Yukiko Kawaguchi

CD200 Expression on Plasma Cell Myeloma Cells is Associated with the Efficacies of Bortezomib, Lenalidomide and Thalidomide

Plasma cell myeloma (PCM) is a devastating disease with a highly heterogeneous outcome, with survival ranging from a few months to longer than 10 years. Treatment of multiple myeloma has changed markedly in the past decade due to the development of new drugs such as bortezomib, lenalidomide and thalidomide, which have greatly improved the outcome of PCM. The clinical and prognostic value of immunophenotyping in PCM remains questionable. The aim of this study was to determine the diagnostic and prognostic significance of CD200 expression in newly diagnosed PCM. We retrospectively reviewed the records of 107 patients newly diagnosed with PCM at Showa University Hospital between January 2004 and September 2013. Expression of CD200 was studied by immunohistochemistry. Clinical and pathological parameters were compared between CD200-positive and CD200-negative cases. CD200-positive PCM cases had lower serum albumin (p = 0.0001) compared to those without CD200 expression. Our results showed no significant difference in median overall survival between patients with CD200-positive and CD200-negative PCM. However, there was a strong correlation between CD200 expression and serum albumin level. In the CD200-negative group, median overall survival was significantly longer in patients who received new drug treatment. These findings suggest that CD200 expression is a useful marker for evaluation of the severity of PCM and that lack of CD200 expression may improve the sensitivity of PCM to therapy with new drugs.

Immunohistochemical CD73 expression status in gastrointestinal neuroendocrine neoplasms: A retrospective study of 136 patients

The WHO 2010 classification divides gastrointestinal neuroendocrine neoplasms (GI-NENs) into neuroendocrine tumor (NET) G1, NET G2, neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) groups. A total of 136 cases of GI-NENs diagnosed at our hospitals as gastrointestinal carcinoids, endocrine cell carcinomas and NENs over the last 11 years, using the WHO 2010 classification were assessed. Among the 136 cases, 88.2% (120/136) were classified into the NET group (NET G1/G2) and 11.8% (16/136) were classified into the NEC group (NEC/MANEC). The incidences of lymphatic and venous invasions were higher in the NEC group compared with in the NET group (P<0.0001 and P=0.0021, respectively). The immunohistochemical staining of cluster of differentiation 73 (CD73) was evaluated in GI-NENs. CD73 is a potentially useful molecule in tumor immunity. In general, CD73 on the tumor cell membrane converts adenosine monophosphate to adenosine, which restrains the production of interferon-γ and cytocidal activity. Although the association between stem cells of pancreatic NENs and CD73 has been reported, few studies have reported on CD73 expression in GI-NENs. Immunohistochemical CD73 expression on the cytomembrane of neuroendocrine cells was detected in 27.2% (37/136) of the GI-NENs. The positive ratio of CD73 was significantly higher in the NEC group compared with in the NET group (P=0.0015). CD73 is also considered as a potential biomarker of anti-programmed death-1 (PD-1) therapy. The expression of programmed death-ligand 1 (PD-L1) on the cytomembrane of GI-NENs was assessed. The positive ratio of PD-L1 was higher in the NEC group compared with in the NET group (P=0.0011). Furthermore, CD73 expression status was significantly correlated with PD-L1 expression (P<0.0001). These results indicate that CD73 may be an interesting candidate for a biomarker for certain prognostic factors and therapeutics concerning PD-1 therapy.

Association of red cell distribution width with clinical outcomes in myelodysplastic syndrome.

Studies showed red cell distribution width (RDW) can improve the detection of morphological changes in red blood cells and the understanding of their contribution to dyserythropoiesis in myelodysplastic syndrome (MDS). The purpose of the study was to evaluate dyserythropoiesis in MDS by RDW analysis and to explore the utility of RDW in clinical practice. We retrospectively analyzed laboratory and clinical data of 101 patients (59 patients was refractory anemia (RA) according to the French-American-British (FAB) classification). In patients with RA, RDW was showed weak inverse correlation with both hemoglobin concentration (Hb) (rs = -0.37, P = 0.0035) and mean corpuscular hemoglobin concentration (MCHC) (rs = -0.36, P = 0.0047). On the other hand, RDW was showed weak correlation with the number of ringed sideroblasts in bone marrow (rs = 0.31, P = 0.023). The increased RDW (≥15.0%) was associated with shorter overall survival (OS) (P = 0.0086). In patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-t), effect of RDW on OS was less evident. These results suggested that increased RDW might reflect dyserythropoiesis, associated with deregulated hemoglobin synthesis and iron metabolism in MDS. Furthermore, increased RDW may have potential to be a prognostic significance in RA.

