Nelarabine-associated myelopathy in a patient with acute lymphoblastic leukaemia: Case report.

INTRODUCTION: Nelarabine is a purine analogue approved for the treatment of patients with T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukaemia (T-ALL) that have relapsed or are refractory to two previous chemotherapy regimens. Adverse reactions to nelarabine include neurological toxicity, the pathophysiological mechanisms of which are unknown, although the administration of intrathecal therapy at therapeutic doses given concomitantly with high-dose systemic chemotherapy that crosses the blood-brain barrier may potentiate neurotoxicity. CASE REPORT: We report a case of a 29-year-old woman with a diagnosis of relapsed T-ALL who developed severe myelopathy and polyneuropathy of toxic origin that led to paraplegia, upper-limb paresis, and dysautonomia after the first cycle of nelarabine. MANAGEMENT AND OUTCOME: Rehabilitation and pharmacological treatments were initiated early, but no evidence of a significant clinical change was obtained. DISCUSSION: Neurotoxicity is a dose-dependent side effect of nelarabine. It is therefore important to consider previously administered neurotoxic drugs before using nelarabine and to monitor patients closely so as to be able to act promptly in case of toxicity. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered possible.

MICA-HLA-B haplotype diversity and linkage disequilibrium in a population of Jewish descent from Majorca (the Balearic Islands).

The major histocompatibility complex class I chain-related A (MICA) gene is located 46 kb centromeric of human leukocyte antigen (HLA)-B and is highly polymorphic, similar to HLA genes. This allelic variation may influence the affinity of MICA molecules to their receptor on natural killer, gammadelta T and CD8+ T cells, NKG2D, and the immune response to organ transplantation and disease susceptibility. In the present study, we typed MICA and HLA-B polymorphisms in 95 individuals from a population of Jewish descent (Chuetas) and 195 individuals of Caucasian origin from Majorca (the Balearic Islands). MICA*008, -*004, and -*002 were the most common alleles and accounted for 53 and 60% in Chuetas and Majorcans, respectively. Other common alleles (frequency >5%) were MICA*016, -*009, -*012, -*007, and -*017 in Chuetas and -*009, -*001, and -*018 in Majorcans. We also studied two-locus haplotype diversity and linkage disequilibrium (LD). Both populations presented haplotypes with significant LD that were shared by other Caucasians populations, but we reported particular haplotypes in the Chueta group: MICA*002-HLA-B*38, MICA*016-HLA-B*35, MICA*012-HLA-B*55, and MICA*017-HLA-B*57. These haplotypes were not reported in other studies at high frequencies. In conclusion, the Chueta population presents a particular genetic pool but has affinities with the host population.

Tc99m-sestamibi scintigraphy and cell proliferation in primary hyperparathyroidism: a causal or casual relationship?

BACKGROUND: Sestamibi scintigraphy has become the fundamental technique for preoperative location of hyperfunctioning glands responsible for hyperparathyroidism, especially in the case of adenomas. However, little is known about the mechanisms of tracer uptake and retention by these glands, mechanisms that have been related to an increased gland metabolism. Our goal was to determine whether there is a relationship between the positive result of gammagraphy with sestamibi, for diagnosing the location of parathyroid adenomas, and the cell proliferation index. PATIENTS AND METHODS: Six glands corresponding to sestamibi false negatives and 12 true positives were studied in patients with single-adenoma primary hyperparathyroidism. The following data were recorded in all the patients: age, gender, clinical and analytical data, gland weight, and parathyroid hormone (PTH)/gland weight ratio. An immunohistochemical study of the glands was also done with the use of Ki67, with determination of the mean proliferation index of each group for comparison purposes. RESULTS: On comparing the 2 groups, we found no differences between the clinical or analytical parameters. Differences were found only for proliferation index-(5.7% in true positive glands versus 0.3% in false negative glands (P <.004). CONCLUSION: Tracer (sestamibi) uptake by hyperfunctioning parathyroid adenomas in primary hyperparathyroidism might be linked to a higher gland metabolism activity, probably related to cell proliferation.