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At least 19 recordsLinked to original sources
PubMed1978

Abnormal CT scans of the brain in asymptomatic children with acute lymphocytic leukemia after prophylactic treatment of the central nervous system with radiation and intrathecal chemotherapy.

Thirty-two asymptomatic patients with acute lymphocytic leukemia, who had received prophylactic cranial radiation (2400 rads) and either intrathecal methotrexate or cytosine arabinoside were studied by computed tomography of the brain 19 to 67 months after initiation of prophylaxis. Seventeen of 32 (53 per cent) had one or more abnormal findings. Dilatation of the ventricles (eight patients) and widening of the subarachnoid spaces (nine patients) were equally distributed among patients in both intrathecal-chemotherapy groups. Areas of decreased attenuation coefficient (hypodense, abnormally radiolucent regions) (four patients) and intracerebral calcification (one patient)--lesions previously described in methotrexate leukoencephalopathy--were found only in those who had received intrathecal methotrexate. Mild central-nervous-system dysfunction was detected in seven patients but did not correlate with the presence of tomographic abnormalities. Nevertheless, these tomographic findings may represent preclinical lesions. The unexpectedly high prevalence of such abnormalities contrasts with the essentially normal tomographic findings in a control group with acute lymphocytic leukemia who received no central-nervous-system prophylaxis. These results suggest that alternative approaches to such prophylaxis be considered.

Adolescent↗
PubMed1976

Intrathecal cytostatic chemotherapy of meningitis carcinomatosa. Clinical manifestation and cerebrospinal fluid cytology in a case of metastatic carcinoma of the breast.

Effects of intrathecal cytostatic chemotherapy on the clinical symptoms and cerebrospinal fluid (CSF) findings are being demonstrated in a case of metastatic carcinoma of the breast with sighns of meningeal irritation and cranial nerve involvement. Clinical symptoms disappeared after repeated intrathecal applications of methotrexate. CSF cell counts were reverted to normal but tumor cells were found to be persistant in CSF over a period of 19 months. Risks of combined intrathecal and systemic cytostatic therapy and possible effects of parenteral citrovorum factor applications are being discussed. The importance of continued intrathecal chemotherapy and of regular and thorough examination of CSF cells in meningitis carcinomatosa is emphasized. Cytological methods included investigations on viable CSF cells.

Adenocarcinoma, Mucinous↗
PubMed1979

Hypothalamic-pituitary dysfunction following CNS prophylaxis in acute lymphocytic leukemia: correlation with CT scan abnormalities.

In an attempt to identify possible adverse effects of CNS prophylaxis (cranial radiation and intrathecal chemotherapy), we examined hypothalamic-pituitary function in 23 patients with acute lymphocytic leukemia (ALL). Of 18 patients who had received both cranial radiation and intrathecal chemotherapy, nine had abnormally low growth hormone responses to insulin-induced hypoglycemia (less than 7.0 ng/ml). Seven of the nine patients with abnormally low growth hormone responses also manifested ventricular dilatation on computed tomography (CT) brain scans, whereas only one of the nine patients with normal growth hormone responses demonstrated this CT scan finding (P = 0.015). The remaining patients, who had not received cranial radiation, had normal growth hormone responses and normal CT scans. There is significant correlation between ventricular dilatation on CT and abnormally low peak growth hormone responses following CNS prophylaxis in ALL.

Adolescent↗
PubMed1978

Acute encephalopathy after initiation of cranial irradiation for meningeal leukaemia.

Five patients experienced severe encephalopathy within hours of receiving their initial dose of cranial irradiation for the treatment of central-nervous-system leukaemia. Neurological findings included cranial-nerve palsies, seizures, ataxia, depressed consciousness, increased intracranial pressure, and signs of herniation. Symptoms developed within 3-30 hours of the first radiation treatment of 50-200 rad. Each patient had also received one or more injections of intrathecal chemotherapy before encephalopathy developed. The aetiology of this syndrome is uncertain but may involve transient cerebral oedema and/or an altered blood-brain barrier produced by the combination of intrathecal chemotherapy and cranial irradiation.

