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Susan O'Brien, Ellin Berman, Joseph O. Moore, Javier Pinilla-Ibarz, Jerald P. Radich, Paul J. Shami, B. Douglas Smith, David S. Snyder, Hema M. Sundar, Moshe Talpaz and Meir Wetzler

Allogeneic hematopoietic stem cell transplant (HSCT) is a potentially curative treatment for patients with CML, but the excellent results with imatinib and other second-generation TKIs have challenged its role. The widespread application of allogeneic HSCT

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Antonio V. Gonzalez, Andrew J. Ullmann, Nikolaos G. Almyroudis and Brahm H. Segal

Invasive fungal infections (IFIs) are a leading cause of infection-related mortality in patients with acute leukemia and prolonged neutropenia and in allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD). Although invasive candidiasis was the principal IFI predating fluconazole prophylaxis, invasive aspergillosis and other mold infections now cause most deaths from fungal infection in this patient population. The availability of broad-spectrum antifungal agents that can be safely administered over prolonged periods has stimulated interest in using mold-active prophylactic agents early as prophylaxis rather than later as therapy for suspected or documented IFIs. Two recent, prospective, randomized trials have shown a clear benefit of posaconazole prophylaxis in patients with myelodysplastic syndrome and acute mye-logenous leukemia with prolonged neutropenia and in allogeneic HSCT recipients with severe GVHD. In contrast, the peer-reviewed published database on the strategy of preemptive antifungal therapy, in which yeast-active prophylaxis (fluconazole) or no antifungal prophylaxis is used initially and modifications are triggered by a combination of laboratory markers and chest CT scans, is currently limited to an open-label feasibility study. Does sufficient evidence currently exist that the net benefit of the preemptive approach is at least on a par with posaconazole prophylaxis in the specific patient groups that were studied? The authors believe not and that more research is needed before the pre-emptive strategy can be recommended.

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Johan Maertens, Kristel Buvé and Elias Anaissie

Management of invasive mold infections in patients with prolonged neutropenia and hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) has been hampered by the difficulty in diagnosing these infections. Definite diagnosis invariably centers on histologic identification of hyphae in tissue or on culture from a sterile body site. Therefore, most practitioners have relied on prophylaxis and empiric therapy. Currently, emphasis is shifting from routine prophylaxis and empiric therapy to screening of patients with neutropenia at high risk so that clinicians can administer appropriate antifungal therapy early, when it can potentially improve patient outcome. Non–culture-based microbiologic tools are at the forefront of this paradigm shift. Commercially available methods to detect fungal antigens and sophisticated techniques to detect fungal DNA may be used as screening tools during the highest risk period. Together with assessment of clinical signs, cultures, and especially CT scanning, these methods are useful for starting antifungal therapy preemptively. While awaiting further evaluation of these tools during the postengraftment period of allogeneic HSCT, mold-active prophylaxis targeting the subgroup of patients with severe acute or chronic GVHD may be justified. However, some critical issues have not yet been adequately addressed, including the generalizability of study results, impact of mucositis and gastrointestinal GVHD on drug bioavailability, need for therapeutic drug monitoring, impact of prophylaxis on the performance of diagnostic assays, and optimal treatment of breakthrough invasive fungal infections.

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Lindsey Robert Baden, William Bensinger, Michael Angarone, Corey Casper, Erik R. Dubberke, Alison G. Freifeld, Ramiro Garzon, John N. Greene, John P. Greer, James I. Ito, Judith E. Karp, Daniel R. Kaul, Earl King, Emily Mackler, Kieren A. Marr, Jose G. Montoya, Ashley Morris-Engemann, Peter G. Pappas, Ken Rolston, Brahm Segal, Susan K. Seo, Sankar Swaminathan, Maoko Naganuma and Dorothy A. Shead

at great risk for common bacterial, viral, and opportunistic infections. 13 – 16 The infectious diseases that can affect allogeneic HSCT recipients with GVHD are distinct from those that can affect patients with neutropenia. These guidelines discuss

