Treatment of primary cardiac diffuse large B-cell lymphoma involving the coronary sinus with R-EPOCH: a case report and literature review.

Primary cardiac lymphomas (PCLs) are a rare clinical entity, in which treatment guidelines remain to be established. Rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) has been proposed, given that it involves a continuous infusion of anthracycline, reducing the risk of a cardiotoxicity and therefore the theoretical risk of perforation. However, the literature on this method of treatment is scarce. Herein, we present a unique case of a 75-year-old male, diagnosed with primary cardiac diffuse large B-cell lymphoma (DLBCL) with relatively unusual involvement of the coronary sinus, treated first with one cycle of R-EPOCH, followed by three cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) to reduce said risk. To our knowledge, this is one of two cases, in which a patient with PCL was treated this way.

Cell-free DNA 5-hydroxymethylcytosine is highly sensitive for MRD assessment in acute myeloid leukemia.

Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML). However, MRD cannot be detected in many patients using current methods. We developed a highly sensitive 5-hydroxymethylcytosine (5hmC) signature in cell-free DNA by analyzing 115 AML patients and 86 controls. The 5hmC method detected MRD in 20 of 29 patients with negative MRD by multiparameter flow cytometry and 11 of 14 patients with negative MRD by molecular methods. MRD detection by the 5hmC method was significantly associated with relapse-free survival. This novel method can be used in most AML patients and may significantly impact AML patient management.

Long-term outcomes in patients with Burkitt lymphoma older than 65 years: an analysis of the Texas Cancer Registry.

Burkitt lymphoma (BL) is an extremely aggressive but curable subtype of non-Hodgkin lymphoma. While younger patients have excellent outcomes in response to aggressive chemoimmunotherapy, the rarity of this disease in older patients and limitations caused by age, comorbidities, and performance status may negate survival advantages. This analysis assessed outcomes of older adults with BL through data provided by the Texas Cancer Registry (TCR). Patients ≥65 years with BL were assessed. Patients were dichotomized into 1997-2007 and 2008-2018. Median overall survival (OS) and disease-specific survival (DSS) were assessed using Kaplan-Meier methodology, and covariates including age, race, sex, stage, primary site, and poverty index were analyzed using Pearson Chi-squared analysis. Odds ratio (OR) with 95% confidence intervals (CI) was used to assess factors contributing to patients not offered systemic therapy. P value <0.05 was considered statistically significant. Non-BL mortality events were also categorized. There were 325 adults, 167 in 1997-2007 and 158 in 2008-2018; 106 (63.5%) and 121 (76.6%) received systemic therapy, a trend that increased with time (p = 0.010). Median OS for 1997-2007 and 2008-2018 was 5 months (95% CI 2.469, 7.531) and 9 months (95% CI 0.000, 19.154) (p = 0.013), and DSS was 72 months (95% CI 56.397, 87.603) (p = 0.604) and not reached, respectively. For patients that received systemic therapy, median OS was 8 months (95% CI 1.278, 14.722) and 26 months (95% CI 5.824, 46.176) (p = 0.072), respectively, and DSS was 79 months (95% CI: 56.416, 101.584) and not reached, respectively (p = 0.607). Age ≥75 years (HR 1.39 [95% CI 1.078, 1.791], p = 0.011) and non-Hispanic whites (HR 1.407 [95% CI 1.024, 1.935], p = 0.035) had poorer outcomes, and patients at the 20-100% poverty index (OR 0.387 [95% CI 0.163, 0.921], p = 0.032) and increasing age at diagnosis (OR 0.947 [95% CI 0.913, 0.983], p = 0.004) were less likely to receive systemic therapy. Of 259 (79.7%) deaths, 62 (23.9%) were non-BL deaths, and 6 (9.6%) of these were from a second cancer. This two-decade analysis of older Texas patients with BL indicates a significant improvement in OS over time. Although patients were more likely to receive systemic therapy over time, treatment disparities existed in patients residing in poverty-stricken regions of Texas and in advancing age. These statewide findings reflect an unmet national need to find a systemic therapeutic strategy that can be tolerated by and augment outcomes in the growing elderly population.

Classification of Acute Myeloid Leukemia by Cell-Free DNA 5-Hydroxymethylcytosine.

Epigenetic abnormality is a hallmark of acute myeloid leukemia (AML), and aberrant 5-hydroxymethylcytosine (5hmC) levels are commonly observed in AML patients. As epigenetic subgroups of AML correlate with different clinical outcomes, we investigated whether plasma cell-free DNA (cfDNA) 5hmC could categorize AML patients into subtypes. We profiled the genome-wide landscape of 5hmC in plasma cfDNA from 54 AML patients. Using an unbiased clustering approach, we found that 5hmC levels in genomic regions with a histone mark H3K4me3 classified AML samples into three distinct clusters that were significantly associated with leukemia burden and survival. Cluster 3 showed the highest leukemia burden, the shortest overall survival of patients, and the lowest 5hmC levels in the TET2 promoter. 5hmC levels in the TET2 promoter could represent TET2 activity resulting from mutations in DNA demethylation genes and other factors. The novel genes and key signaling pathways associated with aberrant 5hmC patterns could add to our understanding of DNA hydroxymethylation and highlight the potential therapeutic targets in AML. Our results identify a novel 5hmC-based AML classification system and further underscore cfDNA 5hmC as a highly sensitive marker for AML.

