Chronic Myeloid Leukemia: Expert Reponses to Frequently Asked Questions

Ms. Galinsky is a research nurse practitioner within the senior leukemia program at the Dana-Farber Cancer Institute, Boston, Massachuesetts. She received her master’s degree in nursing from Northeastern University, Boston. Her research interests include acute and chronic leukemias, myelofibrosis, and myelodysplastic syndromes. Her work has been published in journals such as Blood, The New England Journal of Medicine, and Leukemia Research. She is an active member of the Oncology Nursing Society, Massachusetts Nursing Association, and the American Society of Hematology.

Ilene Galinsky MSN, ANP-C, reported a financial interest/relationship or affiliation in the form of: Consultant, Enzon Pharmaceuticals, Inc.; Speakers’ Bureau, Pharmion Corporation, Enzon Pharmaceuticals, Inc., and Bristol-Myers Squibb Company.

Understanding TKI Therapy and Monitoring of Patients With Chronic Myeloid Leukemia

The introduction of oral tyrosine kinase inhibitors (TKIs) into the therapeutic management of patients with chronic myeloid leukemia (CML) has produced a wide variety of therapeutic pathways for patients with this disease. Although most patients with CML begin therapy with imatinib, up to 30% eventually require treatment with one of the newer agents, either nilotinib or dasatinib. It is very important for clinicians to recognize the indications, doses, and side-effect profile for each of the three commercially available BCR-ABL inhibitors in CML. The indications for switching from imatinib to a newer TKI include primary resistance (failure to achieve “milestones” such as complete hematological response by 3 months or major cytogenetic response by 12 months), secondary resistance (loss of previous hematologic or major cytogenetic response), or intolerance. One reason nilotinib and dasatinib are able to evoke responses in patients with imatinib-resistant CML is their ability to inhibit BCR-ABL mutations, which prevent imatinib binding. Dasatinib and nilotinib may produce myelosuppression. In addition, nilotinib may cause QT prolongation in rare instances while there is a 17% incidence of pleural effusion in patients taking dasatinib. Nevertheless, with careful monitoring and management of side effects, as well as appropriate timing of initiation of a new TKI, patients with CML can expect to enjoy many years of good quality of life with no negative effects from their underlying disease.

Breast Cancer Survivorship Pyschological Support Update

In recent years, cancer survivorship issues have received greater attention and research interest as the number of cancer survivors increases in the United States, and the cancer advocacy movement gains in strength. Cancer survivorship is defined as a continuum from the time of diagnosis to the end of life. It has been conceptualized as a progression through three phases or “seasons” of survival incorporating: (1) surviving the treatment and its side effects, (2) beginning to return to normal life while being monitored for recurrence, and (3) long-term adjustment, when the cancer experience is viewed as an episode in a full life. In 2004, the most recent year with complete Surveillance, Epidemiology, and End Results (SEER) data, there were 10.1 million cancer survivors; of these, more than 2.4 million were breast cancer survivors. Family members, friends, and caregivers of the woman diagnosed with breast cancer are also considered to be cancer survivors.

Psychosocial distress, at varying levels of severity, accompanies the cancer experience. There are calls to consider distress the sixth vital sign; it would then be routinely monitored along with pulse, blood pressure, respiration, temperature, and pain. Periods of highest distress for the woman with breast cancer are associated with transition points in treatment. Completion of treatment may be a cause of increased anxiety rather than joy. There are many potential barriers to meeting the psychosocial needs of women with breast cancer after active treatments ends. The Institute of Medicine of the National Academies has released several reports during recent years describing strategies to acknowledge and meet these needs, declaring that provision of psychosocial services should be a standard of care for survivors of cancer. Oncology nurses play a key role in assessing the patient, family members, and caregivers for signs of distress. In so doing, an atmosphere of compassion and trust is created such that the breast cancer survivor feels free to share psychosocial concerns and have them addressed by appropriate specialists if necessary.

Ms. Goodrich is an acute care oncology nurse practitioner and manager in the Division of Hematologic Malignancies at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland. She received her master’s degree from Johns Hopkins University. Her research interests include immunotherapy, bone marrow transplantation, and stem cell transplantation for hematologic diseases. Ms. Goodrich lectures regularly on B-cell disorders including lymphoma and chronic lymphocytic leukemia.