Status of Natural Killer Cell Recovery in Day 21 Bone Marrow after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Clinical Outcome

Rapid immune recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for clinical outcome prediction. In most studies, immune recovery after allo-HSCT is monitored via peripheral blood. However, few reports regarding the status of absolute lymphocyte subsets in the bone marrow (BM) microenvironment have been undertaken. Therefore, we evaluated the clinical impact of immune recovery in the early period following allo-HSCT using BM samples. We showed that delayed natural killer cell recovery was independently associated with a poor prognosis for overall survival (hazard ratio [HR], 3.07; 95% confidence interval [CI], 1.37- 6.89; P = .007), progression-free survival (HR, 3.42; 95% CI, 1.47-7.94; P = .004), and nonrelapse mortality (HR, 6.68; 95% CI, 1.82-25.0; P = .004) by multivariate analysis. In addition, low NK cell counts were associated with the presence of 1 or more bacterial, viral, or fungal infections. Our results indicate that investigating absolute lymphocyte subsets in BM in the early phase following allo-HSCT can be useful for predicting and improving survival outcomes.

Association of Soluble Interleukin-2 Receptor and C-Reactive Protein with the Efficacy of Bendamustine Salvage Treatment for Indolent Lymphomas and Mantle Cell Lymphoma

Bendamustine has demonstrated favourable efficacy in relapsed or refractory indolent lymphoma and mantle cell lymphoma. We retrospectively evaluated the pre-treatment clinical and laboratory factors and their correlation with the clinical outcome of these lymphomas. We analysed 53 patients who had been treated with bendamustine alone (n = 6) or rituximab plus bendamustine (n = 47). The overall response rate was 81.1%, with a complete response (CR) rate of 39.6%. The CR rate was significantly low in patients who had elevated levels of soluble interleukin-2 receptor (p = 0.024) and C-reactive protein (CRP; p = 0.004). The 1-year overall survival (OS) rate was 79.3%. An elevated CRP was associated with a short OS (p = 0.056). The present findings suggest that the lymphoma microenvironment and immune response were involved in the effects of bendamustine. These findings are also important in order to understand the pathophysiology of refractory lymphoma and to find effective strategies using bendamustine.

Direct Detection of Aqueous CO2 by Infrared Waveguide Spectroscopy with an Amorphous Fluoropolymer Coating Rod

Infrared waveguide spectroscopy using a sapphire rod coated with an amorphous fluoropolymer (Cytop, Asahi Glass Co., ltd, Japan) has been developed in order to directly observe CO2 in aqueous solutions. Since the amorphous fluoropolymer has a relatively high gas-permeability and hydrophobic feature, the aqueous CO2 transmits into the amorphous fluoropolymer coating film, but water cannot penetrate into the film. Good linearity of calibration curves for CO2 in the gas and the aqueous solution were obtained.

Umbilical cord blood transplantation for adults using tacrolimus with two-day very-short-term methotrexate for graft-versus-host disease prophylaxis

Cord blood transplantation (CBT) is an alternative approach to allogeneic stem cell transplantation. However, CBT is associated with issues including pre-engraftment immune reaction (PIR), engraftment syndrome (ES), and graft failure (GF). Tacrolimus (TAC) and short-term methotrexate (sMTX: days 1, 3, 6, and/or 11) are used for graft-versus-host disease (GVHD) prophylaxis during CBT; however, sMTX does not accelerate neutrophil engraftment. Therefore, we hypothesized that lower doses of sMTX [very-short-term MTX (vsMTX): 10 and 7mg/m(2) on days 1 and 3, respectively] with TAC reduce the risk of GF without increasing post-transplantation immune reactions during CBT. We retrospectively analyzed 40 patients who received TAC with vsMTX for GVHD prophylaxis. PIR and ES developed in 4 patients. The cumulative incidence of neutrophil engraft at day 60 was 92.5%. No cases of primary graft failure were noted. The cumulative incidence of grades II-III GVHD was 48.1% at day 100, and the cumulative 100-day incidence of nonrelapse mortality was 12.5%. This study suggests that TAC with vsMTX reduces the risk of PIR and ES during CBT and stimulates neutrophil engraftment, but may be associated with slightly higher aGVHD compared with calcineurin inhibitor and sMTX. Therefore, we recommend vsMTX plus TAC as an option for GVHD prophylaxis during CBT.