Cutaneous squamous cell carcinoma following treatment for acute lymphoblastic leukaemia

The importance of second malignant neoplasms following successful treatment of childhood malignancy is of concern to all professionals involved with the care of these patients. We present an 18 year old patient with a squamous cell carcinoma of his lower lip following prolonged treatment for acute lymphoblastic leukaemia in childhood. The rarity of this tumor in this age group and the aetiological factors involved in developing the second malignancy are discussed. © 1993 Wiley-Liss, Inc.     

Second intracranial neoplasms following treatment of childhood acute lymphoblastic leukaemia

We report a boy with acute lymphoblastic leukaemia (ALL) treated with chemotherapy and prophylactic cranial irradiation to a dose of 24 Gy. Six years after diagnosis he developed a glioma and died. Prior to 1979, four cases of second malignant neoplasm (SMN) of the brain had been reported in children treated for ALL. These SMNs occurred within 2 years of the original diagnosis (median 1.3 years) and at least two of four patients had not received prior radiotherapy. Since 1979, 28 cases of SMN of the brain have been reported including nine of 468 (1.9%) long-term survivors in one study. All occurred more than 3.7 years from diagnosis (median 6.5 years; range 4-13 years) and all received cranial irradiation (median 24 Gy; range 20-48 Gy). These data indicate a change in the pattern of SMNs which is most likely due to the introduction of cranial irradiation. As well, the frequency of SMNs in children treated for ALL appears to have increased, although it is still no greater than the risk of SMNs developing following the treatment of any other primary childhood neoplasm.     

Ovarian function following the treatment of childhood acute lymphoblastic leukaemia

Ovarian function was assessed in 40 long term survivors who had received standard United Kingdom Acute Lymphoblastic Leukaemia (UKALL) protocols and were in first clinical and haematological remission. A menstrual and pregnancy history was taken (median age at assessment: 18.8 (12–34.7) years) and the acquisition of adult secondary sexual characteristics confirmed in each patient. Basal bloods were taken for follicle stimulating hormone (FSH), luteinizing hormone (LH), and serum oestradiol estimations. Serum progesterone concentration was measured in those patients who were in the luteal phase of their menstrual cycle at assessment. In addition, menstrual cycle profiles of salivary progesterone concentrations were derived from daily samples in 12 patients. All patients achieved adult sexual development; median age at menarche was early at 12.4 (9.0–14.6) years and 37 of them have regular menses. Ten patients have had 14 live births, and evidence of ovulation was seen in a further 11 patients assessed in the luteal phase of the menstrual cycle. Four patients had damaged ovaries, two of whom show evidence of ovulation; three of the four received craniospinal irradiation and one received cyclophosphamide as part of her chemotherapy regimen. None of these patients has yet developed total ovarian failure or required sex steroid replacement therapy. The medium term outlook for ovarian function is good for the majority of childhood ALL survivors. The spinal component of craniospinal irradiation is a major risk factor for ovarian damage, and cyclophosphamide may be a contributory factor. A premature menopause remains a possibility if significant follicular depletion has occurred at the time of cytotoxic treatment. © 1993 Wiley-Liss, Inc.     

Mild axonal neuropathy of children during treatment for acute lymphoblastic leukaemia.

Neurophysiological functioning was studied prospectively in children treated for acute lymphoblastic leukaemia with a low dose vincristine regime (8 x 1.5 mg/m2/dose), to obtain more insight into vincristine neuropathy. A WHO neurotoxicity score was estimated and vibration sense and electrophysiological measurements were taken at standardized times during vincristine treatment. The WHO neurotoxicity score showed decreased or disappearance of Achilles tendon reflexes, and mild sensory disturbances, but a grade 3-4 neurotoxicity was not demonstrated by any of the children. Vibration perception thresholds increased progressively during treatment and amplitudes of action potentials of peroneal and sensory ulnar and median nerves decreased, whereas nerve conduction velocities stayed unchanged. Both vibration perception thresholds and the electrophysiological findings hardly exceeded the limits of normality. We conclude that children treated for acute lymphoblastic leukaemia with a low dose vincristine regimen have mild axonal neuropathy which may be responsible for the motor problems in these children.     