Acute Disease↗
PubMed1977

Ocular involvement in leukaemia. Report of three cases.

Three patients with treated acute lymphoblastic leukaemia acquired visual symptoms believed to be caused by ocular infiltration by malignant cells. All three patients had other evidence of systemic disease including bone-marrow involvement at the time. One patient had a previous history of meningeal leukaemia and none had received "prophylactic" cranial irradiation. The ophthalmoscopic appearances were similar in each case and were thought to have been caused by obstruction of axoplasmic flow associated with infiltration of the optic nerve by neoplastic cells. The three patients were treated by local irradiation and two also received intrathecal chemotherapy. Response to treatment was variable but the use of radiotherapy combined with intrathecal cytoxic drugs is probably the best available approach.

Adult↗
PubMed1977

Eosinophilic meningitis complicating Hodgkin's disease. A report of a case and review of the literature.

A case of eosinophilic meningitis as a complication of Hodgkin's disease is reported. Intrathecal chemotherapy with methotrexate and whole brain radiation therapy were effective in clearing the cerebrospinal abnormalities, pathologic evidence of meningeal disease, and the clinical manifestations. The differential diagnosis of eosinophilic meningitis and therapy of lymphomatous meningitis are discussed.

Adult↗
PubMed1978

The clinical pharmacology of methotrexate: new applications of an old drug.

Methotrexate is now used widely for the treatment of acute leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, choriocarcinoma, breast carcinoma, pulmonary and epidermoid carcinoma, and intrathecal chemotherapy. It is also useful in bone marrow transplantation, severe psoriasis, rheumatoid arthritis, dermatomyositis, Wegener's granulomatosis and sarcoidosis. The recent dramatic intensification of methotrexate therapy can be attributed in part to advances in our understanding of the clinical pharmacology of the folate antagonists, as well as to the combination of positive results and their effective dissemination to medical oncologists. The review summarizes the pharmacologic findings and illustrates how they are currently being applied to the treatment of malignant disease.

Absorption↗
PubMed1979

Central nervous system complications of non-Hodgkin's lymphoma. The potential role for prophylactic therapy.

In 38 patients with non-Hodgkin's lymphoma, involvement of the central nervous system (CNS) by malignant lymphoma developed during an eight year period. All patients had lymphomatous meningitis; clinical involvement of the spinal nerves or cranial nerves suggested the diagnosis. Spinal fluid was abnormal in 97 per cent of the patients although a positive cytology could be documented in only 67 per cent by lumbar puncture. The histology in 82 per cent of the patients was diffuse. Involvement of the CNS in nodular lymphoma was uncommon (3 per cent), and the histology in virtually all of these patients had converted to diffuse. At the time of diagnosis of CNS disease, 95 per cent of the patients had other evidence of advanced disease; 66 per cent had bone marrow involvement. In only 18 per cent of the patients did CNS disease develop while they were in clinical remission. Eighty-five per cent of the patients treated with whole brain irradiation and intrathecal chemotherapy had a good clinical response. Knowledge of these risk factors permits definition of a group of patients who may benefit from CNS prophylaxis.

Adult↗
PubMed1977

The effect of oral glycerol on intraventricular pressure in man.

Oral glycerol was administered to eight patients with meningeal carcinomatosis or acute leukemia in whom ventricular catheters and Ommaya reservoirs had been implanted for the purpose of intrathecal chemotherapy or chemoprophylaxis. Intraventricular pressure was monitored continuously via the Ommaya reservoirs before and after single doses of 0.5, 1.0 or l.5 gm per kilogram of body weight. The interrelationship between initial pressure, change in pressure, serum osmolarity, and duration of action was investigated, and the ratio of CSF-to-plasma osmolarity was determined 4 to 5 hours after glycerol administration. The effects of chronic 6-hourly and 4-hourly 1 gm per kilogram glycerol doses were studied in a patient with meningeal carcinomatosis and increased intracranial pressure. Our data suggest that as a cerebral dehydrating agent oral glycerol is most effective in patients with markedly increased intracranial pressure. A single 1 gm per kilogram dose is adequate to lower raised intraventricular pressure acutely, but its effect is short-lived. Continuous oral administration must be carefully monitored to avoid the establishment or a reverse osmotic gradient, secondarily increased intracranial pressure, and clinical deterioration.