Amy Goodrich, RN, MSN, CRNP, reported no areas of conflict.

Understanding TKI Therapy and Monitoring of Patients With Chronic Myeloid Leukemia

Chronic mylogenous leukemia (CML) accounts for up to 20% of all adult leukemias in Western countries, with most being diagnosed between the ages 50 and 70 years. CML is typically diagnosed in chronic phase and the natural history includes progression to accelerated phase, followed by blast crisis. Prognosis worsens with each phase progression. The hallmark of CML is the translocation of chromosomes 9 and 22, t(9;22), which results in the formation of the oncoprotein, BCR/ABL, which activates tyrosine kinases. This results in the upregulation of signals that promote cell survival and the inhibition of programmed cell death (apoptosis).

Tyrosine kinase inhibitors (TKIs) block BCR/ABL-mediated tyrosine kinase activity, thereby inducing significant and prolonged remissions. TKIs, including, imatinib, dasatinib, and nilotinib, are all well-tolerated oral therapies that have revolutionized the treatment, quality of life, and prognosis of patients with CML. Imatinib is approved for use in first-line treatment of CML. In patients exhibiting an initial response, it is expected that 14% will develop imatinib-resistant disease at 5 years of imatinib therapy. Dasatinib and nilotinib are both approved for the treatment of imatinib-resistant or -intolerant CML. Due to recent advances in the treatment and monitoring of CML, the life expectancy for newly diagnosed patients has improved from approximately 6 years a decade ago, to approximately 20 years in 2008.

Update on Clinical Trials of Antiangiogenesis Agents in Breast Cancer/Metastatic Breast Cancer Treatment Update

Metastatic breast cancer (MBC) remains a largely incurable disease. However, survival rates continue to increase as advances in the understanding of the biology of tumorigenesis are made. Angiogenesis plays a major role in tumor formation and therefore, agents targeting this process, including the monoclonal antibody bevacizumab, are particularly successful at treating tumors. In addition, the introduction of the monoclonal antibody trastuzumab has dramatically improved outcomes for women with human epidermal growth factor receptor 2 (HER2)-positive MBC and reaffirmed the value of targeting specific cellular proteins as a means of controlling disease. This has led to the development of a plethora of new agents for the treatment of HER2-positive breast cancer in the metastatic setting, though optimal chemotherapy regimens are still under investigation.

Dr. Shah is assistant professor of hematology/oncology at the University of California, San Francisco, School of Medicine. He received his doctorate in microbiology and molecular genetics and his doctor of medicine from the University of California, Los Angeles. Dr. Shah’s clinical interests include the investigation of alternate inhibitors targeting BCR-ABL in cases of imatinib resistance. He published the first preclinical studies of dasatinib in 2004, and has been intricately involved with the promising early clinical trials of this agent, which is approved by the FDA for the treatment of imatinib-resistant and imatinib-intolerant CML.

Neil Shah, MD, PhD, reported a financial interest/relationship or affiliation in the form of: Consultant, Bristol-Myers Squibb Company and Novartis Pharmaceuticals Corporation.

Update of Clinical Studies in CML and Advances in Treatment

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). Due to its efficacy, tolerability, and favorable influence on survival with 6 years of follow-up, imatinib is now considered front-line therapy in all patients with CML. However, a subset of patients does not respond adequately to imatinib, and some patients lose a previously achieved response. Knowledge of the mechanisms of imatinib resistance has led to the rapid development of two second-generation TKIs, dasatinib and nilotinib, which are approved for the treatment of chronic- and accelerated-phase CML in patients with resistance or intolerance to imatinib. Dasatinib is also approved for imatinib-resistant or -intolerant blast-phase CML. While responses in the chronic phase are durable, accelerated and blast phase cases typically relapse within a relatively short period. Therefore, TKIs should be used as a bridge to transplant whenever possible. Ongoing randomized studies are comparing the effectiveness of dasatinib or nilotinib with imatinib in previously untreated chronic-phase CML.