Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Abstract

Central nervous system (CNS) complications have been described in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Cerebrospinal fluid (CSF) analysis is included in the diagnostic workup in patients with neurological symptoms after alloHCT. CSF donor-recipient chimerism analysis usually is not used to evaluate patients with neurological complications after alloHCT. To assess the potential contribution of CSF donor-recipient chimerism in patients with neurological complications, we analyzed 85 CSF samples from 50 patients with neurological complications after alloHCT. After alloHCT, 21 patients showed the presence of recipient-derived DNA. In 13 of these patients, recurrence of the underlying disease was detected in CSF. There was a moderate correlation between the recipient DNA percentage as detected by short tandem repeat (STR) amplification and the cell concentration in CSF (Spearmann r: 0.66 P = 0.004). The percentage of cells with immunophenotypic abnormalities from patients relapsing in the CNS detected by flow cytometry showed a strong correlation with the percentage of recipient-derived DNA in CSF assessed by STR analysis (Spearmann r: 0.83 P = 0.0008). Donor-recipient chimerism analysis in CSF in patients with neurological symptoms after alloHCT is a practical, feasible and useful complementary method to the already established methodologies included in the diagnostic workup.Bone Marrow Transplantation (2016) 51, 127-131; doi:10.1038/bmt.2015; published online 5 October 2015 INTRODUCTIONNeurological complications after allogeneic hematopoietic cell transplantation (alloHCT) have been reported with a varying incidence between 8% and 42% in bone marrow recipients. 1 Among this type of complication, the incidence of central nervous system (CNS) relapse of the underlying disease ranged from 2.9% to 11% in patients undergoing alloHCT. 2 To begin a proper treatment as early as possible, an accurate and prompt diagnosis is mandatory. However, because of the several etiologies of neurological symptoms and the lack of optimal diagnostic methods, diagnosis could be challenging. In addition to neurological evaluation, several methods can be used to establish an accurate diagnosis.Cerebrospinal fluid (CSF) examination constitutes a part of the diagnostic work-up of patients with neurological symptoms after alloHCT. Cytological analysis is considered to be the gold standard for the detection of malignant cells in CSF. 3 However, cytology exhibits limitations regarding sensitivity and positive predictive value in the identification of malignant cells. Characterization of CSF cells using flow cytometry (FC) improved the detection of malignant and non-malignant cells and constitutes a useful diagnostic complement. 4 The reported use of molecular biology techniques in CSF cells in patients undergoing alloHCT is scarce, and these reports mostly refer to the pediatric population involving small patient cohorts. 5,6 Donor-recipient chimerism routinely used to evaluate hematopoietic chimerism foll...

Low donor chimerism may be sufficient to prevent demyelination in adrenoleukodystrophy

“…The presence of donor cells in the CSF after HSCT for ALD has not been reported. Studies on chimerism analysis of CSF following HSCT for patients with hematological malignancies have revealed the presence of donor cells in the CSF 17,18 . In patients with an inherited metabolic disorder, such as metachromatic leukodystrophy and globoid‐cell leukodystrophy, HSCT works through a mechanism that depends on donor cells crossing the blood–brain barrier (BBB) 19 …”

“…Studies on chimerism analysis of CSF following HSCT for patients with hematological malignancies have revealed the presence of donor cells in the CSF. 17,18 In patients with an inherited metabolic disorder, such as metachromatic leukodystrophy and globoid-cell leukodystrophy, HSCT works through a mechanism that depends on donor cells crossing the blood-brain barrier (BBB). 19 ALD reportedly causes BBB dysfunction, as the deficiency of ABCD1 activity results in greater adhesion and transmigration of monocytes across the endothelium.…”

Donor cell chimerism evaluation in cerebrospinal fluid by short tandem repeat analysis following allogeneic hematopoietic stem cell transplantation

“…Recently, Waterhouse et al reported on the utility of CSF STR analysis in adult patients presenting with neurological complications at different time points following allogeneic HSCT. They reported correlation with disease recurrence between STR and flow cytometry results in some cases [3]. Of note, these symptomatic patients had larger numbers of cells present in the cerebrospinal fluid compared to the asymptomatic pediatric patients presented in this paper.…”

Graft-versus-host disease of the central nervous system after liver transplantation: A rare complication

“…The use of STR loci analysis with polymerase chain reaction in the diagnosis of GVHD after BMT and LT has been well documented . However, this study was primarily done to aid in the detection of a recurrence of underlying malignancy . Here, we describe the use of CSF STR analysis as a tool to aid in the diagnosis of GVHD of the CNS after LT.…”