Patients Reported Outcomes (PROs) Are Still Unsatisfactory Among AML Long-Term Survivors: The Impact of Chronic GvHD in a Prospective Study on 15 Years Transplant Activity

Background Acute myeloid leukemia (AML) represents the main indication to allogeneic hemopoietic stem cell transplantation (HSCT) and improvement of overall survival (OS) has been a major achievement provided by this treatment option. Unfortunately, graft-versus-host disease (GvHD) still represents the main complication affecting HSCT, increasing transplant related mortality (TRM) and worsening quality of life (QoL). While the mortality impact of GvHD is well recognized, the impact on QoL is still poorly characterized. The collection of patients reported outcomes (PROs) in routine practice is limited. The most common PRO measures used are the Lee chronic GvHD (cGvHD) symptom scale, the FACT-BMT and the NIH Form B.

We aimed to analyze the perception of QoL in AML long-term survivors after HSCT according to the FACT-BMT scale.

Methods Our analysis consisted of a prospective single-center study in a cohort of 510 patients affected by either de novo AML or secondary AML and treated with HSCT between January 2004 and December 2019 at our Institute. Data were censored April 1^st, 2022. The follow-up was performed according with our Long Term Follow Up institutional program.

The FACT-BMT questionnaire was administered as a paper questionnaire. A written consent was given in accordance with the Declaration of Helsinki.

Results Overall, the 2-year OS was 51% and the 5-year OS for patients alive at 2 years was 80% (95% CI - 74-85%). For patients alive and in complete remission at 2 years post-HSCT the probability of 5-year OS was 84.5% (95% CI - 78-89,2%), the 5-year TRM 6.3% (95% CI - 0.5-23.3%) without evidence of a "plateau” effect, while the 5-year relapse incidence was 12.91% (95% CI - 4.91-24.91%) reaching a plateau.

Both univariate and multivariate analysis showed that age and status of disease at transplant have a significant impact on long-term survival; univariate analysis instead did not show any impact of the year of treatment and of GvHD prophylaxis.

Overall, among 195 patients alive and in complete remission at last follow-up, 70 patients completed the questionnaire. PROs analysis confirmed a better perception of QoL for patients that did not experience cGvHD versus patients affected by cGvHD; no difference emerged according to age and time after transplant. Of note, patients affected by cGvHD showed worst functional well-being (p 0.0293), worst physical well-being due to side effects (p <0.0001), less satisfaction about the appearance of their body (p 0.0152) and less satisfaction about their sexual life (p 0.0445 - 10 patients preferred not to answer). Overall, among patients without cGvHD, other side effects after HSCT were not perceived worse than they had imagined, while among those with cGvHD, most patients complained about this perception (p 0.0009).

Conclusion QoL in patients cured from AML by HSCT is still far from being satisfactory, most of all among patients with cGvHD. Dedicated counselling and support to address QoL is a relevant unmet medical need. Systematic evaluation of PROs will optimize the care of HSCT survivors, potentially enhancing patient-provider communication and allowing the development of measure for both prevention and treatment of GvHD.

Ciceri:Kite Pharma: Consultancy.