Benyam Muluneh

Successful clearance of cutaneous acyclovir-resistant, foscarnet-refractory herpes virus lesions with topical cidofovir in an allogeneic hematopoietic stem cell transplant patient

Cidofovir is a deoxycytidine monophosphate analog with broad spectrum activity against various deoxyribonucleic acid viruses. Cidofovir is marketed as an injectable for intravenous use; however, there is a topical cidofovir formulation utilized for viral dermatologic infections. Here, we present a case of a successful clearance of a perianal acyclovir resistant and foscarnet refractory herpes simplex virus (HSV1) ulcer in a 34 year-old woman who had undergone allogeneic hematopoietic stem cell transplantation. After 1 week of therapy with cidofovir gel, the patient’s ulcer was clinically improved, and the lesion was negative for herpes simplex virus transcripts by real-time polymerase chain reaction testing. The wound remained herpes simplex virus negative by real-time polymerase chain reaction on repeat testing 1 week later. Based on this and other reports in HIV/AIDS patients, we believe that cidofovir gel has utility in the management of cutaneous, acyclovir-resistant HSV infections.

Vemurafenib-associated pancreatitis: case report.

Vemurafenib is a novel BRAF kinase inhibitor indicated in metastatic melanoma patients with V600E mutation. We report the first case of vemurafenib‐associated pancreatitis. Two weeks after initiation of vemurafenib, a patient presented to the emergency department with severe epigastric pain and a serum lipase of 1544 units/L. Drug‐induced pancreatitis was diagnosed on exclusion of all other potential causes. Vemurafenib was rechallenged at half the daily dose and the patient subsequently developed exacerbated symptoms of pancreatitis after two doses. The strong temporal relationship between drug exposure and toxicity, along with the positive results from a rechallenge study, strongly support a conclusion of causality. To our knowledge, this is the first report of vemurafenib‐induced pancreatitis.

Blood pressure control in patients receiving bevacizumab in an outpatient cancer center

Purpose. Hypertension is a common adverse effect of vascular endothelial growth factor (VEGF) signaling inhibitors, such as bevacizumab, with an incidence upwards of 35%. The management of bevacizumab-induced hypertension is important in order to avoid dose interruption/discontinuation and/or end organ damage. The efficacy of antihypertensive medications for this cause of hypertension has not been demonstrated. This study seeks to determine if antihypertensives are effective in treating anti-VEGF-induced hypertension from bevacizumab and determine which classes of antihypertensive agents are effective. Methods. A retrospective review of all patients who received bevacizumab between January 2007 and September 2009 at two medical centers was conducted. Patients were included if they experienced new onset or exacerbation of preexisting hypertension, during bevacizumab treatment. Efficacy of antihypertensives was determined by recording a 28-day change in systolic blood pressure from the initiation or dose increase of individual antihypertensive medications. Secondary endpoints included an efficacy analysis of antihypertensive classes. Results. Five-hundred thirteen patients were identified as receiving bevacizumab during the indicated time period. Fifty-seven patients met the full inclusion/exclusion criteria for analysis. The average systolic blood pressure declined by 23 mm Hg with 4 weeks of treatment (p < 0.0001). Each class had a statistically significant decline in systolic blood pressure of 15.5–57 mm Hg with the exception of diuretics and a group of miscellaneous antihypertensives. Conclusions. This is the first data that demonstrates individual classes of antihypertensives are effective in bevacizumab-induced hypertension. Most antihypertensives were effective in reducing blood pressure, with the exception of diuretics and miscellaneous antihypertensives, which may be due to a limited sample size.

Patient perspectives on the barriers associated with medication adherence to oral chemotherapy

