Acyclovir Prophylaxis Research Articles

Acyclovir Prophylaxis Predisposes to Antiviral-Resistant Recurrent Herpetic Keratitis

Long-term acyclovir (ACV) prophylaxis, recommended to prevent recurrent herpes simplex virus type 1 (HSV-1) ocular disorders, may pose a risk for ACV-refractory disease due to ACV resistance. We determined the effect of ACV prophylaxis on the prevalence of corneal ACV-resistant (ACV(R)) HSV-1 and clinical consequences thereof in patients with recurrent HSV-1 keratitis (rHK). Frequencies of ACV(R) viruses were determined in 169 corneal HSV-1 isolates from 78 rHK patients with a history of stromal disease. The isolates' ACV susceptibility profiles were correlated with clinical parameters to identify risk factors predisposing to ACV(R) rHK. Corneal HSV-1 isolates with >28% ACV(R) viruses were defined as ACV(R) isolates. Forty-four isolates (26%) were ACV-resistant. Multivariate analyses identified long-term ACV prophylaxis (≥12 months) (odds ratio [OR] 3.42; 95% confidence interval [CI], 1.32-8.87) and recurrence duration of ≥45 days (OR 2.23; 95% CI, 1.02-4.87), indicative of ACV-refractory disease, as independent risk factors for ACV(R) isolates. Moreover, a corneal ACV(R) isolate was a risk factor for ACV-refractory disease (OR 2.28; 95% CI, 1.06-4.89). The data suggest that long-term ACV prophylaxis predisposes to ACV-refractory disease due to the emergence of corneal ACV(R) HSV-1. ACV-susceptibility testing is warranted during follow-up of rHK patients.

Herpesviruses and oral ulcerations in hematopoietic SCT recipients

We have read with great interest an article by van der Beek et al.1 published in Bone Marrow Transplantation. The authors reported that HSV-1 shedding in oral fluid after hematopoietic SCT (HSCT) is a significant predictor for oral mucosal ulcerations in adult patients, thus being a promising marker of the epithelial lesion. However, the conditioning regimen proved to be a non-significant predictor of ulcerative mucositis (UM) in this study. Therefore, we would like to discuss some interrelations between intensity of conditioning therapy, viremia rates and UM frequency in our pediatric setting. Some of these cases were reported elsewhere.2 Our study involved 120 patients of 1–21 years old (a mean of 12.4±5.9), comprising 56% males and 44% females, treated at R. Gorbacheva Memorial Institute of Children Hematology and Transplantology from 2002 to 2010. The patients with oncohematological disorders (mostly, acute leukemias, 73% of the total) underwent allo-HSCT from HLA-matched related or unrelated donors (38% and 62% of total group, respectively). The patients received peripheral blood stem cells or BM (60% and 40% of the total, respectively). Sixty-one recipients (51%) underwent myeloablative conditioning treatment (basically, BuCy protocols), while other patients were subjected to reduced-intensity conditioning (RIC), mostly, fludarabine-based treatment. GVHD prophylaxis was performed with CYA and MTX, at a standard schedule. In non-related HSCTs, antilymphocyte globulin treatment was added in 91 cases (76%), at 20 mg/m2 daily. Acyclovir prophylaxis since day 0 was performed in 31 patients (26% of total).

Photo Quiz: An 80-Year-Old Female with Acute Myeloid Leukemia and Induction-Associated Neutropenic Fever

An 80-year-old female presented to Geisinger Medical Center for evaluation of a subacute onset of dyspnea on exertion and was found to have moderate normocytic anemia and mild thrombocytopenia, with the presence of a high percentage of blasts in a peripheral blood smear. She underwent a bone marrow biopsy that showed acute myeloid leukemia. She underwent a transfusion and was discharged home to start induction chemotherapy with a 5-day course of clofarabine. She also received allopurinol, fluconazole, and acyclovir for prophylaxis. During her induction chemotherapy, she developed severe neutropenia and thrombocytopenia associated with fever and malaise that prompted a second hospital admission. At the time of this admission, the patient was hemodynamically stable and found to have moderate mucositis. The remainder of her physical examination was unremarkable, and she was placed on vancomycin, cefepime, and fluconazole. An extensive infectious-disease workup that included two initial sets of blood cultures was initiated, resulting in the isolation of Gram-negative bacilli from two FN anaerobic-blood-culture bottles (bioMerieux, Durham, NC). The hematology service was consulted and initiated therapy with filgrastim and sargramostim to improve her neutropenia. The patient also required transfusions of red blood cells and platelets. Her fever persisted for 10 days, although two additional sets of blood cultures collected 2 days after the initiation of antimicrobial therapy were negative. The patient underwent computed-tomography (CT) scans of her chest, abdomen, and pelvis in an unsuccessful attempt to identify the source of her bacteremia. The causative agent of her bacteremia is shown in Fig. 1. Fig 1 Gram stain of growth from a positive-blood-culture bottle. Magnification, ×1,000 (oil). (For answer and discussion, see page 737 in this issue [doi:10.1128/JCM.01156-12])

