Adjuvant radiotherapy to an initial bulky mass in diffuse large B-cell lymphoma: lack of survival benefit.

The role of adjuvant radiotherapy to the site of the initial bulky mass in lymphoma remains to be determined. We retrospectively analyzed clinical data for 35 consecutive patients with diffuse large B-cell lymphoma who had an initial bulky mass were treated successfully by chemotherapy reaching complete remission or complete remission unconfirmed according to International Workshop Criteria. Median age was 57 years. Median follow-up period for surviving patients after completion of chemotherapy was 45 months. Twenty patients (group A) received adjuvant radiotherapy to the bulky mass, while 15 (group B) did not. Median dose of radiation in group A was 40 Gy (range, 30-60 Gy). In group A, four relapses occurred, all from other sites; group B included three relapses from bulky and one from other sites. Overall survival (P = 0.15) and recurrence-free survival (P = 0.48) did not differ significantly between groups. Although adjuvant radiotherapy to the initial bulky site is useful for controlling local disease, no survival benefit was seen.

Human herpesvirus-6 encephalitis after unrelated cord blood transplantation.

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.

Immune reconstitution assessed during five years after allogeneic bone marrow transplantation.

Immune reconstitution is an important component of successful allogeneic bone marrow transplantation. Immune reconstitution was evaluated for 5 years after transplantation. While the number of CD8+ T cells and CD56+ cells recovered early post transplantation, a low number of CD4+ and CD4+ CD45RA+ T cells and reversal of the CD4/CD8 ratio continued up to 5 years. Although early recovery of IgG and IgM was seen at day 100 post transplantation, serum concentration of IgA was below the normal range at 6 months and increased gradually up to 5 years. Development of acute GVHD did not affect the numbers of CD4+, CD8+, CD4+ CD45RA+ and CD4+ CD29+ T cells, but the number of CD56+ cells in patients who developed grades II-IV acute GVHD was low. The number of CD4+ CD29+ T cells had a tendency to be higher in the patients with extensive chronic GVHD than in those without chronic GVHD 2 years after transplantation whereas the number of CD4+ CD45RA+ T cells was low in spite of the absence of chronic GVHD. Serum concentration of IgA was lower in patients with extensive chronic GVHD than in those without chronic GVHD at 180 days. The number of CD4+ CD45RA+ cells in 10-19-year-old patients was higher than that in 40-49-year-old patients. Response to the Con A and PHA in 10-19-year-old patients was higher than that in older patients at 1 and 2 years. There was no significant difference in the ability of immune reconstitution between related transplant recipients and unrelated transplant recipients. These results suggest that chronic GVHD and age of patients affected immune reconstitution post transplant.

[Sequential analysis of p210- and p190-bcr-abl by RT-PCR after allogeneic bone marrow transplantation for p210/p190-bcr-abl double positive acute lymphoblastic leukemia].

In patients with both p210-bcr-abl (p210) and p190-bcr-abl (p190)-positive acute lymphoblastic leukemia, the number of p190 transcripts is lower than that of p210 transcripts. It is speculated that the p190 transcript occurs as a consequence of alternative splicing or missplicing events in the BCR gene. Four patients with both p210- and p190-positive acute lymphoblastic leukemia were studied for expression of p210 and p190 by RT-PCR before and after allogeneic bone marrow transplantation. p190 negativity was documented in all four patients, followed by p210 negativity one to two months later in three patients. These results suggest that negativity for p190 indicates an ongoing decrease in the small number of residual leukemic cells. In one patient p190 appeared transiently in spite of prolonged negativity for p210 18 months after bone marrow transplantation. We conclude that analysis of p210 and p190 is useful for following up patients with both p210- and p190-positive acute lymphoblastic leukemia.

Severe cardiac toxicity in hematological stem cell transplantation: predictive value of reduced left ventricular ejection fraction.

