Decreasing Dose and Duration of Dexamethasone Therapy for Low-Risk Childhood Acute Lymphoblastic Leukemia Aiming to Avoid Serious Viral Infections Results in Significant Increase in Isolated CNS Relapse: A Prospective Study
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Acute lymphocytic leukemia
Childhood leukemia
Optic nerve infiltration is relatively rare in acute lymphoblastic leukemia. We present a case of a -53 year-old-man who was diagnosed with T- acute lymphoblastic leukemia (ALL). The patient was treated with ALL national protocol and the central nervous system (CNS) prophylactic management. On treatment, the patient presented with sudden severe vision deterioration of both eyes. Fundoscopic examination of the eye and magnetic resonance imaging of the orbits were in favor of an infiltration of the optical nerve. An isolated extramedullary relapse of the optical nerve was retained. The patient was treated with salvage chemotherapy systematic and intrathecal. Waiting forthe beginning of radiotherapy, the patient presented a bone marrow relapse. He died of a severe hemorrhagic syndrome. Conclusion: Optic nerve leukemic infiltration has a severe prognosis. Ophthalmic assessment is essential in patients with ALL in order to diagnose an early ocular involvement and the patient's vision can be preserved if treatment is initiated promptly.
Infiltration (HVAC)
Acute lymphocytic leukemia
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ABSTRACT. Purpose: To describe the treatment of cytomegalovirus (CMV) retinitis with intravitreal sustain‐release ganciclovir devices in a 16‐year‐old patient in third remission of acute lymphoblastic leukemia after stem cell transplantation. Methods: The patient received a stem cell transplant from an unrelated bone marrow donor after which he contracted a serious CMV infection manifested in the lungs and retinae. His immune system at this time was almost completely depleted. Implantation of a sustained‐release ganciclovir device was performed in both eyes when retinitis progressed in spite of aggressive antiviral intravenous treatment. Results: No per‐ or postoperative complications were noted. Infiltrates, hemorrhages and macular edema present preoperatively dissolved over a period of six months. The final visual acuity was 1.0 in both eyes. The patients immune system and lung function slowly recovered during the same time period. Conclusions: The intravitreal ganciclovir implant provides safe and effective therapy against CMV retinitis, and should be considered in patients acquiring the infection after stem cell transplantation.
Cytomegalovirus retinitis
Cytomegalovirus
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Intrathecal chemotherapy and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system disease in hematologic malignancies. However, intrathecal treatment has some adverse effects, such as arachnoiditis, progressive myelopathy, and leukoencephalopathy. The authors describe six children in whom myelopathy and adhesive arachnoiditis developed after administration of intrathecal chemotherapy including methotrexate, cytosine arabinoside, and prednisolone. Urinary retention and incontinence, the main presenting complaints in all patients, developed within 12 hours after intrathecal therapy and spontaneously resolved within 7 days. Two patients were unable to walk. In these two, weakness in the lower extremities gradually recovered by 1 month but urinary incontinence did not improve. None of the children had sensory loss. On follow-up periodic recurrent urinary tract infection was noted in four patients. MRI findings corresponded to arachnoiditis. No response was recorded on tibial nerve somatosensory evoked potentials in all patients. Intrathecal chemotherapy, especially methotrexate, can cause spinal cord dysfunction in children with acute lymphoblastic leukemia and non-Hodgkin's lymphoma. Arachnoiditis should be kept in mind as a causative factor in recurrent urinary tract infection in patients receiving intrathecal chemotherapy.
