Pneumocystis Jirovecii Pneumonia Prophylaxis Research Articles

Dynamo: A Phase 2 Study Demonstrating the Clinical Activity of Duvelisib in Patients with Relapsed Refractory Indolent Non-Hodgkin Lymphoma

Dynamo: A Phase 2 Study Demonstrating the Clinical Activity of Duvelisib in Patients with Relapsed Refractory Indolent Non-Hodgkin Lymphoma

Temporal Profiles of Lymphocyte Subsets and the Correlation with Infectious Events in Idelalisib-Treated Patients

Introduction: Idelalisib (IDELA) is a targeted PI3Kd inhibitor approved as monotherapy in relapsed follicular lymphoma and in combination with rituximab in relapsed chronic lymphocytic leukemia (CLL). Increased rates of adverse events (AEs) were recently observed in the IDELA vs placebo arms of randomized controlled trials (RCT) evaluating IDELA added to standard therapies in front-line CLL and early-line indolent non-Hodgkin lymphoma (iNHL). AEs leading to death were mainly infectious and included pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV). This analysis across trials in the relapsed population evaluated whether quantitative changes in lymphocyte subsets may have contributed to these AEs.Methods: Peripheral blood immunophenotypic data available for analysis from patients (pts) (n = 1,480) treated in 5 IDELA RCTs were analyzed. Three studies (n = 787) included pts with relapsed CLL (NCT01569295: IDELA + bendamustine-rituximab [BR] vs placebo + BR; NCT01539512: IDELA + R vs placebo + R and NCT0165902: IDELA + ofatumumab [O] vs placebo + O) and 2 studies (n = 693) included R/R iNHL pts (NCT01732913: IDELA + R vs placebo + R and NCT01732926: IDELA +BR vs placebo + BR). Absolute numbers of T (CD4+ and CD8+), B (CD19+) and NK (CD16+/CD56+) cells were analyzed longitudinally in both IDELA and placebo pts across the 5 studies. Lymphocyte subsets were analyzed separately in those who died and then correlated with specific grade ≥3 AEs including infections, febrile neutropenia, and respiratory (acute respiratory failure, pneumonitis) events. Analysis was conducted within individual study and for all studies combined. Of note, samples were collected more frequently during the first 6 months (during combination therapy) and collection times varied among the 5 studies.Results: There was no specific trend noted with the CD8+ T-cells between treatment groups across the studies. Generally, NK-cells were decreased to a similar degree in both IDELA and placebo pts at weeks 10 to 12 with recovery starting around week 24. There were no differences in median NK- and CD8+ T-cell counts between pts with grade ≥3 AEs and no AEs within either group. In both BR trials, CD4+ T-cells nadir to <200 cells/µl occurred at week 22 in both groups. Recovery of CD4 to ≥200 cells/µL occurred at week 30 in CLL pts and at week 72 in iNHL pts. Median CD4+ T-cells in pts on the BR trials were lower in groups both with and without AEs, compared with non-BR trials (Table 1). There were a total of 31 cases of PJP (13 in the BR trials) and 32 cases of CMV infection (28 in the BR trials). Analysis of PJP and CMV pts with available immunophenotypic data (n = 46) revealed that 33 pts had CD4 <200 cells/µL; 31 of these were treated with IDELA plus combination therapy (Figure 1). Finally, while there were more grade ≥3 AEs within IDELA arms, these did not occur at any specific CD4 level and, in fact, grade ≥3 AEs were noted even in pts with CD4 >900 cells/µL.Conclusion: Within 5 RCTs evaluating IDELA vs placebo in combination with an anti-CD20 mAb or BR in R/R CLL or iNHL, there was no correlation between grade ≥3 AEs and NK- or CD8+ T-cell counts. Median CD4+ T-cells in pts on the BR trials were lower in both groups in those with and without AEs, compared with non-BR trials. In addition, pts with PJP and CMV infections were noted to have CD4+ T-cells <200 cells/ µL, and this was more common in IDELA-treated patients, especially when combined with BR, suggesting that the lymphosuppressive effect of IDELA may augment the myelosuppressive effect of bendamustine. While this current study involves the quantitative analysis of various immune cell subsets, it may be the qualitative function of these cells that contributed to infections. Assays evaluating the qualitative function of these cells are being investigated. All IDELA trials have been amended to include PJP prophylaxis and CMV monitoring. [Display omitted] [Display omitted] DisclosuresSharman:Gilead Sciences, Inc.: Honoraria, Research Funding. Salles:Mundipharma: Honoraria; Amgen: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding. Jurczak:Celltrion, Inc: Research Funding; Janssen: Research Funding; Gilead Sciences: Research Funding; Acerta: Research Funding; Bayer: Research Funding. Jones:AbbVie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Gilead Sciences: Consultancy, Research Funding; PCYC: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Owen:Janssen: Honoraria; Gilead: Honoraria, Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria, Research Funding; Abbvie: Honoraria; Lundbeck: Honoraria, Research Funding; Novartis: Honoraria; Roche: Honoraria, Research Funding. Munugalavadla:Gilead Sciences: Employment, Equity Ownership. Dreiling:Gilead Sciences: Employment, Equity Ownership. Xiao:Gilead Sciences: Employment, Equity Ownership. Rao:Gilead Sciences: Employment, Equity Ownership. Flinn:Janssen: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Gilead Sciences: Research Funding; ARIAD: Research Funding; RainTree Oncology Services: Equity Ownership. O'Brien:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria.