Purpose Appropriate use of oral chemotherapy is a challenge for patients and clinicians. The purpose of this study was to analyze cancer patients’ use of oral chemotherapies and identify opportunities to improve adherence. Methods We developed a 30-question survey to address frequency and reasons for reducing/skipping doses; sources of information for oral chemotherapy use; perceived importance of food–drug effects; and ease of understanding labeling directions. Results Ninety-three patients taking oral chemotherapies with chronic myeloid leukemia, renal cell carcinoma, breast cancer, and colorectal cancer completed the survey. This was a well-educated population with 69% (n = 62) having completed some college; 51% (n = 47) female and 59% (n = 54) older than 50 years of age. Thirty percent of patients reported forgetting to take their oral chemotherapy at least “sometimes”. Younger patients (<50 vs. ≥50, p = 0.002), shorter treatment duration (<6 vs. ≥6 months p = 0.03), or with chronic myeloid leukemia (vs. other diagnoses, p = 0.015) forget to take their oral chemotherapy at higher rates. Twenty-three percent (n = 21) indicated they intentionally skipped their oral chemotherapies and 38% (n = 8) of those did not inform their physicians. Forty-one percent (n = 28) taking drugs with significant food–drug effects did not think about their last meal before taking their oral chemotherapy and 80% (n = 55) did not understand the potential interactions. Additionally, 39% (n = 36/92) never looked at labeling and 15% (n = 14/91) had difficulty understanding label directions. Conclusion There are three main barriers associated with appropriate use of oral chemotherapies: misunderstanding about the timing of drug with food; stopping drug without informing physicians; and difficulty understanding labeling directions. A multipronged approach is needed to optimize communication of directions for optimal oral chemotherapy use.

A Comparison of Clofarabine-based (GCLAC) and Cladribine-based (CLAG) Salvage Chemotherapy for Relapsed/Refractory AML

Background Salvage regimens for patients with relapsed/refractory acute myeloid leukemia (rrAML) lack comparative data for superiority. Thus, we conducted a retrospective analysis of clofarabine‐based (GCLAC; granulocyte colony‐stimulating factor [filgrastim], clofarabine, high‐dose cytarabine) versus cladribine‐based (CLAG; cladribine, cytarabine, granulocyte colony‐stimulating factor [filgrastim]) regimens in rrAML. Patients and Methods We identified 41 consecutive patients with rrAML who had received either GCLAC or CLAG from 2011 to 2014. The primary outcome measure was the complete remission (CR) rate defined according to the International Working Group criteria. The secondary outcomes included the proportion of patients who underwent allogenic stem cell transplantation and the rate of relapse‐free survival and overall survival. Results We found no significant differences in the baseline characteristics of the patients treated with GCLAC (n = 22) or CLAG (n = 19). The outcomes with these 2 regimens were not significantly different. Patients treated with GCLAC had a CR/CR with incomplete blood count recovery rate of 64% compared with 47% for the patients treated with CLAG (P = .36). Of the GCLAC patients, 45% underwent allogeneic stem cell transplantation compared with 26% of the CLAG patients (P = .32). The median relapse‐free survival after GCLAC and CLAG was 1.59 years and 1.03 years, respectively (P = .75). The median overall survival after GCLAG and CLAG was 1.03 years and 0.70 years, respectively (P = .08). The drug costs were significantly different for GCLAC versus CLAG. Using an average wholesale price, the cost per patient per cycle was

Clonal evolution of Philadelphia chromosome in acute myeloid leukemia after azacitidine treatment

60,821.60 for GCLAC and

Improved Adherence Rates and Clinical Outcomes of an Integrated, Closed-Loop, Pharmacist-Led Oral Chemotherapy Management Program

4910.60 for CLAG. Conclusion A single‐institutional retrospective analysis found no significant differences in the outcomes between GCLAC and CLAG for rrAML patients, although formal comparisons should be performed in a randomized clinical trial. The cost of GCLAC was greater than that of CLAG, which should be considered when evaluating the choice for the salvage chemotherapy options. Micro‐Abstract The data for savage regimens in relapsed/refractory AML is largely based on phase 2, single arm studies and comparative data is scarce. The purpose of this retrospective study was to compare two salvage AML chemotherapy regimens, GCLAC (clofarabine‐based) and CLAG (cladribine based) in 41 patients (22 and 19 in each arm, respectively). There were no statistically significant differences in complete response rates (GCLAC = 64%; CLAG = 47%, P = .36) as well as other endpoints including safety endpoints. GCLAC was associated with significantly higher costs compared with CLAG (

Pharmaceutical assistance programs for cancer patients in the era of orally administered chemotherapeutics

60,821.60 vs

Impact of an integrated oral chemotherapy program on patient adherence

4910.60 per cycle using AWP pricing, respectively).

Obstacles to affordable cancer treatments.

