Evaluation of Inhaled Procaterol for Potential Assist Use in Patients with Stable Chronic Obstructive Pulmonary Disease.

OBJECTIVES: International guidelines recommend the use of long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease (COPD), but the usefulness of short-acting bronchodilator assist use for stable COPD remains uncertain. The purpose of the present study was to objectively demonstrate the effects of assist use of procaterol, a short-acting ß2-agonist, on the respiratory mechanics of stable COPD patients treated with a long-acting bronchodilator using forced oscillation technique (FOT) and conventional spirometry. We also confirmed the length of time for which procaterol assist could significantly improve the pulmonary function. METHODS: We enrolled 28 outpatients with mild to severe COPD (Global Initiative for Obstructive Lung Disease stages I-III), who had used the same long-acting bronchodilator for longer than 3 months and who were in stable condition. All measures were performed using both FOT and spirometry sequentially from 15 min to 2 h after inhalation. RESULTS: Compared to baseline, inhaled procaterol assist use modestly but significantly improved spirometric and FOT measurements within 2 h after inhalation. These significant effects continued for at least 2 h. -Significant correlations were found between parameters -measured by spirometry and those measured by FOT. CONCLUSIONS: Procaterol assist use modestly but significantly improved pulmonary function determined by spirometry and respiratory mechanics in patients with stable COPD treated with long-acting bronchodilators. Thus, inhaled procaterol has the potential for assist use for COPD.

[A CASE OF PULMONARY MYCOBACTERIUM ABSCESSUS INFECTION THAT DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY FOR MYASTHENIA GRAVIS WITH RECURRENT THYMOMA].

A 58-year-old man developed cough, sputum, and low-grade fever during immunosuppressive treatment with corticosteroids and cyclosporine for myasthenia gravis with recurrent thymoma. Since chest CT revealed diffuse nodular opacities in both lung fields, he was referred to our department. Mycobacterium abscessus was repeatedly cultured from his sputum, and he was diagnosed with pulmonary M. abscessus infection. Although both chest radiological findings and clinical symptoms were mild, he required treatment with immunosuppressive agents and systemic anesthesia for resection of the recurrent thymoma. Based on complications and according to the patient's preference, oral treatment with clarithromycin 600 mg/day, levofloxacin 500 mg/day, and faropenem 600 mg/day was initiated on an outpatient basis. Following these treatments, his chest CT findings and clinical symptoms subsided, and the thymoma was successfully resected. Our experience with the present case suggests a possible treatment strategy for M. abscessus infection in immunocompromised and complicated cases.

European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients.

The Sokal and Hasford scores were developed in the chemotherapy and interferon era and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS) scoring system was developed. We performed a multicenter retrospective study to validate the effectiveness of each of the three scoring systems. The study cohort included 145 patients diagnosed with CML in chronic phase who were treated with imatinib. In the EUTOS low- and high-risk groups, the cumulative incidence of complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (P = 0.797) and the 5-year overall survival rate was 92.6% and 93.3% (P = 0.871), respectively. The cumulative incidence of CCyR at 12 months, 5-year event-free survival and 5-year progression-free survival were not predicted using the EUTOS scoring system. However, there were significant differences in both the Sokal score and Hasford score risk groups. In our retrospective validation study, the EUTOS score did not predict the prognosis of patients with CML in chronic phase treated with imatinib.

[Fatal nontuberculous mycobacterial lung disease caused by Mycobacterium kyorinense: a case report with five years of follow-up].

An 85-year-old man with dementia first visited our hospital 5 years ago, complaining of hemoptysis. He was hospitalized 2 years later owing to fever, cough, and dyspnea. A chest computed tomography scan showed infiltration with a cavity in the left upper lobe. He was diagnosed with nontuberculous mycobacterial lung infection on the basis of the presence of acid-fast bacilli in the sputum and repeated bronchoalveolar lavage specimens; however, we were unable to identify the isolate by DNA-DNA hybridization. Although his general condition had slightly improved after treatment initiation, intermittent chemotherapy owing to the adverse effects of the drugs and dementia led to rapid disease progression and death. After his death, the isolated mycobacterium was identified as Mycobacterium kyorinense by sequence analysis of the hsp 65 and rpoB genes.

R-CHOP therapy alone in limited stage diffuse large B-cell lymphoma.

Long-term observation has identified a pattern of continuing relapse in limited stage diffuse large B-cell lymphoma (DLBCL) treated by three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved-field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R-CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the 'standard' strategy of three cycles of R-CHOP followed by involved-field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R-CHOP alone.

