Acute leukemia during pregnancy: an investigative survey of the past 11 years.

INTRODUCTION: The management of pregnant women with acute leukemia is usually challenging. We collected data concerning pregnant women with acute leukemia in the Kanagawa area in Japan. METHODS: A questionnaire was sent to 24 institutions in the Kanagawa area. RESULTS: Data were obtained for 11 patients, median age of 31 years (range, 20-36). Eight patients had acute myeloid leukemia and three had acute lymphoblastic leukemia. Six patients were diagnosed in the first trimester of pregnancy, one in the second trimester, and four in the third trimester. Five of six patients diagnosed in the first trimester had abortions before chemotherapy, and one had an elective abortion after receiving chemotherapy. All patients diagnosed in the second or third trimester delivered live infants. Of the six patients diagnosed in the first trimester, two died of recurrent leukemia, and four remained in remission. Of the five patients diagnosed in the second or third trimester, four achieved complete remission and remained in remission. One patient died of sepsis 4 days after cesarean section. CONCLUSIONS: Careful surveillance and monitoring of the fetus and close co-operation among hematologists, gynecologists, and pediatricians are essential to successfully treat pregnant women with acute leukemia.

Disseminated Cunninghamella bertholletiae infection with septic pulmonary embolism after allogeneic bone marrow transplantation.

Mucormycosis in immunocompromised patients is often reported. We report a patient who developed non-thrombotic pulmonary embolism due to Cunninghamella bertholletiae after allogeneic stem cell transplantation.

Development and validation of a tuberculosis prognostic score for smear-positive in-patients in Japan.

BACKGROUND: No scoring system has ever been used to estimate the prognosis of individual tuberculosis (TB) patients. OBJECTIVE: To develop and validate a tuberculosis prognostic score. METHODS: This retrospective cohort study conducted in Japan comprised the development (n = 179; mean age 65.9 ± 18.8 years) and validation (n = 244; mean age 64.3 ± 20.1 years) of a tuberculosis prognostic score among patients with newly diagnosed smear-positive non-multidrug-resistant pulmonary tuberculosis without human immunodeficiency virus infection. The score (raw score) was defined by modifying a logistic regression formula using known risk factors as independent variables and in-patient death as a dependent variable. RESULTS: The raw score was calculated as follows: age (years) + (oxygen requirement, 10 points) - 20 × albumin (g/dl) + (activity of daily living: independent, 0 point; semi-dependent, 5 points; totally dependent, 10 points). The raw scores were grouped into risk groups 1 (raw score < -30) to 5 (raw score ≥ 60) using 30-point intervals. Every increase in risk group was equivalent to a 7.3-fold increase in the odds ratio for in-hospital death (P < 0.001). The area under the receiver operating characteristics curve by risk group for in-patient death was 0.875 (P < 0.001). CONCLUSIONS: In this study we were able to develop and validate a tuberculosis prognostic score.

Simultaneous evaluation of long-lasting knee synovitis in patients undergoing arthroplasty by power Doppler ultrasonography and contrast-enhanced MRI in comparison with histopathology.

OBJECTIVES: We simultaneously assessed ultrasonography (US) and magnetic resonance imaging (MRI) in comparison with histopathological changes in the knee joints of long-lasting arthritis patients. METHODS: We studied 15 patients with rheumatoid arthritis and 5 patients with osteoarthritis, who underwent total knee arthroplasty. On the day before surgery, the joints were examined by US and contrast-enhanced MRI. In US, synovitis was graded with 0-3 grey scale (GSUS) and power Doppler (PDUS). In MRI, synovitis was graded according to OMERACT-RAMRIS (grade 0-3). Synovial tissue samples were obtained during arthroplasty and evaluated on the basis of inflammatory cell infiltrates (grade 0-3), synovial lining layer thickness (grade 0-3) and vascularity (grade 0-3). RESULTS: Positive findings of PDUS and contrast-enhanced MRI were 45% and 85% of 20 operated joints, respectively. GSUS, PDUS and MRI synovitis were well correlated with overall histopathological grades of synovitis (Spearman correlation coefficients 0.48, 0.84 and 0.48, p<0.05, p<0.01 and p<0.05, respectively). Moreover, positive PDUS findings were closely associated with all pathological comportments of synovitis including inflammatory cell infiltrates, synovial lining layer thickness and vascularity. CONCLUSIONS: The present study revealed that positive PDUS findings more faithfully illustrated active synovitis than MRI, whereas contrast-enhanced MRI was more sensitive in detecting synovitis in patients with long-lasting arthritis. It is important to understand distinct features of the both modalities for clinical assessment of chronic joint diseases.

