Microalbuminuria in Perinatally HIV-Infected Children and Adolescents in the United States.

Background: The kidney is a common target for human immunodeficiency virus (HIV), making renal disease a common noninfectious complication of HIV. Microalbuminuria is an important marker that can detect early renal damage. Timely detection of microalbuminuria is important to initiate renal management and stop the progression of renal dysfunction in people with HIV. Limited data are available about renal abnormalities in people with perinatal HIV infection. The objective of this study was to determine the prevalence of microalbuminuria in a cohort of perinatally HIV-infected children and young adults receiving combination antiretroviral therapy and investigate correlations between microalbuminuria and clinical and laboratory findings. Methods: This was a retrospective study of 71 patients with HIV followed in an urban pediatric HIV clinic in Houston, Texas, between October 2007 and August 2016. Demographic, clinical, and laboratory data were compared between subjects with persistent microalbuminuria (PM) and those without. PM is defined as a microalbumin-to-creatinine ratio ≥30 mg/g on at least 2 occasions separated by at least 1 month. Results: Sixteen of 71 patients (23%) met the definition of PM. In univariate analysis, patients with PM had significantly higher CD8+ T-cell activation and lower CD4+ T-cell nadir. Multivariate analysis demonstrated increased microalbuminuria to be independently associated with older age and CD8+ T-cell activation measured as CD8+HLA-DR+ T-cell percentage. Conclusions: Older age and increased activation of CD8+HLA-DR+ on T cells correlate with presence of microalbuminuria in this cohort of HIV-infected patients.

CD31 Expression on CD4+ Cells: A Simple Method for Quantitation of Recent Thymus Emigrant CD4 Cells.

Measurements of CD4+CD31+ cells gave results consistent with those expected for recent thymus emigrant (RTE) CD4+ cells. The method was markedly simpler than established procedures for measurement of CD4+ RTE cells and is usable in locations with limited facilities and budgets.

Recent Thymus Emigrant CD4+ T Cells Predict HIV Disease Progression in Patients With Perinatally Acquired HIV.

BACKGROUND: Robust immune restoration in human immunodeficiency virus (HIV)-positive patients is dependent on thymic function. However, few studies have investigated thymic function and its correlation with disease progression over time in HIV-positive patients. METHODS: In this longitudinal prospective study, we followed 69 HIV-positive patients who were perinatally infected. Peripheral blood mononuclear cells were stained with monoclonal anti-CD4 and anti-CD31 and recent thymic emigrants (CD4+recently emigrated from the thymus (RTE), CD4+CD31+) quantified by flow cytometry. Statistical analysis used Wilcoxon rank sum test, Kruskal-Wallis, Spearman correlation, and Kaplan-Meier estimates; Cox regression models were performed for the longitudinal analysis. RESULTS: Median age of HIV positive patients enrolled was 13 years (interquartile range [IQR], 8.6). CD4+RTE% decreased with age and was higher in females. Median CD4+RTE% was 53.5%, IQR, 22.9. CD4+RTE% was closely related to CD4+% and absolute counts but independent of viral load and CD8+CD38+%. Antiretroviral compliance as well as higher nadir CD4+% were associated with higher CD4+RTE%. Low CD4+RTE% predicted poor progression of VL and CD4+% over time. CONCLUSIONS: CD4+RTE% predicts disease progression and may reflect history of disease in HIV-positive patients and adolescents. They are easy to measure in the clinical setting and may be helpful markers in guiding treatment decisions.

Incidence and predictors of antiretroviral resistance in perinatally HIV-1 infected children and adolescents.

