Hideyuki Takamatsu

Brain Natriuretic Peptide Is a Predictor of Anthracycline-Induced Cardiotoxicity

Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m2. The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.

Successful treatment of transfusion‐associated graft‐versus‐host disease

Summary. We present an immunocompetent patient with transfusion‐associated graft‐versus‐host disease (GVHD), in which chimaerism of peripheral blood lymphocytes was demonstrated by analysis of a highly polymorphic genome. The patient was treated successfully with anti‐CD 3 monoclonal antibody, OKT3 and cyclosporin A. Although it is undoubtedly important to prevent transfusion‐associated GVHD by irradiation of cellular blood components, intensive therapy with OKT3 and cyclosporin A in the early phase of onset may be effective for treatment of this potentially fatal condition. The mechanism of the effectiveness of this treatment for transfusion‐associated GVHD is discussed.

CD8-depleted donor leukocyte transfusions for cytomegalovirus antigenemia in patient with acute lymphoblastic leukemia treated with allogeneic CD34(+) cell transplantation.

A 24‐year‐old man with acute lymphoblastic leukemia received an allogeneic CD34+ cell transplant from an HLA‐mismatched sibling because of refractory disease. The CD34+ cells were enriched by the immunomagnetic method. One month after the transplant his situation became complicated due to cytomegalovirus (CMV) antigenemia, which was resistant to treatment with ganciclovir. He was treated with CD8+ cell‐depleted donor lymphocyte transfusions (CD8‐depleted DLT). After CD8‐depleted DLT, the CMV antigenemia disappeared completely. This case report suggested that CD8‐depleted DLT was an effective therapy for CMV antigenemia after allogeneic CD34+ cell transplantation. Am. J. Hematol. 65:278–280, 2000.

Relative erythroid hyperplasia in the bone marrow at diagnosis of aplastic anaemia: a predictive marker for a favourable response to cyclosporine therapy

Predicting the treatment response of aplastic anaemia (AA) is essential when considering cyclosporine (CyA) therapy among several treatment options, because it requires at least 2 months to determine whether the therapy is beneficial to a patient with AA. To identify the characteristics of patients with AA who are likely to respond to CyA therapy we retrospectively reviewed the clinical records and bone marrow smears of patients treated with CyA. Among 30 patients who received the therapy for at least 3 months within 1 year after diagnosis of AA, and who had not been exposed to antilymphocyte or antithymocyte globulin, 16 (53%) responded with disease remission. CyA‐responsive patients had a significantly higher ratio of erythroblasts to granulocytes (E/G ratio) in the bone marrow at the time of diagnosis as compared with patients refractory to therapy (P = 0.004). Multivariate analysis revealed that a high E/G ratio (>0.6) was significantly associated with a good response to CyA (P = 0.03): 15 (83%) of the 18 patients with an E/G ratio >0.6 responded, but only one (8%) of the 12 with an E/G ratio ≥0.6 did. Although the presence of subclinical paroxysmal nocturnal haemoglobinuria was suspected from the relative erythroblastosis observed in the bone marrow of these patients, flow cytometric analysis of neutrophils in the peripheral blood failed to reveal neutrophils deficient for glycosyl‐phosphatidylinositol (GPI) anchored membrane proteins in all but one case. Identification of the presence of relative erythroid hyperplasia in the bone marrow when AA is diagnosed may help to predict a favourable response to CyA therapy, and therefore facilitate the selection of optimal therapy for AA.