Long term outcomes in older patients with primary central nervous system lymphoma: an analysis of the Texas Cancer Registry.

Primary central nervous system lymphoma (PCNSL) is an aggressive subtype of non-Hodgkin lymphoma that carries a poor prognosis in the elderly. The aim of this study is to investigate treatment patterns and survival trends in patients ≥ 65 years with PCNSL through data provided by the Texas Cancer Registry. Adults ≥ 65 years diagnosed with PCNSL and followed between 1995-2017 were identified and separated into three eras: 1995-2003, 2004-2012, and 2013-2017. Baseline covariates compared included patient demographics and treatments administered. Pearson's chi-squared test and Cox proportional hazard models compared covariates; overall survival (OS) and disease-specific survival (DSS) were assessed via Kaplan-Meier methodology. There were 375 patients; 104 (27.7%) in 1995-2003, 146 (38.9%) in 2004-2012, and 125 (33.3%) in 2013-2017. There were 50 (48.1%), 55 (37.7%), and 31 (24.8%) in 1995-2003, 2004-2012, and 2013-2017, respectively, that did not receive treatment. At last follow up, 101 (97.1%), 130 (89.0%), and 94 (75.2%) in each era died, of which 89 (85.6%), 112 (76.7%), and 70 (56.0%) were attributed to PCNSL. Median OS per era was eight (95% confidence interval [CI] 5.06-10.93), six (95% CI, 2.30-9.69), and five months (95% CI, 2.26-7.73) (p = 0.638). DSS per era was nine (95% CI: 0.00, 26.53), 10 (95% CI: 5.14, 14.86), and 19 (95% CI, 0.00-45.49) (p = 0.931) months. Spinal cord as primary disease site (HR: 0.668 [95% CI, 0.45-0.99], p = 0.049), and chemotherapy (HR 0.532 [95% CI, 0.42-0.673], p = < 0.001) or chemotherapy + radiation (HR, 0.233 [95% CI, 0.11-0.48] p < 0.001) had better outcomes compared to no therapy or radiation therapy alone. Survival in older patients ≥ 65 with PCNSL has not improved per our analysis of the TCR from 1995-2017 despite increasing trends of treatment utilization. Strategies to augment recruitment of older individuals in trials are needed in order to determine who would derive treatment benefit and minimize treatment toxicities.

Cell-free DNA 5-hydroxymethylcytosine is an emerging marker of acute myeloid leukemia.

Aberrant changes in 5-hydroxymethylcytosine (5hmC) are a unique epigenetic feature in many cancers including acute myeloid leukemia (AML). However, genome-wide analysis of 5hmC in plasma cell-free DNA (cfDNA) remains unexploited in AML patients. We used a highly sensitive and robust nano-5hmC-Seal technology and profiled genome-wide 5hmC distribution in 239 plasma cfDNA samples from 103 AML patients and 81 non-cancer controls. We developed a 5hmC diagnostic model that precisely differentiates AML patients from controls with high sensitivity and specificity. We also developed a 5hmC prognostic model that accurately predicts prognosis in AML patients. High weighted prognostic scores (wp-scores) in AML patients were significantly associated with adverse overall survival (OS) in both training (P = 3.31e-05) and validation (P = 0.000464) sets. The wp-score was also significantly associated with genetic risk stratification and displayed dynamic changes with varied disease burden. Moreover, we found that high wp-scores in a single gene, BMS1 and GEMIN5 predicted OS in AML patients in both the training set (P = 0.023 and 0.031, respectively) and validation set (P = 9.66e-05 and 0.011, respectively). Lastly, our study demonstrated the genome-wide landscape of DNA hydroxymethylation in AML and revealed critical genes and pathways related to AML diagnosis and prognosis. Our data reveal plasma cfDNA 5hmC signatures as sensitive and accurate markers for AML diagnosis and prognosis. Plasma cfDNA 5hmC analysis will be an effective and minimally invasive tool for AML management.

Use of ifosfamide, carboplatin and etoposide in combination with brentuximab vedotin or romidepsin based on CD30 positivity in relapsed/refractory peripheral T-cell lymphoma.

