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T-large granular lymphocyte leukaemia with natural killer cell-like cytotoxicity and expression of two different alpha- and beta-T-cell receptor chains.

We describe a case of cytotoxic T-large granular lymphocyte leukaemia showing typical morphological features, expressing antigens characteristic for cytotoxic T cells and exhibiting marked natural killer-like cytotoxicity towards different target cells. Moreover, characterization of the T-cell receptors revealed simultaneous expression of two different types of beta-chains as well as alpha-chains by the malignant cell clone. The patient had an 8 year history of indolent disease, before progressing to an aggressive clinical course hardly responsive to chemotherapeutic treatment. This is the first description of a peripheral T-cell neoplasm expressing four distinct types of T-cell receptor molecules.

Disease Progression↗

Clearance of maternal leukaemic cells in a neonate.

A 36-week pregnant woman was diagnosed with acute lymphoblastic leukaemia. Delivery was initiated prematurely, and a healthy child was born. Cord blood and peripheral blood samples from the neonate (obtained at 6 weeks, 3 months and 6 months) were analysed for the presence of minimal residual disease by polymerase chain reaction analysis of a leukaemia-specific IGH gene rearrangement and the E2A--PBX1 fusion gene transcript. In the cord blood sample, a tumour load of approximately 4 x 10(-4) was found, whereas all later blood samples were negative. Our data indicate that the maternal leukaemic cells did not engraft in the neonate.

Female↗

Prolonged molecular remission in advanced acute promyelocytic leukaemia after treatment with gemtuzumab ozogamicin (Mylotarg CMA-676).

We report a patient with acute promyelocytic leukaemia (APL) who received two doses of gemtuzumab ozogamicin for advanced disease. Previous treatments included front-line all-trans retinoic acid and anthracyclines, polychemotherapy consolidation, salvage chemotherapy for the first relapse followed by autologous stem cell transplantation (ASCT), arsenic trioxide for the second relapse followed by a second ASCT and then high-dose methotrexate for more advanced systemic disease with central nervous system involvement. The patient achieved prolonged haematological and molecular remission after monotherapy with gemtuzumab ozogamicin given at the time of the third relapse.

Adult↗

Intraocular relapse of childhood acute lymphoblastic leukaemia.

Relapse of childhood acute lymphoblastic leukaemia (ALL) involving the eye is a rare but challenging problem. Twenty cases occurred in patients treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia XI and ALL97 trials between 1991 and 2001, representing 2.2% of ALL relapses. Seventeen occurred as a first relapse, either in isolation or combined with relapse at another site, and three occurred as a second relapse. All patients with intraocular disease at first relapse were treated with both chemotherapy and radiotherapy, but the doses and protocols used varied. Eleven of these 17 patients are alive and in complete remission with a median follow up of 4 years 2 months from relapse. All 11 children that were treated with a full chemotherapy relapse protocol, together with local radiotherapy have survived. Patients treated with chemotherapy of shorter duration and intensity, despite radiotherapy and/or bone marrow transplantation, did poorly with only one survivor, currently in chronic relapse. Consequently, we suggest that children with eye relapse of ALL be treated with an intensive relapse chemotherapy protocol with local ocular radiotherapy, whether the relapse occurs in isolation or in combination with relapse at another site.

Antineoplastic Combined Chemotherapy Protocols↗

Constrictive pericarditis in B cell chronic lymphatic leukaemia.

We report a case of B-cell chronic lymphatic leukaemia (B-CLL) complicated by constrictive pericarditis. The pericardial involvement was confirmed histologically to be leukaemic in nature. We draw attention to this complication which is amenable to surgical correction. To our knowledge this has been described only once before as an autopsy finding and has not been encountered ante-mortem.

Arthritis, Infectious↗

Retinal findings in adult leukaemia: correlation with leukocytosis.