Administration, Oral↗
PubMed1977

Blindness during remission in two patients with acute lymphoblastic leukemia: a possible complication of multimodality therapy.

Two patients with acute lymphoblastic leukemia treated on the same protocol became blind during complete remission. Therapy consisted of systemic combination chemotherapy, prophylactic central nervous system irradiation and monthly intrathecal cytosine arabinoside. Eight months after CNS irradiation visual acuity in both patients began to decrease. Meningeal leukemia in the area of the chiasm was suspected but despite additional radiotherapy, steroids and continued intrathecal therapy, both patients were blind within 6 months. Numerous lumbar punctures were negative for leukemic cells. Extensive investigation, including craniotomy in one case, failed to reveal the cause of blindness. Biopsy of the optic nerve in one case was compatible with radiation toxicity. We postulate that potentiation of radiation toxicity to the optic nerves and chiasm by systemic chemotherapy, intrathecal chemotherapy, or both, may have led to blindness. The patients continue in complete hemotologic and CNS remission 12 and 29 months after becoming blind.

Acute Disease↗
PubMed2026

Serial CSF CA19-9 monitoring and CSF genomic profiling in ERBB2-mutant lung adenocarcinoma with leptomeningeal metastasis: a case report.

Leptomeningeal metastasis (LM) from ERBB2-mutant lung adenocarcinoma is difficult to treat and monitor because systemic disease and leptomeningeal disease may evolve discordantly. Evidence regarding cerebrospinal fluid (CSF) genomic profiling and serial CSF tumor marker monitoring in ERBB2-mutant non-small cell lung cancer with LM remains limited. We report a 48-year-old woman initially diagnosed with stage IB mucinous lung adenocarcinoma harboring an ERBB2 exon 20 p.G776delinsVC mutation. After surgery and adjuvant chemotherapy, she developed nodal recurrence and later presented with lower back pain and lower-limb numbness. LM was clinically diagnosed based on neurological symptoms, magnetic resonance imaging and CSF cytopathology. She received craniospinal irradiation, systemic therapy and subsequent intrathecal treatment. At month 33, CSF CA19-9 was markedly elevated despite no clear radiographic systemic progression. CSF next-generation sequencing(NGS) detected the same ERBB2 exon 20 p.G776delinsVC mutation as the primary lung tumor, with a higher variant allele fraction in CSF than in lung tissue.The patient subsequently received trastuzumab deruxtecan and sequential intrathecal therapy with pemetrexed, etoposide, cytarabine and pemetrexed rechallenge. Intrathecal treatment was adjusted according to serial CSF CA19-9 levels, neurological status, imaging findings, systemic disease activity and treatment-related toxicities. CSF CA19-9 was not used as a stand-alone criterion for progression or treatment modification.At the latest follow-up, she remained alive more than 36 months after the clinical diagnosis of LM. This case suggests that CSF NGS and serial CSF CA19-9 may provide further insights into disease activity within the integrated assessment of systemic and leptomeningeal disease. Their clinical applicability is still under investigation and necessitates future validation.

CA19-9↗
PubMed1979

Acute ascending poliomyelomalacia after treatment of acute lymphocytic leukemia.

This paper reports the case of a 16-year-old girl with acute lymphoblastic leukemia who received chemotherapy including intrathecal injections of methotrexate and preventive irradiation of the brain, but not of the spinal cord. Several months later, she died from an acute ascending poliomyelitic syndrome evolving during 10 days. Clinical, bacteriological, and viral investigations failed to demonstrate any pathological agent. Autopsy revealed an acute ischemic lesion involving both anterior horns of the whole spinal cord and extending from the lower segment up to the mesencephalic region, without significant alteration of the white matter. Neither tumoral invasion, nor vascular obstruction was found. The pathogenesis of this yet undescribed lesion remained unclear but a metabolic disorder seemed the most plausible pathological factor.