Bendamustine, Bortezomib and Dexamethasone (BBD) As First-Line Treatment of Patients with Multiple Myeloma Who Are Not Candidates for High Dose Chemotherapy: Toxicity Comparison of Two Dose Schedules

AbstractAbstract 4047 Background:Despite significant advances, multiple myeloma is an incurable plasma cell disorder with an eventual fatal outcome. In newly diagnosed MM, combinations of bortezomib, steroids and alkylating agents, such as melphalan and prednisone, have achieved response rates in excess of 70% and have been established as a standard of care in patients (pts) who are ineligible for high dose chemotherapy. Bendamustine is a bi-functional alkylating agent with a purine-like benzimidazole ring effective as a single agent and in various combinations for the treatment of relapsed/refractory MM (Poenisch et al, 2007, Fenk et al, 2007). In this study, the combination of bendamustine, bortezomib and dexamethasone (BBD) was evaluated as a first-line therapy for patients with MM. Methods:Patients with newly diagnosed active multiple myeloma who were not candidates for high-dose chemotherapy and met standard eligibility criteria with regards to renal, hepatic and hematologic function were enrolled. The original treatment schema (schema A) consisted of: bendamustine 80 mg/m2 IV on days 1, 4; bortezomib 1.3 mg/m2 IV on days 1, 4, 8, 11; and dexamethasone 40 mg on days 1, 2, 3, 4 with cycles repeating every 28 days. Patients had the option to continue on maintenance bortezomib. An interim analysis found this combination to be efficacious but relatively toxic. As a result the treatment schema was amended to the following (schema B): bendamustine 80 mg/m2 IV on days 1, 2; bortezomib 1.3 mg/m2 IV on days 1, 8, 15; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16 every 28 days for a total of 8 cycles or 2 cycles beyond documented CR, whichever occurred first. Again, patients had the option to continue maintenance bortezamib. Acyclovir or equivalent viral prophylaxis was recommended on schema A and became required on schema B. Responses were assessed using the IMWG criteria. AEs were assessed using the CTCAE Version 4.0. We report the results of an interim safety assessment of the amended BBD combination and compare the results to those seen with the original regimen. Results:Treatment schema A accrued 18 patients between 5/2010 and 2/2011. Ten patients were accrued from 10/2011 and 4/2012 and treated on treatment schema B. The median ages of treatment schemas A and B were 75 and 72.5 respectively, with all other characteristics within expected distributions and no major differences between the groups. No grades 4 hematologic Adverse Events (AEs) were seen. Grade 3 hematologic AEs were similar in both arms seen in 33% of patients on treatment schema A and 40% of patients on treatment schema B. Grade 3/4 non-hematologic AEs were seen in 72% of patients on treatment schema A and 60% of patients on treatment schema B. Although the preliminary Serious Adverse Events (SAEs) were similar with 39% of patients on treatment schema A compared to 30% of patients on treatment schema B, a large proportion of patients on treatment schema A (39%) were unable to complete the study due to toxicity or related issues. The incidence and severity of neuropathy and herpes zoster infections were significantly different between the two schemas. Schema A had 72% of patients with any grade neuropathy, with 56% being grade 2 or worse while schema B had 40% of the patients with any grade neuropathy, all but one grade 1. Likewise, 44% of patients on the original treatment reported herpes zoster while there were no cases of herpes zoster reported for patients on the revised treatment schema. Thus far, the early response rates appear similar. Schema A had an ORR of 78% (56% >vgPR) while schema B had an ORR of 90% (40% >vgPR). Conclusions:The combination of bendamustine, bortezomib and dexamethasone is feasible and efficacious in an elderly patient population. Using the revised schema, we were able to lower treatment toxicity without adversely impacting initial efficacy. Updated results will be presented at the meeting. Disclosures:Off Label Use: Off-label use of Bendamustine in the treatment of Multiple Myeloma. Chu:Millennium: Research Funding; Cephalon: Research Funding.