The Philadelphia (Ph) chromosome occurs due to a balanced translocation between chromosomes 9q34 and 22q11, resulting in a fusion protein BCR-ABL1 with differing protein sizes depending on the break point, p210 (e13a2 or e14a2), p190 (e1a2) and p230 (e19a2). Ph chromosome is pathognomonic of chronic myeloid leukemia (CML). It is also present in approximately 2–3% of children and 20–30% of adults with acute lymphoblastic leukemia (ALL). Acute myeloid leukemia (AML) with BCRABL1 is a rare entity with an incidence of approximately 2% and has been included in the 2016 World Health Organization classification as a provisional entity [1]. It is clinically challenging to differentiate de novo CML-myeloid blast crisis from AML with BCR-ABL1. The absence of a history of a hematologic disorder, basophilia or splenomegaly may favor AML with BCR-ABL1 over CML blast crisis. Nonetheless, the secondary acquisition of the Ph chromosome in treated AML patients is an extremely rare event. We describe the first known report of a secondary Ph chromosome occurring in an AML patient after treatment with azacitidine. A 62-year-old female with a history of cirrhosis secondary to nonalcoholic steatohepatitis, hypothyroidism, diabetes mellitus-2, obstructive sleep apnea, hypertension and hyperlipidemia presented with significant joint pains and myalgias over a period of 5 months. At presentation, her white blood cell count (WBC)1⁄4 2.8 10/L, absolute neutrophil count (ANC)1⁄4 0.6 10/L, hemoglobin1⁄4 9.6 g/dL, hematocrit1⁄4 29.0, and platelet count1⁄4 29 10/L. A bone marrow biopsy revealed a hypercellular (80%) bone marrow with reduced trilineage hematopoiesis, 51% blasts consistent with AML. Flow cytometry revealed 27% aberrant myeloblasts expressing CD34, CD117, CD71, HLA-DR, CD13, dim CD33 and partial myeloperoxidase positive. Cytogenetics revealed a normal female karyotype with normal FISH for AML/MDS. A targeted molecular panel revealed no evidence of Fms-like tyrosine kinase 3 (FLT3) or nucleophosmin-1 (NPM1) mutations consistent with intermediate-1 risk de novo AML based on the 2010 European Leukemia Net classification [2], although there was no CEBPa mutational analysis performed at diagnosis. She was initiated on 7þ 3 induction with continuous infusion cytarabine (100mg/ m IV days 1–7) and idarubicin (12mg/m IV days 1–3). She achieved a complete remission (CR1) and then received consolidation therapy on an institutional trial with high dose lenalidomide 50mg, followed by maintenance at 10mg daily (NCT01578954). The patient was not interested in allogeneic stem cell transplant in CR1. She received 3 cycles of maintenance lenalidomide and then developed cytopenias. A bone marrow biopsy revealed 40% cellularity and 31% blasts consistent with relapsed AML. Cytogenetics revealed two abnormal clones: an addition of chromosome 12 and a subclone with a t(3;20)(p23;q11.2). A molecular analysis was not performed at the time of relapse. She was treated with salvage cladribine 5mg/m IV days 1–5, cytarabine 2 gm/m IV days 1–5 and G-CSF days 0–6 (CLAG) and a recovery bone marrow biopsy revealed a normocellular (40%) bone marrow with 3% blasts consistent with a CR2. Cytogenetics/FISH revealed absence of the original trisomy 12 clone but two abnormal unrelated clones consisting of t(11;20)(p11.2;q11.2) and t(1;6)(q44;q21), respectively, of unclear significance. She then received two cycles of consolidation chemotherapy with high-dose cytarabine dose reduced for age (1.5 gm/m IV Q12 hours days 1, 3 and 5). Bone marrow biopsy after recovery from cycle 2 of consolidation therapy revealed variably cellular bone marrow (10–80%) with 13% blasts consistent with recurrent AML (second relapse). Cytogenetics revealed a trisomy 12 clone in 1/20 metaphases consistent with her previous documented karyotypic abnormality. The patient then received azacitidine 75mg/m SQ days 1–7 for her relapsed AML. A repeat bone marrow biopsy after 3 cycles of azacitidine revealed stable disease with 8% blasts and cytogenetics evolved to an abnormal clone