Risk Evaluation and Outcome of Pneumocystis jirovecii Pneumonia in Kidney Transplant Patients

Pneumocystis jirovecii pneumonia (PJP) affects immunocompromised patients. As a result of effective prophylaxis in the 1st months after kidney transplantation, PJP is increasingly diagnosed in the long term after transplantation. The present study evaluates course and outcome of PJP in a single transplant center from 2010 to 2015. Twenty-three patients presented with PJP at a mean of 53.7 ± 50.2 months after transplantation. Of these, 3 patients underwent ABO-incompatible (ABO-i) living-donor transplantation and 3 patients were treated with the use of belatacept. For risk estimation, 3 control cohorts were defined: a control group of all kidney transplant patients presenting for routine follow up (n = 575), all patients transplanted in an ABO-i setting (n = 45), and all patients treated with belatacept in our clinic (n = 69). Mortality in patients with PJP was 3/23 (13%) and graft loss after PJP was 3/23 (13%) resulting in patient and graft survivals of 87% and 73.9%, respectively. All patients were without PJP prophylaxis at time of diagnosis. Five of the 23 PJP patients received rejection therapy or dose escalation of immunosuppression 6 months before PJP infection, and 1 patient experienced acute rejection within 6 months after PJP treatment. In the course of PJP, 8 patients developed acute respiratory insufficiency. At time of PJP diagnosis, patients presented with severe lymphopenia (mean ± SD lymphocyte count, 0.64 ± 0.27/nL; normal range: 1.5–3/nL). Patients after ABO-i transplantation, as well as patients treated with belatacept, showed an increased risk for PJP (7.3% and 4.3%, respectively); however, in belatacept patients, other risk factors, such as age, low estimated glomerular filtration rate (eGFR), and lymphopenia seemed to contribute to this increased risk.

Pneumocystis jirovecii pneumonia in systemic autoimmune rheumatic disease: A case-control study.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that affects the immunocompromised. Patients with systemic autoimmune rheumatic disease are increasingly recognised as an at-risk clinical population with a high mortality. This case-control study examined differences in the characteristics and peripheral blood parameters between patients with systemic autoimmune rheumatic disease who developed PJP and gender, age and disease-matched controls. Historical data collected between 2002 and 2013 at the Royal Melbourne Hospital, Australia were reviewed. Cases were defined by having a systemic autoimmune rheumatic disease and a diagnosis of PJP (either a positive toluidine blue O stain or P. jirovecii PCR, with a concurrent respiratory illness that was clinically consistent with PJP). Controls were matched for age, gender and disease in a 4:1 ratio. Peripheral blood results were retrieved from an in-house pathology database. Clinical information including glucocorticoid exposure, PJP prophylaxis, comorbidities and month of admission were retrieved from medical notes. After adjustment for corticosteroid exposure and C-reactive protein, lymphocyte count on admission (0.4 vs. 1.3; p = 0.04) and at nadir (0.2 vs. 0.8 × 109/L; p = 0.05) was significantly lower in cases than in controls. Cases (n = 11) were more frequently Caucasian rather than non-Caucasian (81.8% vs. 65.9%; p = 0.04). In addition, cases more commonly presented in autumn (March to May) than in other seasons (OR = 7.3; 95% CI: 1.4-38.7; p = 0.02). These data demonstrate that patients with systemic autoimmune rheumatic disease who develop PJP have significantly greater lymphopenia than age, gender and disease-matched controls, independent of corticosteroid exposure, as well as a potential ethnicity and seasonal predilection to PJP. This may help to inform prophylactic guidelines for PJP in these patients.

