IBRORS-MCL study: a Spanish retrospective and observational study of relapsed/refractory mantle-cell lymphoma treated with ibrutinib in routine clinical practice.

This retrospective study evaluated 66 patients diagnosed with relapsed and/or refractory mantle cell lymphoma (R/R MCL) treated with ibrutinib in Spain in routine clinical practice. At diagnosis, patients had a median age of 64.5 years, 63.6% presented with intermediate/high sMIPI (simplified prognostic index for advanced-stage mantle cell lymphoma), 24.5% had the blastoid variant, and 55.6% had a Ki67 > 30%. Patients had received a median of 2 prior lines of therapy (range 1-2; min-max 1-7). Overall response rate was 63.5%, with 38.1% of patients achieving complete response (CR). With a median duration of ibrutinib exposure of 10.7 months (range 5.2-19.6; min-max 0.3-36), the median progression-free survival (PFS) and overall survival (OS) were 20 months [95% confidence interval (CI) 8.8-31.1] and 32 months (95% CI 22.6-41.3), respectively, and were not reached in patients achieving CR. No grade ≥ 3 cardiovascular toxicity or bleeding was reported. This study supports that treatment with ibrutinib leads to high response rates and favorable survival outcomes in patients with R/R MCL.

Panel Sequencing for Clinically Oriented Variant Screening and Copy Number Detection in Chronic Lymphocytic Leukemia Patients.

According to current guidelines, in chronic lymphocytic leukemia (CLL), only the TP53 molecular status must be evaluated prior to every treatment's initiation. However, additional heterogeneous genetic events are known to confer a proliferative advantage to the tumor clone and are associated with progression and treatment failure in CLL patients. Here, we describe the implementation of a comprehensive targeted sequencing solution that is suitable for routine clinical practice and allows for the detection of the most common somatic single-nucleotide and copy number variants in genes relevant to CLL. We demonstrate that this cost-effective strategy achieves variant detection with high accuracy, specificity, and sensitivity. Furthermore, we identify somatic variants and copy number variations in genes with prognostic and/or predictive value, according to the most recent literature, and the tool provides evidence about subclonal events. This next-generation sequencing (NGS) capture-based target assay is an improvement on current approaches in defining molecular prognostic and/or predictive variables in CLL patients.

Effect of CD8⁺ cell content on umbilical cord blood transplantation in adults with hematological malignancies.

Total nucleated (TNCs) and CD34(+) cells are considered major determinants of outcome after umbilical cord blood (UCB) transplantation but the effect of other cell subtypes present in the graft is unknown. This single-center cohort study included patients with hematological malignancies who received UCB transplantation after a myeloablative conditioning regimen. UCB units were primarily selected according to cell content, both TNCs and CD34(+) cells, and also according to the degree of HLA matching. Counts of several cell subtypes of the infused UCB unit, together with HLA disparities and other patient- and transplantation-related characteristics, were analyzed by multivariable methodology for their association with myeloid and platelet engraftment, graft-versus-host disease, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Two hundred patients (median age, 32 years) were included in the study. In multivariable analyses, a greater number of CD8(+) cells was significantly associated with better results for myeloid (P = .001) and platelet (P = .008) engraftment, NRM (P = .02), DFS (P = .007), and OS (P = .01). CD34(+) cell content was predictive of myeloid engraftment (P < .001). This study suggests that the outcome after UCB transplantation in adults with hematological malignancies could be better when UCB grafts had a greater CD8(+) cell content.

Single-nucleotide polymorphism array-based karyotyping of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), but additional chromosomal abnormalities (ACA) and other rearrangements can contribute in the development of the whole leukemic phenotype. We hypothesized that some ACA not detected by conventional techniques may be informative of the onset of APL. We performed the high-resolution SNP array (SNP-A) 6.0 (Affymetrix) in 48 patients diagnosed with APL on matched diagnosis and remission sample. Forty-six abnormalities were found as an acquired event in 23 patients (48%): 22 duplications, 23 deletions and 1 Copy-Neutral Loss of Heterozygocity (CN-LOH), being a duplication of 8(q24) (23%) and a deletion of 7(q33-qter) (6%) the most frequent copy-number abnormalities (CNA). Four patients (8%) showed CNAs adjacent to the breakpoints of the translocation. We compared our results with other APL series and found that, except for dup(8q24) and del(7q33-qter), ACA were infrequent (≤3%) but most of them recurrent (70%). Interestingly, having CNA or FLT3 mutation were mutually exclusive events. Neither the number of CNA, nor any specific CNA was associated significantly with prognosis. This study has delineated recurrent abnormalities in addition to t(15;17) that may act as secondary events and could explain leukemogenesis in up to 40% of APL cases with no ACA by conventional cytogenetics.

Results of a preoperative autologous blood donation program for patients undergoing elective major spine surgery.

BACKGROUND AND OBJECTIVES: Spinal surgery has been shown to have a high blood transfusion requirement. Preoperative autologous blood donation (PABD) is a strategy to reduce the allogeneic transfusions in this subset of patients. MATERIAL AND METHODS: We retrospectively reviewed transfusion outcome of patients undergoing elective major spinal surgery from 2005 to 2011, and included in the PABD program. Transfusion outcome was compared with a group of patients that did not enter in the program during the same period. RESULTS: A total of 148 patients were included in the program during the analyzed period. Patients in the PABD program benefited from reduced exposure to allogeneic blood (Odds Ratio: 0.077, 95% confidence interval 0.043-0.140). However, 12.16% (n=18) of these patients received also allogeneic blood (total 40 red blood cell units). Univariate analysis showed the following parameters as significantly predictors of transfusion: inclusion in the program (p<0.000), number of levels fused (Odds Ratio: 1.143, p=0.010), and number of autologous red blood cells donated (Odds Ratio: 1.906, p<0.000). CONCLUSIONS: The preoperative autologous blood donation program designed in our hospital was effective for reducing allogeneic transfusion in mostly young patients under major elective spinal surgery. However and as expected, their inclusion in the program increased the risk to be transfused.