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Mesenchymal Stromal Cells in the Clinic
December 12, 2011 2:45 PM-4:15 PM
San Diego Convention Center
(Room 10)
Mesenchymal stromal cells (MSCs), termed mesenchymal stem cells by some investigators, have emerged as a major focal point in cell therapy and hold great promise for hematology, hematopoietic stem cell transplantation, and regenerative medicine. These cells, which are critical components of the marrow microenvironment, can be readily harvested and then substantially expanded <i>ex vivo</i>. Thus, MSCs are ideal for cell therapy applications and are currently under study in a variety of clinical settings. Initially, MSCs were thought to be tissue stem cells with the capacity to differentiate into many mesenchymal tissues, and research was directed toward regenerative medicine. Hematologists focused on the capacity of MSCs to regenerate the bone marrow microenvironment after HSCT conditioning in efforts to enhance hematopoietic recovery. More recently, it has been recognized that <i>ex vivo</i> expanded MSCs do not substantially differentiate to targeted tissues after infusion but rather secrete a broad array of cytokines with varied biologic activities, most notably the capacity to modulate the host immune response. This latter characteristic has led to active investigation in immune disorders such as graft-versus-host disease (GVHD). Dr. Edwin Horwitz will discuss the current understanding of MSC biology, MSCs' critical role in the marrow microenvironment, and their proposed mechanisms of action in the clinical arena, focusing on hematopoiesis. Dr. Richard Maziarz will review the various clinical trials assessing MSC safety and efficacy in the management of GVHD and will discuss heterologous applications in the regenerative medicine field that may be applicable to patients with hematologic disorders.
CoChair(s):
Edwin
M.
Horwitz, MD, PhD
The Children's Hospital of Philadelphia
Philadelphia,
PA,
USA
Richard
T.
Maziarz, MD
Oregon Health and Science University
Portland,
OR,
USA
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MicroRNA for the Clinician
December 11, 2011 4:30 PM-6:00 PM
San Diego Convention Center
(Room 10)
MicroRNAs (miRNAs) represent a new mechanism of molecular control in both normal development and disease. Unlike messenger RNAs (mRNAs), miRNAs do not encode proteins, but rather bind mRNAs, regulating their stability and translation into proteins. A single miRNA can target hundreds of mRNAs resulting in very large effects on the molecular constitution of cells. miRNAs can also be found in the plasma of humans and may play a role in transferring information between cells. Loss and gains in miRNAs have been found to be associated with various human diseases, including cancer. miRNAs have promise as biomarkers of disease, and pharmacologic modulation of endogenous miRNAs or development of their synthetic counterparts are being developed as innovative therapeutic strategies in hematologic malignancies. This session will introduce the basic biology of miRNAs and discuss their potential as biomarkers, molecular targets, and novel therapeutic agents. Dr. Robert Blelloch will discuss how miRNAs are encoded and regulated, how they recognize and influence their targets, and how they ultimately have an impact on the biology of the cell. Dr. Guido Marcucci will discuss the role of miRNAs in prognostication, risk-adapted treatment stratification, and individualized therapeutic approaches for leukemia patients.
CoChair(s):
Robert
Blelloch, MD, PhD
University of California, San Francisco
San Francisco,
CA,
USA
Guido
Marcucci, MD
The Ohio State University
Columbus,
OH,
USA
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New Anticoagulants
December 12, 2011 10:30 AM-12:00 PM
San Diego Convention Center
(Room 9)
The oral direct thrombin inhibitor dabigatran etexilate is approved by the U.S. Food and Drug Administration (FDA) and marketed for primary stroke prevention in non-valvular atrial fibrillation. Dabigatran and several other novel anticoagulants are in completed or advanced clinical trials as prophylaxis or therapy for several other indications; these drugs likely will be approved and marketed in the near future. Compared to established treatment, these novel anticoagulants have several advantages and disadvantages that must be considered when advising anticoagulation management for the individual patient. This session will use a case-based format to illustrate these important issues, focusing on dabigatran etexilate for non-valvular atrial fibrillation. Dr. Elaine Hylek will discuss dabigatran pharmacology and the RE-LY trial that compared dabigatran to warfarin in non-valvular atrial fibrillation. Dr. John Heit will discuss laboratory assays for dabigatran, periprocedural dabigatran management, and management of bleeding complications while on dabigatran.
CoChair(s):
John
A.
Heit, M.D.
Mayo Clinic
Rochester,
MN,
USA
Elaine
M.
