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Key Points The NGS-MRD assay detected clonotypic DNA in 100% of CSF samples from patients who had lymphoma with parenchymal CNS involvement.Clonotypic DNA in CSF was present in 36% of newly diagnosed aggressive lymphomas and was associated with a 29% risk of CNS recurrence., Visual Abstract, The diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied the results of a next-generation sequencing (NGS)–based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-minimal residual disease (NGS-MRD) assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement. They included 7 patients with parenchymal brain disease only, whose CSF tested negative by standard cytology and flow cytometry, and 6 historical DNA aliquots collected from patients at a median of 39 months before accession, which had failed to show clonal rearrangements using standard polymerase chain reaction. For risk prognostication, we prospectively collected CSF from 22 patients with newly diagnosed B-cell lymphomas at high clinical risk of CNS recurrence, of whom 8 (36%) had detectable clonotypic DNA in the CSF. Despite intrathecal prophylaxis, a positive assay of CSF was associated with a 29% cumulative risk of CNS recurrence within 12 months of diagnosis, in contrast with a 0% risk among patients with negative CSF (P = .045). These observations suggest that detection of clonotypic DNA can aid in the diagnosis of suspected parenchymal brain recurrence in aggressive lymphoma. Furthermore, the NGS-MRD assay may enhance clinical risk assessment for CNS recurrence among patients with newly diagnosed lymphomas and help select those who may benefit most from novel approaches to CNS-directed prophylaxis.

Clinical trials comparing bendamustine/rituximab (BR) with cyclophosphamide-based regimens (RCHOP/RCVP) have pooled various histologies of indolent B-cell lymphomas. We examined real-life outcomes of older patients with follicular (FL), mantle cell (MCL), or marginal zone/lymphoplasmacytic lymphoma (MZL/LPL), treated with these first-line regimens. We identified Medicare beneficiaries with FL, MCL, or MZL/LPL, who received either first-line BR or RCHOP/RCVP in 2009-2016, and matched groups using a propensity score. Outcomes of claims-based event-free survival (EFS), overall survival (OS), toxicity, secondary cancers, and costs were compared in the aggregate cohort (N = 2736), and in separately matched histology-specific subcohorts. In the aggregate cohort, EFS was better with BR than with RCHOP/RCVP (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.70-0.87). Acute toxicity was lower with BR, including rates of hospitalizations (33% vs 45%), infections (21% vs 30%), cardiovascular events, and transfusions, yet OS did not differ (HR, 1.03; 95% CI, 0.91-1.17) and Medicare spending was higher. There was no difference in the cumulative incidence of secondary cancers (subhazard ratio, 1.11; 95% CI, 0.83-1.48). The EFS advantage of BR was pronounced in MCL (N = 690; HR, 0.64; 95% CI, 0.54-0.76), but less so in FL (N = 1330; HR, 0.83; 95% CI, 0.69-0.98) and absent in MZL/LPL (N = 574; HR, 0.92; 95% CI, 0.73-1.17). Despite improved EFS and lower toxicity, the shift from RCHOP/RCVP to BR in clinical practice did not improve OS for older patients with indolent B-cell lymphomas. Frequent infections and hospitalizations underscore the need for safer treatment approaches in this population. Secondary cancers do not appear to be increased after BR compared with RCHOP/RCVP.

Induction chemotherapy for acute myeloid leukemia (AML) is based on the "7+3" cytarabine/anthracycline regimen. A nonhypocellular day 14 (D14) bone marrow sample with a blast count5% to 10% is suggestive of residual leukemia, for which a second course of induction chemotherapy has been recommended. Although the prognostic value of D14 bone marrow findings has been established, its use as a decision point is controversial because the benefit of repeat induction has been questioned.In the present single-center retrospective study of 113 patients with newly diagnosed AML, we evaluated the role of cellularity on the clinical outcomes of patients with residual morphologic leukemia (blasts ≥ 5%). Among 64 patients with D14 bone marrow samples, 31 had residual morphologic leukemia.The complete remission (CR) rates were greater for the hypocellular (11 of 16) than for the nonhypocellular (4 of 15) patients (P = .03). The median overall survival (OS) for the hypocellular D14 patients was longer than that for the nonhypocellular patients (17 vs. 8 months; P = .02). No significant difference between the receipt of reinduction therapy and CR or OS was found on logistic or survival model analysis. The specificity for residual leukemia on D14 bone marrow samples was better for cellularity ≥ 20% and blasts ≥ 20% than for blasts ≥ 5%.The results of our study have shown that patients with 20% cellularity and 20% blasts on the D14 bone marrow assessment should continue observation until recovery rather than receive additional immediate therapy.

