Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid.

We investigated the frequency, predictors, and evolution of acute lymphoblastic leukemia (ALL) in patients with CNS relapse and introduced a novel method for studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analyzed in two PETHEMA clinical trials. All achieved complete remission after imatinib treatment. Of these, 30 (23%) experienced a relapse after achieving complete remission, and 13 (10%) had an isolated CNS relapse or combined CNS and BM relapses. We compared the characteristics of patients with and without CNS relapse and further analyzed CSF and BM samples from two of the 13 patients with CNS relapse. In both patients, classical sequencing analysis of the kinase domain of BCR-ABL1 from the cDNA of CSF blasts revealed the pathogenic variant p.L387M. We also performed ultra-deep next-generation sequencing (NGS) in three samples from one of the relapsed patients. We did not find the mutation in the BM sample, but we did find it in CSF blasts with 45% of reads at the time of relapse. These data demonstrate the feasibility of detecting BCR-ABL1 mutations in CSF blasts by NGS and highlight the importance of monitoring clonal evolution over time.

Neuropsychological syndromes in multiple sclerosis.

BACKGROUND: Cognitive impairment in multiple sclerosis (MS) is common (45-65%).Deficits occur in speed of information processing (SIP), memory, attention, executive functions (EF) and visuoconstruction.Involvement of cognitive functions like language and gnosis is rare and lesser known. Our aim is to describe the cognitive function and the clinical and radiological features of five patients with MS and with neuropsychological syndromes (NPS). METHOD: Retrospective review of MS patients with NPS studied, using specific tests of SIP, memory, attention, EF, visuo-spatial abilities, praxis and language. RESULTS: The sample included four women (3 relapsing-remitting MS/1 secondary progressive MS) and one man with primary progressive MS (aged between 30-55 years). Cognitive symptoms were the initial complaint in three cases. Three cases presented apperceptive agnosia and constructive apraxia, one case presented alexia with agraphia and the fifth patient presented motor aphasia. Four patients suffered cognitive dysfunction considered typical of MS. Magnetic resonance imaging (MR) in all cases showed high lesion volumes in T1 and T2-weighted sequences. A good correlation was observed between cognitive deficits and the location of the lesions in four patients. CONCLUSIONS: NPS may be the initial complaint in MS patients, often associated with other cognitive deficits, and it shows a close relationship with lesion location.

[Prognostic-factor-related survival in a series of patients with renal cell carcinoma]. / Supervivencia en relación a los factores pronósticos en una serie de pacientes con carcinoma de células renales.

OBJECTIVES: To analyze the survival rate in a series of patients with the diagnosis of renal cell carcinoma over a 19 year period based on prognostic factors usually employed in clinical practice. METHODS: Retrospective study of 259 consecutive patients with the diagnosis of renal cell carcinoma undergoing surgery in our department between 1988 and 2006. From clinical, pathological, and follow-up data we performed a survival study comparing the impact of usual prognostic factors: stage, tumor size, nuclear grade, etc. RESULTS: 264 surgical procedures were performed in 259 patients, with a mean age of 6 1.91 yr. The most frequent way of diagnosis was incidental finding (52.12% of the cases); radical nephrectomy was performed in 72.97% of the cases in comparison with 26.25% partial nephrectomies. Clear cell carcinoma was the most frequent histological diagnosis (69.88%). Patients with clear cell carcinoma, symptomatic tumors, bigger size, and greater Fuhrman nuclear grade presented worse survivals, mainly in tumors with stage >pT3a. The presence of involved lymph nodes or distant metastases is associated with a much lower cancer-specific survival. Global five-year cancer-specific survival was over 80%. CONCLUSIONS: The classical prognostic factors used to predict survival in renal cancer are still useful, mainly pathological stage pT. We observed a better survival in comparison with older series, but this kind of tumors continue generating important morbidity-mortality.