OBJECTIVES: Individuals with perinatally acquired HIV infection have benefited from antiretroviral therapy. However, they often have complex patterns of major resistance mutations that limit the effectiveness of available antiretroviral medications. Knowledge of incidence rates of major antiretroviral resistance mutations should provide a benchmark enabling comparisons of different HIV care delivery modalities. METHODS: We test the hypothesis that incidence rate of major antiretroviral resistance mutations will decline with improvement in HIV care between 1998 and 2009 to NRTI, NNRTI, PI and triple class resistance in perinatally HIV infected individuals. Logistic regression is used to evaluate predictors of single and triple class resistance. RESULTS: Sixty-six individuals are included from a total population of 97 perinatally HIV infected individuals. The incidence rate of NRTI, NNRTI, PI and triple class resistance decreases with decreasing age in parallel with the introduction of new HIV treatment regimens. The youngest children (born 2000-2007) are free of triple class resistance. Mono-therapy associates with major resistance mutations to NRTI (OR 8.7, CI 1.5-50.9, P 0.02); NNRTI exposure associates with major resistance mutations to NNRTI (OR 24.4, CI 5.7-104.5, P 0.01) and triple class resistance (OR 10.7, CI 1.8-67.1, P 0.01). Cumulative viral load is an important predictor of PI resistance (OR 4.0, CI 1.3-12.3, P 0.02). CONCLUSIONS: There is a progressive decrease in the incidence rate of major resistance mutations to antiretroviral drugs and triple class resistance from the oldest to the youngest birth cohort; where adolescents have the highest risk of harboring resistant viruses. The incidence rate of major antiretroviral resistance mutations provides a benchmark for the comparative measurement of effectiveness of different HIV care delivery modalities.

High-dose caspofungin as a component of combination antifungal therapy in 91 patients with neoplastic diseases and hematopoietic stem cell transplantation: a critical review of short-term and long-term adverse events.

The antifungal activity of echinocandins is concentration dependent. Previously, we demonstrated that high-dose caspofungin (HD-CSP; 100 mg daily) was well tolerated in 34 immunosuppressed patients with cancer and may have favorably influenced outcomes. We retrospectively assessed all 91 patients in whom HD-CSP was given for the treatment of invasive fungal disease (IFD). The median number of doses was 18.5 ± 21.5, and in 8 (9%) patients more than 40 doses were given. Most (62%) of the patients had leukemia. A total of 45 (49%) patients had undergone stem cell transplantation; 80% received allogeneic grafts and 47% had graft-versus-host disease. High-dose corticosteroids were given during antifungal therapy in 26 (29%) patients. In all, 8 (9%) patients had new elevation in serum bilirubin during HD-CSP therapy; normalization occurred after voriconazole and HD-CSP were discontinued in 4 patients each. No other short-term or delayed adverse events were observed. In all, 40 (44%) patients died of IFD. High-dose corticosteroids during HD-CSP (odds ratio [OR] 8, 95% confidence interval [CI] 2.1-30.4; P < .002) and starting HD-CSP in the critical care unit (OR 67.5, 95% CI 5.25-868.9; P < .001) were associated with death from fungal disease. Prolonged HD-CSP therapy was well tolerated. Drug-induced hyperbilirubinemia may pose a potential limitation for continued HD-CSP use in highly susceptible patients with hematologic neoplasms and stem cell transplantation.

Persistently high perinatal transmission of HIV: assessment of risk factors.

BACKGROUND: Despite dramatic decreases in rates of perinatal mother-to-child-transmission (PMTCT) of HIV in the United States, rates in some groups remain above the national average. Our objective was to examine factors contributing to a high rate of PMTCT of HIV. METHODS: We conducted a retrospective chart review of HIV-exposed infants and their mothers referred to the University of Texas-Houston Pediatric HIV Clinic from January 2000 to June 2007. RESULTS: Of 367 newborns studied, 22 (6%) acquired HIV infection perinatally. Associated risk factors included inadequate prenatal care, failure to receive antiretroviral therapy during pregnancy, detectable viral load and intravenous drug abuse. CONCLUSIONS: The composite rate of PMTCT in this high risk cohort was at least 3-fold higher than expected from the current standard of care. Reduction of rates of PMTCT in our population will require ensuring access to appropriate prenatal care, including delivery of antiretroviral therapy and addressing issues of illicit drug use.

Impact of cytotoxic and targeted antineoplastic drugs on the validity of the mitogen-induced interferon-gamma release assay for latent tuberculosis infection: results of a prospective trial at a comprehensive cancer center.