Arachnoiditis
Urinary retention
Prednisolone
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Leukemias are the most frequent malignant neoplasms in childhood; acute lymphoblastic leukemia (ALL) is the most frequent. The addition of intrathecal methotrexate to chemotherapy regimens has been beneficial in preventing relapse to the central nervous system and avoiding the use of radiation therapy. Due to its mechanism of action, by inhibiting the enzyme dihydrofolate reductase, when it is used systemically, it has multiple expected adverse effects such as mucositis, myelosuppression and it has also been observed after intrathecal administration or high intravenous doses, acute, subacute neurotoxicity where stroke like syndrome is found. We present an 11-year-old patient diagnosed with T-ALL, who manifested after 8 days of intrathecal administration of methotrexate, faciobrachial hemiparesis and acute onset expression aphasia. The diagnosis of subacute encephalopathy reversible by methotrexate was reached by excluding other Encefalopatía subaguda reversible por metotrexato: notificación de un caso pediátrico Methotrexate-induced stroke-like syndrome: A pediatric case report more frequent pathologies and the typical evolution, with spontaneously ad integrum resolution of the symptoms.Las leucemias son las neoplasias malignas más frecuentes en la infancia; la leucemia linfoblástica aguda (LLA) es la más frecuente. Desde principios de los 80, la adición de metotrexato intratecal a los esquemas de quimioterapia ha sido beneficiosa para prevenir la recidiva en el sistema nervioso central y evitar el uso de radioterapia. Su mecanismo de acción es la inhibición de la enzima dihidrofolato reductasa, por lo que posee múltiples efectos adversos (neurotoxicidad aguda, subaguda o crónica) después de la infusión intratecal o de dosis altas por vía intravenosa. Se presenta un paciente de 11 años con diagnóstico de LLA de línea T (LLA-T), que presenta hemiparesia faciobraquial y afasia de expresión de instauración aguda 8 días después de la administración intratecal de metotrexato. Luego de excluir otras patologías más frecuentes de origen vascular y la evolución típica del cuadro, con resolución espontánea ad integrum de los síntomas, se arribó al diagnóstico de encefalopatía subaguda reversible por metotrexato.
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Intrathecal
Acute lymphocytic leukemia
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Acute lymphoblastic leukaemia (ALL) is one of the most common malignancies of childhood. ALL is treated with high doses of methotrexate (MTX) to prevent central nervous system (CNS) and haematological relapses. MTX is administered intravenously and via intrathecal route.1 MTX can cause neurotoxicity by disrupting CNS folate homeostasis or by direct neuronal damage. MTX-induced acute toxic leukoencephalopathy can result in acute neurological deficit, seizures or encephalopathy.2 We report a 27-year-old diagnosed case of ALL who presented with neurological symptoms 2 years after she was started with intensive and maintenance phase of chemotherapy. She took multiple cycles (24) of intrathecal MTX in her intensive phase and …
Neurotoxicity
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Acute lymphocytic leukemia
Maintenance therapy
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The occurrence of major neurologic disturbances is a rare complication of intrathecal cytotoxic drug administration. We describe the case of a 30-year old man with relapsed lymphoblastic lymphoma and CNS involvement who was treated by systemic chemotherapy (ESHAP) and intrathecal injections of methotrexate, cytarabine, thiotepa and hydrocortisone. Thereafter he developed persistent paraplegia with sensory and sphincteric insufficiency. The role of the drug in causing this syndrome was suspected when more common causes, such as a meningeal carcinomatosis, had been excluded by means of CNF analysis and radiological examinations. We review this and other published cases and discuss the possible pathogenesis, as well as the clinical and paraclinical findings in paraplegia following intrathecal chemotherapy. Patients particularly at risk are those who receive intrathecal chemotherapy for over CNS disease rather than as prophylaxis, those who receive several injections and patients who are concomitantly treated with radiotherapy to the brain or systemic high-dose methotrexate or cytarabine.
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ThioTEPA
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Pneumonitis
Immunosuppression
Etiology
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A 40-year-old Hispanic man with acute lymphoblastic leukemia was treated with a single dose of intrathecal methotrexate 12 mg for prophylaxis against leptomeningeal spread of tumor. The day after methotrexate administration, the patient complained of severe back pain and urinary retention. The diagnosis of encephalomyelitis was made on day 3 after methotrexate administration, and by day 6 mechanical ventilation was begun secondary to ascending paralysis. By day 8 the patient was comatose, with minimal signs of brain activity and little hope for recovery; on day 12 he died. Although neurotoxicity is a frequent complication of methotrexate therapy, fatal acute neurotoxicity is extremely uncommon, especially in adults. The mechanisms of methotrexate toxicity remain unclear, and no effective treatment exists to prevent its occurrence. This patient rapidly progressed from mild neurotoxicity to fatal encephalopathy after one dose of intrathecal methotrexate during his third cycle of chemotherapy. Clinicians should be aware of the signs and symptoms of neurotoxicity during treatment, as well as predisposing factors that put patients receiving methotrexate at risk for neurotoxic effects.
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