Prescription of Pneumocystis Jiroveci Pneumonia Prophylaxis in HIV-Infected Patients.

The US treatment guidelines recommend Pneumocystis jiroveci pneumonia (PCP) prophylaxis for all HIV-infected persons with a CD4 count <200 cells/mm3 (ie, eligible for PCP prophylaxis). However, some studies suggest PCP prophylaxis may be unnecessary in virally suppressed patients. Using national data of HIV-infected adults receiving medical care in the United States during 2009 to 2012, the authors assessed the weighted percentage of eligible patients who were prescribed PCP prophylaxis and the independent association between PCP prophylaxis prescription and viral suppression. Overall, 81% of eligible patients were prescribed PCP prophylaxis. Virally suppressed eligible patients were less likely to be prescribed PCP prophylaxis (prevalence ratio: 0.84; 95% confidence interval: 0.80-0.89). Although guidelines recommend PCP prophylaxis for all eligible patients, some HIV care providers might not prescribe PCP prophylaxis to virally suppressed patients. Additional data on the risk for PCP among virally suppressed patients are needed to clarify this controversy.

Safety and Effectiveness of Intravenous Pentamidine for Prophylaxis of Pneumocystis jirovecii Pneumonia in Pediatric Hematology/Oncology Patients.

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection that can lead to significant morbidity and mortality in immunocompromised pediatric hematology/oncology patients. Trimethoprim/sulfamethoxazole is the gold standard for prophylaxis. Intravenous (IV) pentamidine is the preferred second-line agent for PCP prophylaxis at our institution and is used first-line under certain circumstances. The purpose of this study is to evaluate the effectiveness and safety of IV pentamidine for PCP prophylaxis in pediatric hematology/oncology patients. A retrospective analysis of pediatric hematology/oncology patients (N=121) who received ≥1 dose of IV pentamidine between January 2009 and July 2014 was conducted. Electronic health records were reviewed to determine baseline characteristics, rate of breakthrough PCP infection, characteristics of IV pentamidine use, and adverse events. The follow-up period was 6 months after the last reported IV pentamidine dose or the last recorded clinic visit/hospital admission. No patients developed PCP during the entirety of their IV pentamidine course or during the follow-up period. Nineteen patients (16%) experienced adverse events and 5 of the 19 patients required discontinuation of IV pentamidine. IV pentamidine is a safe, tolerable, and effective agent for PCP prophylaxis in pediatric hematology/oncology patients and may be considered a reasonable therapeutic alternative when trimethoprim/sulfamethoxazole cannot be used for PCP prophylaxis.

The Role of Arterial Blood Gas in Distinction of Intravascular Hemolysis in a Patient with Lupus Nephritis.

Dapsone is a Leprostatic agent routinely used for Malaria, Leprosy and as a prophylaxis for Pneumocystis jiroveci pneumonia (PCP), as well as Toxoplasma gondii in immunocompromised patients. Methemoglobinemia is an adverse effect of dapsone which can be life-threatening. Detailed is a case of dapsone-induced methemoglobinemia in a young woman with lupus nephritis treated with chronic immunosuppressant medications.

Preventing Infections in Children with Cancer.