Eighty patients receiving hematological stem cell transplantation (HCT) with a preparative regimen consisting of total body irradiation (12.5 Gy), cyclophosphamide (4000 or 4500 mg/m2), and thiotepa (400 mg/m2) were evaluated for the development of cardiac toxicity. Patients in whom the pretransplant cumulative dose of anthracycline was more than or equal to 300 mg/m2 showed a lower left ventricular ejection fraction (EF) before HCT compared to patients with less than 300 mg/m2 (0.61 +/- 0.09 vs 0.67 +/- 0.06, P = 0.0010). Patients who had undergone more than or equal to six courses of chemotherapy showed a decreased EF before HCT compared to those after less than six courses (0.67 +/- 0.05 vs 0.63 +/- 0.09, P = 0.03). Three of seven patients (43%) whose pretransplant EF had been less than or equal to 0.55 developed severe cardiac toxicity, characterized by congestive heart failure (CHF) compared with none of 83 patients (0%) whose pretransplant EF had been more than 0.55 (P = 0.00026). Of the three patients who developed severe cardiac toxicity, two were given more than 300 mg/m2 of cumulative anthracycline and underwent 23 courses and six courses of chemotherapy, while the other patient received only two courses of chemotherapy with a total dose of 139 mg/m2 of anthracycline. These results indicate that an increased cumulative dose of anthracycline and number of chemotherapy treatments are correlated with a decrease of the EF and that the EF before HCT is useful for predicting the risk of cardiac complications for recipients who have received chemotherapy.

[Treatment outcome in elderly patients with aggressive non-Hodgkin's lymphoma].

Seventy-one patients aged 61-84 years with previously untreated aggressive non-Hodgkin's lymphoma were treated with a doxorubicin-containing regimen and evaluated retrospectively. The patients comprised 49 men and 22 women with a median age of 68 years. The median observation period was 544 days. Histological examination revealed 17 cases of diffuse small cleaved, 11 cases of diffuse mixed, 40 cases of diffuse large, and 3 cases of immunoblastic lymphoma, classified according to the International Working Formulation. When the patients were divided according to the age-adjusted international index, group A (61-64 years; n = 21) comprised 5 low (L)-, 4 low-intermediate (LI)-, 7 high-intermediate (HI)-, and 5 high (H)-risk patients. The corresponding numbers in group B (> or = 65 years; n = 50) were 14, 12, 16, and 8, respectively. The overall three-year survival rate was 50%, being 78% in group A and 36% in group B (P = 0.02), and 77% for L + LI patients and 34% for HI + H patients (P = 0.003). The respective three-year survival rates for L + LI and HI + H patients were 100% and 67% in group A, and 68% and 16% in group B. HI + H patients in group B showed shorter survival than L + LI patients in group B (P = 0.002) and HI + H patients in group A (P = 0.03). The cause of death in most group B HI + H patients was lymphoma, although the dose intensity of doxorubicin, cyclophosphamide and vincristine did not differ significantly from that in the other groups. Thus, HI + H patients aged 65 and over had an essentially poor prognosis.

CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) regimen with granulocyte colony-stimulating factor (G-CSF) for patients with aggressive non-Hodgkin's lymphoma: a pilot study. The Adult Lymphoma Treatment Study Group (ALTSG).

We conducted a multi-institutional collaborative study to examine the usefulness and safety of third-generation chemotherapy CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) combined with granulocyte colony-stimulating factor (G-CSF) in the treatment of aggressive non-Hodgkin's lymphoma (NHL). Subjects included patients with aggressive NHL who were 60 yr of age or younger and had been diagnosed as having a low-intermediate, high-intermediate, or high risk using the International Prognostic Index (IPI). A total of 24 patients were enrolled in the study between May 1997 and March 1998, including 9 low-intermediate-risk cases, 13 high-intermediate-risk cases and 2 high-risk cases. Although all 24 patients were originally enrolled in the study, one adult T-cell leukemia/lymphoma case was subsequently excluded. Thus, in the end, 23 cases were evaluated. Evaluation of the efficacy of therapy revealed complete remission in 20 patients (87%). Of these 20 patients, 8 were low-intermediate-risk cases (89%) and 12 were either high-intermediate- or high-risk cases (86%). Partial remission was achieved in 2 patients (8.7%). The 2-yr survival rate was 91.3%, and the 2-yr disease-free survival rate was 81.8%. Grade 3 or higher adverse reactions were granulocytopenia (87%), thrombocytopenia (17.4%) and liver dysfunction (4.3%). CyclOBEAP therapy has been associated with a high remission rate for aggressive NHL. When combined with G-CSF, a high relative dose intensity was maintained for each drug administered (0.94-0.97). Furthermore, although the observation period was short, both the survival rate and disease-free survival rate were good. Hence, we concluded that there were no problems associated with the procedure in terms of safety.

Predictive factors for central nervous system involvement in non-Hodgkin's lymphoma: significance of very high serum LDH concentrations.

