James N. Butera

Acute myelogenous leukemia

Acute myeloid leukemia (AML) is a heterogeneous disease with outcomes dependent upon several factors, including patient age, karyotype, mutational status, and comorbid conditions. For younger patients, approximately 60% to 80% achieve complete remission with standard therapy involving cytarabine and an anthracycline. However, only 20% to 30% have long-term disease-free survival. For adults older than 60 years of age, only 40% to 55% achieve a complete remission, with dismal long-term survival rates. Unfortunately, the median age at diagnosis for AML is 70 years. Significant advances in our understanding of the molecular biology of AML have led to newer therapies that specifically target molecular abnormalities. Examples of such therapies include the immunoconjugate gemtuzumab ozogamicin, FMS-like tyrosine kinase 3 inhibitors, farnesyl transferase inhibitors, histone deacetylase inhibitors, DNA hypomethylating agents, multidrug-resistance inhibitors, BCL-2 inhibitors, antiangiogenesis agents, and various nucleoside analogs. This review summarizes the standard treatments for AML and discusses the role of novel therapies.

Clinical and pathological differences between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is a distinct variant of diffuse large B-cell lymphoma initially described in HIV-positive patients. Several studies have reported the occurrence of PBL in HIV-negative patients, but comparative data are lacking. The goal of this study was to compare the characteristics of HIV-positive and HIV-negative patients with PBL. A MEDLINE search was undertaken through August 2009 for cases of PBL in HIV-positive and HIV-negative patients. Cases were identified and clinicopathological data were gathered. χ2 was used to compare categorical and t-test to compare continuous variables between groups. Calculated Kaplan–Meier survival estimates were compared using the log-rank test. Cox proportional-hazard regression was used for multivariate analysis. From 228 identified cases of PBL, 157 were HIV-positive and 71 HIV-negative. HIV-positive patients were younger, and more likely to be men, present with oral involvement, respond to chemotherapy, and express CD20, CD56, and EBV-encoded RNA than HIV-negative patients. In univariate analysis, age ≥60, advanced stage, bone marrow involvement, no chemotherapy, Ki-67 expression >80%, and HIV-negative status were associated with worse overall survival. In multivariate analysis, advanced stage and no chemotherapy were independent adverse prognostic factors. In conclusion, HIV-positive and HIV-negative patients with PBL have different clinicopathological characteristics, including a better response to chemotherapy and longer survival in HIV-positive patients.

Prognostic Factors in Chemotherapy-Treated Patients with HIV-Associated Plasmablastic Lymphoma

BACKGROUND Plasmablastic lymphoma (PBL) is a variant of diffuse large B-cell lymphoma commonly seen in the oral cavity of HIV-infected individuals. PBL has a poor prognosis, but prognostic factors in patients who have received chemotherapy have not been adequately evaluated. METHODS An extensive literature search rendered 248 cases of PBL, from which 157 were HIV(+). Seventy cases with HIV-associated PBL that received chemotherapy were identified. Whenever possible, authors of the original reports were contacted to complete clinicopathological data. Univariate analyses were performed calculating Kaplan-Meier estimates and compared using the log-rank test. RESULTS The mean age was 39 years, with a male predominance. The mean CD4(+) count was 165 cells/mm(3). Advanced clinical stage was seen in 51% and extraoral involvement was seen in 43% of the cases. The expression levels of CD20 and Epstein-Barr virus-encoded RNA were 13% and 86%, respectively. The overall survival duration was 14 months. In a univariate analysis, early clinical stage and a complete response to chemotherapy were associated with longer survival. There was no apparent difference in survival with regimens more intensive than cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). CONCLUSIONS Patients with HIV-associated PBL have a poor prognosis. Prognosis is strongly associated with achieving a complete clinical response to CHOP or CHOP-like chemotherapy. The role of more intensive regimens is currently unclear. Further research is needed to improve responses using novel therapeutic agents and strategies.

HIV-negative plasmablastic lymphoma: not in the mouth.