Abstract The T-SPOT.TB test (TS.TB), an interferon-gamma (IFN-γ) release assay (IGRA), is superior in diagnosing latent tuberculosis infection compared with the conventional tuberculin skin test (TST). However, whether cytotoxic chemotherapy and treatment with new-generation antineoplastic monoclonal antibodies affects the TS.TB is not certain. We evaluated the feasibility of using the TS.TB in this population. Sixteen cancer patients at high risk for tuberculosis exposure were prospectively evaluated with the TST and TS.TB. Blood samples were obtained 7.5 ± 89.3 days after the most recent cycle of antineoplastic therapy. Six patients (38%) were febrile within 24 h of blood sampling; high-dose corticosteroid therapy and profound treatment-induced neutropenia were present in 1 patient each. In all patients, TS.TB showed no evidence of latent tuberculosis infection. A robust mitogen-induced IFN-γ response was seen in samples from 14 patients (88%) despite therapy with high-dose corticosteroids, cyclophosphamide, fludarabine, gemtuzumab ozogamicin, and alemtuzumab. The presence of fever or profound neutropenia did not negatively impact mitogen response by peripheral lymphocytes. The 2 patients whose peripheral blood lymphocytes (> 500 cells/ml) failed to generate a cytokine response to ex vivo mitogen stimulation had refractory advanced cancer. Unlike the TST, a negative TS.TB provided interpretable results even in cancer patients undergoing new-generation immunosuppressive therapy.

Use of healthy-donor granulocyte transfusions to treat infections in neutropenic patients with myeloid or lymphoid neoplasms: experience in 74 patients treated with 373 granulocyte transfusions.

BACKGROUND/AIMS: Despite limited evidence for efficacy, granulocyte transfusions (GTX) are used to prevent and treat opportunistic infections in patients with neutropenia. METHODS: Three hundred and seventy-three GTX given to 74 patients were assessed retrospectively. RESULTS: GTX were discontinued because of clinical improvement more often in patients with severe infections than in patients without severe infections (27 vs. 12%; p ≤ 0.002), whereas deaths resulted in discontinuation of GTX therapy less often in patients with severe infections than without (8 vs. 39%; p ≤ 0.002). Patients who died by 12 weeks after GTX initiation were more likely to have leukemia (p = 0.03), not to have recovery of neutrophil counts (p < 0.0001), and to have started GTX during a critical care unit stay (p < 0.001). Uses of granulocyte colony-stimulating factor (p ≤ 0.02) and interferon-γ (p ≤ 0.04) were more common in patients who survived. In patients with comorbidities (31%; odds ratio, OR, 12.6; 95% confidence interval, CI, 2.4-65.7; p ≤ 0.003), GTX was started in the critical care unit (OR 8.8; 95% CI 2.5-30.9; p < 0.001), and a high total bilirubin level at the end of GTX (OR 2.1; 95% CI 1.1-4.2; p = 0.03) had a higher probability of death 12 weeks after GTX therapy commenced. CONCLUSIONS: The possibility that a niche population may benefit from GTX requires further assessment.

Aerosolized amphotericin B lipid complex as adjunctive treatment for fungal lung infection in patients with cancer-related immunosuppression and recipients of hematopoietic stem cell transplantation.

STUDY OBJECTIVE: Aerosolized amphotericin B lipid complex (aeABLC) has been successfully used to prevent fungal disease. Experience with aeABLC as treatment of fungal lung disease is limited. DESIGN: We evaluated the safety and efficacy of aeABLC adjunct therapy for fungal lung disease in a retrospective study of 32 immunosuppressed adults. All values are given as ± standard deviation. SETTING: National Cancer Institute-designated Comprehensive Cancer Center. PATIENTS: Acute leukemia (69%) and severe neutropenia (63%) were common. Fifty-six percent of patients had undergone allogeneic hematopoietic stem cell transplantation 185 ± 424 days prior to aeABLC was commenced. MEASUREMENT AND MAIN RESULTS: High-dose corticosteroids were administered during aeABLC in 28% of patients. Fungal lung disease was proven or probable in 41% of patients. Most patients (78%) received concurrent systemic antifungal therapy for a median of 14 ± 18 days before aeABLC. The median cumulative aeABLC dose was 1050 ± 2368 mg, and the median duration of aeABLC therapy was 28 ± 130 days. Most patients (78%) received 50 mg aeABLC twice daily. Partial or complete resolution of fungal lung disease was noted in 50% of patients. In three patients (9%) modest cough, mild bronchospasm, and transient chest pain with accompanying nausea and vomiting resolved completely after discontinuation of aeABLC. No patient required hospitalization for drug toxicity or had a serious (grade III or IV) drug-related adverse event. CONCLUSION: Treatment with aeABLC was tolerated without serious toxicity and may be considered in the setting of severe immunosuppression, cancer, and/or hematopoietic stem cell transplantation in patients with difficult-to-treat fungal lung disease.

