[Successful detection of MYD88 L265P mutation in Waldenström's macroglobulinemia complicated with myelofibrosis using highly sensitive digital PCR].

A 78-year-old man with anemia (Hb 9.6 g/dl) and elevated serum immunoglobulin M (IgM 3,577 mg/dl) levels was referred to our hospital. Bone marrow aspiration yielded a dry tap, and bone marrow biopsy revealed the infiltration of CD20 positive lymphoplasmacytic lymphoma cells and myelofibrosis. The patient was diagnosed with Waldenström's macroglobulinemia complicated with myelofibrosis. TGF-ß plasma concentration was elevated. Further, after chemotherapy with bendamustine and rituximab, remission of both Waldenström's macroglobulinemia and myelofibrosis was achieved, and TGF-ß levels normalized. MYD88 L265P mutation was detected using highly sensitive digital PCR, which compared with currently used direct PCR product sequencing, has a superior sensitivity. The use of digital PCR has additional advantages toward MYD88 L265P detection, particularly when the available amount of sample DNA is limited owing to myelofibrosis.

[Drug resistance of Pseudomonas aeruginosa in four community hospitals: influence of antimicrobial use density].

We investigated the relation between hospital antimirobial use density (AUD) and minimum inhibitory concentrations (MIC) for Pseudomonas aeruginosa in four community hospitals. Subjects were a total of 476 strains isolated from urine, sputum, and pus during a total of seven years since 2002, for which 50- and 90-percentile MICs were analyzed. Hospitals A, B, and C moved in 2000, 2005, and 2009, respectively, but MIC50 and MIC90 were stable. MIC values showed significance in five drugs, in which Hospital B showed maximal values in five and Hospital D showed minimal values in four drugs. AUD values were different in nine drugs, Hospital B showing the highest data in meropenem, flomoxef, and sulbactam/cefoperazone while Hospital D having the lowest data in meropenem, ceftazidime, cefotaxime, and sulbactam/cefoperazone. Thus MIC for P aeruginosa may show resistance in the presence of high AUD with wide antimicrobial spectrum.

The consequences of tacrolimus blood concentrations during the four weeks following marrow transplantation from an unrelated donor: a single-center experience.

In our institute, tacrolimus was started at a dose of 0.03 mg/kg/day and adjusted to maintain a blood concentration between 10 and 20 ng/mL combined with short term methotrexate after bone marrow transplantation from an unrelated donor. Dose adjustment was performed strictly, in order to prevent grade II-IV acute graft-versus-host disease (GVHD)while avoiding renal toxicity of tacrolimus. Then, in this study, we retrospectively evaluated the tacrolimus blood concentration during the first 4 weeks after transplantation. The mean tacrolimus concentration of the eligible 52 patients was 17.41+/-4.84(range, 9.5-33.4)ng/mL in the 1st week after transplantation, but declined to 13.7+/- 4.0(range, 8.1-25.6)ng/mL in the 2nd week. The dose of tacrolimus was decreased as follows: 0.022+/-0.005 mg/ kg/day(range 0.011-0.039)in the 1st week, and 0.018+/-0.007 mg/kg/day(range 0.004-0.040)in the 2nd week. The incidence of grade II-IV GVHD was 63.0% and grade III-IV was 13.9%. The individual variations of tacrolimus blood concentration did not affect the incidence of grade II-IV acute GVHD, as far as the concentration being maintained in the range of 14.82+/-4.22 ng/mL during the first 4 weeks after transplantation. In addition, the variations of tacrolimus concentration didn?t associate statistically with renal toxicity.

Successful stem cell transplantation without cryopreservation from a microchimeric haploidentical sibling for refractory acute myeloid leukemia complicated with critical thrombophlebitis and cellulitis.

We describe the case of a 38-year-old male patient who had acute myeloid leukemia and developed prolonged neutropenia after induction chemotherapy. He developed thrombotic complications at multiple sites. Thrombophlebitis of the hemorrhoidal plexus became exacerbated and developed into critical cellulitis. Because the patient had no human leukocyte antigen-identical sibling, we considered an alternative donor. Because of the necessity for early neutrophil recovery to resolve the critical infection, we proceeded with allogeneic peripheral blood stem cell transplantation (PBSCT) from a microchimeric haploidentical sibling donor. We infused peripheral blood mononuclear cells directly into the patient without cryopreservation and thawing procedures. We aimed for the contaminating granulocytes to act as a granulocyte transfusion. Actually, the neutrophils increased to 1.6 x 10(9)/L on day 1, when the patient showed a temporary resolution of infection. Engraftment was achieved shortly after neutropenic nadir, and acute graft-versus-host disease (GVHD) has been well controlled. Although the patient experiences extensive chronic GVHD, he has been well as an outpatient with a 90% Karnofsky performance status score. The leukemia has been in complete remission for more than 1 year. These findings suggest the clinical utility of a salvage therapy with allogeneic PBSCT from a microchimeric haploidentical donor to treat refractory leukemia concurrent with life-threatening infection.