Plasmablastic lymphoma (PBL) is an aggressive variant of non-Hodgkin lymphoma initially reported in the oral cavity of HIV-positive individuals. Since its original description, several cases have been reported in patients who do not have HIV infection. However, despite its recognition as a distinct subtype of diffuse large B-cell lymphoma several years ago, comprehensive reviews of this entity are lacking. A MEDLINE search through June 2010 was performed to identify cases with a pathologic diagnosis of HIV-negative PBL based on morphology and minimal immunohistochemical criteria. Our study included a total of 76 cases. The median age was 57 years (range, 1 to 90 years) with a male-to-female ratio of 1.7. Seventy-four percent of cases did not have an apparent association with immunosuppression, 18% had a concurrent lymphoproliferative or autoimmune disorder and 9% developed PBL after solid organ transplantation. Oral involvement was observed in 21%, advanced stage in 60%, Epstein-Barr virus-encoded RNA expression was positive in 45% and Ki-67 expression of greater than or equal to 80% in 61% of the cases. Chemotherapy was documented in 43 patients, from which 43% received the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like regimens. The median and the 2-year overall survival for the whole group were 9 months and 10%, respectively. Patients who had HIV-negative PBL have distinct clinicopathological characteristics, such as short overall survival and lower rates of oral involvement and Epstein-Barr virus-encoded RNA expression than the previously reported in HIV-positive patients.

EBV-positive diffuse large B-cell lymphoma of the elderly: A case series from Peru

EBV‐positive diffuse large B‐cell lymphoma (DLBCL) of the elderly is an entity recently included in the WHO classification of lymphoid tumors. We have reviewed our experience and clinical outcomes of this distinct subtype of DLBCL. Between 2002 and 2009, cases of DLBCL were identified from medical records of the Hospital Nacional Edgardo Rebagliati Martins in Lima, Peru, and underwent pathological evaluation including immunohistochemistry for CD20, CD10, bcl‐6, MUM1/IRF4, and EBV‐encoded RNA in situ hybridization. Clinical data were gathered, tabulated, and reported descriptively. Survival analyses were performed using Kaplan‐Meier estimates. Out of 199 cases of DLBCL, 28 cases of EBV‐positive DLBCL of the elderly were identified. The median age was 75 years with male predominance (1.5:1). B‐symptoms were present in 43%, advanced stage in 50% and International Prognostic Index (IPI) score > 2 in 57% of patients; 68% of patients had a nongerminal center (NGC) phenotype. The complete response rates to R‐CHOP and CHOP were 63% and 33%, respectively. The median overall survival (OS) for the group was 5 months. In the univariate analysis, age ≥70 years, lymphocyte count <1.0 × 109/L, and advanced clinical stage were associated with worse OS in patients treated with chemotherapy with and without rituximab. EBV‐positive DLBCL of the elderly is a clinically aggressive entity with a short OS and typically presents with advanced stage, high IPI score, and a NGC phenotype. Further studies are needed to investigate if rituximab‐containing regimens are associated with better response and OS rates in EBV‐positive DLBCL of the elderly. Am. J. Hematol. 86:663–667, 2011.

Epstein-Barr virus as a prognostic factor in de novo nodal diffuse large B-cell lymphoma.

Although the International Prognostic Index (IPI) score is a valuable prognostic tool in diffuse large B-cell lymphoma (DLBCL), other risk-stratifying factors may be of value. The aim of this study was to define the prognostic value of EBV expression in de novo nodal DLBCL. Seventy-four cases were selected between January 2002 and December 2007. Clinical data were reviewed and tissue samples were evaluated for expression of CD20, CD10, bcl-6, MUM1, and EBV-encoded RNA (EBER). Of 74 evaluated cases, 53 cases (72%) were of non-germinal center-like subtype and 11 cases (15%) were positive for EBER. In a univariate analysis of the 57 patients who received chemotherapy, factors associated with survival were EBV status, performance status, LDH level, and IPI score. Using a multivariate analysis, a prognostic model was developed using IPI score and EBV status, which showed statistical significance. Our study supports EBV status as a powerful prognostic factor in de novo nodal DLBCL. Prospective studies should be carried to validate this hypothesis.

Are We Training Our Fellows Adequately in Delivering Bad News to Patients? A Survey of Hematology/Oncology Program Directors