Metabolism of fibrinogen in children with acute lymphoblastic leukaemia

The metabolism and in vivo kinetics of fibrinogen were studied using homologous ¹²⁵I-labelled fibrinogen in 21 children with acute lymphoblastic leukaemia (ALL). Ten patients were undergoing induction therapy, 11 children were in complete remission on maintenance therapy.Results in the patients undergoing induction therapy were: plasma fibrinogen levels were normal in all except one patient, the plasma fibrinogen pool was elevated in six cases, seven patients had a shortened fibrinogen half-life and increased fractional catabolic rate for fibrinogen. The absolute catabolic rate for fibrinogen was elevated in six cases. This shortened fibrinogen half-life together with the correcting effect of heparinisation on the fibrinogen turnover indicated that fibrinogen was consumed by chronic disseminated intravascular coagulation. Inhibition of the fibrinolytic system with epsilon-aminocaproic acid in five patients had no influence on the fibrinogen half-life in three of them but resulted in its prolongation in two patients.All except two children in complete remission had normal fibrinogen levles. Six patients had elevated plasma fibrinogen pools and in all of the cases survival and fractional catabolic rate of fibrinogen were normal. The absolute catabolic rate for fibrinogen was normal in eight, elevated in three of the patients. This observation indicates that fibrinogen synthesis remains accelerated in some cases of ALL in complete remission, but the cause of this is not known.Abbreviations ALL acute lymphoblastic leukaemia - DIC disseminated intravascular coagulation - PTT partial thromboplastin time - PT prothrombin time - TT thrombin time - EG ethanol gelation test - ELT euglobulin clot lysis time - FDP fibrinogen/fibrin degradation products - FCR fractional catabolic rate constant - ACR absolute catabolic rate - IFP intravascular plasma fibrinogen pool - PV plasma volume     

Potential benefits of physical activity for children with acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is the most common form of paediatric leukaemia. The survival rate in children with ALL has improved significantly over the past several years, which makes quality of life an important focus for researchers. Some of the side effects of treatment (i.e. osteoporosis and obesity) are not realized until years after conclusion of therapy. Few studies have addressed the impact of physical activity (PA) on the side effects that occur during treatment of children with ALL. This paper discusses the increased risk for both osteoporosis and obesity due to treatment for ALL and suggests ways that PA may attenuate bone loss and risk of obesity by discussing what is known about effects of PA in healthy children and children with other chronic diseases. Recommendations will be made for PA interventions and future research in children with ALL.     

The course of biological parameters and 6-mercaptopurine pharmacokinetics during maintenance treatment of children with acute lymphoblastic leukaemia

Twenty patients on maintenance therapy (MT) for acute lymphoblastic leukaemia (ALL) with oral 6-mercaptopurine (6-MP) and methotrexate (MTX) were studied. White cell and red cell indices and platelets counts were monitored every second week as were drug levels. Mean values for 6-MP and MTX doses, and blood component parameters were calculated for each 6-month period for the whole patient group. 6-MP plasma concentrations and liver-function tests were determined once every six months and mean values calculated. 6-MP and MTX mean doses did not change significantly during MT. The mean area under the concentration versus time curve (AUC) 0-4 hours varied slightly from the start to the end of the MT (257 and 296 ng/ml.h, respectively). The mean plasma peak concentration increased from 98 ng/ml to 195 ng/ml (p less than 0.01) during the same period. There were significant decreases between the initial white blood cell counts (WBC) and red blood cell counts (RBC) as compared to levels at the end of therapy (p less than 0.01 and 0.02, respectively). A linear correlation was found between 6-MP peak concentrations and both WBC (r = 0.96) and RBC (r = 0.87). At the end of MT liver function tests became normal in all except 6 patients. In conclusion, MT have moderate effects on bone marrow and liver and monitoring 6-MP plasma concentration might be of value for determination of the optimal WBC levels during MT.     

Longitudinal anthropometric study in children with acute lymphoblastic leukaemia

In four groups of patients with acute lymphoblastic leukaemia, anthropometric variables were investigated every 3 months for 2 years. Group 1 (n = 7) was treated with a high-risk protocol, group 2 (n = 13) with a standard-risk protocol including cranial irradiation, group 3 (n = 13) with a standard-risk protocol without cranial irradiation and group 4 (n = 8) was followed after completion of treatment. A height retardation of 0.4-0.6 SD was observed during therapy in groups 1-3. A catch-up of 0.5 SD was found in group 4. The retardation of armspan was significantly larger than the retardation of sitting height when groups 1-3 were taken together. Head circumference was not affected. The anthropometric variables reflecting nutritional status showed a growth above normal during and after treatment. Corticosteroid medication and not cranial irradiation is the most likely explanation for our findings.     