Successful treatment with lenalidomide for relapsed adult T-cell leukemia/lymphoma after cord blood cell transplantation.

The prognosis for relapsed adult T-cell leukemia/lymphoma (ATL) after allogeneic hematopoietic stem cell transplantation is poor. Here, we report the case of a 67-year-old man who survived for 26 months after treatment with lenalidomide for post-transplant relapsed ATL. He underwent induction therapy with two cycles of modified VCAP-AMP-VECP and achieved complete remission. He received cord blood cell transplantation following a reduced-intensity conditioning regimen. Seven months after transplantation, swelling of the systemic lymph nodes appeared, and relapsed ATL was diagnosed based on a biopsy of the cervical lymph node. Treatment with 10 mg of lenalidomide induced partial remission. At 18 months after transplantation, skin tumors were successfully treated by increasing the dose of lenalidomide to 15 mg with the emergence of skin graft-versus-host disease. Although he died from ATL at 34 months after transplantation, systemic relapsed lesions were controlled by treatment with lenalidomide for 26 months. Our case suggests that lenalidomide is well tolerated and is an effective option for the treatment of post-transplant relapsed ATL.

Primary uterine lymphoma: The Yokohama Cooperative Study Group for Hematology (YACHT) study.

AIM: Primary malignant lymphomas arising from the female genital tract are very rare, with an incidence rate of 0.5%. Because of its rarity, its clinical characteristics, prognosis and optimal treatment are still unclear. Here, we retrospectively evaluated female patients with uterine lymphoma. METHODS: Between January 2000 and October 2016, 4362 patients were newly diagnosed with malignant lymphoma by the participating institutions of YACHT. Among these 4362 patients, we retrospectively evaluated 14 adult patients with primary uterine lymphoma. RESULTS: The median follow up time was 41 months. The median age at diagnosis was 68 years. Of 14 patients, 10 (72%) were diagnosed with diffuse large B-cell lymphoma. Seven patients presented with vaginal bleeding and three with abdominal pain. Eleven patients (79%) had advanced stages at diagnosis. Three patients (21%) had ovarian involvement and 2 (14%) had vaginal involvement. Induction chemotherapy regimens were R-CHOP in seven patients (50%), CHOP in three (21%) and other regimens in four (29%). Among 14 patients, 12 patients (86%) achieved a complete response and 2 (14%) experienced disease progression. Three patients (21%) showed relapse. Five patients (36%) died because of malignant lymphoma. The 3-year overall survival rate was 57.9%. Soluble interleukin-2 receptor levels > 5000 U/mL, anemia, a bulky mass and the presence of > 1 extranodal sites, B symptom at diagnosis were associated with a poor prognosis. CONCLUSION: Female genital lymphoma is very rare, and further study of more cases is warranted.

Analysis of predictive parameters for the development of radiation-induced pneumonitis.

INTRODUCTION: Prevention and effective treatment of radiation-induced pneumonitis (RP) could facilitate greater use of radiation therapy (RT) for lung cancer. The purpose of this study was to determine clinical parameters useful for early prediction of RP. METHODS: Blood sampling, pulmonary function testing, chest computed tomography, and bronchoalveolar lavage (BAL) were performed in patients with pathologically confirmed lung cancer who had completed ≥60 Gy of RT, at baseline, shortly after RT, and at 1 month posttreatment. RESULTS: By 3 months post-RT, 11 patients developed RP (RP group) and the remaining 11 patients did not (NRP group). RT significantly increased total cell counts and alveolar macrophages in BAL of the NRP group, whereas lymphocyte count was increased in both groups. Matrix metallopeptidase-9 (MMP-9) increased and vascular endothelial growth factor decreased significantly in the BAL fluid (BALF) of the RP group following RT. Serum surfactant protein D (SP-D) increased significantly in the NRP group. SP-D in BALF from the RP group increased significantly with a subsequent increase in serum SP-D. Pulmonary dilution decreased similarly in both groups of patients. CONCLUSIONS: Increased SP-D in BALF, rather than that in serum, could be useful biomarkers in predicting RP. The MMP-9 in BALF might play a role in the pathogenesis of RP. Pulmonary dilution test may not be predictive of the development of RP.

Successful pregnancy and delivery via in vitro fertilization with cryopreserved and thawed embryo transfer in an acute myeloid leukemia patient after allogeneic bone marrow transplantation.

