[Haploidentical stem cell transplantation for acute myeloid leukemia associated with adult-onset Shwachman-Diamond syndrome].

A 21-year-old man presented with bone marrow failure, short stature, fatty degeneration of the pancreas on CT images, and Shwachman-Bodian-Diamond syndrome (SBDS) gene abnormalities (exon 2: c.258+2T>C and deletion of exon 3). Thus, the patient was diagnosed with Shwachman-Diamond syndrome (SDS). In the clinical course, the patient developed acute myeloid leukemia (AML). Hematopoietic stem cell transplantation from the human-leukocytic-antigen-haploidentical father of the patient was performed. The patient was conditioned with 150 mg/m2 fludarabine, 6.4 mg/kg busulfan, and 4 Gy total body irradiation. Graft-versus-host disease prophylaxis included tacrolimus, micophenolate mofetil, and posttransplant cyclophosphamide. Although the patient achieved a complete remission on day 21, AML relapsed on day 434 after the transplantation. He died of sepsis. The prognosis of patients with SDS and AML is poor. Adult-onset cases must be recognized, and transplantation should be performed during bone marrow failure.

Relapsing Infectious Mononucleosis-Like Symptoms Associated with Liver Insufficiency in a Chronic Hepatitis B Patient with Common Variable Immunodeficiency.

BACKGROUND Common variable immunodeficiency (CVID) is a rare disease. Infectious mononucleosis-like symptoms due to Epstein-Barr virus reactivation in adulthood are also rare. Here, we aimed to report a case of Epstein-Barr virus reactivation presenting with relapsing infectious mononucleosis-like symptoms with liver failure in common variable immunodeficiency with chronic hepatitis B virus infection. CASE REPORT A 36-year-old Japanese woman with chronic hepatitis B virus infection developed relapsing fever, lymphadenopathy with marked splenomegaly, and ascites 6 months after treatment with propagermanium, a nonspecific immune modulator, and subsequent treatment with entecavir and pegylated interferon sequential therapy. Although the hepatitis B virus load was controlled, Epstein-Barr virus deoxyribose nucleic acid was detected in her serum. Seven months later, her symptoms improved following corticosteroid treatment. Prior to sequential therapy, she developed pneumonia 4 times in 2 months and exhibited consistent hypoimmunoglobulinemia before corticosteroid treatment. Further examinations showed low amounts of switched memory B cells, and absence or barely detectable levels of isohemagglutinins. Subsequently, she was diagnosed with common variable immunodeficiency. CONCLUSIONS Epstein-Barr virus reactivation with relapsing infectious mononucleosis-like symptoms can occur following immune modulation therapy in patients with common variable immunodeficiency, and this can affect the patient's primary disease. Therefore, immunoglobulin screening along with the consideration of CVID in all patients is required before immune modulation therapy is planned.

Efficacy of Recombinant Human Soluble Thrombomodulin in Treating Disseminated Intravascular Coagulation Complicating Allogeneic Hematopoietic Stem Cell Transplantation.

The prognosis for patients who experience hemostatic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. However, no report has investigated disseminated intravascular coagulation (DIC) caused by the complications of allo-HSCT without infection. Recombinant human soluble thrombomodulin (rhTM) was used to treat 12 episodes of DIC (n = 10; group 1) caused by allo-HSCT complications such as acute graft-versus-host disease (aGVHD) or thrombotic microangiopathy (TMA), and the clinical outcomes were compared with those of historical controls (n = 9; group 2) treated for DIC without rhTM. In group 1, the mean DIC score was significantly improved after using rhTM. Fibrinogen degeneration product (FDP), C-reactive protein (CRP), and the inflammatory cytokine high-mobility group box 1 (HMGB1) were also significantly decreased. Serial changes from the baseline values of platelet counts and levels of FDP were significantly better in group 1 than in group 2. The recovery rate from DIC was significantly higher in group 1 than in group 2. These findings suggest that rhTM is effective against both DIC and systemic inflammatory complications after allo-HSCT.

General Anesthetic Management of a Patient With Hypertrophic Cardiomyopathy for Oral Surgery: Did Digitalis Contribute to Bradycardia?

Stabilization of circulatory dynamics is a critical issue in the anesthetic management of patients with hypertrophic cardiomyopathy (HCM). In this report, we managed general anesthesia for a 74-year-old male patient with nonobstructive HCM who developed circulatory instability intraoperatively. Severe bradycardia measuring 35 beats/min and hypotension measuring 78 mm Hg systolic were observed during surgery. Using stroke volume variation and stroke volume from the FloTrac as indices, successful circulatory management was performed with dopamine. The hypotension and bradycardia were thought to be the result of methyldigoxin and possibly associated with our perioperative management. Cardiology consult should have been obtained. We demonstrated that the FloTrac can be beneficial in diagnosing and managing cardiovascular instability and administration of dopamine in the anesthetic management of nonobstructive HCM patients.

Severe de novo Hepatitis B Recovered from Late-Onset Liver Insufficiency with Prolonged Ascites and Hypoalbuminemia due to Hepatitis B Virus Genotype Bj with Precore Mutation.