A case of bilateral ureteric obstruction in an allogeneic stem cell transplant recipient

Mr. MN, a 19 year old male, was treated for Acute Lymphoytic Leukaemia initially according to the UKALL12 regimen, and hen with Bone Marrow Transplantation after total body irraiation, CamPath and cyclophosphamide conditioning. Following ransplantation he initially made a good recovery, but at week post-transplant began to suffer from mucositis and haemorhagic cystitis. The cystitis failed to improve with conservative anagement including intravenous hydration, bladder irrigation nd modification of his immunosuppressive regimen. He received dose of intravesical cidofovir. During this period he received stanard acyclovir prophylaxis and showed no signs of graft-vs.-host isease. On day 17 his renal function deteriorated acutely and severely, ith creatinine rise from 89 to 287 over a 12 hour period, with oncurrent anuria. The acute presentation and severity of the renal ailure combined with anuria raised the suspicion of post-renal bstructive failure. CT imaging of the renal tract revealed mild ilatation of the proximal ureters bilaterally but no urolithiasis r mass lesions. However blood was noted within the severely hick walled bladder, consistent with severe haemorrhagic cystiis (Fig. 1). Subsequent bilateral nephrostomies showed multiple lling defects within the collecting systems and ureters secndary to clots (Fig. 2). Due to the patient’s acutely deteriorating linical condition he was admitted to the intensive care unit here haemofiltration was initiated. MN was also treated with a hort course of intravenous human immunoglobulin. The ureteric bstruction was treated with the insertion of bilateral ureteric rains under radiographic guidance which alleviated the acute

Low‐dose acyclovir prophylaxis for bortezomib‐induced herpes zoster in multiple myeloma patients

Low‐dose acyclovir prophylaxis for bortezomib‐induced herpes zoster in multiple myeloma patients

Practice Patterns and Opinions in the Management of Recurrent or Chronic Herpes Zoster Ophthalmicus

The objective of this study was to determine current practices and opinions among cornea specialists for treating and preventing recurrences of herpes zoster ophthalmicus (HZO). In November 2010, a survey of 15 questions was distributed to The Cornea Society listserv. Questions identified respondents' treatment practices for recurrent HZO and opinions regarding prolonged antiviral prophylaxis and zoster vaccine. Of 100 respondents, the majority were cornea specialists (83 of 98, 85%). Eighty-seven percent (84 of 97) reported treating recurrent or chronic cases of HZO in the last year. The most common choice of treatment in the posed recurrent HZO clinical scenario was a combination of oral antiviral and topical corticosteroid (63 of 100, 63%), although significant variability existed in the duration of oral antiviral administration. Fifty-four respondents (56%) believed that prolonged acyclovir prophylaxis could reduce recurrent signs of HZO; 28% (27 of 98) believed that recurrences of HZO could be reduced after the period of acyclovir administration. For patients with a history of HZO, most respondents reported not recommending the adult zoster vaccine (63 of 98, 64%), but 46% (43 of 94) believed that the vaccine could reduce recurrent signs or did not know. Many cornea specialists are managing recurrent or chronic cases of HZO, but there is variability in the use of topical corticosteroids and antivirals. Additionally, no consensus exists on the efficacy of prolonged antiviral therapy or the adult zoster vaccine to reduce chronic or recurrent disease. These results demonstrate the need for further systematic study of treatment and prophylaxis for recurrent and chronic HZO.

Low incidence of adenovirus hemorrhagic cystitis following autologous hematopoietic stem cell transplantation in the rituximab era

Low incidence of adenovirus hemorrhagic cystitis following autologous hematopoietic stem cell transplantation in the rituximab era

Acyclovir prophylaxis against cytomegalovirus in high risk paediatric kidney transplant recipients

Aims Cytomegalovirus (CMV) is an important infectious pathogen after kidney transplantation causing significant morbidity and mortality. Several prophylactic antiviral treatments are used and the aim of this study was to review the efficacy of acyclovir prophylaxis to prevent CMV infection in paediatric kidney transplant recipients. Methods The clinical records of kidney transplant recipients over a 20 year period were reviewed. Details of recipient and donor CMV serostatus were recorded together with information regarding prophylaxis received, evidence of CMV infection, and CMV related complications. All patients were scheduled to receive 5 mg/kg loading dose acyclovir peri-operatively and then acyclovir 200 mg qds for 90 days. Results 192 kidney transplants were performed in 177 children between 1991 and 2010. Only first grafts were considered in subsequent analysis. 36 recipients were identified as being at risk of CMV after transplant (i.e. recipient CMV IgG negative, donor CMV IgG positive). All of these patients received oral acyclovir prophylaxis and 58% received an intravenous loading dose. Of these 36 patients, 9 (25%) developed CMV viraemia with a positive CMV PCR. 7 patients met the criteria for CMV disease. 8 of the 9 patients developed viraemia whilst on acyclovir indicating active CMV replication despite treatment. There were no cases of severe infection or tissue invasive disease. There was no graft loss as a consequence of CMV infection. Conclusions The evidence supporting the choice of prophylactic treatment for CMV in paediatric kidney transplant recipients is limited. Recent data from the adult population indicate rates of disease are substantially lower in kidney transplant recipients treated with valganciclovir. These data indicate that in high risk individuals there is substantial risk of CMV disease despite prophylaxis with acyclovir and suggest that prophylaxis with valganciclovir is likely to result in significantly lower rates of CMV disease.

