Clonal cytopenia of undetermined significance (CCUS)-associated reversion of donor-derived, transient αß T-cell large granular clonal lymphocytosis, emerging post-transplant in a patient with a history of γδ T-cell large granular lymphocytic leukemia.

Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) has revolutionized the therapy of hematolymphoid malignancies. Yet, how to best detect or predict the emergence of HSCT-related complications remain unresolved. Here, we describe a case of donor-derived, transient Alpha Beta (αß) T-cell large granular clonal lymphocytosis and cytopenia that emerged post-HSCT in a patient with a history of gamma delta (γδ) T-cell large granular lymphocytic leukemia (T-LGLL). Clonal unrelatedness of post-transplant T-LGL lymphocytosis to the patient's pretransplant T-LGLL was first identified by T-cell receptor (TCR) PCR showing different sized fragments of rearranged gamma chains, in addition to shift from γδ to αß TCR expression by flow cytometry analyses. Donor-derivation of the patient's post-transplant clonal lymphocytosis was confirmed by serial chimerism analyses of recipient's blood specimens demonstrating 100% donor DNA. Moreover, oncogenic DNMT3A and RUNX1 mutations were detected by next-generation sequencing (NGS) only in post-transplant specimens. Intriguingly, despite continued increase in DNMT3A and RUNX1 mutation load, the patient's clonal lymphocytosis and anemia eventually largely resolved; yet, the observed mutation profile with persistent thrombocytopenia indicated secondary clonal cytopenia of undetermined significance (CCUS) in the absence of overt morphologic evidence of myeloid neoplasm in the marrow. This case illustrates the utility of longitudinal chimerism analysis and NGS testing combined with flow cytometric immunophenotyping to evaluate emerging donor-derived hematolymphoid processes and to properly interpret partial functional engraftment. It may also support the notion that driver mutation-induced microenvironmental changes may paradoxically contribute to reestablishing tissue homeostasis.

Introduction of human papillomavirus vaccines into developing countries - international strategies for funding and procurement.

This paper explores different international vaccine financing and procurement strategies used by the Pan American Health Organization, United Nation's Children's Fund, the Global Alliance for Vaccines and Immunization, the Gulf Cooperation Model, and the Advanced Market Commitments. The aim is to identify lessons learned to help ensure equitable distribution of life-saving vaccines for cervical cancer prevention, with particular emphasis on sustainability. A critical first step in the cascade of activities necessary for Human papillomavirus (HPV) vaccine introduction should be the creation of an informed policy decision making process that is grounded in the best available information at a national level. This process will help ensure that decisions are financially sustainable. Any vaccine purchasing mechanisms should address the following essential points: 1) prioritization of cost-saving interventions; 2) flexible participation; 3) sufficient support to confront in-country challenges for managing vaccine procurement mechanisms; 4) a definite time-line for country ownership of vaccine purchases; 5) accuracy of vaccine demand forecasting; 6) maintenance of vaccine supply chains; and 7) well-functioning surveillance and regulatory bodies. In mapping the way forward, using the lessons learned and maintaining flexibility of financing and procurement mechanisms remain critical issues.

Immunization and the Millennium Development Goals: progress and challenges in Latin America and the Caribbean.

The child mortality rate has been greatly reduced in Latin America and the Caribbean (LAC). More than half of the gains in reducing child mortality are attributable to immunization. The Revolving Fund of the Pan American Health Organization contributed to this achievement by catalyzing policy innovations that sustained national immunization programs, such as vaccine legislation and budgetary decrees to ensure delivery of services. In addition to measuring the impact of immunization on the child mortality reduction target of the Millennium Development Goals in the LAC region, this paper provides a policy framework to ensure that the rest of the target is reached.

Regional group purchasing of vaccines: review of the Pan American Health Organization EPI revolving fund and the Gulf Cooperation Council group purchasing program.

