HLA Mismatching as a Stragtegy to Reduce Relapse after Alternative Donor Transplantation
HLA mismatches are targets of alloreactive T cells, mediators of graft versus leukemia and graft versus host disease after alternative donor transplantation. Exploitation of HLA mismatching in order to reduce relapse is hampered by necessary interventions aimed at controlling graft versus host disease on the one hand, and by the possibility of immune escape through selective loss of mismatched HLA in relapsing leukemia on the other. Retrospective studies reporting the impact of HLA mismatches on post-transplant relapse need to be interpreted with caution, due to many confounding factors including disease and use of T cell ...
Source: Seminars in Hematology - January 15, 2016 Category: Hematology Authors: Katharina Fleischhauer, Dietrich W. Beelen Source Type: research
Supportive Care in Alternative Donor Transplantation
Alternative donor hematopoietic cell transplantation (HCT) using umbilical cord blood, haploidentical or mismatched unrelated donors is a viable option for patients without HLA-identical sibling or matched unrelated donors. The same principles of supportive care as conventional graft sources apply to alternative donor HCT recipients. However, there are some unique supportive care issues related to post-transplant complications, engraftment, graft-versus-host disease, immune reconstitution and infections that are unique to each of the three alternative graft sources, both in the early and late post-transplant period. (Sourc...
Source: Seminars in Hematology - January 15, 2016 Category: Hematology Authors: Shuang Fu, Navneet S. Majhail Source Type: research
Haploidentical Transplantation: Selecting Optimal Conditioning Regimen and Stem Cell Source
Recently, haploidentical donor transplant (HIDT) has emerged as a viable option for patients in need of an allogeneic stem cell transplant without an immediately available well-matched human leukocyte antigen (HLA) sibling or unrelated donor. Given the near immediate availability of haploidentical donors, along the high likelihood of a haploidentical match within a patient’s first degree family, HIDT is becoming increasing attractive, particularly for patients with high risk disease. In the last decade, several strategies of T-cell replete bone marrow or peripheral blood HIDT has been developed with diverse conditioning ...
Source: Seminars in Hematology - January 15, 2016 Category: Hematology Authors: Salyka Sengsayadeth, Bipin N. Savani, Didier Blaise, Mohamad Mohty Source Type: research
Transplantations from HLA-identical Siblings Versus 10/10 HLA-matched Unrelated Donors
The clinical outcome after allogeneic stem cell transplantation from an HLA-matched sibling donor as well as an HLA-matched unrelated donor has clearly improved due in part to the progress made in the domains of HLA-typing techniques. Although HLA-matched sibling transplantation is still held as the “gold standard,” transplantation from HLA-A, -B, -C, -DRB1, and -DQB1-matched unrelated donors (so called 10/10) represent the first choice for patients without a suitable related donor. Several studies have shown that unmanipulated marrow transplantation from an HLA allele-matched unrelated donor resulted in similar outcom...
Source: Seminars in Hematology - January 15, 2016 Category: Hematology Authors: Ibrahim Yakoub-Agha Source Type: research
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Source: Seminars in Hematology - January 1, 2016 Category: Hematology Source Type: research
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Source: Seminars in Hematology - January 1, 2016 Category: Hematology Source Type: research
Gene Therapy for Hemophilia: Past, Present and Future
After numerous pre-clinical studies demonstrated consistent success in large and small animal models, gene therapy has finally seen initial signs of clinically meaningful success. In a landmark study, Nathwani and colleagues reported sustained factor IX (FIX) expression in individuals with severe hemophilia B following adeno-associated virus (AAV)-mediated in vivo factor IX (FIX) gene transfer. As the next possible treatment-changing paradigm in hemophilia care, gene therapy may provide patients with sufficient hemostatic improvement to achieve the World Federation of Hemophilia’s aspirational goal of “integration of o...
