. We do think there is a need to understand the drivers of the association of sVTE and inferior survival outcome so factors other than VTE–associated mortality are involved.” – by Alexandra Todak

Reference:

Forbrigger Z, et al. Abstract 393. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosure: The researchers report no relevant financial disclosures.

Perspective

Julia Jaffray, MD

Pediatric hematologists/oncologists have looked at the incidence of venous thrombotic events in our pediatric oncology patients, and we have compared incidence in patients with leukemia vs. brain tumors and other types of malignancies. There have been studies looking at VTE mortality risk in pediatrics in general, in which they’ve seen increased mortality rates with VTE, but there has not been a focus on oncology patients.

This is particularly important because we’re starting to focus more on pediatric VTE in general. These results may suggest that, rather than just saying a child needs to receive a blood thinner (anticoagulant) — which requires a few months of receiving shots and affects morbidity and quality of life — we should focus on preventing VTE because it is going to impact their mortality. It’s a very important topic of study to look at it.

It is tough to tease out where the increased mortality risk comes from. I have a feeling these kids are sicker and at high risk already for getting VTEs, plus possibly earlier mortality. If we can identify a really high-risk group and have them undergo prophylactic anticoagulation, perhaps we can take out one component that is adding to their increased mortality risk. For example, in children who are really sick, like those with congenital heart disease, if we can eliminate one risk factor and stop them from getting blood clots, maybe we could reduce their mortality risk.

There is not yet enough information to identify which patients are at high risk for VTE. There have been a few studies conducted in adolescents — because VTE is becoming a problem in all patient populations — and there are some ongoing studies trying to predict VTE risk in patients, but we don’t yet have data from big global (multi-institutional) studies. We are years away from figuring out who is at risk and how to prevent VTE, but our pediatric community is finally really trying to evaluate this, which is exciting.

One thing to consider is that this study has a high rate of symptomatic VTE — almost half of their population in pediatric cancers had symptomatic VTE. I’ve seen such a high rate when they are not symptomatic VTEs, when researchers are screening with ultrasound, but the symptomatic VTE rate is not usually that high. The reason the researchers may be seeing this unusually high VTE rate is because they are accessing another group’s database. It is difficult to evaluate other people’s databases, because you can’t go back to the patients’ charts and validate the data, but it would be interesting for this group to perhaps make their own database to really validify these data.

This study is a great starting point; however, it was conducted in a small part of the word, which may not be applicable to everywhere. This same group or another group of oncologists could take this same kind of thinking – does the VTE risk actually add to mortality in pediatric leukemia? — and broaden the question to a larger group of patients. It will take a deeper look to figure out how to predict and prevent VTE.

Julia Jaffray, MD

Children’s Hospital Los Angeles

Disclosures: Jaffray reports no relevant financial disclosures.