Patrick J. Kiel

The human metapneumovirus: A case series and review of the literature

S. Shahda, W.G. Carlos, P.J. Kiel, B.A. Khan, C.A. Hage. The human metapneumovirus: a case series and review of the literature
Transpl Infect Dis 2011: 13: 324–328. All rights reserved

Clinical Management of Thymoma Patients

Thymoma and thymic carcinomas are rare epithelial tumors that arise from the thymus gland. Current management depends on staging, with surgery being the mainstay of therapy for stages I and II disease. Combined modality therapy, including radiation and chemotherapy, is recommended for patients who have invasive and metastatic disease. Relapse has been documented decades after initial therapy with options for treating recurrent advanced stage disease. Prospective studies have been limited, and current studies aim to evaluate novel treatment options.

Peripheral blood stem cell mobilization tactics.

OBJECTIVE To evaluate the methods and collection techniques currently used in stem cell mobilization for patients undergoing autologous transplantation. DATA SOURCES Literature search was performed through PubMed (1948-August 2009) and MEDLINE (1977-August 2009). Reference citations from publications identified were also reviewed. STUDY SELECTION AND DATA EXTRACTION All literature identified was reviewed for inclusion. Original research and retrospective cohorts, along with previously published systematic reviews of stem cell mobilization and growth factors, were evaluated. Abstract data on plerixafor were also reviewed. DATA SYNTHESIS Successful mobilization of an adequate number of progenitor cells can help ensure and improve time to neutrophil and platelet engraftment. A variety of methods have been studied to find the safest and most predictable mobilization of CD34+ progenitor cells, including use of single agents or the combinations of hematopoietic growth factors, chemotherapy, and a novel chemokine receptor 4 antagonist. Currently, granulocyte colony-stimulating factor (G-CSF) 10 Mg/kg daily started 4 days prior to apheresis remains the standard of care for initial mobilization therapy. In patients who fail to mobilize or who are at high risk for mobilization failure, cyclophosphamide in conjunction with G-CSF may be used. Plerixafor, a novel chemokine receptor antagonist, in combination with G-CSF has demonstrated superiority for achieving collection goals compared to G-CSF alone in 2 Phase 3 trials. CONCLUSIONS The optimal mobilization strategy is still unknown; however, colony-stimulating factors remain the most commonly used mobilization agents. Currently, chemotherapy or plerixafor in combination with G-CSF is a reasonable option in heavily pretreated and hard-to-mobilize patients with non-Hodgkins lymphoma and multiple myeloma.

Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers

Patients and Methods Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ≥ 1.3 were deemed to have a meaningful improvement in PFS. Results From April 2014–October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ≥ 1.3 vs. 3 of 57 (5.3%) treated with non-genomically guided therapy (p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy (p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs. 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84). Conclusion Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.

Observations of second primary malignancy in patients with multiple myeloma

BACKGROUND Advances in the treatment of multiple myeloma have resulted in immunomodulatory (IMiD) agents becoming integral to the standard treatment armamentarium. IMiD agents are effective in the initial and relapsed settings of multiple myeloma. Three studies evaluating the duration of remission in maintenance lenalidomide vs. placebo reported an increased incidence of second primary malignancies in patients receiving maintenance therapy. The purpose of this study was to evaluate the incidence of second primary malignancies after IMiD exposure for standard induction and relapsed therapy in myeloma. PATIENTS AND METHODS A retrospective chart review was conducted at the Indiana University Simon Cancer Center in Indianapolis, Indiana. Patients were older than 18 years and had been diagnosed with multiple myeloma. Patients with a previous diagnosis of cancer were excluded. The primary objective was to assess the incidence of second primary malignancies in all patients. Secondary objectives included the type of malignancy, whether patients had been previously treated with IMiD therapy and the time from treatment initiation to diagnosis of a second malignancy. RESULTS Three hundred twenty-five patients were reviewed and 279 were included in the study. Ten patients were diagnosed with a second primary malignancy (3.5%). Nine of the 10 patients were treated with IMiD therapy before diagnosis (P = .169). The mean time to diagnosis was 360 days for all patients. CONCLUSION The incidence of second primary malignancy was not statistically significant in the IMiD-treated patients. Further long-term follow-up is needed to better assess the potential adverse events of these novel agents.

An evaluation of amikacin nephrotoxicity in the hematology/oncology population.

Amikacin is an aminoglycoside commonly used to provide empirical double gram-negative treatment for febrile neutropenia and other suspected infections. Strategies of extended-interval and conventional dosing have been utilized extensively in the general medical population; however, data are lacking to support a dosing strategy in the hematology/oncology population. To evaluate amikacin-associated nephrotoxicity in an adult hematology/oncology population, a prospective, randomized, open-label trial was conducted at a university-affiliated medical center. Forty patients with a diagnosis consistent with a hematologic/oncologic disorder that required treatment with an aminoglycoside were randomized to either conventional or extended-interval amikacin. The occurrence of nephrotoxicity by means of an increase in serum creatinine and evaluation of efficacy via amikacin serum concentrations with respective pathogens were assessed. The occurrence of nephrotoxicity was similar between the conventional and extended-interval groups, at 10% and 5%, respectively (P = 1.00). Six patients in the conventional group had a positive culture, compared with none in the extended-interval group (P = 0.002). The occurrence of nephrotoxicity was similar between the two dosing regimens, but the distribution of risk factors was variable between the two groups. Efficacy could not be assessed.

Possible correlation of sirolimus plasma concentration with sinusoidal obstructive syndrome of the liver in patients undergoing myeloablative allogeneic hematopoietic cell transplantation.

To determine the frequency of sinusoidal obstructive syndrome (SOS) in patients undergoing allogeneic hematopoietic cell transplantation who received graft‐versus‐host disease (GVHD) prophylaxis with sirolimus and tacrolimus, and to assess whether the occurrence of SOS correlates with immunosuppressant levels.

Clinical Outcomes of a Pharmacy-Led Blood Factor Stewardship Program.

To report the results of a pharmacist-directed blood factor stewardship program targeting off-label utilization designed to limit use to established organizational guidelines in high-risk populations. Prospective evaluation of recombinant factor VIIa and prothrombin complex concentrate orders beginning June 2013 through May 2014 and a matched retrospective cohort from June 2012 to May 2013. Matched cohorts were evaluated for 28-day mortality, change in international normalized ratio (INR), adverse events, concurrent blood product use, and cost savings. Forty-two orders for blood factor were ordered between June 2013 and May 2014, 70 orders in the year before (N = 112). Twenty eight–day mortality was not different between the cohorts: 53.9% versus 50% (P = 0.77). Blood factor use with underlying liver failure and active bleeding was strongly associated with 28-day mortality: odds ratio (95% confidence interval), 2.9 (1.5–7.14) and 2.91 (0.01–2.91), respectively. Blood products dispensed increased over the year with plasma products the most significant (1 vs. 4 P = 0.004). All other clinical outcomes were nonsignificant. An annual cost savings of

Disease-free survival following high dose or standard dose therapy in patients with amyloidosis

375,539 was achieved, primarily through a significant reduction in recombinant factor VIIa and avoidance in high-risk patients. Use of off-label blood factors can be controlled through a pharmacist-led stewardship program. Twenty eight–day mortality was not different between the 2 cohorts; however, identification of risk factors for death associated with blood factor use allows for restriction in high-risk populations, creates a discussion of futile care, and yields cost savings.

Thiamine Deficiency Following Umbilical Cord Blood Transplant

Keywords: bortezomib; melphalan; autologous haematopoietic cell rescue; treatment related mortality