Tomomi Toubai

Successful micafungin (FK463) treatment of invasive pulmonary aspergillosis in a patient with acute lymphoblastic leukemia in a phase II study.

We treated a 52-year-old woman with acute lymphoblastic leukemia (ALL) who developed invasive pulmonary aspergillosis (IPA) as a result of neutropenia following remission-induction chemotherapy. Although serological test results, such as those for platelia and pastrex, were all negative and the serum level of β-D—glucan was low,Aspergillus DNA was detected in blood by the polymerase chain reaction method. A clinically documented diagnosis of IPA was made on the basis of chest x-rays, computed tomography scan findings, and the detection ofAspergillus DNA. Micafungin (FK463), a candin class anti-fungal agent, was administered at a dose of 75 to 150 mg/day, because other antifungal agents were not effective. The increase in serum concentration of micafungin was dose-dependent and was accompanied by improvement of symptoms and objective findings. Micafungin was effective for the treatment of IPA in this patient with ALL.

Abnormal expansion of naïve B lymphocytes after unrelated cord blood transplantation : a case report

A 33-year-old woman underwent unrelated cord blood transplantation (U-CBT) for myelodysplastic syndrome (MDS)-related secondary AML. She showed impressive increases in the number of CD19+ B cells in bone marrow and CD19+27−IgD+ B cells in peripheral blood from about 1 month to 3 months after U-CBT. The serum level of IL-6 temporarily increased after transplantation, and this increase seemed to be correlated with the expansion of CD19+ B cells. Although, compared with BMT, little is known about the kinetics of hematological and immunological reconstitution in U-CBT, there was initial B-cell recovery after CBT as some described. This B cell recovery may be associated with a high number of B-cell precursors present in cord blood (CB). The phenomenon of naïve B lymphocyte expansion that we found might be associated with a high number of B-cell precursors present in CB.

Effect of granulocyte colony-stimulating factor on IL-12 p40 production during chemotherapy for B-cell lineage non-Hodgkin's lymphoma patients

Abstract:u2002 Interleukin (IL)‐12 is a 70‐kDa cytokine comprised of two disulfide‐linked proteins (p35 and p40) and is essential for the initiation of effective immune response. Granulocyte‐colony stimulating factor (G‐CSF) affects the balance in the production of anti‐inflammatory cytokines. We investigated the serum IL‐12 p40 and IL‐12 Mix (p40 and p70) production in 28 patients with B‐cell lineage non‐Hodgkins lymphoma (NHL) treated with chemotherapy (e.g., CHOP regimen) with or without G‐CSF administration and eight healthy volunteers. We found that serum levels of IL‐12 p40 (191.2u2003±u2003150.0u2003pg/mL) and IL‐12 Mix (277.4u2003±u2003274.5u2003pg/mL) in the patients before chemotherapy were higher than those in the healthy volunteers (IL‐12 p40: 76.4u2003±u200325.3u2003pg/mL, IL‐12 Mix: 48.5u2003±u200333.4u2003pg/mL) (Pu2003=u20030.04 and 0.02, respectively). Next, we examined the serum IL‐12 p40 and IL‐12 Mix levels in nine patients receiving chemotherapy with administration of G‐CSF (CG group, nu2003=u20039) and without G‐CSF (C group, nu2003=u20039). Serum IL‐12 p40 and IL‐12 Mix levels were decreased on 10u2003d after chemotherapy in both groups, and those in CG groups were significantly lower than those in C group. These results indicated that administration of G‐CSF decreased serum IL‐12 p40 and IL‐12 Mix levels. Overall survival (OS) at 24u2003months was not significantly different in the two groups (58.3% in group C vs. 80.0% in group CG, Pu2003=u20030.67). However, the survival rate of patients at clinical stages III and IV in CG group (nu2003=u20036, 66.0%) was significantly better than that of patients in C group (nu2003=u20034, 25.0%) (Pu2003=u20030.02). Long‐term administration of G‐CSF appears to influence the survival rate by reducing immunosuppressive IL‐12 p40 production.

Chimerism and T-cell receptor repertoire analysis after unrelated cord blood transplantation with a reduced-intensity conditioning regimen following autologous stem cell transplantation for multiple myeloma.

A 65‐year‐old Japanese male was diagnosed as multiple myeloma with Bence Jones kappa type, clinical stage IIIA. His disease status reached partial remission after chemotherapy. Thereafter, he received tandem transplantation, consisting of high‐dose chemotherapy with autologous stem cell transplantation (ASCT), followed by unrelated cord blood transplantation (U‐CBT). U‐CBT with a reduced‐intensity conditioning regimen (RI‐CBT) was performed in August 2003. HLA mismatch between the patient and the CBT donor was present at two serological loci (B and DR). A total nucleated CBT cell dose of 2.45u2003×u2003107/kg body weight was infused on day 0. Graft‐vs.‐host disease (GVHD) prophylaxis consisted of cyclosporine A and short‐term methotrexate. Neutrophil engraftment (>0.5u2003×u2003109/l) was obtained on day 46. He developed positive cytomegalovirus antigenemia, grade II acute GVHD involving skin and liver, varicella–zoster virus infection, septic shock, hemorrhagic cystitis caused by adenovirus and acute hepatitis B virus infection after U‐CBT. We retrospectively analyzed T‐cell receptor (TCR) repertoire diversity and found that TCR repertoire diversity decreased continuously after U‐CBT. Therefore, low‐TCR repertoire diversity in this patient appears to be associated with various infections caused by immunodeficiency.