Treatment of invasive fungal disease using anidulafungin alone or in combination for hematologic patients with concomitant hepatic or renal impairment / / Tratamiento de infecciones fúngicas invasivas con anidulafungina sola o combinada en pacientes hematológicos con insuficiencia hepática o renal concomitante

Background. Invasive fungal disease (IFD) treatment is challenging in hematologic patients due to drug interactions and toxicities that limit the use of the antifungal agents. Aims. To analyze retrospectively in terms of safety and potential efficacy anidulafungin therapy, alone or in combination. Methods. Our institutional guidelines recommended anidulafungin treatment in hematologic patients with suspected IFD and concomitant renal or liver impairment (to avoid drug interactions and preserve organ function). Results. From 2008 to 2013, 24 episodes of IFD occurring in 21 patients were classified as proven (4 cases), probable (15 cases) and possible (5 cases). Anidulafungin was administered alone (13%) or in combination (88%). Eight (33%) episodes were resolved, using monotherapy (1 out of 3, 33%) or a combined therapy (7 out of 21, 33%). Twelve cases (50%) were registered as failure (death due to IFD progression in 4 patients, and treatment change due to lack of efficacy in 8), and 4 cases (17%) were not evaluable (death unrelated to the IFD). Anidulafungin was not withdrawn in any case due to toxicity. Conclusions. Anidulafungin therapy, alone or in combination, could be considered in hematologic patients with IFD and concomitant liver or renal impairment. Due to the low number of patients, we cannot draw any conclusion about efficacy (AU)

Antecedentes. El tratamiento de una infección fúngica invasiva (IFI) supone un importante desafío en los pacientes hematológicos debido a las interacciones farmacológicas y a la toxicidad de los agentes antifúngicos, que restringen su uso. Objetivos. Analizar de forma retrospectiva el tratamiento con anidulafungina, sola o combinada, en términos de su seguridad y posible eficacia. Métodos. En los pacientes hematológicos con sospecha de IFI e insuficiencia renal o hepática concomitante, las guías clínicas de nuestro entorno recomendaban el tratamiento con anidulafungina (para evitar las interacciones farmacológicas y preservar la función orgánica). Resultados. De 2008 a 2013 se documentaron 24 episodios de IFI en 21 pacientes, que se clasificaron como IFI demostrada (4 casos), IFI probable (15 casos) e IFI posible (5 casos). Se administró anidulafungina como monoterapia (13%) y en combinación (88%). Se resolvieron 8 episodios (33%), 1 caso de 3 tratados con monoterapia (33%) y 7 casos de 21 tratados con terapia combinada, (33%). En 12 casos (50%), el tratamiento fracasó (muerte por progresión de la IFI en 4 pacientes y cambio de tratamiento por falta de eficacia en 8). Por último, 4 casos (17%) no se pudieron evaluar (muerte no relacionada con IFI). En ningún caso se retiró el tratamiento con anidulafungina por toxicidad. Conclusiones. El tratamiento con anidulafungina, sola o combinada, podría considerarse apropiado para pacientes hematológicos con IFI e insuficiencia hepática o renal concomitante. Debido al reducido número de pacientes incluidos, no es posible extraer conclusiones respecto a la eficacia(AU)

Passenger lymphocyte syndrome in liver transplant recipients: a description of 12 cases.

BACKGROUND: Passenger lymphocyte syndrome is an important cause of immune haemolysis after solid organ transplantation. It mainly occurs in minor ABO and Rh mismatched transplants. The haemolysis is usually mild and self-limited. We present our experience in passenger lymphocyte syndrome and liver transplantation and review the literature. MATERIALS AND METHODS: We reviewed liver transplants performed in our centre from January 2002 to September 2013, searching for ABO or Rh incompatibility and serological findings of haemolysis. A direct antiglobulin test was systematically performed in each pre-transfusion assessment. RESULTS: A total of 1,217 liver transplants were performed and 12 passenger lymphocyte syndromes were detected: of the 56 cases with minor ABO incompatibility, ten patients developed passenger lymphocyte syndrome (17.9%) and of 147 cases with minor Rh incompatibility, two patients developed the syndrome (1.40%). All patients with passenger lymphocyte syndrome had haemolysis, a decrease of haemoglobin (median 6.8 g/dL) and an increase of bilirubin (median 5.15 mg/dL). The treatment of passenger lymphocyte syndrome consisted of increasing the dose of corticosteroids that the patients were receiving as post-transplantation immunosuppressive therapy and, in the majority of cases, transfusion of donor compatible red blood cells. DISCUSSION: Passenger lymphocyte syndrome in liver transplantation has significant clinical consequences. It is, therefore, important to make the diagnosis rapidly, performing pre-transfusion direct antiglobulin tests, and manage the problem correctly with donor compatible red blood cell transfusions and/or immunosuppressive treatment.

The role of bone marrow biopsy and FDG-PET/CT in identifying bone marrow infiltration in the initial diagnosis of high grade non-Hodgkin B-cell lymphoma and Hodgkin lymphoma. Accuracy in a multicenter series of 372 patients.

