ALBERT

Description: Abstract 4638 According to the CDC the incidence of HIV-infection in women of child bearing age continues to increase in the era of Highly Active Anti-Retroviral Therapy (HAART). In 1992, women accounted for 14% of all adults and adolescents living with HIV/AIDS, but by the end of 2005 women accounted for 23% of all HIV/AIDS cases [1]. As Hodgkin lymphoma (HL) is the most common non-AIDS defining malignancy, we anticipate that the number of cases of HIV-associated Hodgkin lymphoma (HIV-HL) in pregnant women will increase in the near future. Herein, we describe the case of a pregnant 30-year-old HIV-infected Ethiopian woman with a CD4+ count of 254 cells/μ;L and an HIV viral load of 1200 copies/mL who presented to medical attention with progressive neck adenopathy and fatigue, but no fevers, night sweats, or significant weight loss. An incisional biopsy of a cervical lymph node revealed Reed-Sternberg cells (CD30+, CD15+, CD20-, CD3-) and an absence of sclerosis consistent with Classical Hodgkin Lymphoma, mixed cellularity subtype. A subsequent unilateral posterior iliac crest bone marrow aspirate and biopsy was unremarkable with normal trilineage hematopoiesis. Following a spontaneous miscarriage ten weeks into her pregnancy, a 18F-fluorodeoxy-D-glucose PET and fusion CT scan demonstrated disease above and below the diaphragm, establishing stage IIIA HL. The patient subsequently began HAART consisting of a co-formulation of emtricitabine and tenofovir (Truvada®) and nevirapine, in conjunction with chemotherapy (AVD x 8 cycles). Thirty three months post-completion of chemotherapy, the patient remains disease free without evidence of recurrent HL. Through a literature search, we identified only two additional case reports describing HIV, HL, and pregnancy. One patient received three cycles of chemotherapy, refused further treatment, delivered a HIV-positive girl, and died shortly after from complications of presumed pneumocystis jiroveci pneumonia [2]. The second patient received both active antiretroviral therapy and chemotherapy, delivered a HIV-negative boy, and remained without evidence of HL at nine months follow-up [3]. The paucity of reported cases in the medical literature precludes any evidence based recommendations for the care of pregnant patients with HIV-HL. However, we recommend that medical providers use the same precautions to ensure the safety of both the mother and the child as recommended for pregnant HIV-negative patients with HL. Pregnant patients with HL should not be staged with imaging techniques that require significant radiation exposure including plain radiographs, CT, and PET scans. The extent of substantial mediastinal and pulmonary disease can be safely determined with a postero-anterior radiograph of the chest with proper shielding of the abdomen. Abdominal ultrasounds and magnetic resonance imaging may provide adequate information for the management of disease without placing the fetus at risk [4]. We also suggest controlling the underlying HIV infection when initiating HL treatment as using HAART in parallel with chemotherapy has been correlated with a dramatically improved prognosis for HIV-HL patients [5]. In the hopes of developing more specific management guidelines, we encourage other clinicians to publish their experiences with HIV-HL in pregnant patients.Centers for Disease Control and Prevention. HIV/AIDS Among Youth–United States, 2008. http://www.cdc.gov/hiv/resources/Factsheets/youth.htmOkechukwu CN, Ross J. Hodgkin's Lymphoma in a Pregnant Patient with Acquired Immunodeficiency Syndrome. J Clin Oncol 1998; 10:410-411.Kelpfish A, Schattner A, Shtalrid M,et al. Advanced Hodgkin's Disease in a Pregnant, HIV Seropositive Woman: Favorable Mother and Baby Outcome Following Combined Anticancer and Antiretroviral Therapy. Am J Hematol 2000; 63:57-58.Connors, Joseph. “Challenging Problems: Coicident Pregnancy, HIV infection, and Older Age.” In: Hematology 2008: American Society of Hematology Education Program Book. Gewirtz AM, Muchmore EA, Burns LJ, editors. Washington, D.C.: American Society of Hematology; 2008. p. 334-39.5.Tirelli U, Errante D, Dolcetti R, et al. Hodgkin's Disease and Human Immunodeficiency Virus Infection: Clinicopatholgic and Virologic Features of 114 Patients From the Italian Cooperative Group on AIDS and Tumors. J Clin Oncol 1995; 13:1758-67. Disclosures: No relevant conflicts of interest to declare.

