Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
Department of Neurosurgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
Cell Transplant. 2022 Jan-Dec;31:9636897221117532. doi: 10.1177/09636897221117532.
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) 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. The patient was enrolled in a clinical trial of and .
我们提出了一例女性急性淋巴细胞白血病（ALL）患者在接受单倍体造血干细胞移植（haplo-SCT）后颅内病变的鉴别诊断。该患者接受了抗 CD19 嵌合抗原受体（CAR）T 细胞治疗难治性 B 细胞 ALL，并获得了微小残留病（MRD）阳性（0.03%）的完全缓解（CR）。然后患者接受了单倍体造血干细胞桥接治疗。桥接治疗后，患者骨髓中维持了 MRD 阴性和完全供者嵌合状态，外周血 EBV-DNA 阴性。haplo-SCT 后 91 天，患者出现头晕和疲劳，磁共振成像（MRI）显示颅内病变。最初考虑孤立性骨髓外复发（IEMR）的诊断。然后下一代测序（NGS）在脑脊液中发现了阳性 EBV-DNA，尽管外周血 EBV-DNA 阴性。此外，脑组织中 NGS 检测到的阳性 EBV-DNA 和完全供者嵌合状态证实了中枢神经系统移植后淋巴组织增生性疾病（CNS-PTLD）的诊断。然而，EBV 编码的小 RNA（EBERs）杂交呈稀疏阳性。随后患者接受了抗 CD22-CAR T 细胞联合 Zanubrutinib 治疗，但疾病迅速进展并死亡。局部活检的供者嵌合状态检查为 PTLD 的诊断提供了重要证据。此外，与外周血 EBV-DNA 检测相比，局部病变中 EBV-DNA 的 NGS 检测对 PTLD 的诊断更有价值。患者入组了 和 的临床试验。
