Retrospective analysis of primary plasma cell leukemia in Kansai Myeloma Forum registry.

We retrospectively analyzed twenty-six patients with primary plasma cell leukemia (pPCL) registered from May 2005 until April 2015 by the Kansai Myeloma Forum. Twenty patients received novel agents (bortezomib or lenalidomide), and their median survival of was 34 months. The median survival of patients who underwent autologous stem cell transplantation (SCT) was 40 months, those undergoing allogeneic SCT 55 months, and those undergoing both types of SCT (auto-allo) 61 months; whereas for those who did not undergo SCT it was 28 months (p = 0.845). The only statistically significant risk factor identified by multivariate analysis was hypercalcemia.

Identification of polyethylene glycol-resistant macrophages on stealth imaging in vitro using fluorescent organosilica nanoparticles.

An in vitro imaging system to evaluate the stealth function of nanoparticles against mouse macrophages was established using fluorescent organosilica nanoparticles. Surface-functionalized organosilica nanoparticles with polyethylene glycol (PEG) were prepared by a one-step process, resulting in a brush-type PEG layer. A simultaneous dual-particle administration approach enabled us to evaluate the stealth function of nanoparticles with respect to single cells using time-lapse fluorescent microscopic imaging and flow cytometry analyses. Single-cell imaging and analysis revealed various patterns and kinetics of bare and PEGylated nanoparticle uptake. The PEGylated nanoparticles revealed a stealth function against most macrophages (PEG-sensitive macrophages); however, a stealth function against certain macrophages (PEG-insensitive macrophages) was not observed. We identified and characterized the PEG-resistant macrophages that could take up PEGylated nanoparticles at the same level as bare nanoparticles.

Double-hit lymphoma with a feature of follicular lymphoma concurrent with clonally related B lymphoblastic leukemia : a preference of transformation for the bone marrow.

We describe a 65-year-old woman with follicular lymphoma (FL), grade 1, stage IV, which occurred concurrently with B lymphoblastic leukemia/lymphoma. Through the evaluation of FL, the cells that were morphologically suspected of having undergone transformation were found in the bone marrow, and flow cytometric and cytogenetic analyses detected the transformed population that suggested concomitant t(8;22) with typical t(14;18) FL cells. Repeated analyses of the lymph nodes demonstrated the typical morphological, phenotypic, and cytogenetic features of FL. The patient received several multiagent chemotherapy regimens, but the disease gradually became resistant, and the patient died of leukemic progression. In B-cell malignancies, cases involving both BCL2 and MYC translocations simultaneously, so-called "double-hit leukemia/lymphoma (DHL)", have occasionally been reported. Patients with this type of translocation have a very poor clinical outcome, and no standard therapy has been established. In our case, FL was supposed to have transformed into B lymphoblastic leukemia via Burkitt's lymphoma-like phase. Our case is unique in that the transformed DHL cells, derived from clonally related FL cells, showed ongoing transformation from Burkitt-like feature to B lymphoblastic leukemia exclusively in the bone marrow, which suggests that the bone marrow may provide a preferable milieu for malignant transformation. Similar cases should be accumulated and analyzed carefully.

Progressive multifocal leukoencephalopathy in myelodysplastic syndrome involving pure red cell aplasia.

Progressive multifocal leukoencephalopathy (PML) is a rare and fatal demyelinating disease of the central nervous system caused by JC polyomavirus (JCV) reactivation in an immunocompromised host. We describe a case of PML in a 76-year-old woman with myelodysplastic syndrome, who had been treated with azathioprine for a pure red cell aplasia-like condition. PML was diagnosed based on the neurologic symptoms, the magnetic resonance imaging patterns and the detection of JCV DNA in the cerebrospinal fluid. She died ten months after the diagnosis. An autopsy confirmed the diagnosis, and JCV DNA was detected in the cerebrum. Azathioprine might have triggered PML.

Refractory Evans syndrome after autologous stem cell transplantation for multiple myeloma: management with a second transplantation.

The development of autoimmune disease after autologous stem cell transplantation (ASCT) is very rare in multiple myeloma (MM). We describe the first case of Evans syndrome after ASCT for MM. A 60-year-old man with MM received ASCT and subsequently developed Evans syndrome following two febrile episodes. The syndrome was refractory to conventional therapies but it was managed with a second ASCT. This unique complication was thought to have been triggered by an infection during the recovery of the immune system. We assumed that reconstructing the immune system via ASCT might eliminate infection-induced autoantibodies to platelets and erythrocytes.

Optimal stimulation for CD70 induction on human monocyte-derived dendritic cells and the importance of CD70 in naive CD4(+) T-cell differentiation.

Studies in mice have shown that CD70 on dendritic cells (DCs) is sufficient to convert T-cell tolerance into immunity and hence induce anti-tumour immune responses. Therefore, it is important to investigate (i) optimal stimuli to induce CD70 on human monocyte-derived DCs (MoDCs), which are widely used for tumour immunotherapy, and (ii) the role of CD70 in functional differentiation of naive CD4(+) and CD8(+) T cells stimulated with MoDCs. We show that interferon-alpha (IFN-alpha) is a key cytokine to differentiate monocytes into DCs with the capacity to express CD70 upon maturation. CD70 expression on IFN-alpha-induced MoDCs was elicited by different categories of maturation-inducing factors (Toll-like receptor ligands, CD40 ligand and pro-inflammatory mediators), among which prostaglandin E(2) was most effective. Naive T cells stimulated with MoDCs also expressed CD70. Stimulation with MoDCs promoted naive CD4(+) T cells to acquire the ability to produce T helper type 1 and 2 cytokines in a CD70-dependent manner. In contrast, the CD70-CD27 interaction diminished the production of an immunoregulatory cytokine IL-10. The CD27 signal did not play a dominant role in the induction of effector molecules in naive CD8(+) T cells during the stimulation with MoDCs. This study adds a novel function to the versatile cytokines, type I IFNs, that is, the induction of CD70 on MoDCs. CD70 promotes naive CD4(+) T cells to acquire immunostimulatory activity through the DC-T-cell and T-cell-T-cell interactions during the stimulation with MoDCs. Hence, the CD70-CD27 interaction may play an important role in inducing effective immune responses in DC-based immunotherapy.

Epstein-Barr virus-induced infectious mononucleosis after two separate episodes of virus-associated hemophagocytic syndrome.

A 24-year-old man, who had suffered previous two episodes of non- Epstein-Barr virus (EBV)-associated hemophagocytic syndrome (HPS) at the ages of 16 and 18, developed EBV-induced infectious mononucleosis. His antibody pattern to EBV highlighted the initial infection. The disease took a self-limited course without developing into HPS. No reactivation of EBV infection was noted over the following 6 years. The patient may have attained immune competency in adulthood, which was somehow impaired during his adolescence.

First case report of sepsis caused by Mycobacterium wolinskyi in chronic myelogenous leukemia.

Infections caused by Mycobacterium wolinskyi have rarely been reported, and essentially all were cellulitis and/or osteomyelitis related with traumatic event or surgical wound. Here, we present the 1st case of septic complication due to this organism in a patient with chronic myelogenous leukemia of the 1st but late chronic phase.