Gastrointestinal toxicity of high-dose melphalan in autologous hematopoietic stem cell transplantation: identification of risk factors and a benchmark for experimental therapies.

Gastrointestinal side effects are the dose-limiting toxicity of high-dose melphalan (HDM) in autologous hematopoietic stem-cell transplantation, but there are limited contemporary data on the incidence and severity of gastrointestinal toxicity associated with this regimen. We retrospectively studied 100 consecutive patients who received HDM alone or in combination with other conditioning agents. Patients had a median age of 56 (range 20-73); underlying diseases were myeloma (42%), lymphoma (42%), or amyloidosis (16%) and melphalan dosages were 200 (40%), 140 (59%), or 100 mg/m2 (1%). Ninety-seven percent of patients experienced diarrhea with a range of 1-18 bowel movements per day, 88% developed nausea, and 60% experienced vomiting. Abdominal CT scans rarely altered patient management, but stool studies were useful in identifying a treatable infectious source. Grade ≥ 2 diarrhea was associated with longer duration of diarrhea, longer length of stay, worse hypoalbuminemia, higher use of antibiotics, abdominal imaging, electrolyte repletions, and anti-diarrheal agents. Risk factors for severe diarrhea were female sex, melphalan dose, age > 50, creatinine clearance < 60 ml/min, and having a plasma cell neoplasm as opposed to lymphoma. Female sex was also associated with more severe nausea and vomiting. In summary, diarrhea remains an important toxicity of HDM and novel therapies for chemotherapy-induced diarrhea for patients undergoing stem-cell transplantation are needed. Grade 2 or higher diarrhea is associated with significant clinical consequences and should be used as the primary endpoint in prospective clinical trials.

Granulocyte Colony-Stimulating Factor Use after Autologous Peripheral Blood Stem Cell Transplantation: Comparison of Two Practices.

Administration of granulocyte colony-stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (PBSCT) is generally recommended to reduce the duration of severe neutropenia; however, data regarding the optimal timing of G-CSFs post-transplantation are limited and conflicting. This retrospective study was performed at NewYork-Presbyterian/Weill Cornell Medical Center between November 5, 2013, and August 9, 2016, of adult inpatient autologous PBSCT recipients who received G-CSF empirically starting on day +5 (early) versus on those who received G-CSF on day +12 only if absolute neutrophil count (ANC) was <0.5 × 109/L (ANC-driven). G-CSF was dosed at 300 µg in patients weighing <75 kg and 480 µg in those weighing ≥75 kg. One hundred consecutive patients underwent autologous PBSCT using either the early (n = 50) or ANC-driven (n = 50) G-CSF regimen. Patient and transplantation characteristics were comparable in the 2 groups. In the ANC-driven group, 24% (n = 12) received G-CSF on day +12 and 60% (n = 30) started G-CSF earlier due to febrile neutropenia or at the physician's discretion, 6% (n = 3) started after day +12 at the physician's discretion, and 10% (n = 5) did not receive any G-CSF. The median start day of G-CSF therapy was day +10 in the ANC-driven group versus day +5 in the early group (P < .0001). For the primary outcome, the median time to neutrophil engraftment was 12 days (interquartile range [IQR] 11-13 days) in the early group versus 13 days (IQR, 12-14 days) in the ANC-driven group (P = .07). There were no significant between-group differences in time to platelet engraftment, 1-year relapse rate, or 1-year overall survival. The incidence of febrile neutropenia was 74% in the early group versus 90% in the ANC-driven group (P = .04); however, there was no significant between-group difference in the incidence of positive bacterial cultures or transfer to the intensive care unit. The duration of G-CSF administration until neutrophil engraftment was 6 days in the early group versus 3 days in the ANC-driven group (P < .0001). The median duration of post-transplantation hospitalization was 15 days (IQR, 14-19 days) in the early group versus 16 days (IQR, 15-22 days) in the ANC-driven group (P = .28). Our data show that early initiation of G-CSF (on day +5) and ANC-driven initiation of G-CSF following autologous PBSCT were associated with a similar time to neutrophil engraftment, length of stay post-transplantation, and 1-year overall survival.