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Deborah S. Yolin-Raley, Ibiayi Dagogo-Jack, Heidi B. Niell, Robert J. Soiffer, Joseph H. Antin, Edwin P. Alyea III and Brett E. Glotzbecker

and allogeneic HSCT suggest that additional investigational studies, particularly chest radiographs (CXRs), should be obtained in patients with clinical signs and symptoms suggestive of respiratory infection. 7 – 11 However, the studies from which

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Joseph C. Alvarnas, Patrick A. Brown, Patricia Aoun, Karen Kuhn Ballen, Naresh Bellam, William Blum, Michael W. Boyer, Hetty E. Carraway, Peter F. Coccia, Steven E. Coutre, Jennifer Cultrera, Lloyd E. Damon, Daniel J. DeAngelo, Dan Douer, Haydar Frangoul, Olga Frankfurt, Salil Goorha, Michael M. Millenson, Susan O'Brien, Stephen H. Petersdorf, Arati V. Rao, Stephanie Terezakis, Geoffrey Uy, Meir Wetzler, Andrew D. Zelenetz, Maoko Naganuma and Kristina M. Gregory

intensification (for patients with a complete remission [CR] postinduction) with contemporary chemotherapy combination regimens. Patients with a CR after induction received allogeneic HSCT (for patients < 50 years old and with HLA-compatible siblings), autologous

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Margaret R. O'Donnell, Camille N. Abboud, Jessica Altman, Frederick R. Appelbaum, Daniel A. Arber, Eyal Attar, Uma Borate, Steven E. Coutre, Lloyd E. Damon, Salil Goorha, Jeffrey Lancet, Lori J. Maness, Guido Marcucci, Michael M. Millenson, Joseph O. Moore, Farhad Ravandi, Paul J. Shami, B. Douglas Smith, Richard M. Stone, Stephen A. Strickland, Martin S. Tallman, Eunice S. Wang, Maoko Naganuma and Kristina M. Gregory

achieved. Many institutions also use HLA typing to select platelet donors for allogeneic HSCT. Principles of AML Treatment Treatment of acute leukemia has been divided into induction chemotherapy and postremission (or consolidation) therapy

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Susan O’Brien, Jerald P. Radich, Camille N. Abboud, Mojtaba Akhtari, Jessica K. Altman, Ellin Berman, Peter Curtin, Daniel J. DeAngelo, Michael Deininger, Steven Devine, Amir T. Fathi, Jason Gotlib, Madan Jagasia, Patricia Kropf, Joseph O. Moore, Arnel Pallera, Vishnu VB. Reddy, Neil P. Shah, B. Douglas Smith, David S. Snyder, Meir Wetzler, Kristina Gregory and Hema Sundar

-CML (see CML-6, page 1593). Allogeneic HSCT can be considered based on response to TKI therapy. Omacetaxine is a treatment option for patients with resistant disease and/or intolerance to 2 or more TKIs. TKI therapy alone or in combination with

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Susan O'Brien, Camille N. Abboud, Mojtaba Akhtari, Jessica Altman, Ellin Berman, Daniel J. DeAngelo, Steven Devine, Amir T. Fathi, Jason Gotlib, Madan Jagasia, Joseph O. Moore, Javier Pinilla-Ibarz, Jerald P. Radich, Vishnu V.B. Reddy, Neil P. Shah, Paul J. Shami, B. Douglas Smith, David S. Snyder, Meir Wetzler and Furhan Yunus

subset of patients who will be eligible for allogeneic HSCT. Management of Resistance Dose escalation of imatinib up to 800 mg daily has been shown to overcome some of the primary resistance, but the duration of responses has typically been short

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Margaret R. O'Donnell, Camille N. Abboud, Jessica Altman, Frederick R. Appelbaum, Steven E. Coutre, Lloyd E. Damon, James M. Foran, Salil Goorha, Lori J. Maness, Guido Marcucci, Peter Maslak, Michael M. Millenson, Joseph O. Moore, Farhad Ravandi, Paul J. Shami, B. Douglas Smith, Richard M. Stone, Stephen A. Strickland, Martin S. Tallman and Eunice S. Wang

contraindications to high-dose therapy. In a recent retrospective study by the European APL Group, patients who received a PCR-negative autograft had a 7-year overall survival rate of 75%, compared with 52% in those receiving an allogeneic HSCT. 44 The differences