The Ph chromosome is a translocation (9;22)(q34;q11), that results in the constitutive activation of the BCR/ABL tyrosine kinase. The incidence of BCR/ABL in Acute Lymphoblastic Leukemia (ALL) increases with age, from less than 5% in younger children to 20-30% in older adults, with a peak incidence in patients aged 35-50 years. BCR/ABL1 has diverse breakpoints, in adult patients with Ph+ ALL the p190BCR/ABL transcript e1a2/e3a2 may be documented in 50-70%; p210BCR/ABL b2a2/b3a2 in 15-30% of patients and <1% having both breakpoint. Childhood patients with Ph+ ALL fusion genes present p190BCR/ABL transcipt e1a2/e3a2 in 90% and the remaining present other fusion transcrit or co-expression of both p190 and p210 BCR-ABL. OBJETIVE. The aim of this study was identify the occurrence of fusion genes to p190 and p210 BCR-ABL rearrangements in adult and childhood patients with ALL. METHODS. We include between 2008-2015 870 patients with ALL de novo from seven different hospitals from México, the 45% (394) were childood and the rest 55% (476) were adults. All patients were studied to RT-PCR multiplex and nested in RNA for fusion transcripts 190 and p210 BCR-ABL, at diagnosis, according to the international BIOMED-1 protocol. RESULTS. From 870 patients with ALL, the most frequent subtype FAB were L2 (87%) and second L1 (13%). The immunophenotype by B-ALL was to 80%, bilineal in 5% and the rest have not data. The overall incidence to BCR-ABL in both children and adults with ALL were to 17% [147/870]. The analysis by age group were; in 476 adults with ALL, their average age was 37 years old (range 17-84 years) and their incidence of BCR-ABL positive was 20% (95/476 cases). The distributions by type of fusion transcript were 83% p190 and 17% p210; we did not observe co-expression of transcripts to BCR-ABL. In children patients the average age was 9 years old (range 0.1-16 years), the incidence of BCR-ABL was 13.2% (52/394 cases). The distributions by type of fusion transcript to BCR-ABL were p190 78.8%; p210 13.4% and their co-expression by both isoforms 8%. CONCLUSION. The 20% frequency for BCR-ABL1 in adults with ALL is concordant with others reports published, with values from 17% to 37% with predominancy of p190 (83%). In our pediatric patients group with ALL, document a frequency of 13.2% by BCR-ABL1 positive; it is higher than other populations reporting 5-10%. The distributions of fusion transcript p190 and p210 coincides with previous prevalence estimates in other countries where p190 transcript was the most frequent. But the coexpression of both isoforms [p190/p210] were 8% it has not been reported in this age group with ALL. In conclusion, we recommend to identify the BCR-ABL transcript type in every patients with ALL at diagnosis, using a RT-PCR verified method for P190/p210 and followed the patient by mesure the impact clinical and will be adjust the treatment like o plus the cytogenetic studies. Disclosures No relevant conflicts of interest to declare.
Purpose: To evaluate efficacy, safety, Disease-Free Survival (DFS) and Overall Survival (OS) in patients with indolent non-Hodgkin’s lymphoma (NHL) treated with chemotherapy vs. immunotherapy vs immunochemotherapy as first-line therapy, an up-date report. Methods: Patients with indolent NHL were randomized to receive: (A) Rituximab x 6/w, (B) CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisone) x 6 or (C) R-CNOP x 6, at standard doses. Results: 195 patients were included, 183 are evaluable for OS and toxicity (A:62, B:55 and C:66), 144 are evaluable for overall response rate (ORR) and DFS (A:53, B:41 and C:50). Clinical characteristics: 89 male (45.6%), mean age 59±14 (±SD), 148 (75.9%) in stage (III/IV), without significant differences between groups. Overall Response Rate (CR+PR) was: A: 84.9%, B:83.4% and C:90% (P=0.545). Neutropenia grade 3/4 was more frequent in the chemotherapy groups: A: 4.8%, B: 23.6% and C:18.2% (P=0.001) as it was the infectious toxicity (grade 2/4): A:4.8%, B:5.5% and C:15.2% (P=0.07). DFS at 24 months was: A 68%, B:65% and C:70%, (P=0.93) and the OS was A:87%, B:84% and C:78%. P=0.89. Conclusions: We did not find any important differences, between groups, regarding the Overall Response Rate, Disease Free Survival and Overall Survival at 24 months. However, single agent rituximab was better tolerated, with less toxicity in comparison with the chemotherapy containing groups. Based on these findings, it maybe reasonable to use immunotherapy only, as first-line therapy for patients with indolent NHL.
Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of lymphoma in the world and corresponds to a heterogeneous entity, both from the clinical and molecular point of view, being its prognosis of survival very variable The IPI and the NCCN-IPI are powerful risk-stratification tools in patients with DLBCL. Although the IPI risk score is widely used, it doesn't discriminate very high risk patients. In 2014 the NCCN-IPI was published. It has shown a better discrimination of these patients in Asia, Europe and USA. GELL is a recently formed group of study in lymphomas from Latin America that includes eleven countries. The aim of this study was to validate whether the NCCN-IPI is of prognostic value in Latin-American patients with DLBCL. Methods: We included patients with a diagnosis of DLBCL treated at different institution between 2012-2013. IRB approval was obtained before the collection of the data. Pathological samples were reviewed at each participating institution to confirm the diagnosis. Pertinent clinical data were collected through chart review and are presented using descriptive statistics. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted to evaluate hazard ratio (HR) for overall survival (OS). Results: A total of 329 patients with the diagnosis of DLBCL were included in this analysis. The median age at diagnosis was 64 years (range 18-83 years) with a slight female predominance (54%). Clinically, 59% of patients were 60 or older, 34% presented with ECOG >1, 29% with elevated serum LDH, and 70% with extranodal disease; 49% had stage I/II and 51% had stage III/IV. The IPI score distribution was low-risk in 36% of patients, low-intermediate in 25%, high-intermediate in 22% and high-risk 17%. The NCCN-IPI score distribution was low risk in 17%, low-intermediate in 42%, high intermediate in 30% and high risk in 11%. 89% of patients received standard R-CHOP, 2% received R-miniCHOP, and 9% received other regimens. The overall response rate was 83%; 69% had complete response and 14% had partial response. The 5-year overall survival (OS) rate was 65%. DLBCL patients with low, low-intermediate, high-intermediate and high risk NCCN-IPI had 5-year OS rates of 89%, 71%, 55% and 38%, respectively (p<0.001). In a multivariate model adjusting for neutrophil-lymphocyte ratio and lymphocyte-monocyte ratio, NCCN-IPI was an independent prognostic factor. When compared with patients with low-risk NCCN-IPI, patients with low-intermediate (HR 2.0, 95% CI 0.9-4.7; p=0.09), high-intermediate (HR 3.5, 95% CI 1.5-8.0; p=0.003) and high-risk NCCN-IPI (HR 7.2, 95% CI 3.0-17.2; p<0.001) had worse OS. Conclusion: We have validated the prognostic value of the NCCN-IPI in previously untreated Latin American patients with DLBCL. Figure. Figure. Disclosures Chiattone: Janssen: Honoraria, Research Funding. Castillo:Beigene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Millennium: Research Funding; Abbvie: Consultancy, Research Funding.
Follicular lymphoma is frequently associated with the chromosomal rearrangement t(14;18)(q32;q21), which joints one of the JH segments of the heavy chains of immunoglobulins (IgH) gene in 14q32 with the Bcl-2 gene in 18q2, originating a chimeric protein. The frequency of this marker is unknown in the Mexican population. OBJECTIVE: To determine the incidence of the Bcl2-IgH rearrangement in Mexican patients with follicular lymphoma and its frequency as a marker of minimal residual disease after therapy. PATIENTS AND METHODS: 200 patients (102 male and 98 female) were evaluated; the analysis was made in peripheral blood samples (PB) in 64 cases (32%) or bone marrow (BM) in 136 (68%). Genomic DNA was obtained and the Bcl-2/IgH rearrangement was amplified by both PCR and nested PCR using primers for JH and exon-intron 3 region of Bcl-2 (MBR and MCR regions). The Bcl-2/IgH rearrangement was used as a marker to determine minimal residual disease (MDR) in 90 out of 200 patients in clinical remission, with a follow up ranging from 12 to 60 months; The incidence and tissue type analysis were compared using chi-square statistics. RESULTS AND DISCUSSION: We found a positive Bcl-2/IgH rearrangement in 80% of the Follicular NHL cases, with a breakage in the MBR region in 160 cases and in MCR in 10 cases, in the remaining 30 patients the Bcl-2/IgH was negative. We detected the Bcl-2/IgH rearrangement more frequently in the BM samples (86%) than in the PB (42%) (p<0.0001). Fifty of 90 initially Bcl-2/IgH positive patients converted to negative PCR, after treatment. It is also of interest that in this population the molecular response rates in BM were lower (18/50=36%) than in the PB (32/50=64%) (p<0.0001). In conclusion we found a high frequency of Bcl-2/IgH rearrangement in cases of follicular lymphoma in Mexican patients, highlighting the relevance of the molecular analysis at diagnosis and its use as a marker for molecular minimal residual disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.