Factors predictive for central nervous system (CNS) involvement at presentation were investigated in 152 patients with non-Hodgkin's lymphoma (NHL) except for lymphoblastic cell lymphoma and small noncleaved cell lymphoma. Twelve patients developed CNS involvement during their disease course. The incidence was 7.9% of all the patients studied and 17.0% of the patients with serum LDH concentration > or = two times the upper limit of normal (2N). By univariate analysis, stage IV disease (P = .023), a serum LDH concentration > or = 2 N (P = .009), and bone marrow involvement (P = .016) were risk factors for CNS involvement. Multivariate logistic regression analysis identified a serum LDH concentration > or = 2 N (P = .032) as an independent predictor for CNS involvement. All 12 patients who developed CNS involvement were among the 126 patients with diffuse lymphoma, whereas none of the 17 patients with follicular lymphoma developed CNS involvement, although the difference was not statistically significant. The median survival of the patients with CNS involvement was only 4.5 months. We conclude that a serum LDH concentration > or = 2N at presentation is a significant predictive factor for CNS involvement for NHL patients without lymphoblastic lymphoma and small noncleaved cell lymphoma. Therefore, we would suggest that CNS prophylaxis should be considered for patients with a serum LDH concentration > or = 2N at presentation and diffuse lymphoma once a complete remission is achieved.

Strong inverse correlation between serum TPO level and platelet count in essential thrombocythemia.

Serum thrombopoietin (TPO) levels in 50 essential thrombocythemia (ET) patients were measured using a highly sensitive sandwich ELISA. In nine cases, TPO levels were measured at two points with different platelet counts. ET patients showed significantly higher serum TPO levels (n = 59, 2.70 +/- 2.74 fmol/mL, P < 0.0001) than those of normal individuals (n = 29, 0.83 +/- 0.36 fmol/mL). Twenty-three previously untreated ET patients also showed significantly higher serum TPO levels (1.33 +/- 0.75 fmol/mL, P = 0.0066) than normal individuals. Extremely high serum TPO levels (5.46 +/- 3.68 fmol/mL) were observed in ET patients with normal platelet counts. Furthermore, a strong inverse correlation was found between serum TPO levels and platelet counts in ET patients (R = -0.729, P < 0. 0001). This inverse correlation also held for each of nine cases with two-point TPO measurements. In the clinical course of ET, megakaryocyte mass may parallel the platelet mass before and after chemotherapy. Although it is unknown whether overproduction of TPO exists or not in ET, total platelet and megakaryocyte mass, i.e., the total number of c-Mpl, may play a role to regulate serum TPO levels.

[Successful allogeneic bone marrow transplantation following fungal liver abscess treatment in a patient with chronic myeloid leukemia in blastic crisis].

A 40-year-old man was diagnosed as having chronic myeloid leukemia (CML) in December 1990 and received busulfan and hydroxyurea. He developed myeloid blast crisis in February 1996. After DCMP combination chemotherapy, his disease reverted to chronic phase, but right hypochondrial pain developed and low-grade fever persisted. Abdominal CT scan revealed multiple low-density areas in the liver, suggestive of abscess formation. Grocott staining of a liver biopsy sample revealed granuloma and fungus. The patient was treated with intravenous amphotericin B (AMPH-B) without success. AMPH-B was then administered via a catheter placed in the portal vein on January 6, 1997, and an additional catheter placed in the hepatic artery on March 28. AMPH-B was administered through both catheters for more than two months, but later substituted by fluconazole because of renal impairment. On September 10, allogeneic bone marrow transplantation from the patient's HLA-identical brother was performed, despite persistence of the abnormal CT findings. Acute grade III GVHD developed, but there was no evidence of reactivation of the liver abscesses. This case demonstrates that a prior fungal liver abscess is not an absolute contraindication for BMT if prophylactic antifungal drugs are administered and careful observation is conducted.

[Idiopathic mediastinal and subcutaneous emphysema in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation].

A 45-year-old man was diagnosed as having Ph1+ acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy. Allogeneic BMT from his HLA-identical sister was performed on June 11, 1997. Engraftment was relatively quick, but acute GVHD (grade I) developed. The patient was discharged on day 113. Seven months after BMT, in January 1998, exertional dyspnea developed gradually. Chest X-ray examination showed diffuse interstitial pneumonia, for which corticosteroid was started immediately. The symptoms and signs gradually improved. However, on the 20th hospital day (February 23), bilateral subcutaneous emphysema developed in the neck and supraclavicular region. Chest X-ray and CT examinations showed pneumomediastinum without pneumothorax. The pneumomediastinum and subcutaneous emphysema gradually subsided after 3 weeks of bed rest. Subcutaneous emphysema and pneumomediastinum are relatively rare complications of allogeneic BMT.