Microchimerism has generally been shown to protect against cancer (Gilmore et al. in Exp Hematol 36(9):1073-1077, 2008). The mechanism of how this occurs is an area of intense study, as it may lead to new cancer treatments. The leading theory is that microchimeric cells perform immune surveillance by directly fighting cancerous cells and that they also act as stem cells, repairing damaged tissue (Khosrotehrani et al. in JAMA 292:75-80, 2004). However, there is conflicting evidence to support this theory. Several small studies have found few microchimeric cells in tumor tissue (Gadi in Breast Cancer Res Treat 121(1):241-244, 2010; Cirello et al. in Int J Cancer 126:2874-2878, 2010), while another study contradicted these findings by showing microchimeric cells clustered around tumor tissue (O'Donoghue et al. in Reprod Biomed Online 16:382-390, 2008). To date, we have designed the largest and broadest study to investigate this question of whether microchimeric cells really do cluster at tumor tissue. We analyzed 245 samples from a broad range of cancer types. Using PCR for the male chromosome marker TSPY1, we identified only 12 out of 245 samples with microchimerism for a rate of 4.9% (95% confidence interval 2.2-7.6%). Five of these samples were confirmed using Y fluorescence in situ hybridization. This rate of 4.9% microchimerism is the lowest reported in any study. The low percentage of microchimerism observed in our broad study suggests that microchimeric cells do not invade tumors to fight off neoplasm.

Little is known on racial differences in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this retrospective study is to compare characteristics, prognostic factors and outcomes of Asian and Western patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP).Patient-level data was collected from 8 centers. All patients were diagnosed with DLBCL and treated with R-CHOP. Patients were divided into Asian and Western, according to the country of report. Comparisons and univariate/multivariate survival analyses were performed.712 patients, 455 Asian and 257 Western patients were included. Westerners were more likely to present with elevated LDH (64% vs. 48%, p0.01) and advanced stage (58% vs. 49%, p0.01). After a median follow-up of 36 months, there was no difference in progression-free (PFS; p=0.33) or overall survival (OS; p=0.69). There were no PFS or OS differences between races when evaluating separately each age-adjusted International Prognostic Index category. In the multivariate analyses, performance status and stage were associated with PFS and OS in both races.There are no differences in prognostic factors, PFS and OS between Asian and Western patients with DLBCL 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

Abstract 4765 BACKGROUND Gemcitabine induces a 20% response as single agent therapy in patients with relapsed or refractory NHL. We report phase I findings of gemcitabine in combination with standard CHOP chemotherapy with G-CSF support for intermediate grade NHL. The protocol was modified during enrollment to include rituximab in CD 20+ lymphomas. METHODS Patients received CHOP plus gemcitabine at 500 mg/m2 (Cohort 1) or 750 mg/m2 (Cohort 2) on days 1,4 of each 21 day cycle. Accrual was suspended once each cohort was filled. Dose escalation occurred after all patients in the cohort were determined to not have a dose limiting toxicity. RESULTS Between 4/02 and 5/04 10 patients were enrolled and completed the study treatment (6 in cohort 1, 4 in cohort 2). In Cohort 1, grade 3 toxicities included neutropenia, anemia, neuropathy, and constipation. Grade 4 toxicities were febrile neutropenia, and thrombocytopenia. In Cohort 2, grade 3 toxicities included neutropenia, thrombocytopenia, mucositis, anemia and intestinal obstruction. Grade 4 toxicities included febrile neutropenia, neutropenia, and thrombocytopenia. One patient developed MDS 36 months after chemotherapy. Three of four patients in Cohort 2 developed dose limiting toxicities (mucositis and thrombocytopenia) requiring dose reduction of gemcitabine after cycle 1. Overall, the survival rate at 2.5 years was 71%. CONCLUSIONS This Phase I trial concludes that gemcitabine 500mg/m2 on days 1 and 4 of each 21 day cycle is the maximum tolerated dose when combined with standard CHOP chemotherapy with G-CSF support for intermediate grade NHL. Response rates are encouraging for this novel chemotherapeutic regimen. Disclosures: Off Label Use: Gemcitabine was added to standard CHOP chemotherapy in this trial.. Sikov:Eli Lilly: Honoraria.

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

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.

Epstein-Barr virus–positive (EBV-positive) diffuse large B-cell lymphoma (DLBCL) of the elderly is a newly described lymphoproliferative disorder recently included as a “provisional” entity in the most current WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. The objective of this review is to provide a thorough and current summary of the existing knowledge of this subtype of DLBCL. We will review and discuss the incidence of EBV expression in DLBCL, the pathogenesis behind EBV-driven malignant transformation of B cells, the different EBV latency patterns associated with DLBCL, the distinct pathologic characteristics of EBV-positive DLBCL, the potential predictive and prognostic value of EBV tumoral status in patients with DLBCL, and potential strategies for the treatment of this rare entity, which is characterized by a suboptimal response to therapy and poor survival rate.

