Pretransplant serum beta-2 microglobulin level is a potential novel prognostic marker of overall survival after allogeneic hematopoietic cell transplantation - a retrospective observational study.

Although elevated serum beta-2 microglobulin (BMG) has been reported as a poor prognostic marker for various hematological malignancies, no study has assessed its prognostic significance in allogenec hematopoietic cell transplantation (allo-HCT). Therefore, we conducted this retrospective observational study in 227 consecutive patients with available pretransplant serum BMG levels between April 2010 and September 2017 at our institute. We also collected and retrospectively analyzed various pretransplant variables likely related to transplant outcomes. Multivariable analysis, including major prognostic variables, such as the disease risk index and the hematopoietic cell transplant-comorbidity index, showed a significant association between higher serum BMG levels and poorer overall survival (OS) in all three adjusted models [hazard ratio (HR) per its standard deviation (SD) (SD = 1.094): 1.67 (1.35-2.03; P < 0.001), HR per SD: 1.46 (1.14-1.86; P = 0.002), HR per SD: 2.03 (1.62-2.55; P < 0.001)], respectively, due to the significant association between higher serum BMG levels and relapse/progression [HR 1.52 (1.20-1.94; P < 0.001)] instead of nonrelapse mortality [HR 1.06 (0.70-1.60; P = 0.780)]. Moreover, DRI and serum BMG had statistically significantly higher c-statistic estimates for OS compared with DRI alone (c-index 0.74 and 0.68, respectively; P < 0.001). In conclusion, pretransplant serum BMG level may serve as a useful prognostic marker and help clinical decision in allo-HCT.

Prognostic factors and outcome of relapsed/progressive pediatric Ewing sarcoma: single-center 10-year experience.

BACKGROUND: Ewing sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Despite more intensive chemotherapy regimens and improved local control therapy, there is still a considerable rate of recurrent/progressive disease. METHODS: A retrospective study of 50 relapsed/progressive ES patients who were treated at the National Cancer Institute (NCI), Cairo University, during the period from 1st of January 2008 to the end of December 2018, to assess different prognostic variables and disease outcomes. RESULTS: Out of fifty eligible cases, 32 patients (64%) had disease recurrence, and 18 (36%) developed disease progression on treatment. The median follow-up period was 7.4 months. The median overall survival (OS) was 7.5 months, and the cumulative OS was 64% at 6 months and 32.6% at 1 year. The cumulative event-free survival (EFS) was 41.3% at 6 months and 22.3% at 1 year. Patients with disease recurrence had better OS and EFS than patients with disease progression (p = 0.019). Patients who underwent local control at relapse/progression had a significantly better outcome than patients who received chemotherapy only (p < 0.001). Recurrence > 2 years from initial diagnosis was the only independent predictor of better survival outcome. CONCLUSIONS: Patients with relapsing/progressive ES portended a poor outcome, with disease progression on treatment faring worse than relapse. Better outcome was observed in patients who experienced recurrence > 2 years after diagnosis, patients with disease recurrence rather than disease progression on treatment, and patients who underwent local control along with intensive chemotherapy.

Changes in angiogenesis and hypoxia-inducible factor-1α protein expression in relapsed/refractory indolent non-Hodgkin lymphomas.

Angiogenesis is involved in the pathogenesis and progression of non-Hodgkin lymphomas (NHL), and hypoxia-inducible factor-1α (HIF-1α, also termed HIF1A) might contribute to this process. Currently, there is no direct evidence that the clinical progression of indolent NHL is associated with angiogenesis, and the expression of HIF-1α at recurrence is unknown. Matched lymph node biopsies at diagnosis and recurrence of relapsed/refractory indolent NHL patients were analysed by immunohistochemical and morphometric analysis. We observed an increased vascular network and HIF-1α protein expression in the second biopsy, providing direct evidence that angiogenesis is an essential process for disease progression.

Clinical prognostic value of the SMYD2/3 as new epigenetic biomarkers in solid cancer patients: a systematic review and meta-analysis.

BACKGROUND: SET and MYND domain-containing protein (SMYD) family with methyltransferase activity is involved in cancer progression. This novel meta-analysis aimed to evaluate the association of SMYD family with the clinical and survival outcomes in solid cancer patients. METHODS: We systematically searched Embase, PubMed, Scopus and Web of Science to select relevant articles. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals were extracted. Heterogeneity was evaluated by chi-square-based Q and I2 tests, while publication bias by funnel plots and Egger's test. RESULTS: Thirty-two articles (4,826 patients) met inclusion criteria. SMYD2/3 overexpression was statistically associated with poor overall survival (HR = 1.794, P < 0.001), disease/relapse/progression-free survival (HR = 2.114, P < 0.001), disease/cancer-specific survival (HR = 3.220, P = 0.003), larger tumor size (OR = 1.963, P < 0.001), advanced TNM stage (OR = 2.066, P < 0.001), lymph node metastasis (OR = 2.054, P < 0.001), and distant metastasis (OR = 1.978, P = 0.004). Subgroup analysis showed more significant association between SMYD2 overexpression and reduced survival outcomes than that in SMYD3. Conversely, the relationship between SMYD3 and various clinicopathologic factors was stronger compared to SMYD2. CONCLUSION: Enhanced SMYD2/3 expression may be an unfavorable clinical prognostic factor in different solid cancer types.