Granulocyte macrophage colony-stimulating factor in 66 patients with myeloid or lymphoid neoplasms and recipients of hematopoietic stem cell transplantation with invasive fungal disease.

BACKGROUND/AIMS: Adding granulocyte macrophage colony-stimulating factor (GM-CSF) may improve the response to antifungal therapy in immunosuppressed patients with invasive fungal disease (IFD). METHODS: We retrospectively assessed 66 patients in whom GM-CSF was given during antifungal therapy. RESULTS: Severe neutropenia (77%) and refractory/relapsed cancer (65%) were common in the group. Prior to GM-CSF therapy, 15% of patients received high-dose corticosteroids for a median of 30 ± 16 days [median cumulative dose (c.d.) 1,184 ± 1,019 mg], and 9 received steroids during GM-CSF therapy for a median of 16 ± 12 days (median c.d. 230 ± 1,314 mg). Mild toxic effects were noted in 9% of patients; there were no cases of cardiopulmonary toxicity. All-cause deaths were observed in 68% of patients and 48% died of progressive IFD. High-dose corticosteroids prior to GM-CSF (OR 24; 95% CI 2.21-264.9; p ≤ 0.009), GM-CSF started in the intensive care unit (OR 10; 95% CI 1.66-63.8; p ≤ 0.01), concurrent granulocyte transfusions (OR 5; 95% CI 1.27-16.8; p ≤ 0.02) and proven/probable IFD (OR 4; 95% CI 1-16.2; p ≤ 0.05) predicted antifungal treatment failure. CONCLUSIONS: GM-CSF adjuvant therapy was tolerated without serous toxicity and antifungal treatment failure remained a challenge in patients treated with high-dose systemic corticosteroids.

Characteristics of, and risk factors for, infections in patients with cancer treated with dasatinib and a brief review of other complications.

Dasatinib has transformed the treatment of chronic myelogenous leukemia, resulting in durable remissions and prolonged survival. The spectrum of infectious complications during and after dasatinib therapy is not known. Retrospective analysis of records among 69 patients treated with dasatinib showed that 35 (51%) developed 57 episodes of infection. Twenty-nine (51%) episodes occurred during neutropenia, and 25 (44%) were microbiologically confirmed. Compared with patients who did not develop infection with dasatinib therapy, patients with infection were significantly more likely to have acute lymphocytic leukemia (51% vs. 18%; p ≤ 0.005) and to have received high-dose corticosteroids (51% vs. 26%; p ≤ 0.05). Patients with infection were also more likely to have received dasatinib with another antineoplastic agent (57% vs. 35% without infection; p = 0.09). On multivariate analysis, treatment with three or more cycles of dasatinib increased the risk of infection (odds ratio 11.7; 95% confidence interval 2.5-54.3; p = 0.002). The presence of comorbidities tended to increase the risk of infection (odds ratio 3.9; 95% confidence interval 0.9-17.9; p = 0.07). Interestingly, viral infections, including a single case of cytomegalovirus colitis, were uncommon (7%). The rate of death in 57 patients during follow-up was non-significantly higher in patients with infection versus those without infection (35% vs. 18%; p = 0.18). Infection-associated deaths were noted in only two patients (10%) who had an infection and died. The results of our analysis suggest that antibacterial prophylaxis is important in patients who develop neutropenia during dasatinib therapy, although routine antifungal and anti-cytomegalovirus prophylaxis may not be necessary.

De novo T-lymphocyte responses against baculovirus-derived recombinant influenzavirus hemagglutinin generated by a naive umbilical cord blood model of dendritic cell vaccination.