Discordant uptake of Tc-99m PMT and Tc-99m GSA by two hepatocellular carcinoma lesions.

Tc-99m PMT and Tc-99m GSA can be taken up by hepatocellular carcinoma (HCC), but there has been no report concerning HCC showing accumulation of both of Tc-99m PMT and Tc-99m GSA. In this paper we describe a case of two simultaneously developed HCCs, one of which took up both tracers but the other took up neither of them.

Improvement of quality of life after splenectomy in an HTLV-I carrier with T-cell prolymphocytic leukemia.

A 34-year-old woman of HTLV-I carrier with T-PLL, whose quality of life improved and survival was prolonged after splenectomy, is described. The patient had marked splenomegaly, generalized lymphadenopathy and marked proliferation of abnormal lymphocytes in the peripheral blood with an irregular nucleus, deeply basophilic cytoplasm and a single prominent nucleolus, which were positive for CD2, CD3, CD5, CD7, CD4 and CD8. Although the patient had serum antibody against HTLV-I, HTLV-I proviral DNA integration was not detected. She was diagnosed as an HTLV-I carrier with T-PLL and received combination chemotherapy and 15.1 Gy splenic irradiation. However, the generalized lymphadenopathy and splenomegaly did not improve. The patient underwent splenectomy to palliate abdominal distension and hypersplenism. After the operation, her symptoms improved dramatically and within a week her hemoglobin concentration and platelet count normalized. She was discharged from hospital two weeks after the splenectomy, however 11 months later, she relapsed and despite treatment with chemotherapy and alpha-interferon, she died two months after the second admission. Autopsy findings revealed that PLL cells had invaded the bone marrow, lymph nodes, liver, lungs, kidneys, uterus, ovaries and adrenal glands.

Fatal air embolism as a complication of CT-guided needle biopsy of the lung.

A CT-guided needle lung biopsy carries a risk of potential air embolization. We present a rare case of air embolization after this procedure. Postmortem CT revealed air in the cerebral arteries and the left ventricle. This complication is extremely rare; however, it becomes fatal when it happens. Several points to prevent this fatal complication are discussed.

Long-term liver function of recipients with hepatitis G virus infection after bone marrow transplantation.

To clarify the role of hepatitis G virus (HGV) infection in liver dysfunction following allogeneic BMT, we examined cryopreserved serum samples from 33 patients who had a history of blood transfusions before BMT and whose serum samples had been stored periodically, before BMT, on day 100, and thereafter for the presence of HGV-RNA and hepatitis C virus (HCV)-RNA by reverse transcription polymerase chain reaction. Nineteen patients (58%) out of 33 were positive for HGV-RNA before BMT and 10 for HCV-RNA. All patients positive for HCV-RNA were also positive for HGV-RNA. Patients were divided into three groups according to their viral status before BMT; namely, the G+C+ group (n = 10), the G+C- group (n = 9) and the G-C- group (n = 14). Two patients in the G-C- group became positive for HGV-RNA after BMT. One patient in the G+C- group suffered an acute exacerbation of hepatitis, with GPT levels reaching over 1000 IU/l, 2 and 3 years after BMT, showing quite a different clinical course from those in the G+C- group. Excluding these three patients, GPT levels of the patients in the G+C+ group were significantly higher after day 100 and remained higher than those of patients in the G+C- and G-C- groups for at least 4 years. There were no significant differences in post-transplant GPT levels between the G+C- group and the G-C- group at any time point. Of the seven patients followed-up for 5 to 10 years, three patients became HGV-RNA-negative, while four remained positive. In the absence of HCV co-infection, the behavior of GPT values post transplant in patients with HGV infection did not differ from those without HGV infection. With respect to the patient who was G+C- and showed high values of GPT 2 and 3 years post transplant, we suspect that his liver dysfunction might have been caused by some unknown virus or etiology.

Giant cell arteritis associated with rheumatoid arthritis monitored by magnetic resonance angiography.