The associations between retinal findings and haematological parameters in acute leukaemia are controversial. Sixty-three newly-diagnosed acute leukaemia patients, aged 12-77 years, were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton wool spots (CWS) and macular haemorrhages (MH), Thirty-three patients (52.4%) showed at least one retinal abnormality. The prevalence of individual findings was: IRH (30 cases), WCH (20 cases), CWS (5 cases), MH (11 cases). In contrast to previous studies, there was no association between any of these retinal findings and the haemoglobin level or the platelet count. There was a higher median WBC in patients with IRH (68 x 10(9)/l) than in those without IRH (15.4 x 10(9)/l), P = 0.037. When the acute myeloblastic leukaemia cases were considered separately, an association was also found between higher WBC and the presence of WCH and CWS. There was no association between retinal findings and FAB type in the AML cases. We conclude that a high WBC may be at least as important as anaemia and thrombocytopenia in the pathogenesis of the retinopathy of acute leukaemia.

Acute Disease↗

Thyroid function in survivors of childhood acute lymphoblastic leukaemia: the significance of prophylactic cranial irradiation.

OBJECTIVE: Focus on long-term side-effects after cancer therapy in childhood has become of the utmost importance. The hypothalamic-pituitary thyroid (HPT) axis is exposed to irradiation when some children are treated for acute lymphoblastic leukaemia (ALL) with prophylactic cranial irradiation (CIR). Whether this treatment causes hypofunction of the HPT axis remains controversial. DESIGN: We measured plasma levels of total T3 (T3), total T4 (T4) and TSH before stimulation with TRH and plasma levels of TSH, 30 and 150 minutes after stimulation with TRH in 95 patients in first continuous remission of childhood ALL. PATIENTS: Patients diagnosed with ALL before the age of 15 years between 1970 and 1991 and who were in first continuous remission and off treatment for at least one year were studied. The children were aged between 0.5 and 14.8 years (median: 3.9) at diagnosis of ALL. Thyroid function was assessed between 1.2 and 18.3 years (median: 7.6) after completion of therapy. MEASUREMENTS: We measured T4 levels before, and compared TSH levels before and after, stimulation with TRH in patients who were treated with prophylactic CIR (15-24 Gy) (n = 38) (CIR group) with patients who were treated with chemotherapy only (n = 57) (non-CIR group). RESULTS: We found that T3 and T4 levels were normal in all individuals (excluding the women who were on oral contraceptives). The median time from end of treatment to time at follow-up was 9.1 years in the non-CIR group vs. 4.2 years in the CIR group (P < 0.001), and the effect on follow-up time was significant (P = 0.04). It was estimated that just after irradiation, the TSH levels before and 30 and 150 minutes after TRH stimulation was 49% lower in the CIR group; however, after 4.0 years, TSH levels were not significantly different between the two groups. Although within normal limits, the T4 levels were significantly higher in the CIR group compared to the non-CIR group (P = 0.003). It was estimated that, just after the end of treatment, T4 was 19.9% higher in the CIR group. However, in the CIR group, the T4 level decreased significantly over time with -1.5% per year (P = 0.025), while the difference in the non-CIR group was not significant. There was no correlation between T4 and TSH levels and sex, age at diagnosis, age at the end of treatment or age at follow-up. CONCLUSIONS: We conclude that, in our cohort of survivors of childhood ALL, prophylactic cranial irradiation of the central nervous system did not have an adverse effect on hypothalamo-pituitary-thyroid function within a median follow-up time of 8 years.

Adolescent↗

Hemorrhage in the oculomotor nerve as a complication of leukemia.

Oculomotor paralysis of a patient with leukemia was revealed at autopsy to be caused by a hemorrhage in the oculomotor nerve. In a 63-year-old woman with pre-B-cell acute lymphatic leukemia, leukemic invasions occurred in her spinal cord and right oculomotor nerve during a hematological remission state. The oculomotor palsy was aggravated to complete paralysis during a leukemic relapse, which lasted until her death. An autopsy revealed a hemorrhage along with leukemic cells in the right oculomotor nerve at the segment in the upper orbital fissure. Although hemorrhagic oculomotor paralysis is a very rare complication, reports of its occurrence will likely increase with improved survival times of leukemia patients due to advances in chemotherapy.

Acute Disease↗

Acute airway obstruction in a child with acute lymphoblastic leukaemia during central venous catheterization.