Cancer patients and recipients of hematopoietic stem cell transplantation exhibit a negligible response to influenza vaccine. Toward the goal of addressing this issue, we developed an in vitro model of dendritic cell (DC) immunotherapy utilizing DCs generated from naïve umbilical cord blood (UCB). UCB DCs were loaded with purified rHA protein and used to stimulate autologous T-lymphocytes. Upon recall with HA-loaded autologous DC, a 4-10-fold increase in the number of IFN-gamma producing T-lymphocytes was observed in comparison to T-cells stimulated with control DCs. Antigen-specific T-cell functionality was determined by (51)Cr lytic assay. Using a peptide library of predicted HA binding epitopes, we mapped an HA-specific, DR15-restricted CD4 T-cell epitope and observed tetramer positive cells. This model demonstrates that HA-specific immune responses might possibly be generated in a de novo fashion and suggests that dendritic cell immunotherapy for the prevention of influenza in populations of immunosuppressed individuals could be feasible.

Multiple-dose granulocyte-macrophage-colony-stimulating factor plus 23-valent polysaccharide pneumococcal vaccine in patients with chronic lymphocytic leukemia: a prospective, randomized trial of safety and immunogenicity.

BACKGROUND: For the current study, the authors sought to determine whether administration of multiple-dose granulocyte-macrophage-colony-stimulating factor (GM-CSF) could improve response to standard 23-valent polysaccharide pneumococcal vaccine (PPV) in patients with chronic lymphocytic leukemia (CLL). METHODS: Patients were allocated randomly to receive PPV either alone or with 3 doses of GM-CSF (250 microg) given before or after vaccination. Serum was obtained before, 4 weeks after, and 12 weeks after vaccination for antibody determination. Thirty-two patients with CLL were given PPV. They were randomized to receive 3 doses of GM-CSF either before or after vaccination or to receive no GM-CSF. RESULTS: A 4-fold rise in immunoglobulin G (IgG) to capsular polysaccharides from Streptococcus pneumoniae types 4, 6B, 9V, 14, 19F, and 23F occurred in <10% of patients in each of the 3 groups. There were no differences in geometric mean IgG levels in any of the 3 groups 4 weeks or 12 weeks after vaccination. CONCLUSIONS: In patients with CLL, the response to pure polysaccharide pneumococcal vaccine was low despite immune enhancement with multiple doses of GM-CSF. In all patients, reactogenicity was minor.

Infections in 100 cord blood transplantations: spectrum of early and late posttransplant infections in adult and pediatric patients 1996-2005.

Cord blood-derived stem cells are successfully used in the treatment of cancer and congenital disorders in children. This alternative source of stem cells is also explored for adult cancer patients with limited donor options. However, delayed engraftment, prolonged neutropenia, secondary graft loss, and graft-versus-host disease (GVHD) in recipients of cord blood transplantation (CBT) make opportunistic infections a serious concern. We evaluated the spectrum of infections in adults and children undergoing CBT at our National Cancer Institute-designated comprehensive cancer center. The infection incidence rate ratio (total infection episodes/days at risk [survival after CBT] x 100) was 2.4 times higher in 35 adult patients than in 62 children, especially in adults with neutropenia (3 x higher) and GVHD (1.9 x higher). Ninety-two percent of fungal infection episodes occurred within 100 days after transplantation; half of these infections occurred in the first 30 days after CBT. Most bacterial infections (80%) were also diagnosed in the first 100 days, whereas late (>100 d) post-CBT cytomegalovirus and varicella zoster virus infections occurred only in children with chronic GVHD. Multivariate analysis showed that resolution of lymphocytopenia (> or =1000 cells/microL) (hazard ratio [HR] 0.71; p < 0.0001) and successful engraftment (HR 0.20; p < 0.0001) were associated with a low risk of serious infection. Children (HR 0.36; p < 0.0002) with sustained engraftment (HR 0.39; p < 0.004) and those with cancer in remission (HR 0.47; p < 0.007) were less likely to die from infection. More effective measures for surveillance and prevention of late cytomegalovirus and varicella zoster virus infections in children with CBT and chronic GVHD are needed.

Streptococcus pneumoniae infections in 47 hematopoietic stem cell transplantation recipients: clinical characteristics of infections and vaccine-breakthrough infections, 1989-2005.