Source: Seminars in Hematology - October 27, 2015 Category: Hematology Authors: L.A. George, Patrick F. Fogarty Source Type: research
Laboratory Monitoring of New Hemostatic Agents for Hemophilia
Prophylactic infusion of factor replacement products results in a reduction in long-term morbidity and mortality in patients with severe hemophilia. The needed frequency of intravenous access is commonly through central venous access devices, however, which may result in complications such as infections and thrombosis. Available clinical data on extended half-life (EHL) factor replacement products indicates a potential for a significant reduction in the need for frequent infusions, e.g., potentially once a week for factor IX and twice a week for factor VIII. (Source: Seminars in Hematology)
Source: Seminars in Hematology - October 27, 2015 Category: Hematology Authors: Rajiv K Pruthi Source Type: research
Aging among Persons with Hemophilia: Contemporary Concerns
The life-expectancy of persons with hemophilia (PWH) has increased almost 10-fold over the past 7 decades, largely due to access to safe factor replacement products. Concomitant with this success, however, comes the burden of aging. Older PWH are developing similar comorbidities as the general population, including increasing rates of hypertension, obesity, and diabetes, which predispose them to chronic diseases such as cardiovascular disease and chronic kidney disease. How their coagulopathy affects the expression of these conditions remains unclear. (Source: Seminars in Hematology)
Source: Seminars in Hematology - October 27, 2015 Category: Hematology Authors: Dana Angelini, Barbara A. Konkle, Suman L. Sood Source Type: research
Advances in the Clinical Management of Inhibitors in Hemophilia A and B
Inhibitors to factor (F) VIII or FIX are the most serious and challenging complication of hemophilia treatment, increasing morbidity and mortality because bleeds no longer respond to standard clotting factor replacement therapy. For patients with high-titer inhibitors, immune tolerance induction achieved through regular factor exposure is the only proven therapy capable of Inhibitor eradication and is almost always indicated for inhibitors of recent onset. Bypassing therapy is used to treat and prevent bleeding, but neither of the 2 currently available bypassing agents has the predictable hemostatic efficacy of factor repl...
Source: Seminars in Hematology - October 27, 2015 Category: Hematology Authors: Cindy A. Leissinger Source Type: research
Factor VIII/factor IX prophylaxis for severe hemophilia
Experience with clotting factor concentrate (CFC) replacement products over several decades has shown that regular replacement (prophylaxis) is the only way to prevent musculoskeletal damage in hemophilia and impact the natural history of hemophilia. Yet there is a lack of data on the optimal age to start such replacement therapy and the regimens to be used. While very early administration of high doses is certainly more effective in preventing bleeding, cost and compliance are major constraints all over the world. (Source: Seminars in Hematology)
Source: Seminars in Hematology - October 26, 2015 Category: Hematology Authors: Manuel Carcao, Alok Srivastava Source Type: research
Hemophilia in the 21st century: tremendous progress, tremendous opportunity
Since antiquity, when a recognition of a familial, fatal bleeding disorder in males was first recorded [1], the world has been inhabited by individuals who lack adequate plasma activity of coagulation factor (F)VIII or FIX. It was not until 1803, however, that Dr Joseph Conrad Otto, a physician in the United States, published the first description of a case of a heritable bleeding condition transmitted through mothers to some of their sons [2]. Eventually, in additional to spontaneous and traumatic bleeding, the disorder was understood to be distinguished phenotypically by a singular and distinctive tendency for bleeding i...
Source: Seminars in Hematology - October 26, 2015 Category: Hematology Authors: Patrick F. Fogarty Tags: Advances in Hemophilia Source Type: research
Global Assays in Hemophilia
The quest for the ideal method to study hemostasis in the evaluation and management of patients with bleeding disorders such as hemophilia is an ongoing effort. With the rapid evolution of biotechnology and the emergence of several new products for treatment of patients with hemophilia with and without inhibitors, there is a great need for tests that can be used to reliably evaluate and monitor our interventions. Global assays in coagulation allow the study of the interaction between the components involved in the process of hemostasis and are therefore considered by many to be more reflective of the in-vivo hemostatic mec...
Source: Seminars in Hematology - October 26, 2015 Category: Hematology Authors: Meera Chitlur, Guy Young Source Type: research
Advances and Challenges in Hemophilic Arthropathy
Hemophilic arthropathy is a form of joint disease that develops in secondary to joint bleeding and presents with synovial hypertrophy, cartilage and bony destruction. The arthropathy can develop despite clotting factor replacement and is especially disabling in the aging population. Pathobiological tissue changes are triggered by release of hemoglobin and iron deposition in the joint, but the sequence of events and the molecular mechanisms resulting in joint deterioration are incompletely understood. (Source: Seminars in Hematology)
Source: Seminars in Hematology - October 26, 2015 Category: Hematology Authors: Tine Wyseure, Laurent O. Mosnier, Annette von Drygalski Source Type: research
