ASH News Daily 2012 - Monday, December 10, 2012 - (Page A-14)

Page A–14 ® ASH NEWS DAILY Monday, December 10, 2012 CliffsNotes From American Society of Clinical Oncology ASH/ASCO BY MICHAEL R. BISHOP, MD I f one had accidentally walked into Room B405 of the Georgia World Congress Center yesterday and started listening to the presentations without knowing exactly what session it was, they may have thought they inadvertently ended up at a “Best of ASCO” symposium. They would not have been far off, as that was the specific intent of the ASH/ASCO Joint Symposium titled “Clinical Oncology Update: Studies from the 2012 ASCO Annual Meeting.” The overlapping interests of both societies lend themselves to a mutually beneficial relationship that is supremely useful to clinicians and researchers alike. In planning this symposium, Sandra Swain, MD, president of the American Society of Clinical Oncology (ASCO), shared the following: “Dr. Keating and I had several discussions about exciting developments at ASCO. With so many excellent abstracts to choose from, we narrowed it down to several of which were felt to be important for all practicing hematologists and oncologists to be aware.” After hearing these outstanding and interesting presentations, I believe TRANSPLANTATION Whoever Wishes to Foresee the Future Must Consult the Past (in Transplantation) BY MATTHEW HSIEH, MD doubt that Machiavelli was referring to hematopoietic stem cell transplantation (HSCT) when he wrote this, but it does seem prudent. Myeloablative allogeneic HSCT originated with the idea of giving large doses of chemotherapy and/or radiation, in the hopes of eradicating the underlying tumor and making “space” for the incoming cells. This approach, however, has an attendant high risk of non-relapse mortality (NRM) and has excluded many older patients or younger patients with complex medical illnesses. We have come a long way since then, but is a history lesson in transplantation helpful for the future? This and several other questions were addressed yesterday in the Education Program session, “Hematopoietic Stem Cell Transplantation II – Toward Safer Allogeneic Transplantation.” I Didier Blaise, MD, Institut PaoliCalmettes of Marseille, was placed in charge of reviewing how the conditioning regimens have changed over the past decades. He took us on a wonderful tour of moving from myeloablative to reduced intensity and non-myeloablative regimens. These changes have allowed transplantation for older patients and using unrelated donors. He also emphasized the importance of T-cell depletion using rabbit ATG, and there is probably an optimal dose to preserve anti-malignant effect and minimize GVHD. Moving forward, he suggested that randomized studies comparing two or more conditioning regimens are needed to assess the survival benefit. He ended with an interesting thought: Perhaps reduced-intensity and non-myeloablative approaches should really be renamed to “reduced toxicity.” Steven Z. Pavletic, MD, Nation- al Cancer Institute, continued the history lesson through the lens of GVHD. With the changes in conditioning regimen, the timing of GVHD has moved from the classical, before or after day 100, to a much more blended time course. Many GVHD prophylaxis combi- nations have been tested over the past decades, but calcineurin inhibitor and methotrexate remain the most widely used. He showed that corticosteroids remain the frontline treatment for acute or chronic GVHD, but clear efficacious second-line treatments are yet to be defined. Much recent progress in chronic GVHD has built upon the NIH Consensus staging system and how to integrate the severity of organ involvement (mild, moderate, and severe, each with a scoring of 1-3) and quality of life, and can serve as the basis to evaluate future response rates. Kieren A. Marr, MD, Johns Hopkins University in Baltimore, took a “glass-half-full” perspective when she talked about opportunistic infections. The pattern has expanded from gram-negative organisms in the early 1980s to other bacteria, viruses, and fungi. Reduced-intensity conditioning regimens, antimicrobial prophylaxis, and protracted periods of chronic GVHD have delayed the at-risk period. She highlighted the progress in anti-fungal coverage with the availabilities of new azoles, confirmed the benefit of monitoring and pre-emptive treatment for CMV, and underscored that vaccinations, especially against pneumococcus, are under-utilized. While the task of prevention seems so daunting, she reassured the audience that infections are manageable, considering the progress that we have made. This sentiment is reflected with her words, “a surmountable challenge.” With newer conditioning regimen approaches, standardized classification and treatment of acute and chronic GVHD, and better infection monitoring and treatment, alloHSCT indeed has become much safer for a wider range of patients – those who are older and those with complicated co-morbid conditions. It is often said that if you don’t know where you’ve been, you won’t know where you are going. So a history lesson in alloHSCT is certainly essential. Dr. Hsieh indicated no relevant conflicts of interest. that she and Dr. Keating, ASH president, achieved their goal. Two of the abstracts presented were related to supportive care. The first, by Rudolph Navari, MD, PhD, associate dean of Indiana University School of Medicine - South Bend, University of Notre Dame, was focused on the use of olanzapine, which is approved for the treatment of bipolar disorder and schizophrenia, to control breakthrough chemotherapy-induced nausea and vomiting. Breakthrough nausea and vomiting occurs in about 30 percent of patients who are being treated with maximal anti-emetic therapy. This includes patients being treated with drugs such as anthracyclines and cyclophosphamide, which are commonly used for the treatment of hematologic malignancies. In a randomized study, no vomiting was observed in 71 percent of patients with olanzapine compared with 32 percent on metoclopramide. The second presentation related to supportive care was given by Ellen Lavoie Smith, PhD, of the University of Michigan, School of Nursing, who reported on a study on the use of duloxetine for chemotherapy-induced peripheral neuropathy, which affects 20 to 30 percent of patients receiving taxanes or vincristine. Previously there have been very limited effective treatments for chemotherapy-induced neuropathy; however, duloxetine resulted in a significant decrease in pain secondary to the neuropathy compared with placebo. Yael Mosse, PhD, from the Chil- dren’s Hospital of Philadelphia spoke on the use of crizotinib in a subset of children with anaplastic large cell lymphoma (ALCL). Crizotinib is FDA-approved for the treatment of locally advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase (ALK)-positive. Dr. Mosse and colleagues identified several children with ALK-positive malignancies, including ALCL, who they treated with crizotinib; approximately 80 to 95 percent of ALCL patients have ALK abnormalities. Eighty-eight percent of children had complete responses to crizotinib, which lasted for one to two years or more. Responses were also seen in patients with inflammatory myofibroblastic tumors and neuroblastomas, both of which may have ALK abnormalities. Finally, Chaya Moskowitz, PhD, from Memorial Sloan-Kettering Cancer Center, focused on long-term complications related to radiation therapy, which is highly relevant as children, adolescents, and young adults are living longer and longer after primary cancer treatments. Dr. Moskowitz and collaborators found that lower levels of radiation therapy can lead to secondary risk of breast cancer in patients treated for childhood cancer. The study cohort included 6,000 patients on the Childhood Cancer Survivor Study. The incidence of breast cancer by age 50 ranged from 24 to 31 percent in patients who received from 10 to 19 Gy of radiation therapy, which is comparable to women who are BRCA1/2 carriers. This has tremendous implications for earlier screening in these patients and suggests that magnetic resonance imaging (MRI) should be used in some cases due to fibrotic breasts. There are currently 50,000 women in the United States who were treated with less than 20 Gy of radiation therapy who should receive annual screening, as recommended by Children’s Oncology Group. This outstanding session demonstrated the complementary research that occurs between these two great societies. Dr. Bishop indicated no relevant conflicts of interest.

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ASH News Daily 2012 - Monday, December 10, 2012

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