1. Jennifer Lighter-Fisher, MD* 2. Kaitlin Stanley, MD* 3. Michael Phillips, MD† 4. Vinh Pham, MD, PhD† 5. Liana M. Klejmont, PharmD, BCPS‡ 1. *Department of Pediatrics, New York University Langone Medical Center, New York, NY. 2. †Department of Medicine, New York University Langone Medical Center, New York, NY. 3. ‡Department of Pharmacy, New York University Langone Medical Center, New York, NY. After completing this article, the reader should be able to: 1. Provide recommendations for bacterial prophylaxis for children experiencing severe and prolonged neutropenia. 2. Screen and recommend prophylaxis against Mycobacterium tuberculosis for children receiving immunosuppressive regimens. 3. Provide recommendations for secondary prophylaxis against Clostridium difficile infection, a common infection causing morbidity in the pediatric oncology population. 4. Recommend appropriate antifungal prophylaxis for pediatric patients who have high-risk cancers. 5. Review primary and second-line options for Pneumocystis jiroveci (carinii) pneumonia prophylaxis in children who fail trimethoprim/sulfamethoxazole therapy. 6. Prevent reactivation of viral infections in children receiving cancer treatment. 7. Screen for latent parasitic infections in newly diagnosed pediatric oncology patients. 8. Review vaccination regimens for patients receiving oncology treatment as suggested by the Infectious Diseases Society of America. Clear guidelines exist for the prevention of infections in patients undergoing hematopoietic stem cell transplantation (HSCT), (1)(2) but there is no guidance regarding prophylactic antimicrobial therapy for pediatric cancer patients receiving systemic chemotherapy. Infection, whether due to bacterial, fungal, viral, or parasitic pathogens, is a leading cause of morbidity and mortality in this patient population. (3)( 4)( 5) For example, more than 60% of children being treated for acute myeloid leukemia (AML) experienced at least 1 microbiologically documented infection during therapy, and the cumulative infectious mortality rate was 11%. (5) Therefore, infection prevention is of the utmost importance. Due to the lack of standard guidelines for infection prevention in most children being treated for cancer, current …

Pneumocystis jirovecii Pneumonia in the Non–HIV-Infected Population

Summarize data on the pathophysiology, treatment, and prevention options for non-AIDS immunocompromised patients who have Pneumocystis jirovecii pneumonia (PJP); review the epidemiology of patients presenting with PJP; and discuss the first and second-line pharmacological options for treatment and prophylaxis of PJP in this population. MEDLINE (1989-February 2016) searched. Terms searched included combinations of Pneumocystis jirovecii, Pneumocystis carinii, non-HIV, infected, patients, prevention, prophylaxis, Bactrim, treatment, AIDS, opportunistic, immunocompromised, cancer, and pathophysiology Articles included had the most relevant information on PJP pathophysiology, and first-/second-line treatment and prophylactic options. Inclusion criteria were met and evaluated with 43 sources. P jirovecii has a complicated life-cycle; it seeks to find compromised immune systems in order to replicate, causing life-threatening complications. With immunosuppressive medications coming to market for immunomodulating diseases, PJP has become a prevalent opportunistic infection in the non-HIV population. CD4+ lymphocyte count <200 cells/µL is the primary risk factor for PJP presentation in these patients. With data from clinical trials, trimethoprim/sulfamethoxazole (TMP/SMX) has become the primary treatment and prophylaxis of PJP in the non-HIV population, although second-line options are available. PJP is a health problem that may result in an increased concern as more immunomodulating medications to treat various disease states are developed. Patients on these drugs or those with immunosuppressive diseases should have their CD4+ count monitored. Health care providers should continue to use TMP/SMX as the primary option in non-HIV, immunocompromised patients for treatment and prophylaxis of PJP.

Cardiac Infections

Survival following a diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has improved since the introduction of cyclophosphamide-based immunosuppressive regimens and is now almost 80% at 5 years. However, mortality remains 2.6 times greater in the population with AAV than in an age- and sex-matched general population. The greatest risk of harm for patients with AAV is during the first year of diagnosis and from the adverse events associated with treatment rather than with active vasculitis. Infection, cardiovascular disease (CVD) and malignancy are the most common causes of death during follow-up. New regimens including rituximab, although with an efficacy similar to that of cyclophosphamide, have not yet shown a clear reduction in adverse events. Therapy for AAV must currently encompass a much greater focus on preventing harm from treatment through vaccination, Pneumocystis jirovecii pneumonia (PJP) prophylaxis, CVD risk assessment and bone protection measures.

ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients.

The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: ). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen.

Nocardiosis following hematopoietic stem cell transplantation.

Nocardia species are ubiquitous environmental organisms that can cause a diverse spectrum of disease. Clinical manifestations range from localized skin and soft tissue infections to life-threatening pulmonary, central nervous system, and/or disseminated infections. Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) are at risk for nocardiosis, and further data in regard to characteristics of disease in this population are warranted. We performed retrospective chart review of patients post allogeneic HSCT at Moffitt Cancer Center in Florida diagnosed with nocardiosis from 2003 to 2013. In a decade, 15 cases of nocardiosis were identified. The majority of patients were men (11/15). The median age was 55 years (range 25-65). The most common type of transplant was matched-related donor (n = 8), followed by matched-unrelated donor (n = 3), mismatched-unrelated donor (n = 3), and double umbilical cord (n = 1). Ten received myeloablative conditioning (MAC) regimens. Twelve of 15 patients were on prednisone, 10 of which were on a total daily dose ≥20 mg. The median time from transplant to first positive culture was 10 months (range 1.5-93). Pulmonary nocardiosis was the most prevalent manifestation at 87%. Disseminated disease (2 or more sites of infection) was seen in 47%, whereas blood cultures were positive in 27% of the total cohort. The most common species was Nocardia nova (n = 4). At the time of diagnosis, 20% of the patients were receiving prophylaxis for Pneumocystis jirovecii pneumonia (PJP) with trimethoprim-sulfamethoxazole (TMP-SMX). Susceptibility data were available for 8 patients: all 8 samples were susceptible to TMP-SMX. Nocardiosis was treated with 2 or more active drugs in 93% of the patients. Overall mortality was 53%, with nocardiosis attributed as the cause in 62.5% (5/8). The absolute lymphocyte count at time of diagnoses was significantly lower in patients who ultimately experienced treatment failure. Infection with Nocardia species in allogeneic HSCT recipients appears to be a late complication of transplantation and most commonly involves the lung. Two-thirds of the cohort received a MAC regimen and the majority of the patients were receiving steroids at the time of diagnosis. Most patients were not receiving TMP-SMX for PJP prophylaxis at the time of nocardiosis diagnosis, and TMP-SMX may therefore have a protective effect.

Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the Pediatric Hematopoietic Stem Cell Transplant Population.

Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients with mortality above 50%. Trimethoprim-sulfamethoxazole is a standard PCP prophylaxis; pentamidine is frequently used as second-line prophylaxis because of trimethoprim-sulfamethoxazole's potential for cytopenias. Monthly intravenous (IV) pentamidine has variable efficacy with PCP infection rates of 0%-10% in pediatric patients, and higher breakthrough rates in those younger than 2 years. We hypothesized that bimonthly (twice monthly) pentamidine might have equivalent safety and improved efficacy; therefore, we conducted a retrospective analysis of bimonthly pentamidine PCP prophylaxis. We retrospectively reviewed records of all pediatric HCT patients who received bimonthly IV pentamidine between December 2006 and June 2013, and collected data regarding demographics, clinical course, prophylaxis rationale, laboratory values and adverse events. Between December 2006 and June 2013, 111 pediatric HCT patients received bimonthly IV pentamidine (574 doses, 8758 patient-days); 31 patients were younger than 2 years at initiation. In the majority (53% of courses), pentamidine was initiated because of cytopenias. Fourteen patients (12.6% of patients, 2.4% of doses) experienced a side-effect prompting discontinuation, including 3 patients with infusion-related hypotension/anaphylaxis and 3 with acute pancreatic dysfunction. No patients [0% (95% confidence interval: 0-3.2)] developed PCP during or after bimonthly IV pentamidine prophylaxis. Bimonthly IV pentamidine for PCP prophylaxis in the HCT pediatric population has comparable safety to monthly IV pentamidine and was highly effective, including in the very young. Bimonthly IV pentamidine should be considered in pediatric patients as second-line PCP prophylaxis.

