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Neurological Complications Involving the Central Nervous System After Allogeneic Hematopoietic Stem Cell Transplantation During a Period of Evolution in Transplant Modalities: A Cohort Analysis

Colombo, Anna Amelia MD; Marchioni, Enrico MD; Diamanti, Luca MD; Di Matteo, Angela Maria MD; Baldanti, Fausto MD; Furione, Milena MD; Cazzola, Mario MD; Ferretti, Virginia Valeria PhD; Pascutto, Cristiana PhD; Alessandrino, Emilio Paolo MD

doi: 10.1097/TP.0000000000001257
Original Clinical Science—General

Background Neurological complications (NC) after hematopoietic stem cell transplantation (HSCT) are rare events. The evolution of transplant procedures has resulted in improved survival and has allowed elderly patients or those with comorbidity to receive an HSCT. The risk of NC in these patients has still not been well defined. Therefore, we carried out an observational study to estimate the occurrence and identify the risks associated with NC.

Methods The study cohort included 452 adult-allogeneic HSCT recipients, transplanted from 1997 to 2012. The median follow up was 1.3 year (0-15.7). A myeloablative regimen was used in 307 patients. Two hundred patients were grafted from matched unrelated donor (MUD), of these, 129 (64.5%) received an in vivo T-cell depletion.

Results Out of 452 patients, 30 (6.6%) developed NC. Infections were the most frequent causes of NC (30%). Overall survival decreased in patients developing NC (P < 0.001). Univariate survival regression on the cumulative incidence of NC identified period of transplant, linear trend between 4-year periods (1997-2012) (P < 0.001), MUD (P < 0.001), and recipient's age (P = 0.034) as significant risk factors. In multivariate analysis, period of transplant (P < 0.001) and MUD (P = 0.004) remained significant independent risk factors. Matched unrelated donor recipients showed a 3.8-fold elevated risk of developing NC.

Conclusions Analysis highlights a temporal trend of incidence of NC that progressively increased over time and confirms a strong association between donor type and risk of NC. Our observations suggest that, although relatively uncommon, NC after allo-HSCT, may become more frequent due to the improved overall survival in recent years.

The authors report in an observational study of incidence and risk factors of neurological complications in patients receiving an hematopoietic stem cell transplantation. While it remains an uncommon complication, its incidence might be growing with improving results overtime. Donor type is the main risk factor identified.

1 Transplant Bone Marrow Unit, Department of Hematology Oncology Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

2 Istituto Neurologico Nazionale, IRCCS “C. Mondino”, Pavia, Italy.

3 Neuroscience Consortium, University of Pavia, Monza Policlinico and Pavia Mondino, Pavia, Italy; C. Mondino National Neurological Institute, Pavia, Italy.

4 Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

5 Molecular Virology Unit, Virology and Microbiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

6 Department of Hematology Oncology Diseases Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Received 11 October 2015. Revision received 21 March 2016.

Accepted 22 March 2016.

All authors edited and approved the report for final submission.

The authors declare no funding or conflicts of interest.

A.A.C., C.P., V.V.F. are responsible for research design and wrote the article. A.A.C., C.P., and V.V.F. carried out the data collection, analysis, and interpreted results. C.P. and V.V.F. carried out statistical analysis with help from A.A.C. and E.P.A. E.M. L.D., A.M.D.M., F.B., and M.F. carried out the research. M.C., E.P.A. helped in the article and revised it.

Correspondence: Anna Amelia Colombo, Unità Trapianti di Midollo Osseo, Fondazione IRCCS Policlinico San Matteo, Piazzale Golgi 19 27100 Pavia, Italy. (

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