Streptococcus pneumoniae infections can cause serious systemic disease in patients following hematopoietic stem cell transplantation (HSCT), and the response to pneumococcal vaccine is inadequate in most HSCT recipients. We evaluated the clinical spectrum of pneumococcal disease and vaccine-breakthrough infections in HSCT recipients at our cancer center in a retrospective analysis of all consecutive episodes of S. pneumoniae infection from 1989 through 2005. During the study period, 7888 patients underwent HSCT at our center; we identified 47 HSCT recipients with 54 S. pneumoniae infections. The overall incidence of S. pneumoniae infection was 7 per 1000 HSCTs. The incidence was higher in recipients of allogeneic grafts than in recipients of autologous grafts (9 vs. 5 per 1000 HSCTs, respectively; p

Dose-related safety and immunogenicity of baculovirus-expressed trivalent influenza vaccine: a double-blind, controlled trial in adult patients with non-Hodgkin B cell lymphoma.

In 27 patients randomized to receive commercial trivalent influenza vaccine (TIV) containing 15 microg of the hemagglutinin (HA) of influenza A (H3N2 and H1N1) and B virus or a recombinant vaccine (rHAO) containing 15, 45, or 135 microg of each HA, reactogenicity was minor. Among patients with similar prevaccination titers, 40% given 45 microg and 60% given 135 microg of rHAO developed an increase in influenza A/H3 neutralizing antibody levels; there were no increases in 4 given TIV. For each vaccine, the highest frequencies of increases in neutralizing antibody levels and the highest mean titers occurred in those given the 135- microg vaccine.

Recombinant interferon gamma1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions.

BACKGROUND: The response to antifungal therapy alone often is suboptimal in patients with cancer who have therapy-refractory neutropenia, and even donor-derived granulocyte transfusions (GTX) are not always successful. The authors evaluated the safety and efficacy of immune enhancement using recombinant interferon gamma1b (rIFN-gamma1b) in patients with cancer who received GTX for refractory, systemic, opportunistic infections. METHODS: Twenty recipients of high-dose donor GTX ( approximately 5.5 x 10(10) neutrophils per transfusion) who had received concurrent rIFN-gamma1b between October 2001 and December 2004 were evaluated retrospectively. RESULTS: The median age (+/- standard deviation [SD]) was 45 +/- 17 years. Ten patients (50%) were men, 17 patients (85%) had leukemia, and 3 patients (15%) had myelodysplastic syndrome. The median +/- SD Acute Physiology and Chronic Health Evaluation II score was 15 +/- 4 (range, 7-22). Most patients (n = 18 patients; 90%) had recurrent or refractory cancer. In 6 patients (30%) who received allogeneic hematopoietic stem cell transplantation, GTX plus rIFN-gamma1b was given a median +/- SD of 26 +/- 100 days (range, 12-372 days) after transplantation. Seventeen patients (85%) had neutropenia during GTX therapy. Five patients (25%) had possible invasive fungal infection, 3 patients (15%) had probable invasive fungal infection, and 11 patients (55%) had proven invasive fungal infection. One patient (5%) had refractory Pseudomonas aeruginosa sepsis. Eight patients (40%) received corticosteroids during GTX plus rIFN-gamma1b therapy. Patients received a median +/- SD of 8 +/- 7 GTX doses (range, 4-28 doses) and 9 +/- 7 rIFN-gamma1b doses (range, 1-28 doses), for a mean +/- SD cumulative dose (CD) of 400 +/- 2621 microg. Other concomitant cytokines were granulocyte-colony stimulating factor (12 +/- 3 doses; CD, 6720 +/- 4721 microg) in 15 patients (75%) and granulocyte-macrophage-colony stimulating factor (12 +/- 9 doses; CD, 4750 +/- 4410 microg) in 14 patients (70%). Four patients (20%) developed fever, and 2 patients (10%) developed skin rashes. Reversible liver dysfunction (n = 3 patients; 15%) and tachycardia (n = 1 patients; 5%) were considered rIFN-gamma1b-associated adverse reactions; whereas, in 1 patient (5%), transient dyspnea was attributed to GTX. Four weeks after therapy started, 9 patients (45%) had complete or partial resolution of infection; and, in another 3 patients (15%), the invasive fungal infection had become stable. CONCLUSIONS: The current results indicated that no serious adverse events were associated with rIFN-gamma1b immune enhancement in patients with systemic opportunistic infections who received donor GTX therapy.

Cytomegalovirus pneumonia in patients with lymphoma.