Intussusception in children with ALL receiving chemotherapy for acute lymphoblastic leukaemia

Acute abdominal complications of chemotherapy are common but the differential diagnosis wide. We describe two cases of intussuception of the bowel in children receiving chemotherapy for acute lymphoblastic leukaemia (ALL) and discuss how a high clinical suspicion is critical for the correct diagnosis to be made rapidly.     

Virus infections in children with acute lymphoblastic leukaemia.

The pattern of virus isolation and illness was studied in 64 children with acute lymphoblastic leukaemia (ALL) during periods of apparent infection and when the children were well. The virus isolation rate of 2.2 viruses per child a year is similar to that previously found in normal children. In only 32% of children with symptoms were viruses found and 14.5% had viruses isolated when asymptomatic. The children with ALL appear to be more vulnerable to multiple virus infections and to excrete the virus for longer periods. This may be due to failure of production of both local and systemic antibodies. The failure in the past to recognise the true importance of virus infections in ALL may have been due to inadequate diagnostic techniques.     

Academic career after treatment for acute lymphoblastic leukaemia

AIM—To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings.
PATIENTS—Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluation was 20 years; median follow up since diagnosis was 15 years at the time of the study.
METHODS—Patients and their 134 siblings completed a questionnaire on school career. The percentage of referrals to special primary schools for learning disabled, and the final level of secondary education in patients and siblings were compared, using a six point classification. Within the patient group, the effect of possible risk factors (age at diagnosis, irradiation dose, and gender) was investigated.
RESULTS—Significantly more patients than siblings were placed in special educational programmes. A significant difference was found for level of secondary education. No effect of gender or irradiation dose was found, but younger age at diagnosis was significantly related to both referrals and school levels.
CONCLUSION—Treatment for childhood ALL with cranial irradiation and chemotherapy at a young age is clearly associated with poorer academic career.

     

Memory after treatment for acute lymphoblastic leukaemia.

Long term survivors of acute lymphoblastic leukaemia (ALL) often experience cognitive difficulties, which may be related to impairment of memory function. Memory ability has been studied in a group of survivors of ALL along with sibling controls and in children who have received treatment for other forms of cancer. Children in the ALL group were found to have significant deficits in memory function in tasks which required the application of strategic planning behaviour. These deficits are potentially remediable by educational strategies.     

Immune response in families of children with acute lymphoblastic leukaemia

The immune status of 33 mothers, 17 fathers, and 14 sibs of children with acute lymphoblastic leukaemia was studied with the following tests: peripheral blood lymphocyte counts, lymphocyte transformation with phytohaemagglutinin, serum immunoglobulin levels, isohaemagglutinin titres, and levels of antibody to herpes simplex and Epstein-Barr viruses. No significant abnormality was shown by these tests, with the exception of a lymphocytosis detected in parents at an early stage of their child''s disease. The significance of these findings is discussed in the light of the concept that viral infection relates to the aetiology of childhood leukaemia. It is concluded that there is no defect of immunity in these families.     

Clinical neurological findings of children with acute lymphoblastic leukaemia at diagnosis and during treatment

Serial neurological evaluation was performed on 40 consecutive children with acute lymphoblastic leukaemia (ALL) at the time of diagnosis and during treatment. Abnormal neurological signs were found in 23% of the patients, including some without neurological symptoms on admission. Six patients (15%) had abnormal funduscopy findings, papilloedema or preretinal haemorrhages, and 3 of them had increased intracranial pressure measured in connection with a diagnostic lumbar puncture but without blasts in their CSF. The reason for the increased intracranial pressure remained unclear. The development of neurological symptoms caused by peripheral neuropathy during induction therapy was related to the total dose and duration of vincristine therapy. The most severe walking difficulties, patients moving about on all fours for as long as 6 weeks–5 months, occurred in a group who were significantly younger than the other children (P<0.03). Fine and gross motor disturbances occurred in 18% and 30% of the whole patient group, respectively, after 2–3 years of therapy. Impaired short-term memory was observed in 21% of the patients after 2–3 years of therapy, indicating impaired CNS function. The results indicate that chemotherapy also seems to influence CNS abilities, since there was no significant difference between the patients treated with or without cranial irradiation. Neurological evaluation of children with ALL at diagnosis and during treatment is of value with respect to abnormal findings which persist and are not caused by leukaemia, in order to determine the types of difficulties involved and to consider intervention.