De novo hepatitis B is associated with a high risk of hepatic failure often resulting in fatal fulminant hepatitis even when nucleotide analogues are administered. A 77-year-old female developed de novo hepatitis B after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) treatment for diffuse large B-cell lymphoma. Hepatitis B virus (HBV) isolated from the patient was of genotype Bj, with a precore mutation (G1896A) exhibiting an extremely high viral load at the onset of hepatitis. She showed markedly high levels of transaminase with mild jaundice on admission and rapid decrease of prothrombin activity after admission. Although acute liver failure was averted by the administration of entecavir and corticosteroid pulse therapy, liver volume decreased to 860 ml, and marked hypoalbuminemia accompanying massive ascites occurred 2 months after the onset of hepatitis and persisted for 3 months with high levels of HBV DNA and mild abnormal alanine aminotransferase levels. Frequent infusions of albumin solution, nutrition support, and alleviation therapy showed limited effect. However, overall improvement along with HBV DNA reduction was observed after increasing the dose of entecavir and completion of prednisolone that was administered with a minimum dose for adrenal insufficiency. An immediate and sufficient suppression of virus replication with potent antiviral therapy is critical, particularly in patients infected with HBV precore mutation (G1896A) and/or Bj genotype, which may have a high viral replication and direct hepatocellular damage.

Evaluation of care for leukemia and lymphoma patients during their last hospitalization from the perspective of the bereaved family.

We aimed to evaluate care for leukemia and lymphoma patients during their last hospitalization from the perspective of the bereaved family. Questionnaires were sent to the bereaved family members of adult leukemia and lymphoma patients. We used the Care Evaluation Scale (CES) and asked the bereaved family members about care satisfaction and "good death" factors during the patient's last week of life or last admission period. We distributed 177 questionnaires and were able to analyze 103 (58.2%) responses. Compared with the results of a previous study of palliative care units in Japan, the CES scores were significantly lower in 9 out of 10 domains. Assessment of the "good death" components revealed that only 33% of respondents agreed that the patient had been relieved as far as possible of pain and physical distress during the last week of life. Only 21.4% of respondents agreed that the patient had been relieved as far as possible of psychological distress, and 57% of caregivers were not satisfied with the level of care. During the last hospitalizations of leukemia or lymphoma patients, their care was insufficient and a good death was not often achieved. Improvement of end-of-life care for leukemia and lymphoma patients is needed.

Prognosis of patients with core binding factor acute myeloid leukemia after first relapse.

Core binding factor acute myeloid leukemia is known to have a favorable prognosis, however, there have been no detailed analyses on prognostic factors after first relapse. Using a nationwide database, we retrospectively analyzed core binding factor acute myeloid leukemia patients who relapsed after being treated with chemotherapy alone during their first complete remission. Of a total of 397 patients who were diagnosed with core binding factor acute myeloid leukemia, 208 experienced a first relapse, and analyses were performed in 139 patients for whom additional data were available. In the entire cohort, the overall survival rate after relapse was 48% at 3 years. By multivariate analysis, younger age at diagnosis, a longer interval before relapse, and inv(16) were shown to be independently associated with better survival after relapse. Although there was no significant difference in survival after relapse between patients who underwent allogeneic hematopoietic cell transplantation and those who did not in the overall series of relapsed patients, we found that transplantation significantly improved survival among patients who had t(8;21) (54% versus 26% at 3 years, P=0.002). In addition, among patients with t(8;21), those who had different cytogenetics at relapse had a significantly improved survival after transplantation, while those who had same cytogenetics did not. We showed that the prognosis differs significantly and optimal treatment strategies may vary between groups of patients with core binding factor acute myeloid leukemia with different cytogenetic profiles at relapse. These findings may help to guide therapeutic decisions after first relapse.

Comparison of allogeneic hematopoietic cell transplantation and chemotherapy in elderly patients with non-M3 acute myelogenous leukemia in first complete remission.

The benefits of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with acute myelogenous leukemia (AML) in first complete remission (CR1) have mostly been evaluated in younger patients. Although favorable outcomes of allo-HCT over chemotherapy have been reported with the use of reduced-intensity conditioning (RIC) regimens in elderly patients with AML in CR1, information is still limited, especially on the effects of cytogenetic risks and donor sources. We collected data from AML patients aged 50 to 70 years who achieved CR1, and compared the outcome in 152 patients who underwent allo-HCT in CR1 (HCT group) to that in 884 patients who were treated with chemotherapy (CTx group). The cumulative incidence of relapse in the HCT group was significantly lower than that in the CTx group (22% versus 62%). Both overall survival (OS) and relapse-free survival (RFS) were significantly improved in the HCT group (OS: 62% versus 51%, P = .012), not only in the whole population, but also in the intermediate-risk group. Among patients who had a suitable related donor, the outcomes in the HCT group were significantly better than those in the CTx group. The introduction of appropriate treatment strategies that include allo-HCT may improve the outcome in elderly patients with AML in CR1.

[Case of pulmonary MALT lymphoma with follow-up imaging for 10 years].

Although abnormal shadow in the left upper lung of an 84-year-old male patient was confirmed in an examination in November 1996, follow-up observation was discontinued. In July 2006, he first visited our department with a chief complaint of shortness of breath, and was hospitalized because of an abnormal shadow in the left upper lung field and left pleural effusion. Since atypical lymphocytes were found in the pleural effusion, and positive cellular surface markers CD19 and 20, and chromosomal aberration of t (11 ; 18) (q22 ; q21) were confirmed, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was diagnosed. Transbronchial lung biopsy of the left upper lobe confirmed small lymphocyte-like cellular infiltration, as seen in the pleural effusion, and CD20 immunostaining was positive, leading to the diagnosis of MALT lymphoma. In addition, serum immunoelectrophoresis demonstrated the development of macroglobulinemia as a complication. This case is valuable as changes diagnostic image over 10 years can be compared.