Elevation of serum KL-6 levels in patients with hematological malignancies associated with cytomegalovirus or Pneumocystis carinii pneumonia.

The level of serum KL-6 antigen has been reported to be a sensitive indicator of various interstitial pneumonitis, but in patients with hematological malignancies who were accompanied by infective interstitial pneumonitis like Pneumocystis carinii or cytomegalovirus (CMV) pneumonia, it is still unknown whether serum KL-6 level is useful as a good marker for the diagnosis or disease activity. In this study, the serum levels of KL-6 and soluble intercellular adhesion molecule 1 (sICAM-1) were evaluated in five patients with malignant lymphoma or adult T-cell leukemia. Serum KL-6 and sICAM-1 levels at the time of diagnosis of P. carinii or CMV pneumonia were 1220+/-323 U/ml (mean+/-SD) and 1246+/-485 ng/ml, respectively. These levels were apparently high, when compared with standard value of serum KL-6 (<520 U/ml) and that of sICAM-1 (115-306 ng/ml). In patients without P. carinii or CMV pneumonia, who had hematological malignancies or AIDS, serum level of KL-6 was not high (299+/-122 U/ml), but sICAM-1 was high (651+/-495 ng/ml) because of the elevation of sICAM-1 in four of five cases. These findings suggest that, in patients with hematological malignancies, serum level of KL-6 antigen rather than sICAM-1 may be useful in the evaluation of CMV or P. carinii pneumonia.

Early diagnosis and treatment of pulmonary opportunistic infection by using polymerase chain reaction and beta-glucan in patients with hematological neoplasms.

The early diagnosis of 58 patients with hematological neoplasms accompanied by severe pulmonary infections of Pneumocystis carini (Pc), or Cytomegalovirus (CMV) pneumonia was made by polymerase chain reaction (PCR) using sputum samples, and of pulmonary mycosis by measuring blood beta-glucan levels by a Limulus test. The effectiveness of early treatment for opportunistic infection based on these early stage diagnosis was evaluated and the results of pathological analyses of the lung at autopsy were analyzed. PCR identified Pc pneumonia in 7 of the total 58 patients (12.1%), and early treatment was effective in all 7 patients (100%). PCR identified CMV pneumonia in 5 patients (8.6%), and early treatment was effective in 2 of the 5 patients. The level of beta-glucan confirmed mycotic pneumonia in 9 of these 58 patients (15.5%), and early treatment was effective in 7 of these (66.7%). These findings indicate that PCR and the beta-glucan method effectively enabled clinicians to diagnose pulmonary opportunistic infection in the early stage in 21 of the 58 patients (36.2%), and that early treatment was effective in 16 of the 21 patients (76.2%). The results of the pathological analyses of the lung at autopsy were: pulmonary tumor cell infiltration in a total of 5 patients (2 with ATL, 2 with NAE and 1 with AML); infection in a total of 6 patients (2 with ML and 4 with ATL); and diffused alveolar damage in a total of 4 patients (2 with ML, 1 with ATL and 1 with AML). CMV infection was confirmed in a total of 5 patients (2 with ML and 3 with ATL), and mucormycosis in a total of 2 patients (1 with ML and 1 with ATL). Despite these findings, Pc and other fungi or bacteria were not detected. Early diagnosis and treatment by the present PCR and beta-glucan method were useful, but the underlying disease and its disease state influenced the clinical outcomes of patients with terminal pulmonary infection caused by CMV or mucor, suggesting that prevention and early diagnostic measures for these infections remain to be established.

[Clinical study of infection associated hemophagocytic syndrome].