BACKGROUND: Relapsed/refractory peripheral T-cell lymphoma (R/R PTCL) has a poor prognosis. Romidepsin (Ro) and brentuximab vedotin (Bv), combined with ifosfamide, carboplatin, and etoposide (ICE) has not been significantly studied in PTCL. AIM: We report outcomes of Bv-ICE in CD30 (+) and Ro-ICE in CD30 (-) R/R PTCL treated in "Blinded for peer review" Cancer Center. METHODS AND RESULTS: We retrospectively identified R/R PTCL patients treated with BV-ICE or romidepsin-ICE from May 2016 to September 2019. Out of 13 R/R PTCL patients, 6 were treated with Bv-ICE and 7 with Ro-ICE. Bv-ICE had an overall response rate (ORR) of 66.7%, with all the patients achieving a complete response. ORR was 71.4% for Ro-ICE with 57.1% of patients achieving a complete response. Two patients treated with Bv-ICE and three treated with Ro-ICE received transplantation. CONCLUSION: In our experience, treatment with Bv-ICE and Ro-ICE based on CD30 positivity is feasible and effective to treat patients with R/R PTCL.

Use of rituximab in lymphomatoid granulomatosis with isolated central nervous system involvement.

A 33-year-old woman presented to the emergency room with severe headaches. A CT scan of the head revealed two brain lesions with associated vasogenic oedema. Diagnostic resection of one of the lesions followed by pathological analysis revealed grade III lymphomatoid granulomatosis (LYG). Staging investigations elsewhere in the body were negative, isolating this case of LYG to the central nervous system, an atypical presentation. After the resection, she was treated with single-agent rituximab 375 mg/m2 The follow-up MRI demonstrated the resolution of brain lesions and no progression of the disease.

The development of T-cell malignancies in patients with pre-existing myeloproliferative neoplasms: a report of three cases.

Secondary acute myeloid leukaemia complicating the natural disease course of pre-existing Philadelphia chromosome-negative myeloproliferative neoplasms (PN-MPN) is well documented and associated with treatment challenges and significant morbidity. The incidence of a T-cell malignancy developing in patients with pre-existing PN-MPN is uncommon, with one case documented in the literature. We present two cases of angioimmunoblastic T-cell lymphoma (AITL) and one case of T-cell acute lymphoblastic leukaemia (T-ALL) that developed in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively. All malignancies were advanced at diagnosis and exhibited disease progression, regardless of the mutational status of the underlying ET/PMF, presence of cytogenetic abnormalities, type of T-cell neoplasm or systemic chemotherapy utilised. The median time to diagnosis of AITL or T-ALL from the onset of MPN was 4.5 years (range: 6 months-10 years). This single institutional case series demonstrates the possibility of an association between T-cell neoplasms and PN-MPNs.

Multiple myeloma with concurrent immune thrombocytopenic purpura.

Multiple myeloma (MM) is the second most common haematological malignancy in the USA. MM has been linked to various autoimmune disorders in many studies; one systemic review even suggested an increased risk of MM among patients with autoimmune disorders. MM is associated with many haematological, rheumatologic and neurological conditions. A few case reports suggest that MM can be associated with immune thrombocytopenic purpura (ITP), although this is rare. We present a case of MM with concurrent ITP which was refractory of steroids and intravenous immunoglobulin but had a response with anti-neoplastic therapy for MM. We also review all the cases of ITP with MM described in the literature. If conventional treatment for ITP associated with MM fails to improve platelet count, anti-neoplastic therapy for MM should be considered.

Discovery of imatinib-responsive FIP1L1-PDGFRA mutation during refractory acute myeloid leukemia transformation of chronic myelomonocytic leukemia.

The FIP1L1-PDGFRA rearrangement results in constitutive activation of the tyrosine kinase PDGFRA. Neoplasms harboring this rearrangement are responsive to imatinib mesylate at doses much lower than those recommended for the treatment of chronic myelogenous leukemia. Only a single report has described the identification of FIP1L1-PDGFRA in chronic myelomonocytic leukemia (CMML). Herein, we present a case report of a patient in whom the FIP1L1-PDGFRA was discovered as he evolved from CMML to acute myeloid leukemia (AML). The presence of a dominant neoplastic clone with FIP1L1-PDGFRA rearrangement was suspected on the basis of sudden onset of peripheral and bone marrow eosinophilia and confirmed by fluorescence in situ hybridization and molecular diagnostic tests. Whereas the patient was initially refractory to chemotherapy before the rearrangement was detected, subsequent therapy with imatinib led to complete remission.

Targeted therapy for HER2 positive breast cancer.

INTRODUCTION: Breast cancer is the second most common cause of death for women behind lung cancer and the most common cause of cancer deaths for women aged 45-55 years old (CDC.gov 2012). Although there continue to be enormously large numbers of disease incidence, deaths have been declining due to the disease with two hallmark time frames. The first occurred during the mid to late 1980's when hormonal therapy was introduced as a treatment for ER/PR positive breast cancer. The second occurred in the late 1990's when trastuzumab was introduced in treating HER2 positive breast cancer. These remarkable accomplishments in developing novel targeted therapies for breast cancer, along with a better understanding of the disease biology have improved disease outcome over the past 20 years.This article reviews the data presented at 2012 American Society of Clinical Oncology and 2012 San Antonio Breast Cancer Symposium regarding progress made in the field of HER2 positive breast cancer and examines the future of HER2 targeted therapy.