Hylek, MD
Boston Medical Center, Boston University
Boston,
MA,
USA
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Palliative Patients Live Longer: Uncloaking the Mystery
December 12, 2011 2:45 PM-4:15 PM
San Diego Convention Center
(Room 3)
For some, palliative care conjures images of the Grim Reaper descending upon the patient. Quite the contrary, some data demonstrate that patients with palliative care involvement live longer, accompanied by the other positives of improved quality of life and decreased depression. Choice takes precedence. Palliative medicine is an integrated clinical approach that is about matching care to patient and family goals and choices. Quality of life, as defined by the patient and family, is the paramount priority. This approach recognizes that life-threatening illness, whether it can be cured or controlled, carries with it significant burdens of suffering for patients and their families and that this suffering can be effectively addressed by modern palliative care teams. Not surprisingly, reducing patients' misery may help them live longer. Clinicians now have both the means and the knowledge to make palliative care an essential and routine component of evidence-based, high-quality care for the management of serious illness. Dr. Melody Cunningham will discuss pediatric palliative care, the American Academy of Pediatrics (AAP) guideline for integrated palliative care from diagnosis to cure or, finally, death, and how it can satisfy the child's and parents' wishes. Dr. Charles von Gunten will discuss adult data and policy changes as they affect medical care.
CoChair(s):
Melody
J.
Cunningham, MD
Le Bonheur Children's Hospital
Memphis,
TN,
USA
Charles
F.
von Gunten, MD, PhD
The Institute for Palliative Medicine at San Diego
San Diego,
CA,
USA
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Point-Counterpoint: Haploidentical vs. Cord Blood Transplant
December 12, 2011 2:45 PM-4:15 PM
San Diego Convention Center
(Room 9)
For patients who do not have a matched sibling donor or a volunteer matched unrelated donor, or when there is not enough time to line up a donor because of rapid disease progression, there are two readily available donor stem cell sources: an unrelated cryobanked umbilical cord blood or a one- to three-locus mismatched haploidentical family member (parent, sibling, or child of the patient). Practice around the world varies widely: for example, in the United States, cord blood stem cell transplants (CBTs) predominate. In contrast, in China and Japan, haploidentical stem cell transplantation (SCT) is more widely used. CBT and haploidentical related donors share comparable degrees of mismatch. The choice of CB versus haplo donor is therefore worthy of debate.This session will contrast the strengths and weaknesses of the two stem cell sources, as proposed by two experts in the field. The growth of the cord blood transplantation field will be discussed, focusing on the recent improvements in double cord blood transplant, cord blood unit selection, infection prevention, and reduced-intensity conditioning. Data will be presented showing how the major obstacles to the clinical success of full haplotype mismatched transplantation have been conquered and recent advances in rebuilding post-transplant immunity after T-cell depleted HLA haploidentical transplant will be discussed.
CoChair(s):
Karen
K.
Ballen, MD
Massachusetts General Hospital
Boston,
MA,
USA
Massimo
Fabrizio
Martelli, MD
University of Perugia
Perugia,
Italy
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Preimplantation Genetics: The Science, The Medicine, The Bioethics
December 12, 2011 10:30 AM-12:00 PM
San Diego Convention Center
(Room 3)
Preimplantation genetic diagnosis (PGD) has been performed for more than 20 years as an alternative to prenatal diagnosis for those couples at risk of transmitting inherited diseases to their children. Embryos are generated in vitro by standard in vitro fertilization (IVF) technology, and a cell is removed for overnight molecular analysis. Embryos free from the genetic disease can be transferred to the uterus, so the pregnancy is started with the knowledge that any resulting pregnancy will be unaffected by the genetic disease. More recently, this technology has been used successfully for couples who have a child with sickle cell, Fanconi, Diamond- Blackfan, or Schwachman-Diamond anemia, beta-thalassemia, or selected inherited disorders such as Wiskott-Aldrich that can be cured with haploidentical cord blood stem cells from a matched sibling. Embryos produced by the parents that are found to be both free of the disease-causing gene mutation and a human-leukocyteantigen (HLA) match to the sick child can be transferred to the uterus. If a pregnancy results, hematopoietic stem cells from the newborn cord are used for treatment of the sibling. The ethics of such treatment have led to much debate, both in relation to the existing child and the child created by PGD. Dr. Mark Hughes will address PGD, especially in relation to HLA matching for savior siblings. Dr. Joyce Harper will address an update of the current world status, including data from the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium.
CoChair(s):
Mark
R.
