Akiyoshi Miwa

Improved survival from fungaemia in patients with haematological malignancies: Analysis of risk factors for death and usefulness of early antifungal therapy

Abstract: Fourty‐three episodes of fungaemia encountered from 1978 to 1991 in 43 patients with haematological malignancies are reviewed here to analyse the risk factors for death and to evaluate the efficacy of early antifungal therapy. Low serum cholinesterase and elevated serum blood urea nitrogen were significantly associated with fungaemic death, defined as death occurring within 2 weeks after documentation of fungaemia. Overall death rate from fungaemia was 62.8%. Before the introduction of early antifungal therapy in 1986, however, fungaemic mortality was 85.7%; it was reduced to 51.7% thereafter (p = 0.01). Determination of plasma (1→3)‐β‐D‐glucan was helpful in detecting deep fungal infections and initiating antifungal therapy early.

Pyogenic Granuloma of the Tongue Early after Allogeneic Bone Marrow Transplantation for Multiple Myeloma

Oral complications occur frequently after bone marrow transplantation (BMT). Some of them are caused by regimen-related toxicity of the preparative regimen, and others by infections. In addition, oral tissues are targets of graft-versus-host disease (GVHD). Oral granulomatous lesions are not a common complication after BMT, and are especially rare on the tongue. Such rare lesions reported in the literature, developed late after BMT with oral chronic GVHD. We present here a patient who developed pyogenic granuloma of the tongue early after allogeneic BMT done for multiple myeloma. Regimen-related mucositis, oral acute GVHD, the administration of cyclosporine A, and the preexisting macroglossia might be responsible for the formation of granuloma.

Prognostic Significance of Serum Soluble Interleukin-2 Receptor Level in Non-Hodgkin's Lymphoma: A Single Center Study in Japan

Interleukin 2 receptor is expressed not only on the surface of activated T or B lymphocytes, but also on certain lymphoid malignancies. The receptor is released from the cell membrane as soluble form (sIL-2R). Serum sIL-2R level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation or specific tumor cell growth including non-Hodgkins lymphoma (NHL). However, the relevance of serum sIL-2R levels relating to clinical outcome in adult patients with NHL remains uncertain. Therefore, we investigated the serial serum sIL-2R levels in 28 untreated patients with NHL to evaluate its correlation with clinical characteristics. High serum sIL-2R level (>1000 U/ml) at diagnosis was associated with a high incidence of treatment failure (p=0.03) and poor overall survival (p=0.057). The serum sIL-2R levels decreased significantly after achieving complete remission (p=0.003). Further larger studies are required to evaluate whether serum sIL-2R level is an independent prognostic factor or not. However, adding this parameter to those already employed in the International Prognostic Index would perhaps provide a better prognostic index for adult patients with NHL.

High serum lactate dehydrogenase level predicts short survival after vincristine–doxorubicin–dexamethasone (VAD) salvage for refractory multiple myeloma

We evaluated possible prognostic factors just before salvage therapy with vincristine, doxorubicin, and dexamethasone (VAD) for 36 patients with refractory multiple myeloma. The median duration from diagnosis to the first VAD salvage was 14 months (range 2–76 months). Among parameters that have been shown to be associated with poor survival, a high serum lactate dehydrogenase (LDH) level was the sole significant predictor of survival. The median survival of patients with high LDH levels was 4 months, whereas that of patients with low LDH levels was 20 months. A multivariate analysis identified high LDH and high age as independent prognostic factors. More aggressive therapies might be indicated for high‐LDH patients with refractory myeloma. Am. J. Hematol. 65:132–135, 2000.

Prognostic Factors in Elderly Patients with Acute Myelogenous Leukemia: A Single Center Study in Japan

We retrospectively analyzed data of 47 patients aged 60 years or older, hospitalized in our institution with the diagnosis of acute myelogenous leukemia (AML), and searched for prognostic factors. Induction with anthracyclines significantly correlated with better complete remission (CR) rate (P =0.0016) and overall survival (OS) (P <0.001). Another factor significantly affecting CR rate was higher age (>70 years) (P =0.042). Therapy-non-related factors predictive for shorter OS in univariate analyses were age older than 70 years (P =0.003), percentage of blasts in bone marrow more than 80% (P =0.048), serum lactate dehydrogenase level higher than 250   U   l m 1 (P =0.032). In stepwise cox proportional hazard regression model, all the four factors predictive for poor OS remained to be independently and significantly prognostic for shorter OS. Only two patients receiving anthracyclines died within 30 days and the frequency was not different from that in patients not receiving anthracyclines. The use of anthracyclines as induction therapy is recommended even in the elderly patients.

