Forest plots of hazard ratios (HRs) and 95% confidence intervals (95% CIs) for event-free survival endpoints in DLBCL patients with C-MYC gene abnormalities (A), overexpression of C-MYC mRNA (B) and C-MYC protein (C).

<p>Squares represent the HR of each study, and the area of each square was proportional to the weight of each study in the meta-analysis; Horizontal lines, 95% CIs; Closed diamond, pooled HRs with their 95% CIs.</p

PRISMA flow chart of study selection.

<p>PRISMA flow chart of study selection.</p

C-MYC Aberrations as Prognostic Factors in Diffuse Large B-cell Lymphoma: A Meta-Analysis of Epidemiological Studies

<div><p>Objectives</p><p>Various studies have investigated the prognostic value of C-MYC aberrations in diffuse large B-cell lymphoma (DLBCL). However, the role of C-MYC as an independent prognostic factor in clinical practice remains controversial. A systematic review and meta-analysis were performed to clarify the clinical significance of C-MYC aberrations in DLBCL patients.</p><p>Methods</p><p>The pooled hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS) were calculated as the main effect size estimates. The procedure was conducted according to the Cochrane handbook and PRISMA guidelines, including the use of a heterogeneity test, publication bias assessment, and meta-regression, as well as subgroup analyses.</p><p>Results</p><p>Twenty-four eligible studies enrolling 4662 patients were included in this meta-analysis. According to the nature of C-MYC aberrations (gene, protein, and mRNA), studies were divided into several subgroups. For DLBCL patients with C-MYC gene abnormalities, the combined HR was 2.22 (95% confidence interval, 1.89 to 2.61) for OS and 2.29 (95% confidence interval, 1.81 to 2.90) for EFS, compared to patients without C-MYC gene abnormalities. For DLBCL patients with overexpression of C-MYC protein and C-MYC mRNA, pooled HRs for OS were 2.13 and 1.62, respectively. C-MYC aberrations appeared to play an independent role among other well-known prognostic factors in DLBCL. Addition of rituximab could not overcome the inferior prognosis conferred by C-MYC.</p><p>Conclusion</p><p>The present systematic review and meta-analysis confirm the prognostic value of C-MYC aberrations. Screening of C-MYC should have definite prognostic meaning for DLBCL stratification, thus guaranteeing a more tailored therapy.</p></div

Associations between the previously well-known prognostic factors with C-MYC aberrations.

<p>Abbreviations: IPI, international prognostic index; LDH, lactate dehydrogenase; OR, odd ratio; CI, confidence interval.</p

Features summary of the eligible studies in the meta-analysis.

<p>Abbreviations: HR, hazard ratio; OS, overall survival; EFS, event-free survival; IHC, immunohistochemistry; FISH, interphase fluorescent <i>in situ</i> hybridization; RT-PCR, reverse transcription-polymerase chain reaction; qNPA, quantitative nuclease protection assay; LD-PCR, long-distance polymerase chain reaction; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; CyclOBEAP, cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, and prednisone; R-DHAP, rituximab, dexamethasone, aracytine, and cisplatin; R-ICE, rituximab, ifosfamide, etoposide, and carboplatin; NA, not available.</p

Subgroup analyses for the prognostic values of C-MYC aberrations in DLBCL patients.

<p>Abbreviations: HR, hazard ratio; OS, overall survival; EFS, event-free survival; CI, confidence interval; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; without R, treatment without rituximab; NA, not available.</p

<i>SIL-TAL1</i> Rearrangement is Related with Poor Outcome: A Study from a Chinese Institution

<div><p><i>SIL-TAL1</i> rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL), however its prognostic implication remains controversial. To investigate the clinical characteristics and outcome of this subtype in Chinese population, we systemically reviewed 62 patients with newly diagnosed T-ALL, including 15 patients with <i>SIL-TAL1</i> rearrangement. We found that <i>SIL-TAL1⁺</i> T-ALL was characterized by higher white blood cell count (<i>P</i> = 0.029) at diagnosis, predominant cortical T-ALL immunophenotype (<i>P</i> = 0.028) of the leukemic blasts, and a higher prevalence of tumor lysis syndrome (TLS, <i>P</i><0.001) and disseminated intravascular coagulation (DIC, <i>P</i><0.001), which led to a higher early mortality (<i>P</i> = 0.011). Compared with <i>SIL-TAL1⁻</i> patients, <i>SIL-TAL1⁺</i> patients had shorter relapse free survival (<i>P</i> = 0.007) and overall survival (<i>P</i> = 0.002). Our NOD/SCID xenotransplantation model also demonstrated that <i>SIL-TAL1⁺</i> mice models had earlier disease onset, higher leukemia cell load in peripheral blood and shorter overall survival (<i>P</i><0.001). Moreover, the <i>SIL-TAL1⁺</i> mice models exerted a tendency of TLS/DIC and seemed vulnerable towards chemotherapy, which further simulated our clinical settings. These data demonstrate that <i>SIL-TAL1</i> rearrangement identifies a distinct subtype with inferior outcome which could allow for individual therapeutic stratification for T-ALL patients.</p></div

Comparison between <i>SIL-TAL1</i>⁺ and <i>SIL-TAL1⁻</i> T-ALL patients.

<p>LDH, lactate dehydrogenase; WBC, white blood cell; CNS, central nerves system; TLS, tumor lysis syndrome; DIC, disseminated intravascular coagulation; CR, complete remission.</p>*<p>Not all patients were evaluated.</p

Comparison of serum biochemical and coagulation parameters between <i>SIL-TAL1</i>⁺ and <i>SIL-TAL1⁻</i> murine models.

<p>LDH, lactate dehydrogenase; PT, prothrombin time; APTT, activated partial thromboplastin time; FDP, fibrinogen degradation products; VCR, vincristine; DEX, dexamethasone.</p

Drug treatment on murine xanotransplantation model.

<p>(A) The human CD45⁺ cells were detectable 2 weeks after inoculation in all 3 groups, but the peak of human CD45⁺ cell load was lower in vincristine treated group. (B) The survival of dexamethasone treated group (median 35 days) was longer than the vincristine treated group (median 26 days, <i>P</i> = 0.002) and saline control group (median 24 days, <i>P</i><0.001). The difference between saline control and vincristine treatment group was also statistically significant (<i>P</i> = 0.033).</p