We report the case of a seven-year-old girl with recently diagnosed acute lymphoblastic leukaemia (ALL) who suffered acute airway obstruction during insertion of a central venous catheter under general anaesthesia. The central airway obstruction was due to a mixture of leukaemic cells, blood clot and fibrin. There is discussion about airway obstruction both as a complication of central line insertion and secondary to ALL. The pulmonary complications of ALL, with particular reference to pulmonary haemorrhage, are detailed. The management of blood clot obstructing the central airway is discussed.

Airway Obstruction↗

Leptomeningeal involvement in chronic lymphocytic leukemia.

PURPOSE: This review and case report address the rare complication of leptomeningeal involvement in patients with chronic lymphocytic leukemia. OVERVIEW: Chronic lymphocytic leukemia is the most common form of leukemia, with more than 200,000 cases reported in the past 20 years. An uncommon complication of the disorder is central nervous system invasion. To date, only 21 cases have been reported, and their presenting symptoms have been heterogeneous and often nonspecific, including headache, cranial nerve abnormalities, confusion, ataxia, nausea, vomiting, and fever. The diagnosis is confirmed by the presence of a clonal population of lymphocytes in the cerebrospinal fluid. Treatment is either intrathecal or intraventricular chemotherapy with adjuvant radiation therapy or radiation alone. Prognosis is improved by prompt and aggressive therapy. In this case report, a 61-year-old man developed severe ataxia, vertigo, and occipital headaches 4 weeks after diagnosis with otherwise asymptomatic chronic lymphocytic leukemia. After treatment with both radiation to the head and neck and intrathecal methotrexate the patient achieved complete symptom resolution. Thus far, no additional systemic cytotoxic chemotherapy has been necessary. CLINICAL IMPLICATIONS: Because central nervous system invasion is uncommon in chronic lymphocytic leukemia, it may go undiagnosed and under-reported. Providers of patients with this disease need to be aware of possible central nervous system invasion when patients present with cranial nerve signs or symptoms and/or nonspecific neurologic manifestations. Early identification and prompt central nervous system-directed chemotherapy can affect morbidity and quality of life positively.

Antimetabolites, Antineoplastic↗

[Neuropsychological sequelae in children with AML treated with or without prophylactic CNS-irradiation].

BACKGROUND: In study AML-BFM 87 the relapse rate was lower in patients receiving cranial irradiation (CRT). However, CRT has always been associated with adverse cognitive side effects. Therefore, the impact of CRT on neuropsychological function in children with AML was retrospectively evaluated. PATIENTS: We tested 53 children (30 boys, 23 girls) treated according to the AML-BFM-87 protocol (median age at diagnosis: 8.5 years, range 0.3 - 17.5; median time since diagnosis: 5.7 yrs, 3.8 - 10.7 yrs). To avoid any bias from additional therapy elements, patients with relapse or initial CNS involvement and transplanted patients were excluded (n=32). Our cohort was representative of the total group of 104 long term survivors of study AML-BFM 87. CNS prophylaxis consisted of ARA-C i.th., high dose ARA-C i. v. and either no CRT (n=15) or CRT (n=38) at a dose of 12 - 18 Gy depending on age. METHODS: Neuropsychological function was evaluated by psychological tests of attention and concentration (test d2 by Brickenkamp) and an intelligence test (Progressive Matrices by Raven). In addition, patients and their parents were interviewed about the occurrence of learning problems, subjective deficits in concentration and physical impairment. RESULTS: In the total group, no significant differences were seen between irradiated and non-irradiated patients regarding the psychological tests. However, the irradiated patients scored below the non-irradiated control group in test "d2" (concentration: 41st vs. 59th percentile). In the interview, irradiated patients tended to report more learning problems (lp) (10/36 vs. 1/14; p=0.15) and subjective deficits in concentration (con). In irradiated girls (con: 6/15 vs. 0/8; p=0.06; lp: 5/15 vs. 0/8; p=0.12) and younger patients (0 - 5 years at diagnosis; con: 7/12 vs. 2/9; p=0.18; lp 3/10 vs. 1/9; p=0.18) this trend was even more pronounced. CONCLUSION: Children with AML and CRT had no significant intellectual impairment in standardized tests when compared to non-irradiated patients. However, more irradiated patients reported learning problems and subjective concentration deficits.

Adolescent↗