The orthopaedic patient on chronic anticoagulation therapy is at risk of thromboembolism and hemorrhage in the perioperative period. To establish the most effective anticoagulation regimen, patients should be stratified according to the risk of arterial or venous thromboembolism. Timing of surgery, thromboembolic risk, and bleeding risk should be considered when developing an anticoagulation protocol. Retrievable inferior vena cava filters may be a viable alternative to bridging therapy in patients at high risk of venous thromboembolism and/or bleeding.

Background Acute T-cell leukemia/lymphoma (ATLL) is a post thymic (peripheral) T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Historically, the chemotherapy regimen CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) has been the standard treatment of this rare malignancy. However, its prognosis is poor and median survival in the aggressive variants of ATLL is only 6-10 months. Recently, a more aggressive regimen piloted in Japan, vincristine/cyclophosphamide/doxorubicin/prednisone (VCAP)- doxorubicin/ranimustine/prednisone (AMP)- vindesine/etoposide/carboplatin/prednisone (VECP), has been reported to yield better survival results over biweekly CHOP in a phase III trial. However, the hyper- cyclophosphamide/vincristine/doxorubicin/dexamethasone (CVAD) regimen is a much more frequently used regimen for the treatment of aggressive hematologic malignancies, and has a higher intensity then CHOP. Yet, there is little reported experience with hyper-CVAD regimen in ATLL. Case Reports We present 2 patients diagnosed with ATLL who were treated with hyper-CVAD chemotherapy and have achieved a durable complete remission. One of the patients has gone on to receive an allogeneic bone marrow transplantation and has been in complete remission for over 18 months. The other has been in a continuous remission for approximately 12 months. We also review the past published experience with the hyper-CVAD regimen in patients with ATLL. Conclusion A commonly used chemotherapy regimen for aggressive hematologic malignancies, hyper-CVAD, can induce durable remissions in patients with ATLL.

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/mm3. 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.

Until recently, warfarin has been the primary treatment of venous thromboembolism (VTE). Limited data are available regarding physician attitudes toward anticoagulant choice in the setting of novel oral anticoagulant (NOAC) availability. This study sought to evaluate attending physician attitudes toward NOACs. A survey was sent to attending physicians from internal medicine (primary care and hospitalist medicine), family medicine, cardiology, and hematology-oncology asking about their preference and reasoning for choice of oral anticoagulant for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Warfarin was the most common choice of initial treatment of both DVT (85.6%) and PE (89%). Among the specialties surveyed, cardiologists were more likely to use rivaroxaban as initial treatment of VTE as compared to other specialties including internal medicine or hematology (p=0.011 for DVT and 0.004 for PE). Cost-effectiveness and lack of a reversal agent were cited as the major disadvantages for NOAC use.

Acute myeloid leukemia (AML) and other aggressive refractory hematological malignancies unresponsive to upfront therapy remain difficult conditions to treat. Often, the focus of therapy is centered on achieving complete remission of disease in order to proceed with a consolidative stem cell transplant. At issue with this paradigm is the multitude of patients who are unable to achieve complete remission with standard chemotherapeutic options. A major benefit of transplantation is the graft versus tumor effect that follows successful engraftment. However, with this graft versus tumor effect comes the risk of graft versus host disease. Therefore, alternative treatment options that utilize immunotherapy while minimizing toxicity are warranted. Herein, we propose a novel treatment protocol in which haploidentical peripheral blood stem cells are infused into patients with refractory hematological malignancies. The end goal of cellular therapy is not engraftment but instead is the purposeful rejection of donor cells so as to elicit a potent immune reaction that appears to break host tumor tolerance. The trial is a FDA and institutional Rhode Island Hospital/The Miriam Hospital IRB approved Phase I/II study to determine the efficacy and safety of haploidentical peripheral blood cell infusions into patients with refractory hematological malignancies. The primary objective is the overall response rate while secondary objectives will assess the degree and duration of response as well as safety considerations. Patients with refractory acute leukemias and aggressive lymphomas over the age of 18 are eligible. Donors will be selected amongst family members. Full HLA typing of patients and donors will occur as will chimerism assessments. 1-2x108 CD3+ cells/kilogram will be infused on Day 0 without preconditioning. Patients will be monitored for their response to therapy, in particular for the development of a cytokine release syndrome (CRS) that has been previously described. Blood samples will be taken at the onset, during, and following the cessation of CRS so as to study effector cells, cytokine/chemokine release patterns, and extracellular vesicle populations. Initially, six patients will be enrolled on study to determine safety. Provided the treatment is deemed safe, a total of 25 patients will be enrolled to determine efficacy. Cellular Immunotherapy for Refractory Hematological Malignancies provides a novel treatment for patients with relapsed/refractory acute leukemia or aggressive lymphoma. We believe this therapy offers the immunological benefit of bone marrow transplantation without the deleterious effects of myeloablative conditioning regimens and minus the risk of GVHD. Laboratory correlative studies will be performed in conjunction with the clinical trial to determine the underlying mechanism of action. This provides a true bench to bedside approach that should serve to further enrich knowledge of host tumor tolerance and mechanisms by which this may be overcome. NCT01685606 .

