Avascular Necrosis (AVN) Outcomes in Allogeneic Stem Cell Transplant Recipients

Background: Avascular necrosis (AVN) is a complication with high morbidity which impacts quality of life following allogeneic stem cell transplant (alloSCT). The incidence varies from 4.3 to 11.8% in reports. Physical function, patterns of opioid use and outcomes with surgical management in alloSCT recipients is not well described. There is inconsistency in offering joint replacement surgeries to alloHCT recipients, given risks of complications. Our study aimed to evaluate physical function, patterns of opioid use and 3- month survival outcomes with surgical management in alloSCT recipients.

Methods: This retrospective review of adult patients at the University of Kansas Cancer Center used the i2b2 query tool to identify alloSCT recipients from 2003-2021, who also had an AVN. Baseline demographics, disease and transplant-related details, graft versus host disease (GVHD) details, joint replacements, and opioid use patterns were reported. Time to onset of AVN was calculated in years, with high-dose steroids defined as prednisone 60mg/day or higher. This dose cut-off was chosen as “high dose” instead of calculating steroid doses in mg/kg, given changes in weights during the period of the review.

Results:

Demographics: We identified 123 patients in this 18-year period who met criteria, representing 8% of all alloHCT recipents. The median age was 67 years (54-82). The majority were males (54%) and Caucasian (79%). Nine patients (7.3%) had pre-existing AVN as comorbidities at transplant, and 4.9% had pre-existing joint replacements and 41% had a history of opioid use. Diseases included acute myeloid leukemia (40%), acute lymphoid leukemia (14%), lymphoma (14%), myelodysplasia (10%), sickle cell disease (2%), multiple myeloma (2%) and other diseases (19%). The majority had matched unrelated donor transplant (58%), followed by matched related donor (34%), (5.7%) haploidentical (5.7%), and 2.4% other sources. Conditioning intensity was mostly myeloablative (67%), with 30% of patients receiving reduced-intensity conditioning and 3 (2.4%) other conditioning. Total body irradiation was used for 40% of patients. For GVHD prophylaxis, 75% of the patients received Tacrolimus /Methotrexate, 16% post-transplant Cytoxan (PTCy)-MMF-Tacrolimus, and 9% other prophylaxis. Acute GVHD (aGVHD) occurred in 75% of patients, with 30% experiencing ≥ grade 3 aGVHD. The median duration of aGVHD was 2.5 months, and 80% received high-dose steroids. Chronic GVHD (cGVHD) incidence was 85%, with 55% having ≥ grade 3 cGVHD and a median duration of 26 months. 78% of cGVHD patients received high-dose steroids.

At Diagnosis of AVN: At onset of AVN diagnosis, 59% patients used opioids. The median time from alloHCT to AVN diagnosis was 2 years (0.1-12). 50% had involvement of ≥1 joint. At AVN diagnosis, of 81 patients with available ECOG scores, 41% had a score of ≥2. Almost half the patients (49%) had active GVHD, 44% were using steroids, 20% ruxolitinib, 1.6% belumosudil, and 59% were using opioids.

Surgical Intervention: 63 (51%) patients underwent joint replacement surgery. Of these, 62% had replacement of single hip, 27% had replacements of bilateral hips, 3% bilateral knees, 5% single knee, and 4% upper extremity, and 1% bilateral shoulder joints. 40% of these patients had full clinical mobility post-surgery.

At 3 months post-op, 18% used steroids, 8.9% ruxolitinib, 0.81% belumosudil. At 3 months post-op, 39 patients with available ECOG scores, 62% had a score of 0-1. Opioid use after joint replacement decreased to 67%.

Mortality: The overall mortality rate in this cohort was 19%. Top causes included infection (n=4), disease relapse (n=5), respiratory failure (n=2), cardiac arrest (n=1), and GVHD (n=5). There were 0 deaths within 3 months of surgery.

Conclusion: This is the largest report in last decade on outcomes with AVN in adult alloHCT recipients. Our study highlights the morbidity, low performance status and high opioid use associated with AVN even after joint replacement. Surgical management is an important treatment option, and our data highlights that even for patients with ongoing GVHD, the 3 months post op survival was 100%. While efficacy may be variable, joint replacement appears to be a safe modality and should be considered for all alloHCT recipients with AVN.

Mushtaq:Iovance Biotherapeutics: Research Funding. Abdelhakim:Iovance Biotherapeutics: Research Funding. Shune:BMS: Membership on an entity's Board of Directors or advisory committees; Norvatis: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Lutfi:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Sung:Clasado: Other: Research product; Enterome: Research Funding; Janssen: Consultancy; Seres: Research Funding; DSM/iHealth: Other: Research product; Geron: Consultancy; Targazyme: Consultancy; Acrotech: Consultancy; BlueSpark Technologies: Other: Research product; Novartis: Research Funding; Merck: Research Funding. Abhyankar:CSL Behring, Miltenyi Biotec.: Research Funding; Incyte: Consultancy. McGuirk:Sana technologies: Consultancy; Kite: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Caribou bio: Consultancy; Legend biotech: Consultancy; Autolus: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy; BMS: Consultancy. Ahmed:Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.