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Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased-risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: results of the European Organization for Research and Treatment of Cancer 58881 randomized phase III trial.

PURPOSE: The European Organization for Research and Treatment of Cancer 58881 study was designed to test in a prospective multicentric randomized trial the value of high-dose (HD) intravenous (IV) cytarabine (Ara-C) added to HD IV methotrexate (MTX) to reduce the incidence of CNS and systemic relapses in children with increased-risk acute lymphoblastic leukemia (ALL) or stage III and IV lymphoblastic lymphoma treated with a Berlin-Frankfurt-Munster (BFM)-based regimen. PATIENTS AND METHODS: After completion of induction-consolidation phase, children with increased-risk (risk factor > 0.8 or T-lineage) ALL or stage III and IV lymphoblastic lymphoma were randomized to receive four courses of HD MTX (5 g/m(2) over 24 hours every 2 weeks) and four intrathecal administrations of MTX (Arm A) or the same treatment schedule with additional HD IV Ara-C (1 g/m(2) in bolus injection 12 and 24 hours after the start of each MTX infusion) (Arm B). RESULTS: Between January 1990 and January 1996, 653 patients with ALL (593 patients) or lymphoblastic lymphoma (60 patients) were randomized: 323 were assigned to Arm A (without Ara-C) and 330 to Arm B (with Ara-C). A total of 190 events (177 relapses and 13 deaths without relapse) were reported, and the median follow up was 6.5 years (range, 2 to 10 years). The incidence rates of CNS relapse were similar in both arms whether isolated (5.6% and 3.3%, respectively) or combined (5.3% and 4.6%, respectively). The estimated 6-year disease-free survival (DFS) rate was similar (log-rank P =.67) in the two treatment groups: 70.4% (SE = 2.6%) in Arm A and 71.0% (SE = 2.5%) in Arm B. The 6-year DFS rate was similar for ALL and LL patients: 70.2% (SE = 1.9%) versus 76.3% (SE = 5.6%). CONCLUSION: Prevention of CNS relapse was satisfactorily achieved with HD IV MTX and intrathecal injections of MTX in children with increased-risk ALL or stage III and IV lymphoblastic lymphoma treated with our BFM-based treatment protocol in which cranial irradiation was omitted. Disappointingly, with the dose schedule used in this protocol, HD Ara-C added to HD MTX, although well tolerated, failed to further decrease the incidence of CNS relapse or to improve the overall DFS.

Actuarial Analysis↗

Central nervous system lesions in childhood leukemia.

Central nervous system (CNS) lesions were found in 85 of 91 children with acute leukemia. Cerebral atrophy was the most common lesion, occurring in 65 percent. Atrophy was most severe in children treated with intrathecal methotrexate alone or in combination with radiation therapy, in children youngest at time of onset of leukemia, and in children in whom duration of leukemia was shortest. Longer duration was the determining factor among children who were older at onset. Lesions previously reported by other investigators, such as leptomeningeal infiltration of leukemic cells, infection, hemorrhage, degenerative grey and white matter disease and leukoencephalopathy were also seen. Central pontine myelinolysis occurred in four children.

Age Factors↗

Numb chin syndrome secondary to Burkitt's cell acute leukemia.

We describe a case of Burkitt's cell acute lymphoblastic leukemia presenting with the bilateral numb chin syndrome as the initial symptom of the disease. Postmortem study of the trigeminal nerve showed heavy infiltrations of leukemic cells and destruction of axon and myelin by leukemic cells in the mandibular nerve.

Burkitt Lymphoma↗

CNS myelomatosis.

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Bone Marrow Transplantation↗

Magnetic resonance spectroscopy in the evaluation of neurotoxicity following cranial irradiation for childhood cancer.

In order to evaluate the role of proton MR spectroscopy (1H-MRS) in the diagnosis and assessment of long-term radiation-related neurotoxicity, 14 children who had received cranial irradiation for the treatment of childhood leukaemia (n = 6) or brain tumours (n = 8) underwent 1H-MRS, MRI and neuropsychological assessment. Short-term effects at 2 months following treatment were studied in a further three patients. MRI abnormalities were observed in nine patients. No statistically significant differences between patients and controls (n = 17) were seen in any of the calculated 1H-MRS metabolite ratios, in any of the three patient groups. On multivariate logistic regression analysis there was a correlation between the choline/water ratio and a low IQ. It is concluded that any systematic radiation-induced changes in the 1H MRS metabolites must be below the detection threshold of this study.