Spontaneous remission of chronic lymphocytic leukemia (CLL) is an unusual and poorly characterized event. We performed a search for spontaneous remission in patients with CLL. Cases must have had a pathological diagnosis of CLL with disease duration6 months. Spontaneous remission was defined as absence of lymphadenopathy or splenomegaly with lymphocyte counts5 × 10(9)/L for9 months without therapy. We identified 20 cases and included one additional case from our institution. Fourteen cases (67%) showed remission into monoclonal B lymphocytosis (MBL) and seven (33%) into a normal phenotype. There was no difference in age distribution, lymphocyte count or stage between groups. There was a significant difference in the median duration of CLL prior to remission, 13 years in the MBL versus 3 years in the normal phenotype group (p = 0.03). This difference in the duration of CLL prior to remission could be due to a possible distinct pathophysiology for these events.

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 with1 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.

Adult T-cell leukemia/lymphoma is a T-cell malignancy caused by the human T-cell lymphotropic virus type 1. The aggressive forms of the disease carry a poor prognosis with standard therapies. The role of high-dose treatment with blood and marrow transplantation has, therefore, been examined mainly by Japanese groups in the form of retrospective studies. In this study, we review the literature, discuss some of the challenges facing successful transplantation approaches and stress the need for more innovative studies including in the Western hemisphere.

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. χ(2) 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 expression80%, 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.

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.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.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 (p0.001). 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 (p0.001).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 today's 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.

BACKGROUND: A case of donor cell leukemia (DCL) is reported. A 42-year-old female developed acute myeloid leukemia (AML) of donor cell origin 18 months after a bone marrow transplant (BMT) from her brother. At the time DCL presented, the donor-brother was also diagnosed with AML showing identical cytogenetic abnormalities. The classification of DCL and recommendations for laboratory testing of potential hematopoietic stem cell (HSC) donors are discussed. STUDY DESIGN AND METHODS: Marrow specimens were obtained from the posterior iliac crest and analyzed using standard techniques. Leukemic cells were analyzed by flow cytometry. Karyotyping and fluorescence in situ hybridization were performed using standard methods. RESULTS: The recipient-sister's original diagnosis was erythroleukemia. Chromosome analysis showed a 46,XX,t(3;5)(q25;q34) karyotype. Both the recipient's new AML and the donor's AML showed an identical karyotype: 46,XY,inv(3)(q21q26),-7. Both patients were resistant to therapy and died. CONCLUSION: The clinical and biological aspects of DCL are discussed including the distinction between transformation of healthy donor cells to leukemic cells and transmission of preformed leukemic cells. The former represents almost all the reported cases of DCL compared with transmission of leukemic cells from donor to recipient. With an aging donor population, it is estimated that the latter will increase. Increased testing of older donors to include routine morphologic study of blood and marrow, cytogenetic studies, and evaluation for clonal lymphoproliferative disorders is recommended.

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.

We report on two patients with myeloid disorders and complex karyotypes including a dicentric chromosome, dic(17;20)(p11.2;q11.2), resulting in the loss of most of 17p and 20q. The presence of the centromeres of chromosomes 17 and 20 in the dic(17;20), as well as the loss of TP53, were confirmed by fluorescence in situ hybridization. Deletions of 17p and 20q are recurrent abnormalities in hematologic disorders, particularly myelodysplastic syndrome and acute myeloid leukemia). However, a dic(17;20) is an uncommon finding. According to the few reports in the literature, dic(17;20) is associated with an unfavorable prognosis. The key mechanism might be the loss of TP53 as well as other tumor suppressor genes in 20q that may have a critical role in tumor genesis.

Factor VII deficiency, although rare, is now recognized as the most common autosomal recessive inherited factor deficiency. It is usually considered to be associated with bleeding only in the severely affected subject and heterozygotes (>10%) are not considered at risk. The general recommendation for surgery is to achieve a FVII level in excess of 15% (0.15 1U/mL). We present three cases of severe factor VII deficiency, each of whom appeared hemostatically competent based on clinical history. Subject 1 is a 33 year-old African-American female with a baseline FVII of

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.