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Treatment-related hypertension, kidney injury are undertreated in kids with leukemia

By: Neil Osterweil

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05/18/17

At ASPHO 2017

MONTREAL – Hypertension is a frequent, but underrecognized and undertreated, complication of chemotherapy for acute lymphoblastic leukemia (ALL), the most common childhood malignancy, investigators in a single-center U.S. study reported.

Additionally, there is a “concerningly high” incidence of acute kidney injury among children and young adults who undergo multiagent chemotherapy for acute myeloid leukemia (AML), said the authors of a study conducted in Canada.

Both studies were reported in a scientific poster session at the annual meeting of the American Society for Pediatric Hematology/Oncology.

Hypertension in ALL

Although standard induction regimens for childhood ALL contain high-dose steroids, which are known to be associated with increased risk for hypertension, the incidence of hypertension throughout induction, consolidation, and maintenance for ALL in children has not been adequately evaluated, according to Andrew S. Freiberg, MD, and his colleagues at Penn State Children’s Hospital in Hershey, Penn.

To address this situation, they looked at blood pressure readings taken during therapy for ALL in 36 pediatric patients treated at their center in 2004 and 2005. They calculated daily blood pressure averages for each patient and categorized the averages as normotensive, prehypertensive, or stage 1 or stage 2 hypertension. The number of days in which each patient’s average blood pressure readings fell into one of the categories was recorded and arranged by treatment phase, either induction, quarter (Q) 2 (months 4-6 ), Q3 (months 7-9) or Q4 (months 10-12).


“The incidence of hypertension was much higher than the under 5% expected for a healthy pediatric population,” the investigators found.


Of 562 total readings taken during induction, 56% were in the normo- or prehypertensive range, but 30% were classified as stage 1 and 14% as stage II hypertension.


The combined percentage of stage 1 and 2 readings declined slightly over the year from 44% during induction to 35% during Q4 “but remained well above expected for the pediatric population,” the investigators reported.


Despite the high incidence, “I was surprised at how few of the patients with hypertension we actually treated,” Dr. Freiberg said in an interview.


Just 3 of the 36 patients studied received treatment for hypertension, he said, possibly because clinicians assumed that the effect was steroid related and transient.


“Now that we’re paying attention, however, we’re treating more of these patients,” Dr. Freiberg said.


The electronic record system used at his institution now alerts clinicians to hypertensive episodes during treatment, he added.

Kidney injury in AML

Like Dr. Freiberg and his colleagues, Liezl du Plessis, MBChB, from the British Columbia Children’s Hospital in Vancouver, Canada, and her colleagues were similarly taken aback when they looked into the incidence of acute kidney injury (AKI) in children and adolescents undergoing multidrug chemotherapy for AML.

“Chemotherapy agents that are used in acute myeloid leukemia are not considered to be nephrotoxic, so it was quite alarming to us to see that there is such a high rate of kidney injury in these patients,” Dr. du Plessis said in an interview.

Her group conducted a retrospective cohort study of 53 children and young adults treated with chemotherapy for de novo AML from 2005 through 2016. They defined AKI according to Kidney Disease Improving Global Outcomes (KIDGO) criteria.


They found that 34 of the 53 patients (64%) had AKI, with 11 patients having stage 1 (rise in serum creatinine of 1.5 or more times the baseline level), 11 having stage 2 (SCr 2 or more times baseline), and 12 having stage 3 AKI (SCr 3 or more times baseline or the need for dialysis).


Creatinine changes were counted only if they occurred within 7 days from nadir to peak.


AKI occurred in all chemotherapy cycles, with severe injury having the highest frequency in cycle 1.


In a logistical regression model, factors significantly associated with risk for AKI were male sex (odds ratio, 0.2; P = .03) and age 10 years or older (OR, 17.3; P less than .01). Neither sepsis nor aminoglycoside or vancomycin use for more than 3 days was significantly associated with risk for AKI, however.


“I think people need to realize that many of these injuries are happening on the oncology ward, and some of these kids may not even look acutely unwell, so people need to take note.” Dr. du Plessis said.


She recommended curtailing use of nephrotoxic agents whenever possible, and emphasized that clinicians need to document AKI in the medical record.


“A big portion of our AML population goes on to bone marrow transplant, and that is known to be a high risk for further kidney injury. So, I think it would be important to know that before your patient goes for his transplant that he already has certain toxicities and organ injury, so that you can limit things like fluids and get the nephrology team on board to help with the management of these patients,” she said.


The study by Dr. Freiberg was supported by the Four Diamonds Fund. The study by Dr. du Plessis was internally funded. The investigators for each study reported having no relevant financial disclosures.


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