Katarzyna Jamieson

Single Cycle of Arsenic Trioxide–Based Consolidation Chemotherapy Spares Anthracycline Exposure in the Primary Management of Acute Promyelocytic Leukemia

PURPOSE Event-free survival following all-trans-retinoic acid (ATRA) -based therapy for acute promyelocytic leukemia (APL) averages 70% at 5 years. While arsenic trioxide (ATO) can induce remissions in 95% of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents. PATIENTS AND METHODS After induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy. Results Forty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90%; overall survival for all patients was 88%. Despite a total anthracycline dose of only 360 mg/m(2), cardiac ejection fraction decreased by > or = 20% in 20% of patients. CONCLUSION These data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.

Increasing Rates of Fluoroquinolone Resistance in Escherichia coli Blood and Urinary Isolates in Stem Cell Transplant and Hematologic Malignancy Populations

Fluoroquinolone (FQ) antibiotics have been shown to reduce mortality and the number of febrile episodes when used as prophylaxis during neutropenia. Prior studies suggest that prophylaxis may result in increasing rates of FQ resistance. Fluoroquinolone non-susceptibility trends in Escherichia coli isolated from blood and urine cultures were evaluated over a 16-year period during which prophylaxis was initiated in patients with hematologic malignancies and stem cell transplants. Non-susceptibility rates increased after the introduction of prophylaxis, with yearly non-susceptibility rates rising from 30%–33% to 40%–88% in blood isolates. The high rates of non-susceptibility now observed raise concerns about the continued efficacy of FQ prophylaxis. This concern exists particularly in those patients undergoing stem cell transplants where the total FQ non-susceptibility rates over the study period were 82.3%. Further evaluation of the effect of FQ prophylaxis on antibiotic resistance and its efficacy in the setting of increased rates of resistance is warranted.

Effectiveness of an Algorithm-Based Approach to the Utilization of Plerixafor in Patients Undergoing Chemotherapy-Based Stem Cell Mobilization

Autologous stem cell transplantation remains a mainstay of therapy for diseases such as multiple myeloma and relapsed lymphoma. The use of plerixafor has been shown to augment the ability to collect adequate stem cells, but the optimal use of this agent when used with chemotherapy is not yet clear. We utilized an algorithm-based approach with the addition of plerixafor to 54 patients undergoing chemomobilization with reduced-dose etoposide who had a less than optimal preapheresis CD34(+) cell count. We used a CD34(+) precount of 20 cells/μL as a threshold to initiate stem cell apheresis. Ninety-four percent of patients were successfully collected and proceeded to transplantation. Fourteen of 51 (28%) patients who successfully collected required plerixafor to augment stem cell yield. Of the patients who successfully collected, 94% (89% of the entire population) were able to collect in 2 or fewer days. Compared with previous data from our institution, the rate of patients collecting > 4 × 10(6) CD34(+) cells/kg in a single collection was increased from 39% to 69%. The safety profile of this approach was acceptable. The use of this algorithm-based method to determine when and whether to add plerixafor to chemomobilization was shown to be a successful and cost-effective approach to stem cell collection.

Late-phase investigational approaches for the treatment of relapsed/refractory acute myeloid leukemia

Introduction: Acute myeloid leukemia (AML) is a malignant hematologic disorder that affects more than 13,000 adults each year in the USA. Despite continued advances in the understanding of the molecular pathogenesis of the disease and patient management, the cure rate for AML remains relatively low, largely due to a high rate of relapsed or refractory disease. Areas covered: The purpose of this review is to provide an understanding of the unmet needs in relapsed/refractory AML, and to assess promising investigational agents with ongoing or planned Phase III clinical trials. Expert opinion: Although the treatment of relapsed/refractory AML remains a challenge, numerous new chemotherapeutics are currently in development. Enrollment in clinical trials should be strongly considered for patients with relapsed/refractory disease, and emerging data may help identify new agents with significant activity in this setting.

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

Concurrent Disseminated Nocardiosis and GI Mucormycosis in a Stem-Cell Transplantation Recipient

60,821.60 for GCLAC and

Evaluation of a Test Dose Strategy for Pharmacokinetically Guided Busulfan Dosing for Hematopoietic Stem Cell Transplantation

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 (

Coma associated with nelarabine in an elderly patient with T-cell acute lymphoblastic leukemia and severe chronic renal disease

60,821.60 vs

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts

4910.60 per cycle using AWP pricing, respectively).

