Avascular Necrosis(AVN) and Surgical Intervention In Pediatric Acute Lymphoblastic Leukemia(ALL): A Retrospective Cohort Analysis From The Pediatric Health Information Systems (PHIS)
Authors: Heneghan Mallorie B , Rheingold Susan R. , Li Yimei , Seif Alix E. , Huang Yuan-Shung , Fisher Brian T. , Aplenc Richard 
Published: October 2019

Abstract
Cure rates for acute lymphoblastic leukemia (ALL) have improved dramatically, but the incidence of avascular necrosis (AVN) has increased over the past decade. No national administrative data on the incidence of AVN or surgical therapies for AVN exist. We sought to define the incidence of AVN and AVN surgical interventions after treatment for ALL in a national administrative data set.
The Pediatric Health Information System (PHIS) is an administrative database including ICD-9 discharge diagnosis, procedure codes, and billing data for daily resource utilization from 43 free standing pediatric hospitals in the US. This study identified patients with an associated ICD-9 code for AVN (733.4X) in a cohort previously established by our group to have newly diagnosed ALL.
Between January 1999 and September 2011 242(2.25%), of the 10,729 patients in the ALL cohort had at least one admission with AVN with a mean time of 1.6 years from first ALL treatment until a hospital admission with an associated AVN diagnosis. Table 1 compares demographic and treatment characteristics between ALL patients with and without AVN diagnosis. Age 10-18.99 years and prednisone exposure during ALL induction were associated with increased incidence of AVN. Dexamethasone exposure was associated with a decreased incidence of AVN. AVN diagnosis was associated with a statistically significant increase in mortality. The rate of surgical intervention was 13.7%. The type and location of surgical intervention are reported in Table 2.Table 1Demographicsn (%)ALL Patients w/o AVN (n=10,487)ALL Patients with AVN (n=242)PAge<.0001M <1 year295(2.8)0(0.0) 1 to <10 years7,515(71.7)65(26.9) 10 to <19 years2,557(24.4)169(69.8) ≥ 19 years120(1.1)8(3.3)Sex0.2009 Male5,893(56.2)126(52.1) Female4,594(43.8)116(47.9)Race0.1219 White7,927(75.6)193(79.8) Black774(7.4)17(7.0) Asian321(3.1)5(2.1) Native American121(1.2)6(2.5) Other1,019(9.7)14(5.8) Missing325(3.1)7(2.9)Region0.0527 Midwest2,742(26.2)63(26.0) Northeast1,042(9.9)19(7.9) South3,478(33.2)67(27.7) West3,225(30.8)93(38.4)Medication use during induction*Prednisone4,252(40.6)152(62.8)<.0001Pegasparaginase6,540(62.4)150(62.0)0.9041Dexamethasone6,378(60.8)104(43.0)<.0001Concurrent Dex & Pred600(5.7)17(7.0)0.3892Death649(6.2)27(11.2)0.0017** Induction is defined as 60-day period from ALL admissionTable 2Surgical Interventions during first AVN admissionDescriptionPatient countExcision of lesion or tissue of femur10Bone graft of femur9Arthroscopy of knee5Total hip replacement4Arthrotomy of knee3Excision or destruction of lesion of hip joint3Wedge osteotomy of femur2Excision of lesion or tissue of tibia and fibula2Excision of other bone for graft2Bone graft of tibia and fibula2Arthrotomy of hip2Repair of knee2Partial hip replacement2Excision of elbow joint2Excision of lesion or tissue of humerus1Excision of femur for graft1Partial ostectomy of femur1Bone graft of humerus1Arthrotomy of elbow1Arthrotomy of other specified site1Arthroscopy of hip1Excision or destruction of lesion of elbow joint1Excision or destruction of lesion of knee joint1Excision or destruction of lesion of ankle joint1
To our knowledge, this is the first report using a national administrative database to determine the incidence of AVN in ALL. As expected, age was associated with AVN risk. The association of increased in-hospital mortality was unexpected and warrants further study. Surgical interventions typically involved lower extremity procedures. Work is ongoing to define the rates of subsequent surgical procedures and complication rates. These data demonstrate the feasibility of using administrative data to study surgical interventions for patients with AVN.

Disclosures:
Rheingold: Novartis: Research Funding.