Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia

Relapsed acute lymphoblastic leukemia (ALL) usually carries a dire prognosis. We evaluated the effectiveness and long-term complications of intensive rotational combination chemotherapy for late hematologic relapse (median, 16 months after elective cessation of therapy) among 34 children and young adults (ages 4 to 23 years). Concurrent central nervous system (CNS) relapse was present in 3 cases and testicular relapse in 4. Secondary therapy comprised an intensive five-drug reinduction (6 weeks) followed by continuation treatment with four drug pairs, rotated weekly in 4-week cycles over 120 weeks. Intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine) was given three times during reinduction and every 8 weeks during continuation. Treatment was electively discontinued at week 120 in the absence of detectable disease. Thirty-three patients (97%) attained a second complete remission. At a median follow-up of 9.3 years (range, 4.5 to 11.4), estimates of 5-year second event-free and overall survival (+/- SE) are 65% +/- 8% and 79% +/- 7%, respectively. Eleven patients had a second relapse (9 marrow, 2 testicular) and one developed secondary myeloid leukemia. There have been no CNS relapses or deaths in remission. Treatment was well-tolerated and was given largely on an outpatient basis. Late effects are primarily endocrinologic; one child had a second malignant solid tumor (presumed related to initial radiation therapy) that was treated successfully. Intensive treatment with alternating non-cross-resistant drug pairs for late hematologic relapses of ALL is effective and well-tolerated, and produces results similar to those achieved in patients with newly diagnosed ALL. Event- free survival compares favorably with reports of other relapse regimens, including those incorporating bone marrow transplantation.     

Persistence of circulating blasts after 1 week of multiagent chemotherapy confers a poor prognosis in childhood acute lymphoblastic leukemia

Early response to therapy, typically assessed by bone marrow status, is predictive of outcome in childhood acute lymphoblastic leukemia (ALL). Less is known about the significance of early clearance of blast cells in peripheral blood. We reviewed medical records of all patients with ALL enrolled on St Jude Total Therapy Study XI (February 1984 to September 1988) to determine the presence of blast cells in peripheral blood at diagnosis and after 1 week of intensive induction therapy. Of the 358 patients, 59 lacked evidence of circulating blast cells at diagnosis, and data were unavailable for 2 patients. The prognostic significance of persistent circulating blast cells in the remaining 297 patients was assessed in a multivariate analysis that included known adverse prognostic factors. Persistent circulating leukemic blasts were present at day 8 in 41 patients (14%). Compared with the "blast- negative" group, these patients had a significantly higher frequency of several adverse clinical features (leukocyte count > 50 x 10(9)/L, mediastinal mass, central nervous system leukemia, T-cell phenotype, lack of CD10 expression, and L2 morphology) and a significantly poorer 5-year event-free survival (34% +/- 8% [SE] v 77% +/- 3%, P < .01). By multivariate analysis, blast cell persistence at week 1 was the most significant adverse feature in the overall cohort (relative risk, 2.9; 95% confidence interval, 1.8 to 4.8) and in an analysis limited to B- lineage cases (relative risk, 3.6; 95% confidence interval, 1.9 to 7.1). Patients identified by this simple, noninvasive measure may benefit from early modification of therapy.     

High incidence of absent nerve conduction in older patients with bilateral carpal tunnel syndrome

INTRODUCTION

Carpal tunnel syndrome has been reported by some to have a less satisfactory outcome in older patients following surgery. However, this impression is not supported by other investigators but no objective explanation has been suggested for these differences. In our department, such patients are routinely treated with night wrist splints and, if this is unsatisfactory, they are investigated with nerve conduction studies prior to surgery.

PATIENTS AND METHODS

This paper reports the neurophysiological outcome in a young (< 40 years of age) and an older (> 60 years of age) group of patients with clinical bilateral carpal tunnel syndrome who did not benefit from splints.

RESULTS

The results showed that both the motor and sensory conduction speeds are significantly lower in the older age group. More importantly in the older group, half had one or more hands where the sensory conduction was absent. In four out of these 10 patients this finding was bilateral and three patients had unilateral absent motor conduction. In the younger group, no patient had absent conduction.