Myeloablative hematopoietic stem cell transplantation for myelodysplastic syndrome in patients younger than 55 years: impact of comorbidity and disease burden on the long-term outcome.

We retrospectively investigated 31 myelodysplastic syndrome (MDS) patients receiving myeloablative hematopoietic stem cell transplantation (HCT) and focused on prognostic factors affecting the long-term outcome. Patients were classified according to the French-American-British classification and the HCT-comorbidity index was determined. Cytosine arabinoside or thiotepa combined with cyclophosphamide and total body irradiation was used as myeloablative conditioning in eight and 23 patients respectively. After a follow-up period of 0.8-14.2 years from transplantation (median: 6.4 years), 23 patients were alive in complete remission, and the 5-year overall survival (OS) and disease-free survival (DFS) rates were 79% and 72% respectively. The cumulative nonrelapse mortality (NRM) rate was 22% at 5 years. According to multivariate analysis, > or =20% blasts in the bone marrow and an HCT-comorbidity score > or = 3 were significantly associated with poor OS and DFS. Patients with a high HCT-comorbidity score and male patients receiving transplantation from female donors were significantly more likely to have a higher NRM according to the univariate, but not the multivariate analysis. These data suggest that comorbidity and the tumor burden at the time of transplantation may be useful variables for predicting the outcome in MDS patients receiving myeloablative HCT.

Mycobacterium tuberculosis-specific immunospot assay of pleural exudate mononuclear cells is useful for the exclusion of tuberculous pleuritis in patients with lupus pleuritis.

It is often difficult to make a diagnosis of pleuritis associated with rheumatic diseases because of lack of specific diagnostic tools. We report a patient with lupus pleuritis from which tuberculous pleuritis was distinguished by Mycobacterium tuberculosis-specific enzyme-linked immunospot assay of pleural exudate mononuclear cells. After the diagnosis of lupus pleuritis, the patient was successfully treated with prednisolone.

Outcomes after switching from one bisphosphonate to another in 146 patients at a single university hospital.

UNLABELLED: Most patients who switched to a second bisphosphonate continued their treatment long term, although those who stopped their first drug because of adverse events were likely to discontinue the second drug for the same reason. Switching to another bisphosphonate is a reasonable treatment option for some patients with treatment failure. INTRODUCTION: Patients who experience treatment failure with a bisphosphonate because of adverse events (AEs) or other reasons might receive a second bisphosphonate. However, the frequency and benefits of switching bisphosphonates are unknown. METHODS: We retrospectively evaluated 197 men and 1110 women newly treated with bisphosphonates between 1 January 2000 and 30 June 2005 at our university hospital. RESULTS: Among the 497 patients who discontinued bisphosphonate treatment, 146 were switched to a second bisphosphonate. The cumulative probabilities of persistence of treatment after 3 years were 45% with the first bisphosphonate and 65% with the second (P = 0.017). Age >or=65 years, switching bisphosphonates because of AEs, and male gender were associated (P < 0.05) with low persistence of treatment with the second bisphosphonate. Discontinuation of the first drug because of AEs was associated with an increased rate of discontinuation of the second drug because of AEs (hazard ratio, 4.2; 95% confidence interval, 2.1-8.4). CONCLUSIONS: Patients who switched bisphosphonates had high rates of persistence of therapy. Those who stopped their first bisphosphonate because of AEs were at risk of discontinuing the second drug for the same reason. Switching to another bisphosphonate is a reasonable treatment option for some patients with treatment failure.

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.

