7 Moderate/Severe Grade of Chronic Graft Versus Host Disease and Younger Age (Less Than 45 Years Old) Are Risk Factors for Avascular Necrosis in Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Track: BMT Tandem "Scientific" Meeting
Wednesday, February 11, 2015, 4:45 PM-6:45 PM
Seaport Ballroom ABC (Manchester Grand Hyatt)
Sita D Bhella, MD , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Jieun Uhm, MD , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Naheed Alam, MBBS , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Vikas Gupta, MD , The Elizabeth and Tony Comper MPN Program, Princess Margaret Cancer Center, Toronto, ON, Canada
John Kuruvilla, MD , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Jeffrey H Lipton, MD, PhD , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Hans Messner, MD, PhD , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Matthew Seftel , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Dennis (Dong Hwan) Kim , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Audio File Recorded Presentation

Background: Avascular necrosis (AVN) is a debilitating complication of allogeneic hematopoietic cell transplantation (alloHCT).

Methods: A retrospective review of 845 consecutive patients ≥ 17 years of age who underwent alloHCT at Princess Margaret Cancer Centre from 2002 to 2013 was conducted to determine the incidence and risk factors for AVN.  Univariate and multivariate analyses were conducted using EZR using cumulative incidence method considering competing risk.

Results: 48 cases of AVN were identified. Median follow up duration among survivors was 3.4 years.  Frequent locations of AVN were: hip(n=37), shoulder(n=13), knee(n=13), ankle(n=2), wrist(n=1), and elbow(n=1).

Incidence of AVN was 6.3% (95% CI 4.6-8.5%) and 8.9%(6.5-11.8%)  at 4 and 8  years respectively. Risk factor analysis revealed the following were significantly associated with higher risk of AVN in a univariate analysis:  age < 45(p=0.0039), grade 3-4 acute GVHD(vs grade 0-2; p=0.054), development of chronic GVHD(vs no chronic GVHD; p=0.000016), reduced intensity conditioning(vs myeloablative; p=0.017) and a diagnosis of acute leukemia(vs others; p=0.045).  Multivariate analysis confirmed two risk factors: 1) younger age(≤45 years), 9.0% vs 4.4% (p=0.011, hazard ratio (HR) 2.134, 95% CI [1.186-3.843]) and 2) chronic GVHD development, 10.2% vs 1.4% (p=0.0002, HR 5.762, 95% CI [2.289-14.510]).

Incidence of AVN was 15.7% in patients with moderate to severe grade chronic GVHD and 3.6% in those with mild grade GVHD(p=0.00015).

A risk score model was generated assigning 1 score to each risk factor and summing the score thus dividing into three groups: low(score 0, n=349, 41.3%), intermediate(score 1, n=379, 44.9%) and high risk(score 2; n=116, 13.7%). This risk score could stratify the patients according to AVN risk (p=2.49x10-10). The risk of AVN was 1.5%(0.5-3.6%) in low, 6.2%(3.7-9.5%) in intermediate and 20.8%(13.0-29.9%) in high risk group.

Conclusions: Moderate/severe grade of chronic GVHD and younger age(≤45 years old) are key risk factors for AVN following allogeneic HCT.

Figure 1: Incidence of avascular necrosis according to the risk score based on the development of chronic GVHD and age (45 years old or younger)

Disclosures:
Nothing To Disclose
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