Clinical characteristics, management, and outcome of gestational trophoblastic neoplasia patients with brain metastasis: A 10-year experience at the Philippine General Hospital / Philippine Journal of Obstetrics and Gynecology

Objective@#This study aimed to determine the clinical characteristics, management, and outcome of gestational trophoblastic neoplasia (GTN) patients with brain metastasis.@*Materials and Methods@#This was a 10‑year descriptive study that included all patients with brain metastasis from GTN. Patients’ sociodemographic and clinicopathological profiles were described. Using Kaplan–Meier survival curve, the survival time was determined@*Results@#From January 1, 2010, to December 31, 2019, there were 33 GTN patients with brain metastasis. Four were excluded from the study due to incomplete records. Twenty‑nine patients were included in the study. Nineteen (65.51%) patients presented with neurologic symptoms upon diagnosis and one (3.44%) during treatment. All received etoposide, methotrexate, actinomycin, oncovin (EMACO) as first‑line treatment. Five (17.24%) patients were given induction chemotherapy with low‑dose etoposide–cisplatin. Seventeen (58.62%) patients underwent whole‑brain radiation and two (6.89%) were given intrathecal methotrexate. Thirteen patients (44.82%) achieved biochemical remission with EMACO chemotherapy. Four patients (13.79%) had resistance to EMACO and were given Etoposide Cisplatin Etoposide Methotrexate Actinomycin (EP EMA). Four patients (13.79%) underwent an adjunctive hysterectomy. Four patients (13.79%) died during treatment. One patient (3.44%) was unable to continue her chemotherapy because she got pregnant before her first consolidation course. There were eight early deaths (<4 weeks of admission) and hence were excluded in the analysis. Three patients who went into biochemical remission relapsed on the 1st, 2nd, and 3rd months after their last consolidation course, respectively. The median follow‑up time was 27 months. After excluding early deaths, the survival rate between 3 and 7 years after treatment is at 61.9%. The mean survival time was 5.43 years. Six surviving patients were contacted. Five (17.24%) of them had resumed their everyday life, and one is currently undergoing chemotherapy.@*Conclusion@#The study was able to document brain metastasis from GTN to be 14.28% (29/203) among metastatic high‑risk admissions. The biochemical remission rate from first‑line treatment was of 61.90% (13/21) and resistance rate was 19.04% (4/21). Lost to follow up after achieving biochemical remission was a challenge encountered

A Case of Paraplegia Associated with Intrathecal Methotrexate : A case report

The treatment and prophylactic therapy of meningeal leukemia with intrathecal methotrexate in acute lymphoblastic leukemia is the standard method. Intrathecal overdose of methotrexate may produce severe toxicities such as paraplegia. We experienced a case of paraplegia diagnosed by magnetic imaging examination of the spine in a 24-year-old woman received repeated intrathecal methotrexate for meningeal leukemia.

Leukoencephalopathy after CNS Prophylactic Therapy in Pediatric Hematologic Malignancy

PURPOSE: Leukoencephalopathy(LE) is one of the most serious complications in children with hematologic malignancies during the course of treatment. Early recognition is important to reduce the impact and sequelae from LE. We therefore investigated the clinical features of LE following central nervous system(CNS) prophylaxis in children with hematologic malignancies and evaluated the significance of regular check-ups of brain MRI. METHODS: We retrospectively reviewed children with hematologic malignancies who had CNS prophylaxis including intrathecal(IT) methotrexate(MTX) and/or cranial irradiation at the Department of Pediatrics, Kyungpook National University Hospital from Oct. 1995 to May 2002. Fifteen cases of acute leukemia and one case of lymphoma who experienced LE following CNS prophylaxis were included in the study. Clinical data were analyzed from the medical records and brain MRIs were reviewed by neuroradiologists. RESULTS: The ages ranged from 1 to 13 years(median age=5.2 years), and the male to female ratio was 3 : 1. The time interval from the beginning of chemotherapy to the time of diagnosis of LE ranged from 2 to 17 months. They all had IT MTX two to 15 times and ten underwent cranial irradiation(1,800 rads). At the time of diagnosis, ten of them had neuropsychiatric symptoms including seizures, personality changes, headache, etc. After the change of treatment modality, four cases showed significant improvement on follow-up MRIs, six cases had no significant changes and two had worsening of LE. Four patients died of infection and bone marrow relapse. CONCLUSION: CNS prophylaxis with IT therapy and cranial irradiation may cause leukoencephalopathy during the course of treatment. As a result, regular brain MRI check-up is recommended for the early detection and reducing the incidence of LE, along with changes in the treatment modality.

A Case of Encephalopathy Presented with Motor Aphasia and Quadriplegia Following Intrathecal Methotrexate

Intrathecal administration of methotrexate(IT-MTX) has constituted the standard approach to prophylaxis and treatment of central nevous system(CNS) leukemia. We experienced a quadriplegia and motor aphasia in a 14-year-old boy following repeated IT-MTX for the prophylaxis of meningeal leukemia. He was diagnosed as ALL without CNS involvement and treated by CCG- 1882 protocol. IT-MTX was administered for CNS prophylaxis. The patient began complaining of urinary incontinence, motor aphasia and weakness in his right leg from 12 days after the 5th dose of the IT-MTX therapy. Even though the IT-MTX was discontinued, loss of muscle power progressed upward resulting in quadriplegia. The patient showed slow and partial recovery on right extremities over 3 months. We report this case with brief review of literature.

Acute Management of Intrathecal Methotrexate Overdose in a Patient with Acute Lymphocytic Leukemia / 대한혈액학회지

Methotrexate is the most widely used intrathecal antineoplastic agent and is potentially neurotoxic. Accidental intrathecal overdose of methotrexate can produce severe and life-threatening toxicities. A 17-year-old girl with acute lymphocytic leukemia, in complete remission, inadvertently received a 10-fold overdose of intrathecal methotrexate instead of intended dose (100mg vs 10mg). Exchange of lumbar cerebrospinal fluid with normal saline via intrathecal indwelling catheter was started 2 hours later. Leucovorin and dexamethasone were given intravenously. After exchange of cerebrospinal fluid, the total amount of methotrexate removed was about 37mg. Cerebrospinal fluid and plasma methotrexate levels at 18 hours were about 3- to 5- fold higher than those previously reported in patients following standard dose of intrathecal methotrexate who did not develop neurotoxicity. But no methotrexate induced neurologic sequelae were observed in this patient. CSF exchange is a simple and effective method for the treatment of acute intrathecal methotrexate overdose.