The Graft-Versus-Tumor Effect in Pediatric Malignancy

Division of Blood and Marrow Transplantation/Immunology, Center for Cancer and Blood Disorders, Children's National Medical Center, 1 West Wing, 111 Michigan Avenue, NW, Washington, DC 20010, USA.
Pediatric Clinics of North America (Impact Factor: 2.12). 02/2010; 57(1):67-81. DOI: 10.1016/j.pcl.2009.12.002
Source: PubMed


Because severe forms of the graft-versus-host reaction directed against normal tissues (also termed graft-versus-host disease [GVHD]) also contribute to morbidity and mortality following allogeneic hematopoietic stem cell transplantation, major efforts have focused on strategies to separate GVHD from the potentially beneficial immune reactivity against tumor (also called the graft-versus-tumor [GVT] effect). This article focuses on the data supporting the contribution of the GVT effect to cure of malignancy, what is known about the biology of the GVT reaction, and, finally, strategies to manipulate the GVT effect to increase the potency of HSCT.

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Available from: Andre Willasch, Sep 19, 2015
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    ABSTRACT: Infectious complications are a serious cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT), and the lung is a particular target organ post-transplant. Our laboratory has used a murine bone marrow transplant model to study alterations in immunity that occur as a result of transplantation. Our studies focus on immune responses that occur following immune cell reconstitution in the absence of immunosuppressive drug therapy or graft-versus-host disease. We have found that impaired clearance of both bacterial and viral pulmonary infections is related to specific alterations in immune cell function and cytokine production. Our data offer insight into mechanisms that contribute to opportunistic infections in HSCT recipients.
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    ABSTRACT: Patients with hematologic malignancies who relapse after their first hematopoietic stem cell transplantation tend to have poor prognoses. One option for these patients is a second allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there are few reports of second allo-HSCT therapy in children with relapsed hematologic malignancies. Patient outcomes in 27 individuals with acute leukemia who received at least 2 allo-HSCTs at the Samsung Medical Center between May 1997 and September 2010 were analyzed retrospectively. After a median follow-up of 33 months, 11 of 27 patients (40.7%) were alive and in stable remission. The 5-year overall survival rate for all 27 patients was 32.6%. There was no statistically significant difference in the survival rates of patients differing in their sex, the stem cell source, the donor type, or the presence of acute or chronic graft-versus-host disease. Remission before the second allo-HSCT was the only prognostic factor that influenced the survival rates (44.1% vs. 11.1%, P=0.009). Of 16 cases of mortality, 9 mortality cases (56.3%) were associated with relapse and 7 cases (43.7%) were associated with treatment-related mortality. Therefore, a second allo-HSCT offers the chance of stable remission for some patients with acute hematologic malignancies who relapse after their first allo-HSCT.
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