BACKGROUND Medical oncologists often must deliver bad news. The authors were interested in the extent of formal training in delivering bad news in hematology/oncology fellowships in the United States. METHODS An e-mail survey was sent to all hematology/oncology fellowship program directors in the United States. Surveys were e-mailed to 124 program directors and responses were received either via e-mail or regular mail. Program directors were asked the adequacy, the perceived necessity, the quality of this training, and the institutional support provided. It was also intended to elicit responses about the degree of formal training fellows receive in delivering bad news. chi(2) Statistics were used to perform comparisons between items; p values of less than 0.05 were considered statistically significant. RESULTS Sixty-five surveys were completed and returned (52% response rate). The majority of programs, 82%, are in urban areas and 97% of the primary teaching hospitals are considered tertiary care centers and 46% of programs carry a National Cancer Institute (NCI) designation. Median number of fellows in a training program is 6 with the range being 3 to 46. Eighty-nine percent of program directors reported that they themselves received little to no formal training in delivering bad news, but they report 37% of current fellows receive little to no formal training with 40% receiving some training and additional 23% receiving moderate to extensive training (p < 0.001). Sixty-three percent of program directors felt that extensive, formal training is important for skill development in delivering bad news, while an additional 34% felt that some training is useful. Only 3% of respondents did not believe any training is needed. Seventy-six percent of program directors want improvements in how their fellows are trained, but 43% reported little to no institutional support for training (p < 0.001). CONCLUSIONS Of the program directors who responded to our survey, a large majority did not have formal training in delivering bad news. Despite this lack of training, most program directors felt that training was useful for skill development in delivering bad news. The majority of todays fellows do receive training in delivering bad news. However, there was still a significant percentage of program directors who reported little or no formal training for fellows. Most program directors would like to see improvements in how fellows are trained. Specific institutional support for training fellows in delivering bad news remains lacking.

Left sided inferior vena cava duplication and venous thromboembolism: case report and review of literature

The etiology of venous thromboembolism in young patients is frequently associated with hereditary coagulation abnormalities, immunologic diseases, and neoplasia. The advent of radiological advances, namely Computed Tomography (CT) scans and venography has identified vena cava malformations as a new etiologic factor worthy of consideration. In this case report, we describe the unusual occurrence of venous thromboembolism in association with a duplicated inferior vena cava. Duplications of the inferior vena cava (IVC) are seen with an incidence of 0.2% to 3.0% in the general population. Embryogenesis of the IVC is a complex process involving the intricate formation and regression of numerous anastomoses, potentially leading to various anomalies. We present a 23-year-old Caucasian woman with IVC duplication who developed a deep venous thrombosis and multiple pulmonary emboli. Anomaly of the IVC is a rare example of a congenital condition that predisposes to thromboembolism, presumably by favoring venous stasis. This diagnosis should be considered in patients under the age of 30 with spontaneous occurrence of blood clots.

Prognosis in primary effusion lymphoma is associated with the number of body cavities involved.

Abstract Primary effusion lymphoma (PEL) is a rare lymphoma associated with Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), and characterized by a malignant body cavity effusion without solid organ or nodal involvement. Prognostic factors in patients with PEL have not been systematically studied. We conducted a literature search for patients with HHV8-positive PEL to identify potential prognostic factors for survival. Our search identified 147 patients, among which 104 patients were HHV8-positive. The median overall survival was 9 months. The median age was 57 years with a male predominance (6:1). Pathologically, 33% of the patients expressed CD20 and 69% expressed CD30. Patients with PEL with > 1 body cavity involved had a median overall survival (OS) of 4 months compared with 18 months in patients with only one cavity involved (p = 0.003). Additionally, in patients with one involved body cavity, pericardial involvement was associated with a longer median OS than pleural followed by peritoneal involvement (40, 27 and 5 months, respectively; p = 0.04). In conclusion, our study suggests that the number and location of body cavities involved are prognostic in patients with PEL.

The Hans algorithm is not prognostic in patients with diffuse large B-cell lymphoma treated with R-CHOP.

Our objective was to evaluate the non-germinal center (GC) profile as a marker for response and survival in DLBCL and to compare the characteristics of patients with GC and non-GC DLBCL treated with rituximab-containing regimens. In this patient-level meta-analysis, retrospective data from 712 newly diagnosed DLBCL patients treated with chemoimmunotherapy from 7 centers were analyzed. GC and non-GC profiles were defined according to the Hans algorithm. Although the non-GC profile showed a trend towards worse overall survival (HR 1.24, 95% CI 0.92-1.66; p=0.15) and progression-free survival (HR 1.29, 95% CI 0.96-1.73; p=0.09), it did not retain its value in the multivariate survival analysis. Additionally, the non-GC profile was independently associated with worse complete response rates (OR 0.55, 95% CI 0.37-0.83; p<0.01) in the multivariate logistic regression analysis. Interestingly, Asian patients had higher proportion of GC DLBCL (p=0.01).