Impact of Latent Viral Infections in Mechanically Ventilated Patients

Cytomegalovirus (CMV), herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2), human herpes virus 6 (HHV-6) and 7 (HHV-7) and Epstein-Barr virus (EBV) all belong to the family of herpesviridae, are highly prevalent and ubiquitously distributed. In the immunocompetent adult host CMV and HSV infections usually have a benign course. As is the case with other herpesviridae, the initial infection is followed by a lifelong latent infection from which reactivation can occur. Asymptomatic viral shedding of CMV and/or HSV may occur in immunocompetent individuals. This viral shedding in patients without active viral disease makes it difficult to diagnose active disease in patients. In immunocompromised patients severe active disease due to these viruses is known to occur. However, critically ill patients admitted to the intensive care unit (ICU) are considered immunocompetent. Recent studies suggest that active infection with CMV, HSV, EBV or HHV-6 is also relatively common in ICU patients. Furthermore, an association between the presence of a CMV or HSV infection and increased mortality in critically ill patients was found. At present it is not clear whether this is intrinsically related to the micro-organism itself or merely an indication of the patients deteriorating physical condition leading to viral reactivation. To date the value of ganciclovir and acyclovir prophylaxis and/or treatment is unclear. The clinical relevance of active EBV or HHV-6 infection has not been established yet. Keywords: Critically ill patients, viral infection, Cytomegalovirus, herpes simplex virus, Mechanically Ventilated Patients, micro-organism, ventilator-associated pneumonia, Human herpes simplex virus

Herpesviridae Viral Infections After Chemotherapy Without Antiviral Prophylaxis in Patients With Malignant Lymphoma

The herpesviridae family includes, among others, herpes simplex virus, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. Herpesviridae viral infections (HVIs) can lead to serious complications in lymphoma patients undergoing chemotherapy. There is no consensus on the dose and duration of antiviral prophylaxis in these patients. We retrospectively analyzed the incidence and risk factors for HVI in lymphoma patients undergoing chemotherapy. We reviewed the records of 266 patients who were newly diagnosed with lymphoma and received chemotherapy without acyclovir prophylaxis between June 1996 and August 2009. The cumulative incidence rate of HVI was 20.16% for 5 years from the start of chemotherapy. Independent predictive factors for HVI in lymphoma patients were: female sex [hazard ratio (HR) 2.394; 95% confidence interval (CI): 1.245-4.607; P=0.009], cumulative dose of steroids per body surface area of at least 2500 mg/m(2) (HR 7.717; 95% CI: 3.814-18.703; P<0.001), and history of neutropenic fever (HR 0.297; 95% CI: 0.150-0.588; P<0.001). Female sex, high dose of steroids per body surface area, and neutropenic fever were risk factors for HVI in patients with lymphoma undergoing chemotherapy without acyclovir prophylaxis.

Acyclovir Prophylaxis Against Varicella Zoster Virus Reactivation in Multiple Myeloma Patients Treated With Bortezomib-Based Therapies: A Retrospective Analysis of 100 Patients

