Clinician Adherence to Screening and Preventive Practices for Non-Malignant Late Effects Among Allogeneic Hematopoietic Cell Transplant Survivors in the United States

Background: Survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for treatment-related late effects. Published recommendations for screening/prevention of late complications have been available (Majhail, BBMT 2012); however, their utilization by clinicians practicing at U.S. transplant centers (TC) is unknown. We established the Real-World Assessment of Long-term Follow up in HCT (REAL-HCT) collaboration to examine clinician adherence to key screening/preventive practices across U.S. TC. We report our findings related to non-malignant late effects (NMLEs).

Methods: This retrospective study included pts of any age who received first or greater HCT for a hematologic malignancy between January 1, 2016 to December 31, 2016, with any conditioning regimen, donor/graft, and were alive and disease-free at ≥3 yrs post HCT. Prior autologous HCT or CAR-T was allowed but not receipt of a subsequent HCT for graft failure within 3 yrs post HCT. Patient, disease and transplant characteristics, and tests related to bone health/endocrine, metabolic and renal systems, and dental health were abstracted from EMR. “Adherence” to a specific screening test was defined by evidence of a clinician order or test completion between 1-3 yrs post HCT. Two separate multivariable logistic regression models were created to assess the factors associated with NMLEs screening. Model 1 included a best subset of pt and HCT factors [age, sex, race, ethnicity, highest education, preferred language, disease diagnosis, HCT-CI score, conditioning intensity, TBI use, history of aGVHD and/or cGVHD, high-dose corticosteroid (CS) exposure, and primary post HCT survivorship provider (SP)]. Model 2 consisted of TC factors: center type (academic vs. non-academic), TC annual volume, availability of an LTFU/survivorship clinic (L/SC), and provision of a survivorship care plan (SCP) to pt, referring heme/onc provider (HOP) or PCP.

Results: The population included 440 pts [≥ 18 yrs (n=355); <18 yrs (n=85)] from 19 TC. The median age was 46 yrs (range, 0-77), 58% were male, 82% were White, 12% were Hispanic/Latino ethnicity, and English (88%) was the preferred language. The most common HCT indications were AML (43%) and ALL (22%), and a myeloablative regimen and TBI was used for 71% and 42% of pts, respectively. Approximately half of the pts had HCT-CI score <3 (49%), aGVHD (57%) and/or cGVHD (53%) or received CS (51%). The primary HCT team (68%) and PCP (59%) were reported as the most common post HCT SP. Among 19 TC, less than half reported having an L/SC (47%), SCP routinely given to the pt (32%), referring HOP (37%) or PCP (47%) during 2016-2019.

Clinician adherence to NMLE screening practices were as follows: DEXA 44%, vitamin D level 67%, HbA1c 39%, fasting glucose 38%, lipid panel 67%, thyroid test 72%, renal test 71%, and dental exam 56%. Increasing patient age [OR 1.03, 95% CI 1.02-1.05, p<0.001], non-White race [3.24, 1.57-6.67, p=0.001], TBI [2.66, 1.52-4.68, p<0.001], and cGVHD [3.29, 1.89-5.73, p<0.001] were associated with increased DEXA screening while a non-myeloablative (NMA) regimen [0.38, 0.19-0.76, p=0.006] was associated with less adherence to DEXA testing. Only TBI was predictive for an increase in adherence to vitamin D testing [2.50, 1.45-4.31, p<0.001]. An NMA regimen [2.53, 1.44-4.48, p=0.001] and cGVHD [1.91, 1.17-3.11, p=0.01] were associated with HbA1c testing, and increasing age [1.02, 1.01-1.03, p=0.01] for fasting glucose screening. TBI and cGVHD were associated with increased adherence to lipid [TBI: 1.82, 1.08-3.05, p=0.02; cGVHD: 1.87, 1.15-3.03, p=0.01] and renal [TBI: 2.44, 1.37-4.35, p=0.002; cGVHD: 1.93, 1.06-3.52, p=0.03] testing. Provision of a SCP to pt was associated with less adherence to DEXA testing [0.52, 0.31-0.88, p=0.01]. Higher annual TC volume was associated with clinician adherence to all NMLE screening tests.

Conclusion: This is the first report of clinician adherence to recommended screening/preventive guidelines for HCT survivors across 19 TC in the U.S. Less than half of pts were screened for bone density and diabetes while higher adherence to lipid, thyroid, kidney function, and oral health was observed. Several factors were associated with adherence, and these findings will guide the development of interventions to improve clinician adherence to screening/preventive practice guidelines.