Immunotherapy Using Dendritic Cells against Multiple Myeloma: How to Improve?

Multiple myeloma (MM) is a good target disease in which one can apply cellular immunotherapy, which is based on the graft-versus-myeloma effect. This role of immune effector cells provides the framework for the development of immune-based therapeutic options that use antigen-presenting cells (APCs) with increased potency, such as dendritic cells (DCs), in MM. Current isolated idiotype (Id), myeloma cell lysates, myeloma dying cells, DC-myeloma hybrids, or DC transfected with tumor-derived RNA has been used for immunotherapy with DCs. Immunological inhibitory cytokines, such as TGF-β, IL-10, IL-6 and VEGF, which are produced from myeloma cells, can modulate antitumor host immune response, including the abrogation of DC function, by constitutive activation of STAT3. Therefore, even the immune responses have been observed in clinical trials, the clinical response was rarely improved following DC vaccinations in MM patients. We are going to discuss how to improve the efficacy of DC vaccination in MM

A Case of Disseminated and Fulminant Plasmacytomas That Developed during Bortezomib Treatment

Multiple myeloma is an incurable and slow growing plasma cell neoplasm. The introduction of new drugs has increased the number of treatment options. Bortezomib, the first-in-class proteasome inhibitor, has been shown to have a significant antitumor activity in the treatment of relapse/refractory patients with multiple myeloma. Additionally, plasmacytomas have shown significant response to bortezomib. In this case report, we describe a patient who developed disseminated and fulminant extramedullary plasmacytomas during combination chemotherapy treatment with bortezomib within a short period, after having shown clinical improvement

Successful Treatment of Pure Red Cell Aplasia with Rituximab in Patients after ABO-Compatible Allogeneic Hematopoietic Stem Cell Transplantation

Pure red cell aplasia (PRCA) following allogeneic hematopoietic stem cell transplantation (HSCT) has been mostly reported in situations involving major ABO incompatibility between donor and recipient. Conventional treatments such as plasma exchange, erythropoietin, and steroid are often unsatisfactory. Rituximab has been reported to be highly effective for PRCA following major ABO-incompatible allogeneic HSCT. A 49-year-old woman with PRCA following ABO-matched allogeneic HSCT for acute lymphoblastic leukemia, refractory to erythropoietin treatment, received 4 doses of rituximab 375 mg/m2 weekly. After the 3rd dose of rituximab, she exhibited a striking rise in her reticulocyte count with an increase in her hemoglobin level. To our knowledge, this is the first case of PRCA following major ABO-compatible allogeneic HSCT resolving completely after rituximab treatment

FAM167A is a key molecule to induce BCR-ABL-independent TKI resistance in CML via noncanonical NF-κB signaling activation

Abstract Background BCR-ABL-independent drug resistance is a barrier to curative treatment of chronic myeloid leukemia (CML). However, the molecular pathways underlying BCR-ABL-independent tyrosine kinase inhibitor (TKI) resistance remain unclear. Methods In silico bioinformatic analysis was performed to identify the most active transcription factor and its inducer that contribute to BCR-ABL-independent TKI resistance. Tandem mass spectrometry analysis was performed to identify the receptor for the noncanonical NF-κB activator FAM167A. In vitro and in vivo mouse experiments revealed detailed molecular insights into the functional role of the FAM167A-desmoglein-1 (DSG1) axis in BCL-ABL-independent TKI resistance. CML cells derived from CML patients were analyzed using quantitative reverse transcription PCR and flow cytometry. Results We found that NF-κB had the greatest effect on differential gene expression of BCR-ABL-independent TKI-resistant CML cells. Moreover, we found that the previously uncharacterized protein FAM167A activates the noncanonical NF-κB pathway and induces BCR-ABL-independent TKI resistance. Molecular analyses revealed that FAM167A activates the noncanonical NF-κB pathway by binding to the cell adhesion protein DSG1 to upregulate NF-κB-inducing kinase (NIK) by blocking its ubiquitination. Neutralization of FAM167A in a mouse tumor model reduced noncanonical NF-κB activity and restored sensitivity of cells to TKIs. Furthermore, FAM167A and surface DSG1 levels were highly upregulated in CD34+ CML cells from patients with BCR-ABL-independent TKI-resistant disease. Conclusions These results reveal that FAM167A acts as an essential factor for BCR-ABL-independent TKI resistance in CML by activating the noncanonical NF-κB pathway. In addition, FAM167A may serve as an important target and biomarker for BCR-ABL-independent TKI resistance

Multiple Intracranial Tuberculomas Mimicking Granulocytic Sarcomas in Acute Myeloid Leukemia

The diagnosis of incracranial tuberculoma in immune-compromised hosts is often difficult because conventional magnetic resonance (MR) imaging of tuberculoma reveals various findings and neurologic symptoms are not typical. Here, we report a case of a 54-yr old man with multiple intracranial tuberculoma who was treated for acute myeloid leukemia. He complained of right-side paresthesia after the third consolidation chemotherapy without leukemic relapse and fever. MR imaging of the brain showed multiple ring-enhanced lesions in the cerebrum, cerebellar hemisphere, and pons. The lesions appeared to mimic a metastatic tumor or abscess. Cerebrospinal fluid analysis showed no abnormal cells, but the level of adenosine deaminase was elevated (28.8 IU/L, normal 0-8). Stereotactic brain biopsy was performed, but only reactive gliosis was observed. To confirm diagnosis, an open brain biopsy was performed. The histopathology demonstrated chronic granulomatous inflammation with caseous necrosis. Tuberculous-polymerase chain reaction of the biopsy showed a positive result. He was treated with anti-tuberculosis medication and a high dose of steroid. Paresthesia improved, and follow-up brain MR imaging showed the decreased size and numbers of ring-enhanced lesions and improvement of perilesional edema 1 month after treatment. Here, we report on an interesting case of intracranial tuberculoma in acute myeloid leukemia