Persistence with bisphosphonate therapy including treatment courses with multiple sequential bisphosphonates in the real world.

UNLABELLED: The real cumulative persistence probabilities with bisphosphonates after 5 years was 51.7%. Prescriptions by specialists other than gynecologists and rheumatologists (p < 0.001), male sex (p < 0.001), older age (> or =65 years) (p = 0.001), and cyclical etidronate (p < 0.001) were significantly associated with low persistence. Success rates of switching bisphosphonate were 75.6%. INTRODUCTION: Many patients discontinue daily bisphosphonate therapy prematurely due to the stringent dosing procedures and adverse events. Consequently, some patients are receiving two or more sequential bisphosphonates in daily practice. Our objective was to study factors associated with the real cumulative persistence with bisphosphonate therapy including treatment courses with multiple sequential drugs in the real world setting. METHODS: We retrospectively analyzed 1,307 patients (male 197, female 1110) newly prescribed with bisphosphonates between January 1, 2000, and June 30, 2005. RESULTS: The real cumulative persistence probabilities with bisphosphonates after 1, 3, and 5 years were 74.8%, 60.6%, and 51.7%, respectively. Switching of bisphosphonates was observed 168 times in 146 patients. Adverse events occurred 126 times in 124 patients including 86 events with gastrointestinal complaints. Univariate analysis showed that prescriptions by specialists other than gynecologists and rheumatologists (p < 0.001), male sex (p < 0.001), older age (> or =65 years) (p = 0.001), and cyclical etidronate (p < 0.001) were significantly associated with low persistence. Success rates of switching bisphosphonate were 75.6%. CONCLUSIONS: Switching of bisphosphonates was not uncommon. Despite switching bisphosphonates to improve persistence, the real cumulative persistence with bisphosphonate was suboptimal, especially among patients of certain physician specialties and male sex.

Catastrophic antiphospholipid syndrome associated with malignancies (case report and review of the literature).

We describe a 58-year old female patient with rapid development of arterial and venous thromboembolisms, including deep vein thrombosis (DVT) in the lower limbs, recurrent cerebral infarctions and bilateral pulmonary emboli. Her laboratory data on admission showed positive anticardiolipin antibody of IgG isotype (IgG aCL) and positive anti-beta2 glycoprotein-I antibody of IgG isotype (IgG abeta2-GPI), and decreased protein C activity and protein S antigen. Systemic examinations revealed the presence of an ovarian cancer. Surgical resection was attempted, but her cancer infiltrated the pelvic wall and could not be resected. Despite treatment with unfractionated heparin followed by warfarin, she died due to recurrent episodes of cerebral infarction. This case was considered as probable catastrophic antiphospholipid syndrome (CAPS), which might be associated with ovarian cancer. Known as Trousseau's syndrome, arterial and, more commonly, venous thrombosis is a frequent complication of cancer and sometimes a harbinger of occult cancer. Our case indicates that there is an overlap between antiphospholipid syndrome (APS) and Trousseau's syndrome. It is important to bear in mind that a thrombotic event associated with cancer can be the first manifestation of CAPS.

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.

Heme oxygenase-1 inhibits cigarette smoke-induced increase in the tracheal mucosal permeability in guinea pigs in vivo.

OBJECTIVE: To examine whether heme oxygenase (HO)-1 inhibits cigarette smoke (CS)-induced increase in the airway mucosal permeability. METHODS: Mucosal permeability was quantified by monitoring the rate of appearance in the circulation of horseradish peroxidase that had been instilled into the isolated tracheal segment in guinea pigs in vivo, after exposure to CS or room air. RESULTS: Exposure to 10 puffs of CS did not increase the tracheal mucosal permeability but did increase the permeability after pretreatment with zinc protoporphyrin, a competitive inhibitor of HO-1. Moreover, pretreatment with hemin, a potent inducer of HO-1, inhibited the increase in the permeability of the tracheal mucosa induced by 20 puffs of CS exposure. CONCLUSION: It is concluded that HO-1 has an important role in suppressing the increase in the mucosal permeability induced by CS in guinea pig trachea.