Adolescent↗

Tumor-forming acute myeloid leukemia with facial paralysis.

A 55-year-old male with acute myeloid leukemia, which had been well controlled for 2 years, developed a sudden onset of facial palsy. Otologic examinations proved the right mastoid bone to be infiltrated by leukemic cells, which formed a nonchloroma to occlude the right external auditory canal. The precise site for the right facial paralysis by tumor formation was found in the intrastapedial region of peripheral portion of the right facial nerve. Regarding the tumor formation in myeloid leukemia, its frequency (particularly among Japanese subjects), complications (particularly in otologic field), possible pathogeneses, and treatments were discussed.

Audiometry↗

Computed tomography and magnetic resonance findings in two dogs and a cat with intracranial lesions.

Two dogs and a cat with intracranial lesions were evaluated by both computed tomography (CT) and magnetic resonance (MR) imaging. In a dog with vestibular syndrome, better quality images of the medulla oblongata surrounded by thick bones were obtained by MR than by CT, on which the appearance of artifacts impeded the clear image of the area. In a dog with multiple brain metastases of lymphoma, contrast CT delineated lesions more clearly than MR, which was performed one week after CT. During that week dexamethasone which might affect the clarity of MR images of the lesion was administered to reduce brain edema. In a cat with meningeal syndrome of lymphocytic leukemia, only contrast MR imaging identified the width and site of the lesion. These results indicate that it is necessary to select either one of these imaging methods according to the type and site of lesions that are suspected in a particular case.

Animals↗

Fine-needle aspiration of secondary neoplasms involving the salivary glands. A report of 36 cases.

Metastases or secondary deposits account for 16% of the malignant neoplasms involving the major salivary glands. A correct diagnosis of a secondary neoplasm is important to avoid unnecessary radical surgery and to guide further therapy. Fine-needle aspiration biopsy (FNAB) is an excellent noninvasive diagnostic tool for evaluating salivary gland lesions. We reviewed 36 secondary malignant salivary gland neoplasms evaluated by FNAB. Ancillary studies were performed in selected cases. Follow-up included clinical correlation and review of histologic material. For 4 adenocarcinomas, 4 squamous cell carcinomas, 1 undifferentiated carcinoma, 1 cutaneous basal cell carcinoma, 10 cutaneous melanomas including 1 desmoplastic variant, 3 osteosarcomas, 11 non-Hodgkin lymphomas, and 2 multiple myelomas, there was 1 false-negative FNAB result. The desmoplastic melanoma was interpreted as reactive lymphoid hyperplasia. A malignant diagnosis was given in all remaining cases except the secondary basal cell carcinoma, which was diagnosed as a neoplasm with basal cell features. FNAB is a reliable tool to differentiate hematologic malignant neoplasms and melanomas from other salivary gland neoplasms. A complete knowledge of the clinical history, review of previous pathologic materials, and, in some instances, the use of ancillary studies are crucial for recognizing solid malignant neoplasms secondarily involving the salivary glands.

Adult↗

Blastic natural killer cell lymphoma/leukemia: a report of seven cases.

Only a few blastic natural killer (NK) cell leukemias and lymphomas have been reported. As such, the clinicopathologic spectrum of this disease is incompletely understood. We report 7 cases of blastic NK cell lymphoma/leukemia. All patients were men, 5 white and 2 Arab American. All cases exhibited blastic morphologic features and were CD3- and CD56+ with germline T-cell receptor genes. Five cases were CD4+ and involved the skin. Both CD4- cases never involved the skin. Other markers of mature NK cells such as CD16, CD57, and TIA-1 were expressed infrequently. Three cases were CD33+. One CD33+ case had a clonal rearrangement of the immunoglobulin heavy chain gene. Skin and lymph nodes were involved most often, with frequent evolution to a leukemic phase. Initial responses to therapy were achieved in most patients, but the tumors invariably recurred.

Adult↗

Acute myelomonocytic leukemia. Demonstration of pulmonary involvement by bronchoalveolar lavage.

Massive pulmonary infiltration by leukemic cells resulting in respiratory symptoms is a rare complication of acute leukemia. We report the findings in a patient with acute myelomonocytic leukemia presenting with acute onset of fever, dyspnea, and nonproductive cough, in whom the diagnosis of pulmonary invasion by leukemic cells was made by cytochemical analysis of bronchoalveolar cells recovered by lavage.

Bronchi↗