Shifting From Eligibility to Optimization of Transplant in Older Adults With Hematologic Malignancies

In an article published in Blood Advances, researchers from the University of Chicago reported efforts to optimize outcomes after hematopoietic cell transplantation (HCT) in older patients with hematologic malignancies, including establishing a multidisciplinary team approach to transplant guided by multidimensional geriatric assessment. Compared with historic controls, patients who were evaluated in this multidisciplinary team clinic experienced shorter inpatient stays, fewer nursing home admissions, and better early survival rates.

“Our study shifted the approach of performing geriatric assessment from stratification or clearance alone to one of creating avenues for optimization and, ultimately, better outcomes,” the study’s lead author Benjamin A. Derman, MD, of the University of Chicago, told ASH Clinical News. “A geriatric assessment remains an essential component to both uncover vulnerabilities and identify patient strengths.”

Age, comorbidity rating, and performance assessments have traditionally been used to describe the fitness of older adults and estimate their likelihood of surviving HCT, Dr. Derman and co-authors explained. However, to gain a more complete picture of how patients will fare after HCT and cellular therapies, the researchers developed a Transplant Optimization Program (TOP). This approach involved a multidisciplinary group of providers who performed comprehensive, cancer-specific geriatric assessment to evaluate and enhance older patients’ resilience and functioning.

Per study protocol, beginning in March 2013, transplant physicians at the University of Chicago referred allogeneic HCT candidates aged ≥60 years and autologous HCT and adoptive T-cell therapy candidates aged ≥70 years to TOP. At the TOP clinic, patients undergo approximately 5 hours of evaluation by providers, including an HCT advanced practice practitioner, an HCT physician, a geriatric physician (or geriatric oncologist), an infectious disease physician, a physical and/or occupational therapist, a dietitian, and a social worker.

The members then make patient-specific recommendations for evaluation and supportive care (e.g., ensuring follow-up on comorbidities after HCT, prescribing devices to minimize fall risk, or conducting pretransplant family meetings to widen social support network) to optimize outcomes after either HCT or cellular therapy. Finally, they decide whether a patient can achieve “acceptable resilience” and proceed with the planned procedure or whether the procedure should be declined or deferred until established metrics are met.

The geriatric assessment tool used to determine a patient’s physiologic age assessed the following domains:

  • functional status
  • comorbidities
  • cognitive abilities
  • behavioral conditions
  • social and economic support
  • nutritional status
  • polypharmacy

Participants also completed the Short-Form 36 and Health Status Survey to assess patient-reported quality of life.

A total of 247 patients (median age = 67.9 years; range = 43-83 years) were evaluated through the program. Most patients were reviewed to see whether they were candidates for allogeneic HCT (n=149; 60%), while 91 (37%) were being assessed prior to autologous HCT, and 7 (3%) for adoptive T-cell therapy.

Ninety-five of the 247 evaluated patients (38%) either deferred or declined transplant, owing to poor health status (73%), disease status (23%), insufficient social support (3%), and patient preference (1%). Most patients (80%) recommended by the multidisciplinary clinic to proceed with their planned procedure did so: 85 received allogeneic HCT, 31 received autologous HCT, and 5 received T-cell therapy. Only 3.3% of eligible patients who eventually underwent HCT did not attend the clinic for logistical reasons.

Among the patients who received autologous HCT, the median length of inpatient hospital stay was 14 days (range = 11-22 days) from time of HCT infusion. There were no recorded deaths during the initial hospitalization. Only 1 death occurred within 100 days of transplant; this death was due to progressive primary central nervous system lymphoma. Overall, the 1-year overall survival and nonrelapse mortality rates were 97% and 0%, respectively.

In the group who received allogeneic HCT, outcomes were compared with 74 similar patients who underwent transplant in the pre-TOP period between 2005 and 2012. The researchers observed that survival steadily improved after implementation of TOP: Compared with pre-TOP patients, the hazard ratio (HR) for death within 1 year of transplant for the initial TOP group (during the first implementation stages in 2013-2014) was 0.78 (95% CI 0.43-1.40; p=0.399). In the later TOP group (between 2015 and 2017), the HR was 0.37 (95% CI 0.21-0.65; p=0.0005).

The authors added that, in the allogeneic HCT group, length of hospital stay was shorter in the TOP period (14 days vs. 19 days; p<0.001) and fewer patients were discharged to a nursing facility (1% vs. 18%; p=0.0043) or re-admitted to the hospital within 100 days (46.5% vs. 59%; p=0.2).

“If our findings can be confirmed, I believe we can open the door more widely for older patients to potentially benefit from stem cell transplantation,” said Dr. Derman. “We need to view this approach of a geriatric assessment−guided evaluation as an indispensable tool and not an obstacle for our older patients.”

Limitations of the study were its retrospective nature, the recruitment of patients from a single center, and the lack of a concurrent control group.

Dr. Derman and authors stated that additional research is needed to identify the minimum core elements of a geriatric assessment−guided approach. “One concern expressed by physicians has been lack of training and/or staff to administer the geriatric assessment,” he noted. “The patient-completed portion can be completed on paper or electronically, while these bedside functional and cognitive tests require very basic training of a nurse, coordinator, or medical assistant.”

Requiring geriatric assessment as part of the transplant work-up process for older adults, concluded Dr. Derman, has made the multidisciplinary clinic feel routine for both patients and clinicians. “This may help reduce the stigma that patients may feel that they require an evaluation, and we think it helps clinicians in the discussion about the risks and benefits of transplant,” he said.

The authors report no relevant conflicts of interest.

Reference

Derman BA, Kordas K, Ridgeway J, et al. Results from a multidisciplinary clinic guided by geriatric assessment before stem cell transplantation in older adults. Blood Adv. 2019;3:3488-98.