Bone marrow infiltration (BMI), categorized as an extra-nodal site, affects stage and is associated with poor prognosis in newly diagnosed lymphoma patients. We have evaluated the accuracy of PET/CT and bone marrow biopsy (BMB) to assess BMI in 372 lymphoma patients [140 Hodgkin Lymphoma (HL) and 232 High Grade B-cell non-Hodgkin Lymphoma (HG B-NHL), among them 155 Diffuse Large B-Cell Lymphoma (DLCL)]. For HL cases, and taking into account PET/CT, sensitivity, negative predictive value (NPV) and accuracy were 96.7, 99.3, and 99.3% while those of BMB were 32.3, 83.8, and 85%, respectively. For HG B-NHL and considering PET/CT, sensitivity, NPV, and accuracy were 52.7, 81.7, and 84.1%, while those of BMB were 77.6, 90.2, and 90.7%, respectively. In the HG B-NHL group, 25 patients would have been under-staged without BMB. These results lead us to recommend PET/CT and the avoidance of BMB to assess BMI in HL. In the case of HG B-NHL, bone marrow status should be assessed firstly by means of PET/CT; only in either focal or diffuse PET/CT with low borderline SUV max values or in negative cases, should BMB be carried out afterwards. In the HG B-NHL setting and at the present moment, both techniques are complementary.

Transfusion management and immunohematologic complications in liver transplantation: experience of a single institution.

OBJECTIVE: Liver transplantation (LT) has traditionally been associated with major blood loss and consequently high blood transfusion requirements. Our objective was to analyze transfusion management and incidence of immunohematologic complications in patients undergoing LT at our institution. METHODS: A retrospective analysis of immunohematologic events and transfusion outcomes was carried out at La Fe University Hospital in Valencia. Data from 654 patients were reviewed: 654 underwent only one LT while 36 underwent second LT. RESULTS: Patients received a median of 3 red blood cell (RBC) concentrates, 2 platelets concentrates (PCs) and 2 fresh frozen plasma units (FFPs). Variables significantly influencing RBC transfusions were: the MELD score, hemoglobin levels, and the platelet counts before LT. 27 patients (4.1%) had a positive antibody screening before transplant. Immunohematologic events occurred in 8% of the patients, mostly in the first month after LT, and involved hemolysis in 13 cases. Mortality was significantly higher in patients developing immunohematologic disorders (42.8 vs. 18.3%; p < 0.001). In the multivariable analysis, only ABO minor incompatibility between donor and recipient significantly increased the appearance of immunohematologic incidences (OR 4.92, 95% CI 2.31-10.50; p < 0.001). CONCLUSION: Transfusion management of patients that underwent LT can be complicated by immunohematologic problems. Blood banks should implement the DAT test in each transfusion to detect them.

Treatment of invasive fungal disease using anidulafungin alone or in combination for hematologic patients with concomitant hepatic or renal impairment.

BACKGROUND: Invasive fungal disease (IFD) treatment is challenging in hematologic patients due to drug interactions and toxicities that limit the use of the antifungal agents. AIMS: To analyze retrospectively in terms of safety and potential efficacy anidulafungin therapy, alone or in combination. METHODS: Our institutional guidelines recommended anidulafungin treatment in hematologic patients with suspected IFD and concomitant renal or liver impairment (to avoid drug interactions and preserve organ function). RESULTS: From 2008 to 2013, 24 episodes of IFD occurring in 21 patients were classified as proven (4 cases), probable (15 cases) and possible (5 cases). Anidulafungin was administered alone (13%) or in combination (88%). Eight (33%) episodes were resolved, using monotherapy (1 out of 3, 33%) or a combined therapy (7 out of 21, 33%). Twelve cases (50%) were registered as failure (death due to IFD progression in 4 patients, and treatment change due to lack of efficacy in 8), and 4 cases (17%) were not evaluable (death unrelated to the IFD). Anidulafungin was not withdrawn in any case due to toxicity. CONCLUSIONS: Anidulafungin therapy, alone or in combination, could be considered in hematologic patients with IFD and concomitant liver or renal impairment. Due to the low number of patients, we cannot draw any conclusion about efficacy.

Bloodstream infections in adult patients undergoing cord blood transplantation from unrelated donors after myeloablative conditioning regimen.

The incidence, epidemiology, and risk factors of bloodstream infection (BSI) and their impact on transplant outcomes after umbilical cord blood transplantation (UCBT) are not well defined. Between May 1997 and December 2012, 202 isolates in 189 episodes of BSI were registered in 134 of 241 patients who underwent single-unit myeloablative UCBT. Cumulative incidence (CI) of developing at least 1 episode of BSI was 21%, 29%, 34%, 42%, and 52% at days +7, +14, +30, +100, and +365, respectively. The median time of onset for the first BSI episode was day +10 (range, day -7 to +1217). Early BSI before day 7 was associated with increased nonrelapse mortality (relative risk [RR], 1.5; 95% confidence interval [CI], 1.1 to 2.3; P = .04), whereas BSI before day 14 was an independent adverse risk factor for neutrophil recovery (RR, .6; 95% CI, .5 to .9; P = .002). A higher CD8(+) cell dose of the graft was the only variable independently associated with reduced risk of BSI (RR, .1; 95% CI, .02 to .7; P = .02). The gram-negative rod (GNR) to gram-positive bacteria ratio was .9 before day +30 and 1.6 thereafter (P = .03). Escherichia coli (31%) and Pseudomonas sp. (28%) were the most frequently isolated among GNR. The overall crude mortality rate was 12% at day 7 and was higher for GNR (18%) compared with gram-positive bacteria (7%) (P = .03). These findings emphasize the importance of preventing bacterial infections during conditioning and the very early post-UCBT period.