Olaratumab (Lartruvo): An Innovative Treatment for Soft Tissue Sarcoma.

Olaratumab (Lartruvo): an innovative treatment for soft tissue sarcoma.

Safety of anticoagulation in thrombocytopenic patients with hematologic malignancies: A case series.

The incidence of venous thromboembolism is greater among cancer patients than the general patient population, with recurrence rates also much higher in patients with cancer diagnoses. Patients with hematologic malignancies often experience prolonged periods of thrombocytopenia throughout their disease course, making therapeutic anticoagulation a challenge. We describe 13 cases of patients with hematologic malignancies that were therapeutically anticoagulated with either low-molecular-weight heparin or unfractionated heparin during periods of severe thrombocytopenia (platelet counts < 50 × 109/µL). Patients were included if they had a diagnosis code for a hematologic malignancy and venous thromboembolism between 1 January 2010 and 31 December 2012. The diagnosis of venous thromboembolism included both deep vein thrombosis and pulmonary embolism. There was one bleeding event, World Health Organization grade 2, that was documented in a patient receiving enoxaparin dosed twice daily, resulting in an overall bleeding rate of 7.7% in this case series. All 13 patients were administered platelet transfusions during the periods of severe thrombocytopenia. While each patient case must have the risks and benefits weighed individually, we observed that anticoagulation for the treatment of venous thromboembolism during periods of thrombocytopenia may be considered in patients with hematologic malignancies.

Comparison of Subcutaneous versus Intravenous Alemtuzumab for Graft-versus-Host Disease Prophylaxis with Fludarabine/Melphalan-Based Conditioning in Matched Unrelated Donor Allogeneic Stem Cell Transplantation.

The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days -7 to -3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting. Incidences of acute and chronic GVHD were similar between both arms. There was also no difference in reactivation of CMV/EBV viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, relapse, or survival.

Ramucirumab (Cyramza): A Breakthrough Treatment for Gastric Cancer.

Ramucirumab (Cyramza): A breakthrough treatment for gastric cancer.

Risk factors and outcomes for patients with bloodstream infection due to Acinetobacter baumannii-calcoaceticus complex.

Identifying patients at risk for bloodstream infection (BSI) due to Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ABC) and providing early appropriate therapy are critical for improving patient outcomes. A retrospective matched case-control study was conducted to investigate the risk factors for BSI due to ABC in patients admitted to the Detroit Medical Center (DMC) between January 2006 and April 2009. The cases were patients with BSI due to ABC; the controls were patients not infected with ABC. Potential risk factors were collected 30 days prior to the ABC-positive culture date for the cases and 30 days prior to admission for the controls. A total of 245 case patients were matched with 245 control patients. Independent risk factors associated with BSI due to ABC included a Charlson's comorbidity score of ≥ 3 (odds ratio [OR], 2.34; P = 0.001), a direct admission from another health care facility (OR, 4.63; P < 0.0001), a prior hospitalization (OR, 3.11; P < 0.0001), the presence of an indwelling central venous line (OR, 2.75; P = 0.011), the receipt of total parenteral nutrition (OR, 21.2; P < 0.0001), the prior receipt of ß-lactams (OR, 3.58; P < 0.0001), the prior receipt of carbapenems (OR, 3.18; P = 0.006), and the prior receipt of chemotherapy (OR, 15.42; P < 0.0001). The median time from the ABC-positive culture date to the initiation of the appropriate antimicrobial therapy was 2 days (interquartile range [IQR], 1 to 3 days). The in-hospital mortality rate was significantly higher among case patients than among control patients (OR, 3.40; P < 0.0001). BSIs due to ABC are more common among critically ill and debilitated institutionalized patients, who are heavily exposed to health care settings and invasive devices.

