Thrombotic microangiopathy (TMA) impairs long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). As the allogeneic HSCT procedure has developed, addressing risk factors for TMA has become more complicated. The aim of this study was to investigate the impact of transplant-associated factors on TMA incidence in patients who have undergone HSCT in various settings. One hundred twenty-three consecutive allogeneic HSCT patients with hematologic diseases receiving myeloablative and reduced-intensity conditioning were evaluated retrospectively. Of 123 patients, 22 (17.9%) developed TMA after HSCT. Multivariate analysis showed the significance of GVHD grade II-IV, and the use of FK506 and the use of high-dose busulfan (Bu) (16 mg/kg) persisted. The hazard ratios of the use of FK506, the use of high-dose Bu (16 mg/kg), and GVHD grade II-IV for TMA were 8.7 (95% CI 2.0-37), 5.7 (95% CI 1.5-21), and 3.4 (95% CI 1.3-9.1), respectively. In the present study, reduced-intensity conditioning did not have an advantage over myeloablative conditioning in decreasing the incidence of TMA after HSCT. Our results also showed that highdose Bu (16 mg/kg) for the conditioning and FK506 for the prophylaxis of GVHD might contribute more significantly to TMA onset after HSCT than other agents. Am. J. Hematol. 81:525-531, 2006. V V C 2006 Wiley-Liss, Inc.
Immunomodulation induced by dasatinib is reportedly related to better prognosis in chronic myeloid leukemia (CML). However, the underlying mechanism has not yet been fully elucidated. The immunoprofiles of 63 patients in the chronic phase of CML were evaluated during treatment with a tyrosine kinase inhibitor (imatinib, n = 36; nilotinib, n = 9; dasatinib, n = 18). The numbers of CD56 + CD57 + and CD3 + CD57 + cells increased significantly in the dasatinib group. The numbers of regulatory T-cells were comparable among the three groups. Dasatinib markedly enhanced natural killer (NK)-cell reactivity. Only one patient treated with dasatinib showed a slight cytomegalovirus (CMV) reactivation. In contrast, nilotinib suppressed NK-cell reactivity. Plasma levels of interleukin-8 (IL-8), interferon-γ inducible protein-10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all three groups, and plasma levels of granulocyte macrophage-colony stimulating factor (GM-CSF) were significantly elevated in the imatinib and dasatinib groups. Our results suggest the presence of a mechanism for dasatinib-associated immunomodulatory effects that is distinct from CMV reactivation and a decreased number of regulatory T-cells.
CGA is an effective tool for predicting outcomes in older patients with DLBCL. The patients treated with curative intent had significantly better outcomes compared with those receiving palliation, irrespective of CGA stratification. Curative treatment should be considered even for 'unfit' patients.
Thrombotic microangiopathy (TMA) impairs long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). As the allogeneic HSCT procedure has developed, addressing risk factors for TMA has become more complicated. The aim of this study was to investigate the impact of transplant-associated factors on TMA incidence in patients who have undergone HSCT in various settings. One hundred twenty-three consecutive allogeneic HSCT patients with hematologic diseases receiving myeloablative and reduced-intensity conditioning were evaluated retrospectively. Of 123 patients, 22 (17.9%) developed TMA after HSCT. Multivariate analysis showed the significance of GVHD grade II-IV, and the use of FK506 and the use of high-dose busulfan (Bu) (16 mg/kg) persisted. The hazard ratios of the use of FK506, the use of high-dose Bu (16 mg/kg), and GVHD grade II-IV for TMA were 8.7 (95% CI 2.0-37), 5.7 (95% CI 1.5-21), and 3.4 (95% CI 1.3-9.1), respectively. In the present study, reduced-intensity conditioning did not have an advantage over myeloablative conditioning in decreasing the incidence of TMA after HSCT. Our results also showed that highdose Bu (16 mg/kg) for the conditioning and FK506 for the prophylaxis of GVHD might contribute more significantly to TMA onset after HSCT than other agents. Am. J. Hematol. 81:525-531, 2006. V V C 2006 Wiley-Liss, Inc.
There have been many reports of patients with ampulla cardiomyopathy described as takotsubo-shaped cardiomyopathy in the cardiovascular field. This unique cardiomyopathy is characterized by transient apical ballooning and hypokinesis of the left ventricle. We describe 2 cases of ampulla cardiomyopathy associated with hemophagocytic lymphohistiocytosis (HLH). In both of the patients, ventricular dysfunction suddenly occurred during the active phase of HLH. In each case, the findings on ECG, echocardiogram and left ventriculogram were compatible with ampulla cardiomyopathy. To our knowledge, this communication is the first to report cases of ampulla cardiomyopathy associated with HLH. Our cases suggest that HLH hypercytokinemia may have a role in causing ampulla cardiomyopathy.
Chronic impairment of cardiac function can be an important health risk and impair the quality of life, and may even be life-threatening for long-term survivors of allogeneic hematopoietic cell transplantation (HCT). However, risk factors for and/or the underlying mechanism of cardiac dysfunction in the chronic phase of HCT are still not fully understood. We retrospectively investigated factors affecting cardiac function and left-ventricular hypertrophy (LVH) in the chronic phase of HCT. Sixty-three recipients who survived for 41 year after receiving HCT were evaluated using echocardiography. Based on simple linear regression models, high-dose TBI-based conditioning was significantly associated with a decrease in left-ventricular ejection fraction and the early peak flow velocity/atrial peak flow velocity ratio, following HCT (coefficient ¼ À 5.550, P ¼ 0.02 and coefficient ¼ À 0.268, P ¼ 0.02, respectively). These associations remained significant with the use of multiple linear regression models. Additionally, the serum ferritin (s-ferritin) level before HCT was found to be a significant risk factor for LVH on multivariable logistic analysis (P ¼ 0.03). In conclusion, our study demonstrated that a myeloablative regimen, especially one that involved high-dose TBI, impaired cardiac function, and that a high s-ferritin level might be associated with the development of LVH in the chronic phase of HCT.
We evaluated the performance of a fully-automated hematology analyser CELL-DYN 4000 (CD4000; Abbott Laboratories, CA, USA) for T-lymphocyte subset analysis using the samples from 58 patients with hematological disorders. A flow cytometer (CytoronAbsolute; Ortho Diagnostics, NJ, USA) was used for comparison. Good correlations were shown between CD4000 and CytoronAbsolute for the of CD3(+), CD4(+), and CD8(+) T-lymphocyte counts (for each of correlations, r = 0.992, 0.992, and 0.969, respectively). This good correlation was sustained even in 24 cases in which the CD4(+) T-lymphocyte counts were less than 200/microl. In this group the correlation coefficients (r-values) for the comparisons between CD3(+), CD4(+), and CD8(+) T-lymphocytes measured by CD4000 and CytoronAbsolute were 0.991, 0.976, and 0.990, respectively. The CD4000 T-lymphocyte assay is a completely automated method, and does not require opening of the sample tube, which reduces exposure to any biohazards such as HIV. Furthermore, the method is rapid and requires only 7 min for completion of the analysis.
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