Description: BACKGROUND: Recent advances in imaging and the use of prognostic indices and molecular profiling have improved our ability to characterize disease and predict outcomes in diffuse large B cell lymphoma (DLBCL). About 1/3rd of patients with DLBCL have bone marrow involvement (BMI) at the time of diagnosis, and bone marrow aspirate/biopsy (BMAB) is considered the gold standard to detect such involvement. [18F] fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET-CT), has become a standard pre-treatment imaging in DLBCL and may be a noninvasive alternative to BMAB to ascertain BMI. Prior studies have suggested that PET-CT scan may obviate the need for BMAB as a component for staging patients with newly diagnosed DLBCL, but owing to a variety of reasons this is not yet a standard of practice. The aim of this retrospective study which included 99 patients with newly diagnosed de-novo DLBCL, who had undergone both BMAB and PET-CT, was to determine the accuracy of PET-CT in detecting BMI in DLBCL and define overall survival (OS) in these patients based on BMI by BMAB vs. PET-CT. METHODS: This study is a single institution retrospective review of patients' medical records. All patients with newly diagnosed DLBCL at Virginia Mason Medical Center between January 2004 to December 2013 who underwent pretreatment PET-CT and BMAB were included. PET-CT images were visually assessed for BMI including the posterior iliac crest. Patients with primary mediastinal DLBCL, previous history or co-existence of another lymphoma subtype and those with a non-diagnostic BMAB, and in whom the PET-CT did not show marrow signal abnormality were excluded from the analysis. Ann Arbor stage was determined using PET-CT with and without the contribution of BMAB, and the proportion of stage IV cases by each method was measured. RESULTS: 99 eligible patients were identified. The median age was 62 years (range, 24-88), 62 (59%) were male, 53 (50%) had elevated LDH and 17 (16%) had an ECOG performance status of 〉2. Thirteen (12%) patients had 〉 1 extra-nodal site of lymphoma involvement. R-IPI score was 1 in 39 (37%), 2 in 42 (40%), 3 in 20 (19%), and 4 in 4 (4%) patients. A total of 38 (36%) patients had BMI established by either PET-CT (n=24, 19%), BMAB (n=14, 13%), or both (n=12, 11%). 12 of the 24 patients (50%) with positive PET-CT had BMI by DLBCL, while only 2 of the 81 patients (2%) with negative PET-CT showed BMI. BMAB upstaged 1 of the 53 (2%) stage I/II patients to stage IV. The sensitivity of PET-CT scan to detect BMI by DLBCL was 86% while the specificity was 87%. 84 patients (85%) had concordant results between lymphomatous BMAB and PET-CT (12 patients were positive for both, and 72 patients were negative for both), but 15 patients (15%) had a discordant interpretation (3 patients were positive by BMAB and negative by PET-CT, and 12 patients were negative by BMAB and positive by PET-CT). PET-CT was highly accurate for detecting BMI at diagnosis in de-novo DLBCL. Although patients with positive BMAB patients had inferior 5 year OS estimates compared to negative BMAB (66% vs. 85%), no difference was demonstrated between PET-CT positive vs. PET- CT negative patients. (79% vs. 83%) (Table 1) CONCLUSIONS: In patients with newly diagnosed DLBCL, PET-CT is highly accurate in detecting BMI by lymphoma. In clinical practice, routine BMAB may no longer be necessary for all patients with DLBCL, who are staged by PET-CT, unless the results would change both staging and therapy. The prognostic implication of BMI identified by PET-CT compared to BMAB remains unknown. Whether a PET-CT precludes the need for a BMAB in patients with DLBCL remains to be evaluated in a prospective study. Disclosures No relevant conflicts of interest to declare.

Description: ABSTRACT Background: In 2014, the American Society of Hematology (ASH) established a practice improvement module (PIM) incorporating quality metrics for management of diffuse large B cell lymphoma (DLBCL). Such PIMs have allowed physicians to monitor the quality of care in their practice. We implemented a DLBCL quality improvement initiative (QII) at our institution in January, 2015. In an appraisal of this initiative, we reviewed the ASH PIM metrics and included several others to assess adherence to guidelines for treatment of DLBCL and to examine the need for institutional improvement. Methods: Patients who were newly diagnosed with DLBCL and received treatment at our institution from January 2006 through December 2017 were identified. Electronic medical records were reviewed for documentation of ASH PIM quality measures (e.g., key pathologic features of DLBCL, lymphoma staging, screening for hepatitis B virus (HBV) infection in patients receiving rituximab-based chemotherapy, etc). We also reviewed the proportion of patients who had assessment of prognosis by revised International Prognostic Index (r-IPI) score, testing for hepatitis C (HCV), HIV viral infections, chemotherapy education, and the addition of rituximab in the treatment regimen of CD20+ DLBCL. Results: Following implementation of the QII, our institution saw improvement in most quality metrics. Particularly significant were improvements in reporting of key molecular features (45.45% to 91.6%, P 〈 0.0001), screening for HBV (41.82% to 91.67%, P 〈 0.001) and HIV infections (33.94% to 87.5%, P 〈 0.0001). All patients post-QII had a PET-CT scan for staging of DLBCL and there was a significantly lower use of bone marrow biopsy (61.2% to 33.33%, P = 0.011). Conclusion: Implementation of a quality initiative and employing standardized metrics can aid in improving institutional quality of care for patients with newly diagnosed DLBCL, and allows opportunity to build and ensure better adherence to evolving national and professional patient care guidelines. