Impact of Neurological Complications on the Overall Survival in Allogeneic Stem Cell Transplantation
Authors: Ibarrondo Paloma , Bermudez Arancha , Ormazabal Irati , Yáñez Lucrecia , Montes-Gaisán Carmen , De Miguel Carlos , Richard Carlos , Insunza Andrés , Conde Eulogio 
Published: October 2019

Abstract

INTRODUCTION: Neurological complications (NC) are frequently reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but their incidence, characteristics and impact on the overall survival are not well defined. For this reason, we retrospectively analyzed our experience.
PATIENTS AND METHODS: A retrospective study of 506 allo-HSCTs performed in our center from January 2000 to September 2013, including 336 myeloablative and 170 non-myeloablative, 280 sibling and 226 unrelated, and 397 matched and 109 mismatched. All neurological complications, according to NCCN classification, were included.
RESULTS: Seventy seven patients developed neurological complications. Their median age was 48 years (5-70) and 43 (56%) were male. Underlying diseases were Acute Leukemia (34), Myelodysplastic Syndrome (11), Multiple Myeloma (9), Non-Hodgkin Lymphoma (7), Myeloproliferative disease (7), Bone marrow Aplasia (5), Hodgkin Lymphoma (2) and other (2). Thirty eight patients (49.4%) were in CR, 14 (18.2%) in PR, 16 (20.8%) had a refractory disease and 9 (11.7%) had a stable disease. Median preceding treatments were 2 (0-10), including in 24 (31.2%) a preceding HSCT (19 autologous and 5 allogeneic). Fifty seven patients (74%) had received a myeloablative (MA) regimen (14 TBI and 43 chemotherapy). Stem cell source was bone marrow, peripheral blood and umbilical cord blood in 53, 20 and 4 patients, respectively. The donor was unrelated in 47 patients (61%) and mismatched in 25 (32.5%). A calcineurin inhibitor (Cyclosporine or Tacrolimus) was included in all cases as GVHD prophylaxis, combined with Methotrexate (37), Mycophenolate (35) and Prednisone (5).
Seventy seven patients developed 81 NC (74 central and 7 peripheral). The global incidence was 16%, being more frequently reported in unrelated (21.4% vs. 11.4%, p=0.002) or mismatched (24.5% vs. 13.5%, p=0.007) allo-HSCT. Within the group who developed central NC, 48 patients (65%) had an early onset (less than 100 days after HSCT), which consisted of impairment of consciousness (36 patients), focal syndrome (22 patients) or seizures (16 patients). The etiology was toxic-metabolic in 32 patients (posterior encephalopathy in 10 cases), infectious in 21 (viral 10, fungal 6, bacterial 5), vascular in 12 (Thrombotic Thrombocytopenic Purpura 6, hemorrhagic 4, ischemic 2) and relapse in 9. Within the group who developed peripheral NC, 5 patients (71.5%) had a late onset, which consisted of polyneuropathy. The etiology was infectious in 2 cases (viral) and immune in 5 cases.
Twenty four patients are alive (31.2%) with a median follow-up of 10 months (0-110). Excluding relapses, NC was a direct or indirect cause of death in 24 patients (54.5%), due to viral (9) and fungal (8) infections, above all. The development of a NC, specially in the central nervous system, had a negative impact on the overall survival (17 months vs. 40 months; p=0.001) (figure 1)
CONCLUSIONS: In our series, the incidence of NC in the setting of allo-HSCT was 16%, being more frequently found with unrelated and mismatched donor. They were associated with high mortality, having a negative impact on the overall survival and becoming a direct or indirect cause of death in more than half of cases.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.