As the number of young long-term survivors of hematopoietic stem cell transplantation (HSCT) for acute leukemia continues to increase, post-transplant infertility is becoming a significant concern. HSCT, particularly with cyclophosphamide and total body irradiation conditioning, is known to cause secondary premature ovarian failure, resulting in infertility. To preserve post-transplant fertility, several methods have been proposed, including in vitro fertilization (IVF) with embryo cryopreservation. Due to the aggressiveness of acute leukemia, however, patients have little chance to undergo egg harvesting and IVF before they must begin receiving chemotherapy. To the best of our knowledge, there have been no detailed reports of successful pregnancy after HSCT using IVF with embryo cryopreservation and transfer in a patient with acute myeloid leukemia. Here, we report the case of a 42-year-old woman with acute myeloid leukemia who became pregnant 2 years and 2 months after allogeneic bone marrow transplantation via IVF-embryo transfer with an egg collected after induction therapy and delivered a full-term healthy infant.

Intrathecal methotrexate prophylaxis and central nervous system relapse in patients with diffuse large B-cell lymphoma following rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone.

This study evaluated the efficacy of central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX) in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively studied 322 patients who achieved first complete remission (CR) after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The CNS prophylaxis consisted of four doses of IT-MTX (15 mg) with hydrocortisone (25 mg) administered after CR was achieved. Forty patients (12%) received CNS prophylaxis (group A) and 282 patients (88%) did not (group B). Three patients in group A (8%) and eight in group B (3%) experienced isolated CNS relapse during the first CR, although this difference was not statistically significant (p = 0.14). Ten of 11 CNS relapses occurred in the brain parenchyma with (n = 3) or without (n = 7) leptomeningeal involvement, and the remaining patient had exclusive leptomeningeal involvement. In patients with DLBCL attaining CR after R-CHOP, IT-MTX administration was insufficient to prevent CNS relapse.

Successful treatment of a patient with adult T cell leukemia/lymphoma using anti-CC chemokine receptor 4 monoclonal antibody mogamulizumab followed by allogeneic hematopoietic stem cell transplantation.

Adult T cell leukemia/lymphoma (ATLL) is an aggressive peripheral T cell neoplasm caused by human T cell lymphotropic/leukemia virus type-1 and has a poor prognosis. A new anti-CC chemokine receptor 4 monoclonal antibody (mogamulizumab) has been shown to be effective for ATLL. Although mogamulizumab is now available in Japan for patients with ATLL, the influence on allogeneic hematopoietic stem cell transplantation (HSCT) remains unclear. Here we report a woman with ATLL resistant to combination chemotherapy, who achieved complete remission following treatment with mogamulizumab and subsequently received allogeneic HSCT. The patient has remained in complete remission with controlled graft-versus-host disease. To our knowledge, this is the first report of an ATLL patient who received mogamulizumab treatment followed by allogeneic HSCT. We suggest that administration of mogamulizumab to chemotherapy-resistant patients with ATLL may improve their disease status before allogeneic HSCT and result in better survival.

Absolute monocyte count in follicular lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Elevated absolute monocyte counts (AMCs) have been reported to indicate poor prognosis for patients with lymphoproliferative disease, including those with follicular lymphoma (FL) receiving various treatments. We evaluated the prognostic impact of AMC in 150 consecutive FL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Progression-free survival (PFS) did not differ significantly according to the AMC level. Univariate and multivariate analyses did not indicate a prognostic significance of AMC for PFS. Thus, the AMC is not a prognostic factor for FL patients treated with R-CHOP. However, immunochemotherapy might influence the prognostic impact of AMC.

Standard R-CHOP therapy in follicular lymphoma and diffuse large B-cell lymphoma.

The introduction of rituximab (R) has measurably improved the outcome of patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). To evaluate the outcome of patients with FL and DLBCL under R plus CHOP therapy, we performed a retrospective analysis in Yokohama City University Hematology Group in Japan. Five hundred and twenty-six patients (158, FL ; 368, DLBCL) were scheduled to undergo primary therapy with 6 cycles of full-dose R-CHOP therapy with curative intent. The median observation periods in living patients with FL and DLBCL were 45 months and 43 months, respectively. The complete response, 5-year progression-free survival (PFS), and 5-year overall survival (OS) rates were 86%, 50%, and 92% in the FL group, and 89%, 72%, and 80% in the DLBCL group, respectively. Although PFS was significantly better in the DLBCL group than in the FL group, OS was significantly better in FL patients. We also found that the OS and PFS of grade 3 FL patients were not statistically different from those with grade 1-2. These findings indicate that all grades of FL should be categorized simply as "FL" with regard to R-CHOP therapy. Our results also demonstrate the incurability of FL (grade 1-3B), even with R-CHOP therapy.