No abstract

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.

Newly acquired genomic abnormalities can arise during the natural history of chronic lymphocytic leukemia (CLL). Reported frequencies range from 17 to 42%, based on several series with small numbers of patients (n ¼ 31-64) and with a limited follow-up (60-83 months) [1][2][3][4]. It has been shown that this complication appears more frequently in patients with unmutated IGVH (immunoglobulin heavy chain variable region) and after treatment. Deletion (del) of 17p13 is unusual as clonal evolution (CE) in untreated patients, and the same thing applies in patients with mutated IGVH. In the present article we report the data obtained in our series, and show that del(17p13) can occur in untreated patients, as well as in those with mutated IGVH.We retrospectively collected data from two Spanish centers. Overall, 81 patients had at least two fluorescence in situ hybridization (FISH) analyses done. The reason for repeated FISH analysis was clinical progression, although in both centers FISH was not performed on a routine basis. The probes used were: LSI p53/LSI ATM and LSI D13S319/ LSI 13q34/CEP 12 multi-color probe sets (Vysis, UK). Standard cut-off level for a deletion was determined as 10% for the probes LSI D13S319, LSI ATM, and LSI p53, and 5% for trisomy 12. A second independent observer analyzed FISH borderline results. Median time of observation after first FISH analysis was 67 months (range 16-111).The baseline characteristics of patients can be seen in Table I. Seventeen out of 81 (21%) patients had CE. In the first FISH analysis, eight out of these 17 (47%) patients had alterations: seven of them (41%) had one alteration [five cases with del(13q14), two cases with trisomy 12] and one case (6%) had two anomalies (13q 7 6 1/11q7). Median observation time between first FISH and the subsequent study with CE was 30 months (range 8-99).Regarding CE itself, 53% of the patients acquired 17p7, while 35% of the cases acquired 11q7, either an anomaly alone or in combination.The details of all the CE cases can be found in Table II, including the treatment between FISH analyses; IGVH data are added, where available.Ten cases with CE had available IGVH data, and four of these were mutated. A germline homology of 98% was used as the cut-off between VH mutated Table I. Clinical characteristics and prior therapy. With CE Without CE n 17 64 Median age (years) (range) 70 (41-80) 68 (45-86) Female (%) 8 (47) 32 (50) Rai III/IV or Binet C (%) 2/14 (14) 13/57 (23) Binet B þ C (%) 4/14 (50) 27/57 (47) Unmutated VH 6/10 NA Number of prior lines (range) 1 (0-6) 1 (0-7) CD38 þ (%) 5/11 (45) 22/53 (41) ZAP70 þ (%) 3/8 (37) 17/45 (38) Follow-up from diagnosis (months) (range) 80 (15-217) 35 (8-183) CE, clonal evolution; NA, not available.

The prevalence of HCV infection in patients with NHL (both B- and T-type) is higher than that observed in controls, suggesting a role of HCV in lymphoma aetiopathogenesis.

Most of α-thalassemia cases are caused by deletions of the structural α-globin genes. The 12 degree of microcytosis and hypochromia has been correlated with the number of affected α-globin 13 genes, suggesting a promising role of hematologic parameters as predictive diagnostic tools.14 However, cut-off points for these parameters to discriminate between the different subtypes of α- 25