Retrospective review of intravenous pentamidine for Pneumocystis pneumonia prophylaxis in allogeneic hematopoietic stem cell transplantation.

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients. A single-institution retrospective review of electronic medical records was conducted for patients who underwent allo-HSCT between January 2001 and May 2013 and who had received at least 1 dose of IV PEN for PJP prophylaxis. Data collected included patient demographics, diagnosis, previous chemotherapy, pre-transplant conditioning regimen, other medications, microbiology test results, and clinical outcomes. A total of 113 patients were included in the study. The median number of PEN doses administered per patient was 3 (range 1-23). IV PEN was primary PJP prophylaxis in 74 of the patients (65%) and second-line prophylaxis in 39 (35%) post transplant, with the majority switching from oral TMP-SMX. Side effects of IV PEN administration were minimal. No patients who received IV PEN prophylaxis developed PJP infection. No case of PJP was seen in patients who received other agents for PJP prophylaxis. This retrospective study showed that IV PEN is very effective and well-tolerated prophylaxis for PJP; IV PEN can be considered a favorable alternative for PJP in situations where other agents might be contraindicated. Our findings provide strong support for prospective studies of IV PEN for PJP prophylaxis in adult HSCT recipients.

57-Year-Old Man With Hip Pain and Lytic Bone Lesions

57-year-old man presented to his primary care physician with a 2-year history of progressive right hip pain. His medical history was notable for hyperlipidemia. He was up-to-date on sex- and agespecific cancer screening. The patient had no history of chest pain, palpitations, shortness of breath, cough, or other cardiac, respiratory, neurologic, or visual symptoms. He had no recent travel history or occupational or social contact with persons who were ill. Physical examination revealed an obese man (body mass index [calculated as weight in kilograms divided by height in meters squared], 40.34 kg/m 2 ) with normal vital signs and unremarkable findings on cardiac, respiratory, abdominal, neurologic, and lymphatic examination. No pain or tenderness was elicited on examination. He was treated initially with nonopioid pain medications. Sacroiliac corticosteroid injections were minimally beneficial. Results of a complete blood cell count (CBC) and electrolyte panel were normal with the exception of an elevated serum calcium level of 11.7 mg/dL (reference range, 8.9-10.1 mg/dL). Ultimately, magnetic resonance imaging (MRI) of his lumbar spine revealed numerous punched-out lytic lesions in the lumbar vertebra and pelvis. He underwent computed tomography (CT) of his chest, abdomen, and pelvis that identified further lytic lesions as well as multiple splenic lesions concerning for metastases. Two separate CT-guided bone biopsy samples of the lytic lesions in the lumbar vertebra did not elicit an etiology of the lesions.

The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis.

Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a CIBMTR study evaluating the incidence, timing, prophylaxis agents, risk factors, and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs. controls (p=0.0004). After controlling for significant variables, proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs. matched controls (p<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes.

A case of Pneumocystis jiroveci pneumonia after bendamustine-based chemotherapy for refractory diffuse large B-cell lymphoma.

A case of Pneumocystis jiroveci pneumonia after bendamustine-based chemotherapy for refractory diffuse large B-cell lymphoma.

Efficacy of once-weekly dapsone dosing for Pneumocystis jirovecii pneumonia prophylaxis post transplantation.

Pneumocystis jirovecii pneumonia (PCP) remains a concern after organ transplantation. In 2005, the University of Kentucky (UK) Transplant Center implemented a novel dosing regimen of weekly dapsone as an alternative for patients with contraindications or intolerability to trimethoprim-sulfamethoxazole (TMP-SMZ), which remains the drug of choice. The purpose of this study was to compare the efficacy of weekly dapsone with TMP-SMZ in preventing PCP post transplantation. A single-center, cohort, retrospective review of kidney and liver transplant patients from January 2005 to December 2012 was conducted. Patients who were identified as dapsone cases were matched in a 1:1 ratio with TMP-SMZ controls based on type of transplant, age, primary diagnosis, and gender. The primary endpoint assessed was the diagnosis of PCP at 6 and 12 months post transplant. A total of 158 patients were included in the study. No documented cases of PCP occurred in either study group at 6 or 12 months (P = 1.0). In dapsone patients 35 (44%) cases of breakthrough infection occurred, compared to 24 (30%) in the TMP-SMZ group (P = 0.07) within 12 months post transplant. In the dapsone group, 52 (65%) patients were hospitalized within 6 months post transplant compared to 36 (46%) patients in the TMP-SMZ group (P = 0.01). Similar results were seen in patients hospitalized within 12 months post transplant; 49% of patients were switched from TMP-SMZ to dapsone owing to renal dysfunction. No documented cases of PCP occurred in either study group. Future studies are warranted to show the efficacy of weekly dapsone dosing compared to other PCP prophylaxis regimens.