Adolescent↗
PubMed1977

The value of maintenance therapy following treatment of central nervous system leukemia.

The efficacy of intrathecal (IT) maintenance chemotherapy following central nervous system (CNS) leukemia was demonstrated in a retrospective study of 77 such episodes. The median durations of CNS and bone marrow (BM) remissions were significantly longer for the 41 maintained episodes (10+ and 9.5 months, respectively) compared with the 36 unmaintained episodes (4 and 2 months, respectively). Patients were comparable in each of these two groups. For those patients receiving maintenance therapy, there appeared to be an advantage in using four or more doses of IT medications for treatment of CNS leukemia, regardless of the number of doses necessary to clear the cerebrospinal fluid (CSF).

Antineoplastic Agents↗
PubMed1978

The central nervous system in childhood leukemia. III. Mineralizing microangiopathy and dystrophic calcification.

We determined the prevalence, histopathologic features, and clinical correlations of a distinctive vascular lesion within the central nervous system (CNS) of children who died with acute lymphoblastic leukemia (ALL). Of 163 brains examined at autopsy, 28 (17%) had a noninflammatory mineralizing microangiopathy, usually accompanied by varying amounts of necrosis and calcification in adjacent neural tissue. The lesion always involved the lenticular nucleus with or without additional involvement of cerebral cortex. It was not the cause of death in any patient. An analysis of clinical features common to patients with microangiopathy indicated that cranial irradiation, in doses as low as 1500 rad, had induced the degenerative process. Survival beyond 10 months from the time of irradiation and multiple postirradiation CNS leukemic relapses, both had significant influences on the development of the lesion. Chemotherapy, particularly systemic or intrathecal methotrexate, might have contributed to the disease process, but apparently was not the instigating factor. Patients at greatest risk for developing microangiopathy are those under 10 years of age at the time of cranial irradiation, who then live more than 10 months and develop multiple CNS leukemic relapses.

Adolescent↗
PubMed1977

[Simple propositions in the treatment of acute lymphoblastic leukaemia (author's transl)].

Acute lymphoblastic leukaemias which are, at the present time, curable are those which go 01.cfhçinto remission following treatment with the combination prednisone-vincristine, in which lymphoblastic meningitis does not occur after preventive treatment of the central nervous system and which show no recurrence during maintenance chemotherapy. In order that the largest possible number of these potentially curable patients may be transformed into truly cured cases, we propose here a simple outline of treatment: induction of remission by one month of treatment with prednisone 40 mg/m2/day and vincristine 1.5 mg/m2/week, immediately followed by treatment of the central nervous system: 2 400 rads to the brain down to C2 in two weeks and an half and 6 injection (2 per week) of intrathecal methotrexate 5 mg/m2/injection and maintenance chemotherapy for two years with 6 MP, 25 to 50 mg/m2/day and parenteral methotrexate, 10 to 15 mg/m2/week, then immunotherapy with BCG, for a minimum of three years and a maximum of five.

BCG Vaccine↗
PubMed1977

Paraparesis following intrathecal cytosine arabinoside: a case report with neuropathologic findings.

A 65-year-old white male with acute myelogenous leukemia received whole brain irradiation (2550 rads) and intrathecal cytosine arabinoside for CNS prophylaxis. Bone marrow remission had been previously achieved with systemic chemotherapy (vincristine, Adriamycin, prednisone, and cytosine arabinoside). Two weeks following the last intrathecal cytosine arabinoside treatment, the patient developed a spastic paraparesis requiring the use of a walker. A gas myelogram was normal and CSF examination revealed a protein of 50 mg/100 ml but was otherwise unremarkable. Five months later, the patient had improved in that he could stand on his own. A relapse of his leukemia subsequently occurred and the patient died the following month. Striking degenerative changes were found in the spinal cord at postmortem examination. These included microvacuolization, axonal swellings, and loss of myelin with scattered macrophages laden with fat.

Aged↗