Hemophagocytic syndrome (HPS) causes pancytopenia, increased blood LDH level, liver dysfunction, DIC, etc. with macrophages appearing in the bone marrow, spleen, lymph nodes, etc. Adult HPS is mostly secondary to various infections, malignant tumors, etc. and sometimes has a serious outcome. Particularly infection associated HPS (IAHS) is triggered by viral, bacterial and fungal infections. The cases of unknown primary disease and suspected IAHS of unidentified pathogenic microorganism are often encountered in the clinical setting. The authors compared IAHS and malignant associated HPS (MAHS) and classified IAHS into viral associated HPS (VAHS), bacterial associated HPS (BAHS) and fungal types to compare the test values based on the test findings at the onset in the HPS cases treated at our Department. The patients consisted of 21 HPS cases, 11 IAHS cases (VAHS 4, BAHS 5, fungal 2) and 10 MAHS cases. Based on the test findings (WBC, Hb, Plt, LDH, ferritin, myelogram, cytokines, [IFN alpha, TNF gamma, IL-6, sIL-2R, M-CSF], adhesion molecules [sICAM-1, sVCAM-1, sELAM-1, sL-selectin]) at the onset, a comparison between IAHS and MAHS and among the IAHS cases classified by pathogenic microorganism was made. In the comparison between IAHS and MAHS, the Hb value was significantly decreased and sIL-2R tended to be increased at the onset in MAHS. When comparing the IAHS cases by pathogenic microorganism, Plt was significantly decreased and sICAM-1 and sVCAM-1 were increased at the onset in the BAHS, The BAHS cases had serious underlying diseases and poor prognosis with high incidence of DIC complications. We are going to accumulate more cases for early diagnosis and treatment of IAHS.

[Granular lymphocyte-proliferative disorder following initiation of protease inhibitor therapy in a patient with acquired immunodeficiency syndrome].

The authors experienced granular lymphocyte-proliferative disorder (GLPD) with increased lymphocyte and CD4 cell counts after HIV treatment with a protease inhibitor indinavir in a 51-year-old male AIDS patient. GLPD proved to be the chronic type, but we could not differentiate whether it was the T-cell type or the NK-cell type. EB virus was found to be activated and its chronic activity was suggested. We should note in this case that EB virus was involved in the GLPD onset and that GLPD followed the treatment with a protease inhibitor.

[Fatal lactic acidosis in a patient with acquired immunodeficiency syndrome treated with stavudine, lamivudine and indinavir].

Recently, several class-related adverse events have been recognized with antiretroviral drugs. For nucleoside analogue reverse transcriptase inhibitors. (NRTI), lactic acidosis with hepatomegaly and hepatic steatosis have been reported. These appear to occur at a low frequency, but with a high fatality rate. We report a case of fatal lactic acidosis in a patient with acquired immunodeficiency syndrome (AIDS) treated with stavudine (d4T), lamivudine (3TC) and indinavir (IDV). A 48-year-old male AIDS patient was admitted with complaints of general fatigue and dyspnea. His medications at presentation included d4T, 3TC and IDV. Physical examination demonstrated icteric sclerae and abdominal tenderness with hepatomegaly. Laboratory data demonstrated a severe metabolic acidosis with an anion gap due to lactate accumulation. Despite intensive treatment, cardiorespiratory arrest occurred and this could not be resuscitated.

[Serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and carboxyterminal parathyroid hormone-related protein (C-PTHrP) in hematological malignancies with bone lesions and hypercalcemia].

We measured the levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and carboxyterminal parothyroid hormone-related protein (C-PTHrP) in serum of patients with hematological malignancies. ICTP and C-PTHrP levels in serum of multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and adult T-cell leukemia (ATL) patients with bone lesions and hypercalcemia were significantly higher than those of patients without bone lesions and hypercalcemia. ICTP and C-PTHrP levels in ATL were significantly higher than in MM and NHL. There was a correlation between ICTP and C-PTHrP in serum of ATL patients, but no correlation in MM and NHL. Serum ICTP levels tended to correlate with serum beta 2-microglobulin and survival in patients with MM. Therefore, ICTP and C-PTHrP levels in serum may be useful in the diagnosis of bone lesions and hypercalcemia in hematological malignancies. In particular, ICTP may be a useful bone resorption marker in MM.

[Anemia due to chronic lead poisoning].