BACKGROUND: Even when treated with antiviral therapy, cytomegalovirus pneumonia (CMVp) is associated with high morbidity and mortality in immunocompromised patients. CMVp has been rarely reported in patients with lymphoma. METHODS: The authors reviewed the records of patients treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between 1997 and 2003. Collected information included demographics, use of chemotherapy, or corticosteroids, concomitant infections, and outcome. RESULTS: Thirty-one patients with lymphoma with 36 episodes of CMVp were identified. The incidence of CMVp increased between 1997 and 2003 (0 of 1000 treated patients vs. 9 of 1000 treated patients; P = 0.07). Most episodes occurred in patients with non-Hodgkin lymphoma (89%). Most of the patients (92%) had received chemotherapy and corticosteroids (89%) before the onset of CMVp. Concomitant CMV antigenemia was detected in 11 (41%) of the 27 episodes in which testing was performed. In 19 episodes (53%), patients had coinfections within 90 days of the episode of CMVp. Coinfections were present at the onset of CMVp in 11 episodes (31%). The yield for CMV in bronchoalveolar lavage (BAL) specimens was higher with culture methods than with cytologic evaluation or immunohistochemical staining (P < 0.001). The number of CMV antigenemia tests performed increased fourfold over the study period. The CMV-attributed mortality rate was 30% (9 of 30 patients). Independent predictors of death by multivariate Cox regression analysis were high APACHE II score (> 16) at onset of CMVp (P = 0.02, hazards ratio [HR] = 15.5, 95% confidence interval [CI], 1.5-163.7), and development of toxicity to antivirals (P = 0.04, HR = 14.03, 95% CI, 1.2-169.1). CONCLUSIONS: The incidence of CMVp in patients with lymphoma is increasing. CMV detection in BAL specimens was better with culture methods than with cytologic or immunohistochemical methods. High APACHE II score and development of antiviral toxicity were associated with a fatal outcome.

The safety of interferon-gamma-1b therapy for invasive fungal infections after hematopoietic stem cell transplantation.

BACKGROUND: The restoration of normal immune responses, especially of the T-helper type 1 immune response, is an important predictor of fungal infection outcome in patients with malignant disease who undergo hematopoietic stem cell transplantation (HSCT). The authors sought to evaluate the safety of adjuvant recombinant interferon-gamma-1b as an immune-modulatory therapy HSCT recipients. METHODS: Thirty-two patients received interferon-gamma-1b after undergoing HSCT at the author's institution between 1998 and 2003. A retrospective analysis was undertaken after obtaining permission from the Institutional Review Board. RESULTS: Twenty-six of 32 patients (81%) received allogeneic stem cell grafts. All but 1 patient received interferon-gamma-1b and antifungals to treat infections; the other patients received interferon-gamma-1b to promote autologous graft-versus-tumor effect. Interferon-gamma-1b usually was administered at a dose of 50 mug subcutaneously every other day. The median duration (+/- standard deviation) of interferon-gamma-1b therapy was 6+/-6.5 doses (range, 1-29 doses), and the median cumulative dose was 487+/-453 mug (range, 35-2175 microg). During therapy with interferon-gamma-1b, fever was common (n=9 patients; 28%). In 1 patient (3%), new-onset lymphocytopenia occurred but resolved after cytokine therapy was discontinued; there were no interferon- gamma-1b-related episodes of neutropenia, thrombocytopenia, anemia, or liver dysfunction. Interferon-gamma-1b therapy did not precipitate or exacerbate acute or chronic graft-versus-host disease (GVHD). In fact, in 2 of 7 patients (29%) with acute GVHD and in 3 of 10 patients (30%) with chronic GVHD, significant improvements in GVHD were noted during therapy with interferon-gamma-1b. Among the 26 patients with aspergillosis, 14 patients (54%) died. However, 5 of 10 patients (50%) with presumed pulmonary aspergillosis, 3 of 9 patients (33%) with probable pulmonary aspergillosis, 1 of 2 patients (50%) with definite pulmonary aspergillosis, and 3 of 5 patients (60%) with disseminated aspergillosis responded to antifungals and adjuvant interferon-gamma-1b. CONCLUSIONS: Recombinant interferon-gamma-1b was tolerated without serious adverse reactions in HSCT recipients. A large, prospective, randomized study will be needed to evaluate the efficacy of this cytokine in high-risk HSCT recipients who have invasive mycoses.