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4264 Pseudotumor cerebri (PC) is a rare disorder characterized by elevated intracranial pressure with normal cerebrospinal fluid composition, normal cranial imaging findings, and symptoms and signs of increased intracranial pressure. A number of medications have been linked to PC including vitamin A and its derivative all-trans-retinoic acid (ATRA). Herein, we describe the case of a 38-year-old woman who was diagnosed with PC during standard induction treatment for acute promyelocytic leukemia (APL). Her neurologic complaints of severe headache and diplopia improved slightly after ATRA was discontinued and she was treated with acetazolamide, but symptoms did not abate until fluconazole was held five days later. Through a literature review, we identified 41 case reports of APL patients with ATRA-associated PC, 23 of which provided details of clinical presentation and follow-up. The median age at diagnosis of PC was 27 for females and 16 for males; the female-to-male ratio was 1.3:1. All 23 patients complained of headache; papilledema was present in all 21 instances (100%) where a retinal exam was described. ATRA was held due to PC in 20 cases (87%), and neurologic symptoms resolved without further intervention in 7 of 20 (35%). The remaining 13 patients were treated with diuretics (11 of 13 cases, 85%), high-volume lumbar punctures (5, 38%), corticosteroids (4, 31%), and/or analgesics (3, 23%). Including our index patient, eight patients were rechallenged with ATRA after neurologic improvement, and 5 (63%) required further interventions to resolve recrudescent symptoms. We identified one other patient whose neurologic complaints persisted despite dose reductions in ATRA. This patient improved only after fluconazole was discontinued. Because both ATRA and fluconazole are metabolized by the cytochrome P-450 system, we suggest that if taken concurrently, they may exacerbate the risk of PC. Physicians should be aware of this interaction between ATRA and fluconazole and consider discontinuing both fluconazole and ATRA in APL patients who develop PC. Disclosures: No relevant conflicts of interest to declare.

Description: Sweet’s syndrome, also known as acute febrile neutrophilic dermatoses, is a distinct clinicopathologic entity of unknown etiology characterized by acute onset of fever, leukocytosis, and cutaneous plaques. It has been associated with a variety of disorders including infections, neoplasms, and autoimmune diseases. Paraneoplastic Sweet’s syndrome is most often associated with hematologic malignancies, including myelogenous leukemia and myelodysplastic syndrome (MDS), are most often associated. Although patients with neutrophilia are most likely to be diagnosed with Sweet’s syndrome, so, too, may patients who are neutropenic post-cytotoxic chemotherapy. Herein, we describe the clinical course of a 60-year-old Caucasian man with a history of high-risk MDS who, after progressing to AML and while neutropenic post-induction chemotherapy, was diagnosed with Sweet’s syndrome. The patient developed a warm, tender, indurated, erythematous lesion over his left anterior chest on day +6 of induction chemotherapy consisting of idarubicin and cytarabine. Despite broad spectrum antibiotics, the lesion darkened, formed blisters, and progressed rapidly to involve much of his left chest. On day +11, his WBC had fallen to 0.7×109cells/l and the wound was surgically debrided due to concern that he had developed necrotizing fasciitis. Surgical samples showed significant dermal infiltration of neutrophils and severe necrosis of skin and subcutaneous tissue, but no pathologic organisms or leukemic cells. Empiric antibiotic coverage was broadened to include amphotericin B, voriconazole, and valganciclovir, but the patient failed to improve. On day +18, he began taking 60mg Prednisone daily and his lesions quickly improved. Although Sweet’s syndrome most often occurs in conjunction with neutrophilia, it may also occur in neutropenic patients who have received systemic chemotherapy. This association with neutropenia is more frequent than is generally appreciated; as many as 20–50% of patients with hematologic malignancies may be diagnosed with Sweet’s syndrome while recovering from therapy-associated neutropenia. Cancer-associated Sweet’s syndrome may be more severe than that seen in patients without malignancy. Lesions may progress from plaques and nodules to vesicular, bullous, and even ulcerative skin lesions, as was seen in our patient. Our case report serves as a reminder that Sweet’s syndrome may occur in the setting of neutropenia and, if diagnosis and treatment are delayed, can lead to a life-threatening complication. Early skin biopsy and histopathologic assessment followed by corticosteroids is essential for recognition and management of this entity.