Case Report: Cardiac Involvement by Lymphoma: Rare but Heterogeneous Condition With Challenging Behaviors.

Cardiac lymphomas are rare extranodal lymphomas involving primarily and secondarily the heart and/or pericardium. Here we describe three cases of cardiac involvement from lymphoma with specific peculiarities: two primary cardiac Diffuse Large B-cell Lymphomas and one secondary involvement from Marginal Zone Lymphoma (MZL). The first case highlights the issue of early CNS relapse and the possible role for CNS prophylaxis; the second case demonstrates the difficulties of interpretation and possible mistakes of different radiologic techniques adopted to evaluate cardiac involvement by lymphoma during follow-up; the third is a unique case of MZL with cardiac involvement. Our aim is to share the findings observed in these cases putting them in relation with data from the literature.

Autologous Stem Cell Transplantation in Central Nervous System Lymphoma: A Multicenter Retrospective Series and a Review of the Literature.

BACKGROUND: Central nervous system (CNS) lymphoma is associated with poor outcomes. Autologous stem cell transplantation (ASCT) has been reported to improve outcomes when used as a consolidation strategy in primary CNS lymphoma (PCNSL) and as a salvage strategy in patients with disease relapse limited to the CNS. Herein, we describe our experience of using ASCT in PCNSL and secondary CNS lymphoma (SCNSL). PATIENTS AND METHODS: We evaluated clinical outcomes of 18 patients from 2 major academic centers with a median age of 55 (range, 46-72) years. Thirteen patients had PCNSL and 5 patients had SCNSL. Most of the cases were in the first (CR1) or second (CR2) complete remission (CR1 = 7, CR2 = 7) at the time of ASCT. Carmustine with thiotepa (n = 12, 67%) was the most commonly prescribed preparative regimen. RESULTS: The median follow-up from ASCT for surviving patients was 12 (range, 0.9-115) months. The 2-year progression-free survival (PFS) and overall survival (OS) were 74% (95% confidence interval [CI], 48%-99%) and 80% (95% CI, 55%-100%), respectively. Two-year non-relapse mortality was 0%. The 2-year cumulative incidence of relapse/progression was 27% (95% CI, 10%-72%). In subgroup analysis of PCNSL patients, 2-year PFS, OS, and relapse were 71% (95% CI, 38%-100%), 71% (95% CI, 38%-100%), and 29% (95% CI, 9%-92%), respectively. CONCLUSION: In this retrospective study of patients with CNS lymphoma, consolidation with ASCT after high-dose methotrexate-based chemotherapy is safe and effective in reducing disease relapse.

Treatment and clinical outcomes of patients relapsing after allogeneic hematopoietic cell transplantation for myelodysplastic syndrome.

BACKGROUND: Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. METHODS: Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. RESULTS: The median time from HCT to relapse was 6.6 (range, 0.9-136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. CONCLUSION: Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.

Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies.

BACKGROUND: Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies. PATIENT AND METHODS: We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester. White blood cell count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC (ANC: ALC) ratio, absolute eosinophil count, absolute monocyte count (AMC), platelet counts, and myeloid to lymphoid (M:L) ratio at baseline and throughout treatment were assessed. Kaplan-Meier method and Cox proportional hazards model were performed. RESULTS: We treated 146 patients with nivolumab and 11 with pembrolizumab between January 1, 2015 and April 15, 2017. At median follow-up of 20 months, median OS and PFS were 6.0 and 2.6 months, respectively. Higher baseline ANC, AMC, ANC: ALC ratio and M: L ratio correlated with worse clinical outcomes in patients who underwent anti-PD-1 treatment. A baseline ANC: ALC ratio of 5.9 or higher had a significantly increased risk of death (hazard ratio [HR] =1.94; 95% confidence interval [CI], 1.24-3.03; P = 0.004) and disease progression (HR, 1.65; 95% CI, 1.17-2.34; P = 0.005) compared with patients with lower ratio. Similarly, a baseline M: L ratio of 11.3 or higher had significantly increased risk of death (HR, 2.5; 95% CI, 1.54-4.05; P < 0.001), even after a multivariate analysis (HR, 2.31; P = 0.002), compared to those with lower ratio. CONCLUSIONS: Increased baseline ANC: ALC ratio and M: L ratio before initiation of anti-PD1 antibodies were associated with poor PFS and OS in advanced NSCLC patients. The potential predictive value of these readily available biomarkers might help with risk stratification and treatment strategies. These findings warrant further investigation in a larger, prospective study.