This paper reviews the key design features, accomplishments of and lessons learned from two regional group procurement mechanisms dealing with vaccines that have been in operation for more than 25 years. The Pan American Health Organization (PAHO) EPI Revolving Fund purchases vaccines and immunization supplies on behalf of more than 35 countries in the Latin American and Caribbean region. Based on a 'central contracting' model, the program handles most aspects of procurement-from tendering to contracting with and paying producers--using a common fund to pay producers before being reimbursed by countries once goods are received in-country. The Gulf Cooperation Council (GCC) Group Purchasing Program among seven Persian Gulf States issues joint tenders for vaccines, as well as drugs and other medical goods. Through this 'group contracting' program, countries are responsible for contracting with and paying producers on their own, once the group has selected winning bids. Both programs have experienced substantial growth in the past two decades and are considered to have contributed to or accelerated achievements of immunization programs in both regions, including the introduction of new vaccines. The paper identifies several features of both programs--both those designed to attract country participation and those designed to ensure the programs' financial viability--which help explain their success and longevity.

The surgical anatomy of the ansa pectoralis.

Detailed anatomical knowledge of the pectoral nerves is of clinical importance in surgeries as diverse as limb neurotization, mastectomy, orthopedic procedures and operations related to trauma. The brachial plexus of 200 cadavers were examined in an attempt to clarify the normal origins, courses and variations of the nerves with special emphasis on the ansa pectoralis (AP). In 75% the MPN arose from the anterior division of the inferior trunk of the brachial plexus and in 25% it arose from the medial cord. In 40% of specimens, the LPN arose from a single contributing nerve (anterior division of the superior trunk, 11%; anterior division of the middle trunk 18%; lateral cord, 11%). In the remaining 60% of specimens, the LPN arose from the fusion of two rootlets derived variably from the anterior divisions of the superior and middle trunks and the lateral cord. A single AP was found to be present bilaterally in 200 (100%) of the specimens. Classification of the AP was based upon its origin from the upper or lower rootlet of the LPN, the LPN itself, or from the deep branch of the LPN. AP-1 (42%) arose from the deep branch of the LPN; AP-2 (28%) arose directly from the LPN; AP-3 (25%), arose from the lower rootlets of the LPN and rarely, the AP arose from the upper rootlet of the LPN and crossed posterior to the lower rootlet to communicate with the MPN (AP-4, 5%). Irrespective of the aforementioned types, the AP was found to be present, crossing the second segment of the axillary artery in 90% of the specimens. These results could prove useful during the preoperative planning of neurotization and other surgical procedures involving the axilla.

Accelerating policy, deployment, and access to new and underutilized vaccines in developing countries

O ver recent decades, the experi-ence of national immunization programs demonstrates that im-munization is one of the "best buys" in public health. 1 Rapid deployment and use of the traditional vaccines against child-hood killer diseases have been the most im-portant contributors to reductions in child mortality and increased life expectancy in developing countries. In the Americas, polio was eradicated from the region over fifteen years ago, indigenous measles trans-mission was eliminated in November 2002 and neonatal tetanus has been eliminated in all but one of the countries of the re-gion. 2 In 2003, the Pan American Health Organization's (PAHO) Directing Coun-cil, composed of all the ministers of health of the countries of the Americas, unani-mously adopted a resolution to eliminate rubella and congenital rubella syndrome (CRS) from the Americas by 2010, becom-ing the first region in the world to take on this challenge. 3 Immunization will continue to be es-sential in reducing child mortality in de-veloping countries and, thus, will prove critical to meeting the Millennium Devel-opment Goals (MDGs). 4 Immunization is directly associated with the achievement of child mortality reductions (MDG 4) and maternal health (MDG 5). It also con-tributes to a decrease in cancer (such as cervical cancer), a major disease of global and regional importance (MDG 6). The human papillomavirus vaccine has the po-tential to impact this last MDG. Beyond simply achieving the MDGs, further gains in the reduction of child mortality can be achieved through more effective and wider use of immunization strategies. 5 The World Health Organiza-tion's (WHO) Global Immunization Vi-sion and Strategy (GIVS) recognizes that Jon Kim Andrus, MD, oversees technical support to PAHO Member Countries of Latin America and the Caribbean, particularly for strategic planning and all key policy issues regarding vaccines and immunization. Vance Dietz, MD, MPH, TM, is Chief of the Global Measles Branch at the Centers for Disease Control and Prevention (CDC) and oversees measles technical support globally for the CDC. John Fitzsimmons, MURP, coordinates the management of PAHO's Revolving Fund for the purchase of vaccines for all PAHO Member Countries. Carlos Castillo-Solórzano, MD, MPH, works as a Regional Advisor for Immunization at PAHO with a primary focus on rubella elimination.