Previous studies have indicated that, in patients with multiple myeloma (MM), bortezomib is associated with an increased incidence of herpes zoster, resulting from reactivation of latent varicella zoster virus (VZV). Our objective was to determine whether increased risk of VZV reactivation could be abrogated by using prophylactic acyclovir. We retrospectively evaluated 100 consecutive MM patients treated with bortezomib-based therapies at the Roswell Park Cancer Institute for development of herpes zoster. Frontline and relapsed/refractory patients were included, and patients received bortezomib alone or in combination with agents such as doxorubicin, melphalan, or dexamethasone. All patients received >4 weeks of acyclovir prophylaxis (400 mg twice daily), which was initiated prior to starting treatment with bortezomib and discontinued 4 weeks following bortezomib. Median patient age was 62 years, 57% were male, and most (56%) had Durie-Salmon stage IIIA MM. None of the 100 MM patients receiving acyclovir prophylaxis developed herpes zoster during treatment with bortezomib, irrespective of patients receiving a wide variety of concomitant antimyeloma therapies and regardless of response to bortezomib-based therapy. One additional patient, found to be noncompliant with acyclovir therapy, experienced VZV reactivation, having received 3 cycles of bortezomib (3 weeks each cycle) in combination with cyclophosphamide and dexamethasone. Limitations of the study include its small size and retrospective nature. The increased risk of VZV reactivation observed in previous studies of bortezomib-based therapy was completely abrogated in this series of patients who received prophylaxis with acyclovir.

Use of a Super-Saturated Calcium Phosphate Mouth Rinse for Prevention and Treatment of Oral Mucositis Results In Faster Engraftment and Hospital Discharge Than Using a Sodium Bicarbonate Rinse Alone After Autologous Transplantation

Abstract 4569 Background:Oral mucositis is a common toxicity associated with cancer therapies and increases risk for infection, mortality, and extended hospital stay. Prophylactic use of a supersaturated calcium phosphate mouth rinse (SSCPR, Caphosol®) was found in a phase III study to reduce the frequency, intensity, and duration of oral mucositis in patients (pts) undergoing allogeneic or autologous hematopoietic stem cell transplantation (Papas, et al. Bone Marrow Transpl 2003;31:705). That study also found a faster time to recovery of an absolute neutrophil count (ANC) ≥0.2×109/l, but not for other engraftment endpoints, likely a result of the mixed pt population studied. Objective:A single-center retrospective review of two uniform populations undergoing autologous peripheral blood stem cell transplantation (PBSCT) to determine if an effective regimen of mucositis prophylaxis results in faster engraftment and shorter hospital stays. Methods:Two different uniform population of pts ≤70 years of age with Hodgkin or non-Hodgkin lymphoma (HL/NHL) and multiple myeloma (MM) undergoing PBSCT between 1/1/07 and 12/31/09 (Table 1). MM pts were conditioned with single dose melphalan (N= 16 with 140 mg/m2; N= 203 with 200 mg/m2). HL/NHL pts were conditioned with BEAM. Oral ice chips were given during the melphalan infusion for all pts. Filgrastim, 5 ug/kg, was given on days +3, +5, +7, +9 and then daily until granulocyte engraftment. A regimen of oral hygiene using sodium bicarbonate (NaHCO3) tooth cleaning after each meal with as needed rinsing was encouraged. SSCPR was added to this regimen in May 2008 with pts instructed to rinse 4-times daily after teeth cleaning and as needed. Granulocyte engraftment was defined as the first day with a rising ANC ≥0.5×109/l, and platelet engraftment was defined as the first day of a rising platelet count ≥20×109/l. Prospective scoring of mucositis was not performed and the use of intravenous fluconazole, ciprofloxacin, and/or acyclovir prophylaxis was recorded as a surrogate indicator of severe mucositis. Engraftment times and time to hospital discharge were estimated using the method of Kaplan and Meier, and the groups were compared using the log-rank test. The Mann-Whitney U test was used to assess differences in median values of age and CD34 cells infused, and Fisher’s Exact test was used to assess the significance of differences categorical parameters.Results: No differences were found between the control and study populations for age, gender, diagnosis, or CD34+ cell content of the graft (Table 1). For the HL/NHL control group one pt failed to engraft and was censored at the time of infusion of backup PBSC. In the MM groups no pts failed to engraft. No pts for either diagnosis were censored for death or relapse before hospital discharge. For both populations, pts using SSCPR achieved the primary endpoints of engraftment and were discharged home a median of 1 day faster than the respective control group pts (Table 2). 18 pts in the HL/NHL control group and 20 pts in the SSCPR group experienced febrile neutropenia (p=1.0) and 4 pts in each group were given intravenous medications (p=1.0). 73 pts in the MM control group and 53 pts in the SSCPR group experienced febrile neutropenia (p=0.22). 11 pts in the control group and 10 pts in the SSCPR group were given intravenous medications (p=1.0). These retrospective data of sequentially treated cohorts suggest that an effective regimen of mucositis prophylaxis may result in faster engraftment and shorter hospital stays with fewer days of antibiotics and cytokines. This retrospective study lacks detail regarding the incidence of mild/moderate mucositis and a mechanism of this action cannot be discerned from these data.Patient Demographics (NHL/HL & MM)NAge*Gender (M:F)Diagnosis (NHL:HL)CD 34+ Cells/Kg (×E6)*Control Group (NHL/HL)2253.914:816:68.6SSCPR Group (NHL/HL)2549.815:1017:87.5P0.261.00.760.56Control Group (MM)1116468:525.87SSCPR Group (MM)1086270:536.38P0.1561.000.107*Shown are median age and CD34+ cells/kg transplanted.Engraftment Kinetics (NHL/HL & MM)NWBC ≥1.0x109/lANC ≥0.5x109/lANC ≥1.0x109/lPlatelet ≥20x109/lDay DischargeControl Group (NHL/HL)221111111511SSCPR Group (NHL/HL)251010101210P0.0010.0010.0210.0350.015Control Group (MM)1111212121313SSCPR Group (MM)1081111111212P0.0110.0000.0310.0600.002*Shown are median days to achieve a particular endpoint. Disclosures:Rowley:EUSA Pharmaceautical: Speakers Bureau.

