Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jun 2010
Allogeneic stem cell transplantation using myeloablative and reduced-intensity conditioning in patients with major histocompatibility complex class II deficiency.
Major histocompatibility complex class II (MHC II) deficiency is a rare combined immunodeficiency disease. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Between June 1994 and February 2007, 30 children with MHC II deficiency underwent a total of 33 HSCT procedures. ⋯ The overall disease-free survival rate was 66% and 76% after HLA-identical HSCT, with a median follow-up of 6.3 years, which is higher than previously reported. In HLA-identical transplant recipients, reliable donor stem cell engraftment and immune reconstitution were achieved through myeloablative or reduced-intensity conditioning. Further studies and long-term follow-up are needed to determine the appropriate conditioning regimen.
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Biol. Blood Marrow Transplant. · May 2010
Clinical TrialLate-onset hemorrhagic cystitis in children after hematopoietic stem cell transplantation for thalassemia and sickle cell anemia: a prospective evaluation of polyoma (BK) virus infection and treatment with cidofovir.
Little is known about late-onset hemorrhagic cystitis (HC) in children, its relationship to BK virus, and treatment with cidofovir (CDV) following hematopoietic stem cell transplantation (HSCT). We prospectively investigated BK virus reactivation in children who underwent HSCT from a matched related donor for thalassemia or sickle cell anemia following busulfan-cyclophosphamide-based conditioning regimens and analyzed risk factors for development of HC and its treatment with CDV. Grade 2-4 HC occurred in 30 patients with a cumulative incidence of 26% (95% confidence interval [CI] = 18%-34%). ⋯ None of the patients with HC cleared BK viruria when CCR was achieved. We conclude that late-onset HC is more prevalent in children with sustained high BK viruria who are treated with ATG or who develop graft-versus-host disease. Randomized clinical trials are urgently needed to better define the role of CDV in treating BK virus-related HC.
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Biol. Blood Marrow Transplant. · Apr 2010
The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia.
A combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated and effective in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML). The addition of rabbit antithymocyte globulin (ATG) may reduce morbidity and mortality from graft-versus-host disease (GVHD), but lead to increased relapse. To compensate for this effect, we added 400 cGy of total body irradiation (TBI) to the Flu/Bu regimen in 89 patients, and compared outcomes with those achieved in 90 patients who received the drug combination alone. ⋯ This study confirms the importance of regimen intensity in allogeneic HSCT for AML. The combination of daily i.v. Bu, Flu, 400 cGy TBI, and ATG provides a well-tolerated regimen with antileukemic activity in AML comparable to that of other, conventional myeloablative (MA) regimens.
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Biol. Blood Marrow Transplant. · Apr 2010
Expansion of NKG2A-LIR1- natural killer cells in HLA-matched, killer cell immunoglobulin-like receptors/HLA-ligand mismatched patients following hematopoietic cell transplantation.
The prognosis after hematopoietic cell transplantation (HCT) for the treatment of leukemia or lymphoma in humans is influenced by donor-derived natural killer (NK) cells, which enhance the graft-versus-leukemia (GVL) effect. Such alloreactive killer cells can be generated in vivo after HCT if the donor expresses killer cell immunoglobulin-like receptors (KIRs), such as KIR2DL1, KIR2DL2/3, or KIR3DL1, for which the recipient lacks HLA class I ligands. We studied effector cells from 22 KIR/HLA-ligand mismatched and 14 KIR/HLA-ligand matched, primarily HLA-matched patient-donor pairs after allogeneic HCT. ⋯ The numbers of such NKG2A(-) LIR1(-) NK cells increased following HCT in patients transplanted by KIR/HLA-ligand mismatched grafts, compared to KIR/HLA-ligand matched grafts, and in patients transplanted from donors of the A/B, compared to A/A, KIR haplotypes. NKG2A(-)LIR1(-) NK cells expressing only those inhibitory KIRs for which the patient had no HLA class I ligands could be stimulated by HLA class I-deficient cells to express CD107a. Thus, NKG2A(-)LIR1(-) NK cells may be important GVL effector cells following HCT, even in patients transplanted from HLA-matched donors.
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Biol. Blood Marrow Transplant. · Mar 2010
Comparative StudyComparison of two pretransplant predictive models and a flexible HCT-CI using different cut off points to determine low-, intermediate-, and high-risk groups: the flexible HCT-CI Is the best predictor of NRM and OS in a population of patients undergoing allo-RIC.
Patient comorbidities are being increasingly analyzed as predictors for outcome after hematopoietic stem cell transplantation (HSCT), especially in allogeneic HSCT (Allo-HSCT). Researchers from Seattle have recently developed several pretransplant scoring systems (hematopoietic cell transplantation comorbidity index [HCT-CI] and the Pretransplantation Assessment of Mortality (PAM) model) from large sets of HSCT recipients with the aim of improving non-transplant models, mainly the Charlson Comorbidity Index (CCI). The validation of these comorbidity indexes in other institutions and in different disease and conditioning-related settings is of interest to determine whether these models are potentially applicable in clinical practice and in research settings. ⋯ The better predictive capacity for NRM of the flexible HCT-CI than PAM and CCI was confirmed with the c-statistics (c-statistics of 0.672, 0.634, and 0.595, respectively). Regarding the 2-year overall survival (OS), the flexible HCT-CI score categories were also associated with the highest predictive HR. In conclusion, our single-center study suggests that the flexible HCT-CI is a good predictor of 2-year NRM and survival after an allo-RIC.