HCP-17RETROSPECTIVE ANALYSIS OF PNEUMOCYSTIS JIROVECI IN BRAIN TUMOR PATIENTS

Pneumocystis jiroveci pneumonia (PCP) can be a highly lethal infection in patients with HIV or other immunodeficiencies, with a mortality rate estimated at 50%. The use of corticosteroids has been associated with 80-94% of PCP cases in the non-HIV population. In two-thirds of cases, the infection clinically presents during the tapering of steroids, likely reflecting an infection that is unmasked as the patient regains the ability to mount an immune response. The precise influence of dose and duration of corticosteroid treatment regarding susceptibility to PCP infection remains a controversial question. Some studies suggest that patients with brain tumors on steroids for more than 5 weeks are at high risk of PCP, especially during the tapering period. Generally, patients who receive steroid treatment for more than 4 weeks at a dose equivalent to 20 mg of prednisone per day are considered for PCP prophylaxis at most cancer centres, but there is variability across institutions. At the Pencer Brain Tumor Centre at Princess Margaret, there is no established protocol regarding PCP prophylaxis in glioma patients on corticosteroids, as it is felt that the incidence of PCP is rare and side effects of prophylaxis can impact patient's overall well being during treatment. Retrospective assessment of our cohort of patients with primary brain tumors from January 1st 2008 to December 31st 2013 will help determine the incidence of PCP infection in this population in the absence of prophylaxis and will allow evaluation of factors associated with PCP infection, including the dose and the duration of corticosteroid treatment, CD4 count and systemic therapy. We will also determine the proportion of patients who needed to stop their PCP prophylaxis due to side effects and the correlation between PCP infections and the duration/dose of steroid treatment. Results will be available for the SNO meeting.

NTCT-10INCREASED RISK FOR HEMOLYTIC ANEMIA IN GLIOBLASTOMA PATIENTS TREATED WITH DAPSONE

BACKGROUND: Antibiotic prophylaxis against Pneumocystis jirovecii pneumonia (PCP) is recommended for glioblastoma (GBM) patients receiving radiation and temozolomide. Trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, and inhaled pentamadine are accepted antibiotics. Oxidant hemolysis is a known complication of dapsone, typically associated with G6PD deficiency. We report hemolytic anemia in 7/12 GBM patients treated with dapsone. We compare the rate of anemia with TMP-SMX and pentamadine-treated patients. METHODS: Retrospective review of charts of GBM patients treated with radiation and temozolomide 2009 -14 at our institution. RESULTS: Of 52 patients, 23 received TMP-SMX, 17 pentamadine, and 12 dapsone. Seven (58%) of the dapsone treated patients experienced > 2.0 g/dl drop in hemoglobin from baseline. In each patient, G6PD screening was normal. Macrocytosis was present in 4/7 dapsone-treated patients with anemia. Lactate dehydrogenase levels were elevated (range 312-414 U/L) in 3 / 4 in whom it was available. Peripheral smears of 5 demonstrated degmacytes (‘bite cells’). CONCLUSION: Anemia was more common in patients treated with dapsone than with TMP-SMX or pentamadine. The frequency of anemia is higher than anticipated, especially with normal G6PD levels. Evidence of hemolysis is supported by characteristic bite cells, increased LDH levels, with compensatory reticulocytosis suggested by macrocytosis. Close monitoring for anemia in GBM patients treated with dapsone for PCP prophylaxis is required, even with normal pretreatment G6PD levels.