Hughes, MD, PhD
Genesis Genetics Institute
Detroit,
MI,
USA
Joyce
Harper, PhD
University College London Center for Preimplantation Genetics and Diagnosis
London WC1E 6HX ,
United Kingdom
Speaker(s):
Joyce
Harper PhD
University College London Center for Preimplantation Genetics and Diagnosis
London WC1E 6HX , , United Kingdom
PGD 2011: Current Worldwide Status
Mark
Hughes MD, PhD
Genesis Genetics Institute
Detroit, MI, USA
PGD for Genetic Disease and HLA Savior Sibling
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Preserving Fertility in Young Women Receiving Antineoplastic Therapy
December 11, 2011 4:30 PM-6:00 PM
San Diego Convention Center
(Room 9)
The number of young people who survive cancer is growing every year thanks to improved treatments and supportive care. In 2005, there were more than 50,000 people diagnosed with cancer at age 35 or younger. One in 1,000 people in their 30s are cancer survivors, and one in 51 women will be diagnosed with cancer before age 40. Thus, quality-of-life issues such as fertility are taking on greater importance and having greater impact on a growing number of survivors. Evidence suggests that fertility preservation is very important to cancer survivors. Survivors report increased emotional distress if they become infertile due to treatment, and long-term quality of life is affected by unresolved grief and depression, reduced life satisfaction, and increased anxiety. Almost half of all female cancer patients in some studies did not recall a discussion regarding pregnancy risks after cancer treatment, and 25 percent of them reported high levels of anxiety regarding potential infertility. Even when fertility was discussed, only half of these women felt that their concerns were adequately addressed. In a survey of hematology/oncology physicians, just under half reported that they "always" or "often" refer patients to reproductive specialists. This session will provide an overview of anti-neoplastic therapy and fertility in girls and women, including discussions of the mechanisms of chemotherapy-induced infertility, the specific risks of fertility loss associated with various chemotherapy regimens and hematopoietic cell transplantation, how to discuss these risks with patients, the spectrum of fertility preservation options currently available, and the relative pros and cons of each approach. The session will address, in detail, the opportunities available to both pediatric and adult female patients to preserve their reproductive options, with a discussion of both "standard of care" and "state of the art" methods, including active research in novel methods of fertility preservation. Ethical, legal, and insurance issues will also be discussed.
CoChair(s):
Alison
W.
Loren, MD
University of Pennsylvania
Philadelphia,
PA,
USA
H. Irene
Su, MD, MSCE
University of California, San Diego
La Jolla,
CA,
USA
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Transplantation For Myelodysplastic Syndromes - For Whom, When and How?
December 12, 2011 10:30 AM-12:00 PM
San Diego Convention Center
(Room 10)
Hematopoietic cell transplantation (TX) can cure patients with myelodysplastic syndromes (MDS). However, despite considerable progress over the past decade, TX-related toxicity, post-TX relapse, and graft-versus-host disease (GVHD) remain major causes of failure. The development of TX regimens of lower intensity than those used in the past has attenuated TX-related toxicity, but generally at the cost of increased relapse risk. As most patients with MDS are in their 60s or older, typically, only low-intensity regimens are used for conditioning. Further, as several drugs have now been approved for the treatment of MDS, the question often arises, especially in older patients, whether patients should be treated with those drugs and be transplanted only if they do not or no longer respond or should undergo TX at the time of optimum response. In addition, these new treatment modalities may serve to reduce more efficiently the MDS clone prior to TX conditioning. Weighing the pros and cons in view of the potential post-TX complications, especially GVHD, provides a challenging task. GVHD, particularly in its chronic form, occurs in 50 percent to 60 percent of patients. Ongoing trials are directed at optimizing conditioning and GVHD prophylactic regimens to minimize toxicity while maintaining a potent cytotoxic effect with low GVHD incidence. These efforts include various approaches of pre-TX therapy, incorporation of ATG, use of antibody-conjugated radioisotopes, and post-TX administration of chemotherapy, primarily hypomethylating agents. Dr. Theo de Witte will discuss issues related to pre-TX therapies, patient age, and co-morbidities, including the impact of iron overload. Dr. Joachim Deeg will focus on conditioning regimens and GVHD and the potential graft-versus-leukemia effect.
CoChair(s):
H. Joachim
Deeg, MD
Fred Hutchinson Cancer Research Center and University of Washington
Seattle,
WA,
USA
Theo
M.
de Witte, MD
Radboud University of Nijmegen Medical Centre
Nijmegen,
Netherlands
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