A 57-year-old Japanese woman with well controlled rheumatoid arthritis visited our hospital with a severe bitemporal headache and marked fatigue. Based on the classification criteria by the American College of Rheumatology, she was diagnosed as having giant cell arteritis. Magnetic resonance (MR) angiography was performed, from which stenotic changes in the bilateral superficial temporal arteries were strongly suspected. Corticosteroid therapy was quickly started. The patient followed an uneventful course with no complications. Therapeutic effect was confirmed by MR angiographic findings obtained 4 weeks after the initiation of therapy.

Sufficient effect of 1-week omeprazole and amoxicillin dual treatment for Helicobacter pylori eradication in cytochrome P450 2C19 poor metabolizers.

Omeprazole is widely used for the treatment of Helicobacter pylori infection. It is metabolized by cytochrome P450 2C19 enzyme (CYP2C19) in the liver. Because this enzyme exhibits a genetic polymorphism, patients with low metabolic activity (poor metabolizers) may be exposed to higher concentrations of this drug than are patients who are extensive metabolizers. Eighty-six patients with cultured H. pylori-positive gastritis or peptic ulcers who completed the treatment and assessment of anti-H. pylori therapy were analyzed for CYP2C19 genotyping using a polymerase chain reaction-restriction fragment length polymorphism method [the wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both]. Patients were classified into three groups according to the H. pylori eradication regimen: group I (n = 21; omeprazole 40mg/ day and amoxicillin 2000mg/day for 1 week); group II (n = 21; group I regimen plus sucralfate 4000mg/day, for 1 week); group III (n = 44; group I regimen plus clarithromycin 800mg/day, for 1 week). The combination of two mutant alleles (ml/ml, ml/m2, m2/m2-poor metabolizers) was observed in 13 of 86 patients (15%), and all poor metabolizer patients achieved H. pylori eradication regardless of their treatment regimens. In addition, the eradication rates of the poor metabolizers were significantly higher than those of other genotypes who carry homozygous or heterozygous normal allele (extensive metabolizers) in group I or groups I and II combined. CYP2C19 genotyping can provide a new strategy to choose an optimal regimen, and this genotyping is especially useful for Japanese, as the frequency of poor metabolizers is five times greater than that found among Caucasians.

[Pulmonary function after allogeneic hematopoietic stem cell transplantation].

This study was undertaken to identify the factors influencing pulmonary function in patients who underwent hematopoietic stem cell transplantation (HCT). Pulmonary function tests were evaluated before and after HCT in 51 adult patients who underwent HCT between 1993 and 1998. The patients with hematologic malignancies were given total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Six patients suffered from acute GVHD above grade II and 27 patients suffered from chronic GVHD. The post-transplant % diffusing capacity (%DLco) 100 days after HCT was significantly lower than pretransplant values (82 +/- 21% versus 71 +/- 15%, p < 0.01). The %DLco at 100 days was significantly lower in patients with chronic GVHD than in patients without chronic GVHD (66 +/- 16% versus 77 +/- 9%, p < 0.05). These findings suggested chronic GVHD is related to the decreased %DLco values observed 100 days after HCT.

[Usefulness of CT-guided aspiration biopsy in combination with rapid cytology for diagnosis of benign pulmonary lesions].

PURPOSE: To evaluate the diagnostic accuracy of computed tomography (CT)-guided aspiration biopsy in combination with rapid cytology for benign pulmonary lesions. MATERIALS AND METHODS: We performed percutaneous aspiration biopsy under CT guidance in combination with a rapid cytologic examination in 91 patients with pulmonary lesions. A 21-gauge modified Menghini needle coaxially placed through an 18-gauge needle was used in this procedure. Thirty-one lesions that were confirmed as a benign pulmonary lesion histologically, serologically, bacteriologically and/or clinically were evaluated in this study. RESULTS: In 28(90.3%) of 31 lesions, sufficient material for cytologic diagnosis was obtained from the aspiration biopsy. Specific benign diagnosis for benign disease was obtained in 13 lesions (41.9%), while nonspecific diagnosis for benign disease was obtained in 15 lesions (48.4%). The overall accuracy of the rapid cytological examination was 90.3%. Pneumothorax developed in 17 patients (54.8%), with 7 patients (22.6%) requiring chest tube drainage. Only one patient complained of mild hemoptysis, which subsided with hemostatic agents. CONCLUSION: Percutaneous aspiration biopsy combined with a rapid cytologic diagnosis provides a high degree of accuracy in the diagnosis of benign pulmonary lesions.