Description: IVL is an uncommon large-cell lymphoma, usually of B-cell origin. Typically, the CD20+ lymphoma cells possess defects in homing receptors. This leads to limited cell migration from the vessel endothelium, resulting in cell crowding and blockage of intravascular lumens. Patients frequently present with skin lesions, fever, and neurological dysfunction, reflecting the ability of malignant cells to infiltrate various organs. The wide spectrum of clinical manifestations of IVL, along with its propensity to afflict elderly patients with multiple comorbidities, presents a diagnostic and therapeutic challenge; most cases are discovered post-mortem. Anthracycline-based chemotherapy is the standard treatment for this malignancy, but outcomes are disappointing, with most patients destined to die from progressive lymphoma and, less commonly, chemotherapy-induced complications. An 86-year-old female underwent a lesion biopsy after bilateral thigh plaques (the largest of which measured 8 × 13 cm) became increasingly erythematous and painful, despite treatment with antibiotics and corticosteroids. She was diagnosed with subcutaneous CD20+ IVL. Laboratory studies were notable for hematocrit 29% with iron indices consistent with inflammatory block, lactate dehydrogenase 950 IU/L (normal 〈 240 IU/L) and β2-microglobulin 1.8 mg/mL (normal 〈 2.0mg/mL). Whole-body computed tomography and positron emission tomography fusion studies did not suggest lymphoma elsewhere. She received rituximab (375 mg/m2/week × 8 weeks) and achieved a complete remission (CR), with the disappearance of thigh discomfort and resolution of her medial thigh plaques. Three months after completion of rituximab treatment, a new left posterior chest wall mass was biopsied and proved to be recurrent IVL. She declined further treatment and was referred to hospice care. Through a Medline search we were able to identify 12 additional patients who were treated with multi-agent chemotherapy and rituximab (n=10) or rituximab monotherapy (n=2). The patients’ ages ranged from 42 to 86 years. The most common clinical presentations in these cases included fever (n=5), nervous system involvement (n=3), and skin rash (n=2). Excluding one multi-agent therapy patient who died during treatment, all patients in our search achieved CRs, with a median follow-up duration of 14 months (range, 6–36 months). Among various lymphoma subgroups (including elderly patients with high-risk features and those with IVL), rituximab has been used as a single agent and to augment the anti-lymphoma properties of multi-agent chemotherapy. Our case report is the first to describe IVL recurrence following rituximab monotherapy, and highlights the need for further investigation on the use of rituximab in the treatment of this rare lymphoma.

Description: Purpose: Doxorubicin-based chemotherapy (DOX) is commonly administered to patients with diffuse large B-cell lymphoma (DLBCL). Prior to chemotherapy, left ventricular ejection fraction (LVEF) is routinely measured to assess left ventricular dysfunction. While LVEF screening is recommended by many national regulatory bodies, evidence supporting the usefulness of LVEF measurement prior to administering DOX is lacking. Our goal was to perform a retrospective analysis of patients with DLBCL to establish (1) how often LVEF was measured prior to administering DOX, and (2) whether the chemotherapy regimen was modified based on LVEF values. As cumulative doses of doxorubicin greater than 400 mg/m2 have been associated with an increased risk of congestive heart failure (CHF), we also determined the incidence of CHF in patients with DLBCL who did receive DOX. Patients and Methods: We identified 268 patients diagnosed with DLBCL at Virginia Mason Medical Center between 2001 and 2012 and collected the following data: age at diagnosis; stage of lymphoma; type of chemotherapy given; cumulative doxorubicin dose (mg/m2); LVEF status; and incidence of CHF or cardiac disease. We also compared the number of CHF risk factors between patients who did and did not have LVEF measured. Statistical analyses included a Fischer’s exact or Chi-squared test to compare study groups as well as the number of CHF risk factors. The level of significance was set at a P value of 〈 0.05. Results: LVEF was measured in 238 patients (89%) prior to initiation of chemotherapy. LVEF values were normal in 225 patients (95%) and low (〈 50%) in 13 patients (5%). Of the patients with normal LVEF, 193 received DOX (86%), and of these patients, 14 developed CHF post-treatment (7%). For the 13 patients with low LVEF, 8 received DOX (62%) and 1 developed post-treatment CHF (13%). The remaining thirty patients did not have LVEF measured and none received DOX. Of the 268 patients studied, 176 are alive (66%) and 3 were lost to follow-up. The mean follow-up time was 43 months (range 3 d to 12.1 y). The mean number of CHF risk factors did not differ between patients who did and did not have LVEF measured (1.70 vs. 1.65, P = 0.87). Conclusion: Our results suggest that the decision to administer DOX was not directly affected by LVEF values. These findings challenge the existing policy of routinely screening patients with DLBCL with echocardiograms or MUGA scans prior to treatment. Disclosures No relevant conflicts of interest to declare.