Allogeneic Hematopoietic Cell Transplantation for Richter Syndrome: A Single-Center Experience.

BACKGROUND: Recent studies have shown dismal outcomes when chronic lymphocytic leukemia progresses to Richter syndrome after patients receive ibrutinib, with a median overall survival ranging from 2.6 to 3.5 months. Published data on efficacy of allogeneic hematopoietic cell transplantation in Richter syndrome are limited to single-center case series and registry data. PATIENTS AND METHODS: We evaluated the efficacy of allogeneic transplantation in 10 patients, median age of 63 (range, 50-74) years, allografted at a median of 5 (range, 4-25) months from diagnosis of Richter syndrome. All showed an objective response to therapy before transplantation (first complete remission = 7 [70%], first partial response = 2 [20%], second partial response = 1 [10%]). Most received a myeloablative conditioning regimen (n = 7, 70%). Filgrastim-mobilized peripheral blood stem cells was the preferred cell source (n = 10, 100%). RESULTS: Median follow-up of surviving patients was 46 (range, 15-82) months. The 4-year overall survival was 50% (95% confidence interval [CI], 19%-81%). Nonrelapse mortality at 1 year and 4 years post-transplantation were 40% (95% CI, 19%-85%) for both time points. The 4-year incidence of relapse/progression was 10% (95% CI, 2%-64%). CONCLUSION: Allogeneic hematopoietic cell transplantation is an effective treatment for patients with Richter syndrome who show an objective response before allografting. Patients must be referred to transplant centers as soon as the diagnosis is confirmed to evaluate candidacy for the procedure and identify a suitable donor in a timely manner.

Allogeneic hematopoietic cell transplantation in T-cell prolymphocytic leukemia: A single-center experience.

BACKGROUND: T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzumab, an anti-CD52 humanized monoclonal antibody, is the treatment of choice for remission induction. Allogeneic hematopoietic cell transplantation (allo-HCT) has been described to induce durable remissions and improve survival, but data is limited. PATIENTS AND METHODS: We evaluated clinical outcomes of 11 patients, median age of 56 (range, 43-71) years who underwent allo-HCT for T-PLL. The majority of cases were in the first complete remission (CR1 = 9, CR2 = 1, second partial response PR2 = 1) at time of allo-HCT. Myeloablative conditioning was the most commonly prescribed preparative regimen (n = 8, 73%) and tacrolimus plus sirolimus was most commonly prescribed regimen for graft-versus-host disease prophylaxis (n = 5, 46%). RESULTS: The median follow-up for surviving patients was 48 (range, 6-123) months. The 4-year progression-free survival (PFS) and overall survival (OS) were 45% (95% confidence interval (CI) = 13-78%) and 56% (95% CI = 24-89%), respectively. Cumulative incidence of non-relapse mortality (NRM) at 4-year post-transplantation was 34% (95%CI = 14-85%). The 4-year cumulative incidence of relapse/progression was 21% (95% CI = 6-71%). CONCLUSION: Allo-HCT is an effective treatment for T-PLL. Patients must be evaluated for their candidacy for allo-HCT as soon as the diagnosis is confirmed. Efforts are needed to decrease NRM and relapse.

Intrathecal liposomal cytarabine and leptomeningeal medulloblastoma relapse: a valuable therapeutic option.

BACKGROUND: Relapsed medulloblastoma (MB) is a highly lethal disease, requiring for new effective treatment strategies. Intrathecal (IT) therapy both for de novo or relapsed brain tumors with meningeal metastasis is rarely used in first line and relapse protocols. PATIENTS AND METHODS: We report on three cases of children with relapsed MB treated with IT liposomal cytarabine administered after mild sedation every 15 days. RESULTS: The treatment was well-tolerated in all patients, achieving a prolonged progression-free survival (4-11 months) with a good quality of life. CONCLUSION: This experience suggests the need for a phase II trial in brain embryonal tumors with leptomeningeal metastasis to better evaluate the efficacy of IT liposomal cytarabine.

Treatment and clinical outcomes of patients relapsing after allogeneic hematopoietic cell transplantation for myelodysplastic syndrome

BACKGROUND: Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. METHODS: Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. RESULTS: The median time from HCT to relapse was 6.6 (range, 0.9–136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. CONCLUSION: Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.