一例急性淋巴细胞白血病患者单倍体造血干细胞移植后中枢神经系统移植后淋巴增殖性疾病

We present a differential diagnosis of an intracranial lesion following haploidentical stem cell transplantation (haplo-SCT) in a female patient with acute lymphoblastic leukemia (ALL). This patient received an anti-CD19-chimeric antigen receptor (CAR) T-cell therapy for refractory B-cell ALL and obtained minimal residual disease (MRD)-positive (0. 03%) complete remission (CR). Then the patient received a bridging therapy of haplo-SCT.

After bridging therapy, the patient maintained MRD-negative and full donor chimerism in bone marrow (BM) and was negative for Epstein-Barr virus (EBV)-DNA copy in peripheral blood. At 91 days after haplo-SCT, the patient presented with dizziness and fatigue and magnetic resonance imaging (MRI) demonstrated an intracranial lesion.

The diagnosis of isolated extramedullary relapse (IEMR) was temporarily considered. Then next-generation sequencing (NGS) identified positive EBV-DNA in the cerebrospinal fluid, although EBV-DNA in the peripheral blood was negative.

Furthermore, the positive EBV-DNA by NGS and complete donor chimerism in the brain tissue confirmed the diagnosis of central nervous system post-transplant lymphoproliferative disorder (CNS-PTLD).

However, the EBV-encoded small RNAs (EBERs) in situ hybridization was sparsely positive. The patient was subsequently treated with anti-CD22-CAR T cells in combination with Zanubrutinib, but the disease progressed quickly and died. Donor chimerism examination of focal biopsy provides important evidence for diagnosing PTLD.

Furthermore, NGS detection of EBV-DNA in local lesions is more valuable for diagnosing PTLD than detection of EBV-DNA in the peripheral blood. Trial registration: The patient was enrolled in a clinical trial of ChiCTR1800019622 and ChiCTR1800019298 .