A retrospective review of metronidazole and vancomycin in the management of Clostridium difficile infection in patients with hematologic malignancies.

BACKGROUND: The incidence and severity of Clostridium difficile infection has significantly increased over the past decade. Although the epidemiology and treatment of C. difficile infection is well elucidated in the non-oncology population, it is poorly understood among cancer patients. This illustrates great concern as the majority of these patients are immunosuppressed, which puts them at higher risk for developing severe disease. Furthermore, suboptimal treatment of C. difficile infection can compromise care of underlying malignancy. Due to limited amount of data, we conducted this study to better ascertain the epidemiology and treatment outcomes of C. difficile infection in a subset of oncology patients at our institution. OBJECTIVES: The primary objective was to assess the incidence and severity of C. difficile infection in patients with hematologic malignancies, including those undergoing hematopoietic stem cell transplant for a hematologic condition. The secondary objectives were to assess: (a) the outcome of C. difficile infection after therapy with metronidazole and/or vancomycin and (b) mortality following C. difficile infection. METHODS: We performed a retrospective study to assess the incidence and severity of C. difficile infection and to evaluate outcomes of therapy with metronidazole and/or vancomycin among adult patients admitted to the Malignant Hematology/Blood and Marrow Transplantation service at our center from January 2009 to 2012. RESULTS: Of the 390 admitted patients during the 3-year study period, the overall incidence of C. difficile infection was 18.7% (n = 73). Forty-six patients (63.0%) were deemed to have mild-moderate C. difficile infection. With regards to outcome of therapy, less exposure to antimicrobial agents was significantly associated with a higher resolution rate (p = 0.0029). Response rates to metronidazole were 53.7%, vancomycin 50%, and combination therapy 38.5%, although no difference in achievement of resolution was found among the three treatment modalities (p = 0.5533). Older patients were more likely to experience recurrent C. difficile infection (p = 0.0007). It was found that 55 patients (75.3%) were alive at 6 months. CONCLUSIONS: These results highlight the high incidence of C. difficile infection in a subset of cancer patients at our institution. Although most patients presented with mild-moderate disease, severity of C. difficile infection in cancer patients may be underestimated due to the frequent presence of neutropenia. This study is the first analysis conducted, which directly compares outcomes of C. difficile infection after therapy with metronidazole, vancomycin, or combination therapy exclusively in patients with hematologic malignancies, including those undergoing hematopoietic stem cell transplant for a hematologic condition. We found no difference in treatment outcomes among metronidazole, vancomycin, or combination therapy. The recommendation from the literature to use metronidazole as the initial drug of choice for mild-moderate C. difficile infection is a reasonable option, although the rate of cure is low. This study highlights the critical need for better treatment options, due to suboptimal response rates to current therapy. Larger scale studies are needed to better understand the epidemiology and management of C. difficile infection in this patient population.

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia.

Ibrutinib (Imbruvica): a novel targeted therapy for chronic lymphocytic leukemia.

Review of Melatonin Supplementation for Sleep Disorders in Pediatric Special Populations.

OBJECTIVE: To determine which pediatric populations, if any, benefit from exogenous melatonin supplementation. METHODS: PubMed was utilized for the purposes of this systematic review. The studies selected evaluated melatonin use in pediatric special populations and included randomized controlled trials, crossover studies, and meta-analyses. Each study's objectives, measures of outcomes, and dosing strategies of melatonin were reviewed along with the results and author's conclusions. RESULTS: Our analysis of the available data offers mixed results and recommendations with regard to the decision of whether to add supplementation of melatonin. CONCLUSION: With further regulation of melatonin supplements, it may be plausible to hold larger, multicenter trials and come to a firm recommendation in the future. At this time, we believe that the benefit of exogenous melatonin supplementation outweighs the risks of adverse events and therefore would recommend its use in aiding patients in improving their sleep. Exogenous supplementation with melatonin should be used at the physician's and patient's discretion.