Clinical Efficacy of a Bortezomib, Cyclophosphamide and Dexamethasone Compared with Bortezomib, Cyclophosphamide, Thalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

Abstract 1868 Backgrounds & Aims:Salvage therapy such as bortezomib, cyclophosphamide, thalidomide and dexamethasone (Vel-CTD) showed an effective regimen in patients with relapsed or refractory multiple myeloma (MM). However, toxicities of this regimen due to combination bortezomib and thalidomide interrupt the consecutive treatments in a few patients. Therefore, we compared the clinical responses and toxicities between bortezomib, cyclophosphamide and dexamethasone (Vel-CD) and Vel-CTD in patients with relapsed or refractory MM patients, retrospectively. Methods:Eighty-six patients received at least 2 cycles of treatment with Vel-CTD (bortezomib 1.3 mg/m2 i.v. on D1, 4, 8 and 11; cyclophosphamide 150 mg/m2 orally on D1-4; thalidomide 50 mg/day orally every day; and dexamethasone 20 mg/m2 i.v. on D1, 4, 8 and 11 for every 3 weeks) and 67 patients with Vel-CD, which is the same regimen except thalidomide. Vel-CD group was only received low-dose acyclovir for prevention of herpes zoster. Results:17/67 (25%) and 10/86 (12%) of light chain disease was enrolled in Vel-CD and Vel-CTD group respectively (p=0.027) and there was no statistical difference at baseline demographic and disease characteristics between two groups in the others. The median time from diagnosis to treatment in Vel-CD and Vel-CTD was 15.6 months (range, 2–250 months) and 15.7 months (range, 1–230 months), respectively (p=0.54). The median number of treatment cycles was 6 cycles (range, 2–18) in Vel-CD and 8 cycles (range, 2–24) in Vel CTD group, and the number of cycles delivered was 430 and 678, respectively. The overall response rates (≥PR) of Vel-CD and Vel-CTD group were 88% and 90% ( 49% and 48% of complete response, 9% and 14% of very good partial response, 30% and 28% of partial response), respectively (each, p>0.05). There was no difference in progression free survival (p=0.69) and overall survival (p=0.49). Grade 3 or more hematologic adverse events occurred in the same proportion of patients in the both group. In non hematologic toxicities profiles, Vel-CTD group (14%) showed the higher proportion of grade 3 or more sensory neuropathy compared with Vel-CD group (3%) (p=0.02). Dose adjustment of bortezomib in Vel-CD and Vel-CTD were 40% (27/67) and 41%(35/86), respectively (p=0.96). Two patients (3%) in Vel-CD group received acyclovir prophylaxis developed herpes zoster compared with 17 patients (20%) in Vel-CTD group they were not received acyclovir prophylaxis (p=0.002). Three patients showed thrombotic events (2: pulmonary thromboembolism, 1: acute myocardial infarction) in only Vel-CTD group despite aspirin prophylaxis (p=0.16). Conclusion:Vel-CD combination therapy in patients with relapsed or refractory MM is an effective and more tolerable salvage regimen compared with Vel-CTD in the aspect of comparable response rate, less non-hematologic toxicities especially thalidomide associated adverse events. Disclosures:No relevant conflicts of interest to declare.

