Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster II
Hematology Disease Topics & Pathways:
Biological, Therapies, transplantation
METHODS: We retrospectively studied medical records of 459 patients who underwent CBT as the first transplantation at Toranomon Hospital between July 2012 and March 2018. NIMPNs were diagnosed when the patients developed myelopathy or peripheral neuropathy without detection of pathogens tested in cerebrospinal fluid (CSF) or without radiological findings indicating hemorrhage, ischemia, or focal lesions suggestive of infections. We excluded the patients whose ECOG performance status scale was 3 or 4, and who had neurological symptoms before transplantation. Institutional review board of Toranomon Hospital approved the study (research number #1205-H)
RESULTS: NIMPNs developed in 8 patients within 2 years after transplantation (2 myelopathies and 6 peripheral neuropathies [PN]). Their characteristics are as follows: the median age, 53 years (range, 37 - 62); 5 males and 3 females; AML-NOS (n = 5), AML with MRC (n = 1), therapy-related MDS or AML (n = 2). All except one were not in remission before transplantation. The combination of fludarabine, busulfan, and melphalan with or without high-dose cytarabine was used as conditioning regimen. Tacrolimus (Tac) alone (n = 2), Tac and mycophenolate mofetil (n = 5), and Tac and methotrexate (n = 1) were used as GVHD prophylaxis. The cumulative incidence of NIMPNs was 1.74% at 2 years after transplantation (95% confidence interval, 0.54 - 3.93). The median onset day of NIMPNs was 90 days after transplantation for all patients (range, 25 - 255); 40 days for myelopathy, and 100 days for PN. All had varying degree of hypesthesia or paresis and were unable to walk by themselves at diagnosis. All developed neurological symptoms after engraftment. Grade 2 - 3 of acute GVHD preceded NIMPNs in all patients. At diagnosis, the following pathogens were confirmed to be negative by PCR in CSF; HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, BKV, toxoplasma. CSF cell count and protein level did not increase in all of them. Myelin basic protein level in CSF was elevated in 3 out of 6 patients (519 ng/L and 1358 ng/L for myelopathies, 1321 ng/L for PN), which suggested demyelinating changes. Oligoclonal bands were not detected. Spinal MRI study performed in 4 patients showed no abnormality. In line with previous reports, axonal degeneration was confirmed by nerve biopsy in 2 patients with PN. After the diagnosis of NIMPNs, all patients were treated with high dose intravenous immunoglobulin (IVIG) (400 mg/kg for 5 days). The median interval from diagnosis to treatment was 28 days (range, 5 - 71). IVIG was administered monthly for the median of 2 courses (range, 2 - 5). In 2 patients, rituximab or steroid pulse therapy was added on IVIG, respectively. After these treatments, symptoms improved in 6 out of 8 patients and they finally were able to walk by themselves (1/2 of myelopathy and 5/6 of PN). The remaining one died of severe liver acute GVHD and another one is hospitalized until now without recovery. The median follow-up days of survivors was 498 days (range, 74 - 2190). Seven out of 8 patients are currently alive.
CONCLUSION: NIMPNs were observed after CBT with low incidence. Although all patients presented severe neurological symptoms at diagnosis, IVIG and immunosuppressive therapy had a therapeutic benefit, and their prognosis with respect to neurological symptoms and survival was not dismal.
Disclosures: Yamamoto: Bristol-Myers Squibb: Honoraria.
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