dc.description.abstract
This thesis presents the results of five studies that share a common bond; the analysis of organic complications (respiratory, renal and neurological) in a homogeneous cohort of recipients who received an Allo-HSCT-RIC at a single institution. The chosen scope is of particular interest to the extent that patients receiving this type of transplant are usually older, having more comorbidities, having received a greater number of previous treatments. This conditions might influence a higher risk of organic complications. Thus, the study of the organic complications could properly determine the Allo-HSCT-RIC’s tolerance in this specific group of patients. The first paper analyzed the development of pulmonary complications. The second analyzed respiratory viral infections and invasive pulmonary invasive aspergillosis (IA). The third paper evaluated the kidney complications after Allo-HSCT-RIC. The fourth paper was focused on neurological complications in the same cohort of patients.
Results: The first study included 188 recipients of Allo-HSCT-RIC and analyzed the predictive value of pulmonary function test (PFT) in pulmopnary complications (PC). The cumulate incidence of PC was 45% [95% confidence interval (CI.), 38–53%]. Multivariate analysis showed that TLC was significantly associated with PC, nonrelapse mortality (NRM) and overall survival (OS), (Hazard Ratio (HR) 4.2, 95% CI. 2–8.5; HR 3.8, 95% CI. 1.7–8.5; HR 2.3, 95% CI. 1.3–4.1, respectively, P = 0.01), while abnormal FVC had a negative impact on PPC and OS (HR 1.8, 95% CI. 0.98–3.6, P = 0.06 and HR 1.7, 95% CI. 1.1–2.6, P = 0.008). The second included 219 consecutive recipients of Allo-HSCT-RIC. The 4-year incidence of IA was 13% (95% CI, 4–24%). In multivariate analysis, risk factors for developing IA were steroid therapy for moderate-to-severe graft vs host disease (HR 2.9, P<0.03), occurrence of a lower respiratory tract infection (LRTI) by a respiratory virus (RV) (HR 4.3, P<0.01) and CMV disease (HR 2.8, P=0.03). The occurrence of IA had no effect on survival (P=0.5). The third manuscript include 188 Allo-HSCT-RIC recipients. The cumulative incidence of acute renal failure (ARF) at 1 year was 52%. The risk factors associated with ARF in multivariate analysis were: administration of MTX (HR 1.9, P =0.02), more than 3 lines of therapy prior to Allo-RIC (HR 1.8, P <0.01), diabetes mellitus (HR 2.1, P<0.01), and GVHD grade III-IV (HR 2.1, P =0.015). Patients who experienced ARF had lower 1-year overall survival (OS; 53% versus 74%, P<0.05). In the fourth, the author analyzes the characteristics, incidence and risk factors of neurological complications (NC) (both CNS and PNS) in the same patient population Alo-TPH-AIR and how they affect overall survival. The 4-year cumulative incidence of NC was16% (95% CI, 11-23). CNS complications included nonfocal encephalopathies in 11 patients, meningoencephalitis in 5 patients, and stroke or hemorrhage in 4. PNS complications consisted of 5 cases of mononeuropathies and 3 cases of polyneuropathies. Drug-related toxicity was responsible for 10 of the 31 events (32%) (8 caused by CsA). Overall, patients presenting NC showed a trend for higher 1-year nonrelapse mortality (NRM) (37% versus 20%, P=0.08). In patients with CNS involvement, 1-year NRM was significantly worse (42% versus 20%, P5.02). CNS NC also had a negative impact on 4-year overall survival (OS; 33% versus 45%, P5.05).
Conclusions: The organic complications in the Allo-HSCT-RIC setting were diverses, frequent but did not seem more common compared to those reported in the myeloablative Allo-HSCT. The identification of several risk factors for these complications opens a window to explore further protocol modifications by reducing the conditioning doses or the application of prophilactic actions for patients at higher risk of organic complications and NRM.
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