Metronidazole-induced Mania: Recurrence with Re-challenge

Purpose: Antimicrobial-induced mania, termed “antibiomania”, is exceptional and only reported in isolated case reports. Assigning causation of a rare adverse event to a particular therapy or condition is challenging. Definite cause-and-effect relationships are commonly absent. We report a case of metrondiazole-induced mania, reappearing with drug re-administration to alert physicians to a very rare adverse effect of a common medication. Case: A 57 year old man developed watery, non-bloody diarrhea a few days after taking levofloxacin for upper respiratory complaints. He was 3 years post-stem cell transplant for acute myelogenous leukemia and was being treated for graft versus host disease. Medications included prednisone 15 mg/day, tacrilomus, insulin, and long-term sulfamethoxazole- trimethoprim, fluconazole and acyclovir prophylaxis. Metronidazole was begun for symptoms. After 2 doses, he was noted by family, including a physician-daughter, to be hyperactive, expansive, talking excessively, grandiose - claiming special intuition about people with disordered thought processes. The next morning, his mood and thought processes had returned to normal baseline function. Because diarrhea persisted, he took another dose of metronidazole, but not levofloxacin. One hour later, disordered mood and thought reappeared. He went to the Emergency Department, where mania was diagnosed. He was treated with one dose of olanzapine and was normal the next day. Levofloxacin was restarted to finish a 5 day course and vancomycin was used with success for the diarrhea. There was no recurrence of the mania or diarrhea over a 2-year follow-up. Conclusion: Antibiomania is quite rare, most commonly attributed to clarithromycin, isoniazid and fluroquinolones. Less than 10 possible instances have incriminated metronidazole. We postulate that our patient had metronidazole-induced mania, perhaps potentiated by low-dose steroids and other antimicrobials. Further assessment difficulty exists because of single case reports of mania possibly induced by both acyclovir and sulfamethoxazole. Our case is highly unusual because documented recrudescence of symptoms occurred with drug re-administration; thus, this case may satisfy WHO criteria for definite rather than probable or possible causality, rare in single cases of putative drug reactions. Symptoms were of acute onset, temporally related to metronidazole use and self-limited with drug discontinuation. Prompt recurrence with re-challenge is striking. Antibiomania is rare, but should be considered with new onset of acute mania. Contribution of other medications is unclear and the mechanism is speculative.

Long-term follow-up of symptomatic patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia treated with the anti-CD52 monoclonal antibody alemtuzumab

AbstractCD52 is expressed on malignant cells in lymphoplasmacytic lymphoma (LPL), including IgM-secreting Waldenström macroglobulinemia (WM). We examined the activity of alemtuzumab in 28 symptomatic LPL (27 IgM and 1 IgA) patients. The median prior number of therapies for these patients was 2 (range, 0-5) and 43% had refractory disease. Patients received alemtuzumab at 30 mg IV 3 times weekly for up to 12 weeks after test dosing, and also received hydrocortisone, acyclovir, and Bactrim or equivalent prophylaxis. Patients had a complete response (n = 1), a partial response (n = 9), or a MR (n = 11) for an overall and major response rate of 75% and 36%, respectively. Median serum Ig decreased from 3510 to 1460 mg/dL (P < .001 at best response). With a median follow-up of 64 months, the median time to progression was 14.5 months. Hematologic and infectious complications, including CMV reactivation, were more common in previously treated patients and were indirectly associated with 3 deaths. Long-term follow-up revealed late-onset autoimmune thrombocytopenia (AITP) in 4 patients at a median of 13.6 months after therapy, which contributed to 1 death. Alemtuzumab is an active therapy in patients with LPL, but short- and long-term toxicities need to be carefully weighed against other available treatment options. Late AITP is a newly recognized complication of alemtuzumab in this patient population. This study is registered at www.clinicaltrials.gov as NCT00142181.

Onset and complications of varicella zoster reactivation in the autologous hematopoietic cell transplant population

Varicella zoster virus (VZV) infections are a common complication in patients receiving autologous or allogeneic hematopoietic cell transplant (HCT). Recent guideline revisions suggest extending VZV prophylaxis to 1 year after autologous HCT. We retrospectively evaluated reactivation at our center, before implementation of extended acyclovir prophylaxis, to determine onset and outcome in the autologous HCT population. Inclusion criteria consisted of adult patients who received an autologous HCT with documentation for at least 1 year post transplant. Those excluded from review were patients who received acyclovir prophylaxis for >30 days post transplant or subsequently received an allogeneic transplant within 1 year. For patients in whom reactivation occurred, the severity of infection, the timing of onset, treatment of the reactivation, and any complications were recorded. In the final analysis, 56 patients were assessed. Reactivation of zoster occurred in 16% of recipients with a median onset of 4.5 months post transplant. Complications that were observed include postherpetic neuralgia, severe pain, scarring, and motor weakness. Two patients required hospitalization for treatment, with 1 patient requiring 6 months of rehabilitation for motor weakness following the infection. Our study revealed a 16% incidence of VZV reactivation in our autologous HCT population. The onset of these occurrences ranged from 2 to 10 months post transplant, with significant VZV-associated complications. We consider VZV reactivation a serious concern in the autologous transplant setting, requiring extended prophylaxis.