CONCLUSIONS

Poor surgical outcome in some older patients may be because of irreversibly damaged nerves prior to surgery and pre-operative neurophysiology is, therefore, recommended both for clinical and medicolegal reasons.     

NCAM-induced intracellular signaling revisited

The neural cell adhesion molecule (NCAM) plays a crucial role in neuronal development, synaptic plasticity, and regeneration. NCAM works as "smart glue" that not only mediates cell-cell adhesion but also induces activation of a complex network of intracellular signaling cascades on homophilic or heterophilic binding. Stimulation of NCAM by homophilic interactions induces neuronal differentiation through activation of a number of signaling molecules, including the fibroblast growth factor receptor, non-receptor kinases Fyn and focal adhesion kinase, growth-associated protein-43, the mitogen-activated protein kinase pathway, intracellular Ca(2+), and protein kinases A, C, and G. This review presents and discusses the current knowledge in the area of NCAM signaling with a focus on the events involved in NCAM-mediated neurite outgrowth.     

Case of the month: The skin wrinkle test: a simple nerve injury test for paediatric and uncooperative patients

Assessment of the distal neurological status after injuries to the hand and fingers is one of the most frequent parts of standard trauma practice. Two-point discrimination as clinical examination is often sufficient to identify such lesions, but difficulties occur in the comatose, young or otherwise uncooperative patient. This article describes a simple pain-free alternative method of assessing digital nerve integrity by submerging the finger tip in water and observing if wrinkles develop on the skin.     

Effectiveness of the ketogenic diet in a broad range of seizure types and EEG features for severe childhood epilepsies

Background –  Ketogenic diet (KD) is an effective treatment for pharmacoresistant epilepsy: more than half of the patients show a greater than 50% reduction in seizures.
Objective –  To identify clinical or electroencephalogram (EEG) variables predicting the response to KD.
Methods –  Clinical and EEG data were retrospectively analysed from 50 consecutive patients treated by KD for severe, pharmacoresistant epilepsy. Most of the patients (70%) had retarded mental and motor development.
Results –  Three months after the start of the KD two-thirds (33) of the patients were responders (had a more than 50% reduction in seizure frequency). The presence of epileptiform EEG discharges in the temporal region correlated with an unfavourable response ( P  = 0.03). The presence of bilateral synchronous epileptiform discharges, and the presence of complex partial seizures approached significance but all other variables did not.
Conclusions –  Our results further support that KD is efficient in a wide variety of epileptic patients with a broad range of EEG features. However, patients with epileptiform discharges in the temporal region are less likely to achieve therapeutic response.     

Combined use of Amplified Fragment Length Polymorphism and IS<Emphasis Type="Italic">6110</Emphasis> -RFLP in fingerprinting clinical isolates of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> from Kerala,South India

Background  

DNA fingerprinting by IS6110-RFLP has shown a high incidence of Mycobacterium tuberculosis isolates having no and low copies of the insertion sequence in Kerala, South India. Amplified Fragment Length Polymorphism (AFLP) would scan the entire genome rather than a few repetitive elements, we thought that this technique would help us in differentiating the large reservoir of isolates from an endemic region. Here we evaluate the ability of Amplified Fragment Length Polymorphism (AFLP) to type clinical isolates.     

Results of definitive radiotherapy in T1 and T2 glottic carcinoma: Institute of Rotary Cancer Hospital experience

Early glottic carcinomas (T₁ and T₂) constitute only 2% of all laryngeal cancers in our data. Seventy patients were seen between 1985 and 1992. All patients were treated by cobalt-60 small field radiotherapy using a beam directed shell. The total dose delivered was 60–65 Gy in 31 patients and 66–70 Gy in 39 patients. The follow-up period ranged from 5 to 126 months, with a mean follow up of 37 months overall and 55 months in the surgical salvage group. Radiation therapy controlled disease in 71% (50 of 70) of patients overall; 75% with T₁ and 67% with T₂ lesions. Total laryngectomy as salvage surgery was performed in 70% (14 of 20) of patients whose disease recurred. Ultimate control including surgical salvage occurred in 64 (91%) of 70 patients in the present study. The actuarial 5 year survival was 83 and 80% in T₁ and T₂ tumours, respectively (statistically insignificant). This report supports the policy of definitive irradiation, reserving surgical salvage for radiation failures in early laryngeal cancers.