Background. The purpose of this study was to report the response to and toxicity of ultra–low-dose radiotherapy (RT) for B-cell ocular adnexal lymphoma (OAL). Methods. We conducted a retrospective review of patients with indolent B-cell and mantle cell OAL treated with 4 Gy to the orbit(s) in two 2-Gy fractions. Disease response was assessed clinically and/or radiographically at 2 to 4-month intervals after RT. Data collected included rates of overall response, complete response (CR), partial response (PR), and treatment-related toxic effects. Results. Twenty-two patients (median age, 65 years) had the following histologic subtypes: mucosa-associated lymphoid tissue (MALT; 14 patients; 64%); follicular lymphoma (5 patients; 23%); mantle cell lymphoma (MCL; 2 patients; 9%); and unclassifiable (1 patient, 4%). The overall response rate was 100%; 19 patients (86%) had a CR and 3 patients (14%) had a PR. The only acute toxic effect was grade 1 dry eye syndrome in 1 patient. Conclusion. Ultra–low-dose RT in patients with OAL is associated with high response rates and minimal toxic effects, and is much shorter in duration and cost.

Methotrexate and cytarabine arabinoside are frequently administered intrathecally in the prophylaxis and treatment of patients with hematological malignancies. Myelopathy as a complication of intrathecal chemotherapy is rare in adults, with most of the cases described in the literature occurring in the pediatric population. Between January 2010 and March 2014, 587 newly diagnosed B-cell acute lymphoblastic leukemia and 24 chronic myeloid leukemia lymphoid blast phase patients were seen at The University of Texas MD Anderson Cancer Center. This case series discusses 7 adult cases deemed to have intrathecal chemotherapy-induced myelopathy between 2010–2014 at MD Anderson Cancer Center. Five out of the 7 patients had T2 abnormalities involving the dorsal columns of the spinal cord. An elevated myelin basic protein level was noted in the 2 patients in whom it was checked. The wide range of dosage and timing with respect to intrathecal chemotherapy administration suggests an idiosyncratic reaction or individual threshold to the development of myelopathy. By describing the largest case series of myelopathy in adults, we aim to raise awareness about this rare albeit devastating complication. Based on the 7 cases described we would recommend – MRI of the spine with T2-weighted imaging in the sagittal and axial planes in leukemia patients with unexplained myelopathy and consideration to delay intrathecal chemotherapy until after an extensive work-up to rule out CNS leukemia. Though more data are needed on the use of folate metabolites, preliminary results have shown some promise in the treatment of methotrexate-induced myelopathy and may be a potential consideration for future patients suspected to have chemotherapy induced myelopathy.

Intrathecal chemotherapy with methotrexate, a folate antagonist, is widely used to treat central nervous system malignancies. The mechanisms underlying methotrexate-induced neurotoxicity are unclear but may be related to increased homocysteine levels. Intrathecal methotrexate-induced myelopathy mimicking sub-acute combined degeneration, with normal B12 levels, has been documented. We examined treatment and magnetic resonance imaging (MRI) characteristics of 13 patients with leukemia who received intrathecal methotrexate and developed urinary and bowel incontinence, ascending motor weakness, and sensory loss with dorsal column hyper-intensity on MRI between 2000 and 2016. Cerebrospinal fluid evaluation was negative for leukemia in all patients and positive for elevated protein in 12 patients. Seven of 8 patients with available data had reduced serum folate, increased serum homocysteine, or both, implicating methotrexate as the cause of neurotoxicity. Autopsy of one patient revealed loss of myelinated axons in the posterior columns. These findings suggest that methotrexate neurotoxicity may be mediated by folate antagonism. Awareness and a high index of suspicion of these characteristic clinical and radiographic features in patients who develop myelopathy after intrathecal methotrexate may help to avoid additional neurotoxic therapy in such patients.

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Purpose: Cytomegalovirus (CMV) antigens occur in glioblastoma but not in normal brains, making them desirable immunologic targets.Patients and Methods: Highly functional autologous polyclonal CMV pp65-specific T cells from patients with glioblastoma were numerically expanded under good manufacturing practice compliant conditions and administered after 3 weeks of lymphodepleting dose-dense temozolomide (100 mg/m 2 ) treatment. The phase I component used a 3þ3 design, ascending through four dose levels (5 Â 10 6 -1 Â 10 8 cells). Treatment occurred every 6 weeks for four cycles. In vivo persistence and effector function of CMV-specific T cells was determined by dextramer staining and multiparameter flow cytometry in serially sampled peripheral blood and in the tumor microenvironment.Results: We screened 65 patients; 41 were seropositive for CMV; 25 underwent leukapheresis; and 20 completed ≥1 cycle. No dose-limiting toxicities were observed. Radiographic response was complete in 1 patient, partial in 2. Median progression-free survival (PFS) time was 1.3 months [95% confidence interval (CI), 0-8.3 months]; 6-month PFS was 19% (95% CI, 7%-52%); and median overall survival time was 12 months (95% CI, 6 months to not reached). Repeated infusions of CMV-T cells paralleled significant increases in circulating CMV þ CD8 þ T cells, but cytokine production showing effector activity was suppressed, especially from T cells obtained directly from glioblastomas.Conclusions: Adoptive infusion of CMV-specific T cells after lymphodepletion with dose-dense temozolomide was well tolerated. But apparently CMV seropositivity does not guarantee tumor susceptibility to CMV-specific T cells, suggesting heterogeneity in CMV antigen expression. Moreover, effector function of these T cells was attenuated, indicating a requirement for further T-cell modulation to prevent their dysfunction before conducting large-scale clinical studies.