Efficacy of Continuous, Daily, Oral, Ultra-low-dose 200 mg Acyclovir to Prevent Herpes Zoster Events Among Bortezomib-treated Patients: A Report From Retrospective Study

Herpes zoster is the most common infection in patients treated with bortezomib-containing regimens for multiple myeloma. Some clinical trials have reported on the use of acyclovir prophylaxis to decrease the incidence of herpes zoster. However, the appropriate acyclovir dose and duration of prophylaxis remain unclear. The primary objective of this study was to evaluate the efficacy of continuous oral 200 mg/day acyclovir prophylaxis and the secondary objective was to determine the risk factors for developing herpes zoster. We collected medical information from consecutive patients who received bortezomib with or without acyclovir prophylaxis for relapsed or refractory multiple myeloma at our hospital and retrospectively analyzed the efficacy of acyclovir prophylaxis and the parameters for predicting the risk factors for developing herpes zoster. The definition of acyclovir prophylaxis was oral continuous administration of 200 mg of once daily, without cessation, during the entire period of bortezomib treatment. Six of the 33 patients in the study developed herpes zoster during bortezomib treatment. No varicella-zoster virus reactivation was observed in the 19 patients in the acyclovir prophylaxis group. The incidence of herpes zoster was significantly higher in the group that did not receive acyclovir prophylaxis (43%, 6 of 14 patients) than in the group that did (0%, 0 of 19; P = 0.003). The predictive factors for varicella-zoster virus reactivation were male sex (P = 0.035) and the use of acyclovir (P = 0.003). Continuous prophylaxis by oral 200 mg/day acyclovir in multiple myeloma patients receiving bortezomib treatment is effective and sufficient in preventing herpes zoster.

Management and outcome of a varicella exposure in a neonatal intensive care unit: Lessons for the vaccine era

Varicella exposure in health care settings poses a threat to susceptible, immunocompromised hosts. We describe the management and outcome of a varicella exposure in a neonatal intensive care unit. We reviewed the history of the index case, determination of the exposed cohort, medical management of exposed neonates, and assignment of health care workers based on exposure and immune status. We present the results of serologic testing of health care workers related to their history of varicella disease. Of 427 health care workers assessed at the time of the exposure, 13.1% were seronegative for varicella. Among 180 employees recorded as having a previous history of varicella, 9 were seronegative. A total of 34 infants received prophylaxis with intravenous immune globulin; acyclovir prophylaxis was added for those born at <28 weeks gestational age. The exposed cohort was isolated. No secondary cases of varicella occurred among patients or health care workers. Nosocomial varicella exposures require rapid assessment and response, which can be guided by a checklist of actions. Varicella immunity in health care workers cannot be assumed even among those born before 1980; institutional policies should adhere to the 2007 Centers for Disease Control and Prevention's definition of immunity to varicella for health care workers.

Is Prophylactic Acyclovir Treatment Warranted for Prevention of Herpes Simplex Virus Infections in Facial Burns? A Review of the Literature

Both cosmetic facial resurfacing and facial burns cause an injury to the dermal layer of the skin. This injury renders the patient susceptible to primary herpes simplex virus (HSV) infection or, more commonly, to HSV reactivation. This in turn can lead to bacterial superinfection, possibly resulting in scarring and systemic dissemination in the immunosuppressed burn patient. HSV reactivation rates have been reported to be up to 50% in cosmetic procedures without acyclovir prophylaxis and up to 25% in patients with burn injury. Currently, acyclovir prophylaxis is a common practice in facial resurfacing, but no such recommendations have been issued for patients with burn injury. HSV usually presents in a febrile burn patient between the first and third postburn weeks as a cluster of small, umbilicated vesicles or vesicopustules on an erythematous base found within or around the margins of healing partial-thickness wounds. Diagnosis is confirmed through viral culture from the base of an unroofed vesicle, and treatment is begun with intravenous acyclovir. Antiviral prophylaxis should be strongly considered for HSV infection prevention in patients with major burn injury, particularly with burns involving the face. Acyclovir is the primary drug of choice, and contact precautions should be practiced. High suspicion levels and alertness to this entity can help prompt diagnosis and timely treatment while alleviating late complications.