Serum-free liquid marrow culture in patients with acute lymphoblastic leukaemia: a potential application to purge marrow for autologous transplantation

We have previously established a serum-free (SF) culture medium, which supports normal haemopoietic progenitor cell growth for at least 4 weeks as does conventional serum dependent (SD) medium. In the present study, we investigated the efficacy of such a defined SF liquid medium which sustained in vitro residual normal haemopoietic proliferation of marrow derived from ALL patients and which was detrimental for the leukaemic population. Evidence for a potential selective effect of SF culture was obtained by a leukaemic progenitor cell assay (ALL-CFU) and the detection of the bcr/abl translocation by polymerase chain reaction (PCR). In 13 experiments including 12 patients, morphological blast cells and ALL-CFU were dramatically reduced within 3 weeks of incubation in both SF and SD cultures. Likewise, in 5/5 experiments in SD and 2/5 experiments in SF conditions, leukaemic cells expressing the bcr/abl fusion gene disappeared within 3-4 weeks. In contrast, the absolute numbers of supernatant cells harvested weekly from SF and SD cultures were similar. No difference in CFU-GM production was detected for the two culture systems. Erythropoiesis in SF medium exhibited a slower decline than that found in SD. These results indicate that liquid marrow culture may selectively deplete leukaemic lymphoblastic cells and enable repopulation by residual normal haemopoietic cells. This technique may be useful to purge leukaemic cells for clinical autologous bone marrow transplantation in patients with ALL.     

National Athletic Trainers' Association Position Statement: Preparticipation Physical Examinations and Disqualifying Conditions

Objective

To present athletic trainers with recommendations for the content and administration of the preparticipation physical examination (PPE) as well as considerations for determining safe participation in sports and identifying disqualifying conditions.

Background

Preparticipation physical examinations have been used routinely for nearly 40 years. However, considerable debate exists as to their efficacy due to the lack of standardization in the process and the lack of conformity in the information that is gathered. With the continuing rise in sports participation at all levels and the growing number of reported cases of sudden death in organized athletics, the sports medicine community should consider adopting a standardized process for conducting the PPE to protect all parties.

Recommendations

Recommendations are provided to equip the sports medicine community with the tools necessary to conduct the PPE as effectively and efficiently as possible using available scientific evidence and best practices. In addition, the recommendations will help clinicians identify those conditions that may threaten the health and safety of participants in organized sports, may require further evaluation and intervention, or may result in potential disqualification.Key Words: medical history, family history, sudden cardiac death, concussion, sickle cell trait, diabetes, heat illness, hydrationParticipation in organized US athletics continues to rise. During the 2010–2011 academic year, more than 7.6 million high school students took part in organized interscholastic sports, compared with 7.1 million in 2005–2006.¹ Similarly, an additional 444 077 National Collegiate Athletic Association student–athletes participated in intercollegiate athletics in 2010–2011, compared with 393 509 in 2005–2006.² This growth in participation has led to a concomitant rise in sudden death. Most sudden deaths have been attributed to congenital or acquired cardiovascular malformations involving male football and basketball players.^3–5 Other causes of sudden death include heat stroke, cerebral aneurysm, asthma, commotio cordis, and sickle cell trait.^4,5 As sports participation continues to increase and catastrophic death in athletes receives more attention, the medical community should consider adopting a standardized preparticipation examination (PPE) instrument that, at a minimum and to the extent possible, sets out to ensure a safe playing environment for all and to identify those conditions that might predispose an athlete to injury or sudden death.For nearly 4 decades, PPE screening has been used routinely in an attempt to identify those conditions that may place an athlete at increased risk and affect safe participation in organized sports. Few would empirically argue the potential benefits of this practice, yet considerable debate exists as to the current efficacy of the PPE, given the significant disparities that presently characterize the examination and the information gathered. Over time, the PPE has become an integral component of athletics and sports medicine programs; however, the lack of standardization in the process has created confusion. In addition, the failure to adequately define the primary objectives of the PPE has led to the consensus that, in its current form, the PPE does not address the ultimate goal of protecting the health and safety of the player.The American Medical Association Group on Science and Technology⁶ has asserted that every physician has 2 responsibilities to an athlete during the PPE: “(1) to identify those athletes who have medical conditions that place them at substantial risk for injury or sudden death and to disqualify them from participation or ensure they receive adequate medical treatment before participation and (2) to not disqualify athletes unless there is a compelling medical reason.” As the PPE has evolved over the years, it has become increasingly difficult to meet these standards given the many objectives that have been proposed for the screening instrument. Originally, the primary objectives of the PPE were to (1) detect life-threatening or disabling conditions, (2) identify those conditions that predispose the athlete to injury or disability, and (3) address legal and insurance requirements.^7,8 Today, however, those entities charged with developing and revising the PPE (eg, state high school athletic associations, medical associations, state education departments, state health departments, legislators)⁹ often have different missions, and as a result, they have sought to influence the makeup of the PPE to address their specific interests. This has led to the identification of a number of secondary objectives, including but not limited to documenting athletic eligibility, obtaining parental consent for participation and emergency treatment, and improving athlete performance.⁹ Most notably, the PPE represents the sole source of medical evaluation for 30% to 88% of children and adolescents annually^10,11 and an opportunity to identify conditions that, although not necessarily related to or requiring restriction from athletic participation, nonetheless call for additional follow-up.⁹ Some authors¹² have advocated this practice to evaluate the general health of the athlete and to provide an opening to discuss high-risk behaviors, preventive care measures, and nonathletic concerns. Others oppose this view, stating that the PPE “should not be the sole component of health care for athletes”⁶ and that the PPE can only be effective if the goals remain specific and properly directed toward the demands of sport participation.^6,13