Relationship of iothalamate clearance and NRM in patients receiving fludarabine and melphalan reduced-intensity conditioning.

The reduced-intensity conditioning regimen, fludarabine and melphalan, is frequently used in allogeneic hematopoietic stem cell transplantation (HSCT). Melphalan and the active metabolite of fludarabine, F-ara-A, are excreted via the kidneys. Existing methods to assess clearance in this setting are based on serum creatinine, which has known limitations for glomerular filtration rate (GFR) estimation in patients with malignancy. Measured GFR (mGFR) may better predict drug dosing to mitigate toxicity and increase the chances of successful engraftment. The primary objective of this study was to assess the association between mGFR and risk for nonrelapse mortality (NRM) in patients who have undergone allogeneic HSCT receiving conditioning with fludarabine and melphalan. In the 109 included patients, mGFR <65 mL/min/1.73 m2 predicted a significantly higher rate of overall NRM (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.35; P = 04) and 1-year incidence of infection (HR, 2.63; 95% CI, 1.54-4.55; P < .001) in addition to a significantly lower 2-year survival (P = .019). Kidney function estimated via estimated GFR (eGFR) and estimated creatinine clearance did not correlate with posttransplant outcomes. These results suggest that mGFR is a promising approach for assessing clearance in patients who have undergone allogeneic HSCT and may be preferred to standard creatinine-based eGFR strategies.

De Novo Malignancy After Liver Transplantation: Risk Assessment, Prevention, and Management-Guidelines From the ILTS-SETH Consensus Conference.

De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society-Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized.

Risk of relapse in patients receiving azithromycin after allogeneic HSCT.

Following publication of the ALLOZITHRO trial, the FDA released a safety announcement warning that azithromycin should not be given long-term to prevent BOS in patients with a blood or lymph cancer who have undergone allogeneic HSCT. Our site typically initiated azithromycin when patients were diagnosed with BOS post-transplant rather than empirically as prevention. The purpose of our study was to discern whether the use of azithromycin at the time of diagnosis of BOS increased risk of disease relapse in patients who received an allogeneic HSCT for malignant disease. We retrospectively reviewed 432 patients in 3 cohorts: Cohort (1) patients who received greater than or equal to 2 weeks of azithromycin therapy (n = 98); Cohort (2) patients who received azithromycin therapy for less than 2 weeks (n = 63); and Cohort (3) patients who never received azithromycin therapy (n = 271). Neither patients in Cohort 1 (HR 0.44; 95% CI, 0.12-1.53, P = 0.19) nor Cohort 2 (HR 0.66; 95% CI, 0.2-2.19, P = 0.49) were associated with an increased risk of relapse when compared to those who had never received azithromycin. Our data indicate that the prolonged use of azithromycin after allogeneic HSCT is not associated with an increased rate of hematologic relapse.

Thrombocytopenia associated with clonidine in a case of clozapine-induced sialorrhea.

Clozapine is approved by the US Food and Drug Administration for treatment-resistant schizophrenia and mitigation of suicidality in patients with schizophrenia or schizoaffective disorder. Clozapine requires monitoring of adverse events, such as hypotension, myocarditis, cardiomyopathy, seizures, severe neutropenia, and gastrointestinal hypomotility. Sialorrhea is another adverse event that can be bothersome for patients and result in nonadherence or the development of aspiration pneumonia. Clonidine, an α2A adrenergic receptor agonist, is one medication option that can reduce or eliminate sialorrhea. Clonidine is generally well tolerated but can contribute to hypotension and sedation. One adverse event associated with clonidine not described in the literature is thrombocytopenia. Reported is a case of clonidine-associated thrombocytopenia when used for the treatment of clozapine-induced sialorrhea.