Efficacy, Hematologic Effects, and Dose of Ruxolitinib in Myelofibrosis Patients with Low Starting Platelet Counts (50–100 × 109/L): A Comparison to Patients with Normal or High Starting Platelet Counts

Case Report A 58-year-old white man was diagnosed with transformed large B-cell non-Hodgkin lymphoma 7 years after completion of first-line chemotherapy for follicular lymphoma of the small bowel. He received four cycles of chemotherapy with R-CHOP (rituximab, cyclophophamide, doxorubicin, vincristine, prednisone) and achieved a complete remission. He then proceeded to an autologous peripheralblood stem-cell transplantation (PBSCT) with BEAM conditioning regimen (carmustine, etoposide, cytarabine, melphalan). His disease recurred 22 months later. He subsequently received an allogeneic PBSCT with a matched unrelated donor with reduced intensity conditioning with fludarabine and busulfan. On day 95, the patient received a donor lymphocyte infusion for declining unfractionated donor chimerism. His post-transplantation course was complicated on day 140 by graft-versus-host disease (GVHD) of the skin, Lerner grade 2, and of the GI tract, histologic grade 2-3. He was initially started on methylprednisolone at 2 mg/kg, which was transitioned to a tapering prednisone regimen. He continued to have recurrent flares of GVHD of the skin and GI tract and was maintained on prednisone, with concurrent antibacterial (levofloxacin), antiviral (valacyclovir) and antifungal prophylaxis (voriconazole). Voriconazole was switched to micafungin on day 157 due to transaminitis. Posaconazole was not chosen given concern for poor absorption with GVHD of the GI tract. Despite treatment, the patient continued to report persistent loose stools of small volume and weight loss, but denied abdominal pain or decreased appetite. A repeat colonoscopy with random biopsies performed on day 216 revealed resolving GVHD. Micafungin was stopped on day 257 as he was being tapered off prednisone. Fluconazole was restarted on day 263 when he was reinitiated back on prednisone 20 mg daily for recurrent flare of GVHD of the skin. On day 310, the patient presented to the emergency room with a 1-month history of nasal congestion and dry cough, and a 1-day history of left-sided pleuritic chest pain, requiring oxygen supplementation at 2 L/min via nasal cannula. At that time, he was on an alternating prednisone dose of 20 mg and 5 mg every other day. It was noted that he had lost approximately 70 pounds in weight since his allogeneic PBSCT. Chest radiograph revealed a peripheral wedgeshaped opacity in the left lower lobe. Computed tomography (CT) angiogram of the chest excluded pulmonary embolism, but demonstrated dense consolidations in the right middle and left lower lobe. There were also multiple tiny centrilobular nodules with tree-in-bud appearance. He was started on antimicrobial therapy with vancomycin, aztreonam, azithromycin, and antifungal voriconazole. Both blood and bronchoalveolar lavage (performed on day 312) cultures revealed branching rods consistent with Nocardia spp on modified Kinyoun stain (Fig 1) and were identified as Nocardia nova complex via 16S rRNA gene sequencing. Magnetic resonance imaging (MRI) of the brain excluded CNS nocardiosis. The patient was treated with intravenous trimethoprim/sulfamethoxazole and imipenem for treatment of disseminated nocardiosis. His tunneled triple-lumen Hickman catheter was removed. On day 313, the patient reported acute left lower quadrant abdominal pain. CT of his abdomen revealed long segment of small bowel wall and colonic wall thickening, suggestive of enterocolitis, with scattered locules of extraluminal air concerning for microperforation. This was managed conservatively with bowel rest. However, after a few days, any introduction of food resulted in severe abdominal pain. On day 318, the patient underwent sigmoidoscopy, which revealed a normal-appearing mucosa. The pathologic examination of blind biopsies was negative. He then underwent a repeat abdomen CT that revealed worsening pneumoperitoneum. The decision was made to proceed with surgical intervention on day 320. Operative findings demonstrated a 0.5 cm area of induration and pinhole perforation in the ileum, approximately 60 cm from the ileo-cecal valve, which was repaired via a two-layered primary closure. Unexpectedly, pathology of the surgically removed small bowel tissue revealed an ulcer bed with intense acute and chronic inflammation and accompanying hemorrhage with prominent nonparallel hyphae suggestive of mucormycetes. This was confirmed with Grocott’s methenamine silver stain demonstrating wide, ribbon-like, aseptate hyphae within the necroinflammatory debris of the patient’s ulcer bed, consistent with mucormycetes (Fig 2). Subsequently, culture of the small bowel was positive for Nocardia nova and Rhizopus species. Given these findings, voriconazole was discontinued and the patient was started on liposomal amphotericin B and micafungin for Fig 1. JOURNAL OF CLINICAL ONCOLOGY D I A G N O S I S I N O N C O L O G Y