We report a case of anemia due to chronic lead poisoning. A 46-year-old female was admitted to our hospital because of general fatigue and anemia. A peripheral blood smear showed basophilic stippling. There was basophilic stippling and nuclear dysplasia of erythroblasts in the bone marrow. Laboratory findings were as follows: RBC 296 X 10(4)/microliter, Hb 8.5 g/dl, blood lead concentration 67 micrograms/dl, urinary lead concentration 309 micrograms/l, blood delta-ALA dehydrase 0.03 mumol/ml, urinary delta-ALA 25.2 mg/l, urinary coproporphyrin 8,810 micrograms/g.Cr, and blood protoporphyrin 612 micrograms/dl. Chronic lead poisoning was diagnosed and she was treated with Ca-EDTA.

[Soluble interleukin-2 receptor and macrophage colony-stimulating factor (M-CSF) in cerebrospinal fluid in patients with hematological malignancies: clinical significance in adult T-cell leukemia with meningeal infiltration].

We measured soluble interleukin-2 receptor (sIL-2R) and macrophage colony-stimulating factor (M-CSF) levels in the cerebrospinal fluid (CSF) of patients with hematological malignancies with or without meningeal infiltration and meningitis. Levels of sIL-2R and M-CSF in the CSF of adult T-cell leukemia (ATL) patients with meningeal infiltration were significantly higher than those of ATL patients without meningeal infiltration and non-ATL patients with meningeal infiltration. There was a significant positive correlation between sIL-2R levels and numbers of mononuclear cells in CSF of ATL patients with meningeal infiltration. However, M-CSF levels did not correlate with numbers of mononuclear cells. There was no correlation between CSF and serum levels of sIL-2R. There was also no correlation between sIL-2R and M-CSF in the CSF. Therefore, sIL-2R and M-CSF levels in the CSF may be useful in the diagnosis of meningeal infiltration in patients with ATL. In particular sIL-2R may be a sensitive marker.

[Clinical significance of soluble interleukin-2 receptor levels in the cerebrospinal fluid in patients with adult T-cell leukemia complicated with meningeal infiltration].

We measured soluble interleukin-2 receptor (sIL-2R) levels in the cerebrospinal fluid (CSF) of patients with hematological malignancies especially, adult T-cell leukemia (ATL) and non-Hodgkin's lymphoma (NHL) with or without meningeal infiltration. CSF levels of sIL-2R were significantly higher in patients with ATL and NHL with meningeal infiltration than in patients with both diseases without meningeal infiltration. The sIL-2R levels in CSF were elevated in 4/4 ATL patients (100%) and 3/13 NHL patients (23%) with meningeal infiltration. CSF levels of sIL-2R from ATL patients with meningeal infiltration had a tendency to elevate in correlation with numbers of mononuclear cells and lactic dehydrogenase (LDH) in CSF. However, these had no correlation with serum levels of sIL-2R. Therefore, sIL-2 levels in CSF may be useful in the diagnosis of meningeal infiltration in patients with ATL, are probably specific markers for meningeal infiltration of ATL.

[Usefulness of polymerase chain reaction (PCR) technique in making early diagnosis and treatment of cytomegalovirus and Pneumocystis carinii-pneumonia in patients with hematological neoplasms].

Recently, the incidence of opportunistic infections in patients with hematological neoplasms has been markedly increasing. However, early and definitive diagnosis and treatment of these infections remain difficult. In this study, we report three patients, a 47-year-old female with ATL, a 54-year-old female with CML and a 65-year-old female with ATL. All these cases were complicated with pneumonia caused by Pneumocystis carinii (Pc) or cytomegalovirus (CMV). They were successfully treated with sulfamethoxazole/trimethoprim or ganciclovir after detection of the respective microorganisms from sputum samples in the early stage of the infections by polymerase chain reaction (PCR) method. The above clinical evidence demonstrated the PCR technique to be a rapid and sensitive diagnostic procedure for the detection of Pc or CMV and to be helpful for the early initiation of appropriate treatment of the infections in patients with hematological neoplasms.