Clinical Value of Serial Measurement of Serum C-Reactive Protein Level in Neutropenic Patients

C-reactive protein (CRP) is an acute phase reactant of inflammation. We evaluated the clinical value of serial measurement of CRP in neutropenic patients. CRP was shown to be useful to monitor the response to therapy for febrile episodes in neutropenia. However, we failed to show statistically significant differences in CRP levels between febrile episodes with or without clinically documented infection (p = 0.10) and with or without bacteremia (p = 0.55). Also, we could not predict febrile episodes within three days by the elevation of CRP value. The area under receiver-operating characteristic curve depicting the relationship between CRP levels and forthcoming febrile episodes was only 0.60. In conclusion, serial measurement of CRP was considered to be not useful to predict fever within three days, or to differentiate the types of infection.

Treatment of Deep Vein Thrombosis Using Temporary Vena Caval Filters after Allogeneic Bone Marrow Transplantation

Bone marrow transplant (BMT) recipients have risk factors for deep vein thrombosis (DVT) including venous stasis caused by immobilization in the sterile unit, vessel wall damage caused by preparative regimen or indwelling catheters, and hypercoagulability caused by decreased natural anticoagulants. We successfully treated a patient who developed massive DVT in the superior vena cava after BMT with anticoagulation and the use of temporary vena caval filters. Considering the delayed complications, permanent filter is not appropriate for BMT recipients, because the risk factors for DVT associated with BMT are transient. We considered that temporary vena caval filter is a safe and useful device to prevent pulmonary embolism after DVT in BMT recipients.

Clinical role of FDG PET/CT for methotrexate-related malignant lymphoma.

Methotrexate-related malignant lymphoma (MTX-RML) is a type of therapy-related lymphoma, and it often occurs in patients with rheumatoid arthritis. The most distinctive characteristic of MTX-RML is a quick response to withdrawal of MTX. However, because there is a risk of recurrence without a distinctive indicator of disease, close follow-up is needed. We present F-18 2-fluoro-2-deoxyglucose (FDG) postitron emission tomography (PET) or computed tomography (CT) images of MTX-RML along with the characteristic clinical presentation of MTX-RML. FDG PET/CT has the advantage of being able to detect malignant lymphoma in patients who have undergone MTX treatment. After withdrawal of MTX, FDG uptake decreases along with a reduction in the volume of lesions. Although recurrent lesion develops independent to the initial FDG PET/CT findings, FDG PET/CT is useful for early detection of unexpected recurrent lesions. FDG PET/CT allows for the assessment of malignant lymphoma and recurrent lesions in patients who received MTX therapy, which is crucial for the management of MTX-RML.

Effects of the in vivo Administration of Recombinant Human Granulocyte Colony‐stimulating Factor Following Cytotoxic Chemotherapy on Granulocytic Precursors in Patients with Malignant Lymphoma

We examined the effects of the in vivo administration of recombinant granulocytc colony‐stimulating factor (rhG‐CSF) on granulocytic precursors in the bone marrow of 4 patients with malignant lymphoma who received chemotherapy. Patients were treated with rhG‐CSF at doses of 100–800 μg/ m2/day intravenously for 14 days only in the first course of chemotherapy (G‐CSF course) followed by the second course of chemotherapy without rhG‐CSF which was used as a control course. In the G‐CSF course, white blood cell counts (WBCs) demonstrated a biphasic response consisting of a first peak observed within a few days after the initiation of rhG‐CSF administration, and a second peak observed on the last day of rhG‐CSF injection or the day after. In the second peak, the incidence of granulocyte‐macrophage colony‐forming units (CFU‐GM) in mononucleated bone marrow cells did not change significantly after treatment with rhG‐CSF as compared with a control. However, since the number of nucleated cells in the bone marrow increased, the absolute number of CFU‐GM in the bone marrow increased. The number of mature and immature granulocytes in the bone marrow increased. These findings suggest that G‐CSF stimulates the proliferation and differentiation of granulocytic precursors in the bone marrow in granulocytopenic patients who received cytotoxic drugs and causes mature granulocytes to be released from the bone marrow.

Transformation into acute basophilic leukaemia in a patient with myelodysplastic syndrome

We describe a patient with basophilic leukaemia following a 2‐year period with myelodysplastic syndrome (refractory anaemia). The marrow showed 59.4% of blasts with 25.0% of mature and immature basophils. The leukaemic blasts contained granules, positively stained with toluidine blue but negative for peroxidase. The basophilic differentiation was confirmed by ultrastructural analysis demonstrating immature basophil granules. In addition, a morphological transition from immature blasts to more mature basophils was observed. Immunophenotypic analysis of blasts and basophils showed positive for CD5, CD7, CD13, CD33 and CD34. Cytogenetic investigation showed an abnormal karyotype, 46,XY,del(5)(q31q35). in 11% of the cells examined when the initial diagnosis of refractory anaemia was made. However, expansion of the same clone up to 100% was observed concomitantly with transformation to basophilic leukaemia.