Differentiation of Donor-Derived Cells Into Microglia After Umbilical Cord Blood Stem Cell Transplantation.

Recent studies have indicated that microglia originate from immature progenitors in the yolk sac. After birth, microglial populations are maintained under normal conditions via self-renewal without the need to recruit monocyte-derived microglial precursors. Peripheral cell invasion of the brain parenchyma can only occur with disruption of the blood-brain barrier. Here, we report an autopsy case of an umbilical cord blood transplant recipient in whom cells derived from the donor blood differentiated into ramified microglia in the recipient brain parenchyma. Although the blood-brain barrier and glia limitans seemed to prevent invasion of these donor-derived cells, most of the invading donor-derived ramified cells were maintained in the cerebral cortex. This result suggests that invasion of donor-derived cells occurs through the pial membrane.

Post-transplantation consolidation and maintenance therapy with lenalidomide for Japanese patients with multiple myeloma.

BACKGROUND: Post-autologous stem cell transplantation (ASCT) consolidation and maintenance therapies in multiple myeloma (MM) have recently been the central focus of studies. However, there have been no reports of Japanese patients with MM treated with post-ASCT consolidation/maintenance therapies. PATIENTS AND METHODS: We retrospectively evaluated eight Japanese patients with newly-diagnosed symptomatic MM who received ASCT after high-dose melphalan, and three to four courses of bortezomib-plus-dexamethasone and two courses of lenalidomide-plus-dexamethasone followed by maintenance lenalidomide for 6-24 months. RESULTS: Four patients achieved complete response (CR) after ASCT, and five patients (63%) achieved stringent CR after the consolidation and maintenance therapy; two out of these five were in molecular CR. At the median follow-up of 38 months, all patients were alive and only one patient had disease progression following post-ASCT therapy. CONCLUSION: Post-ASCT consolidation and maintenance therapy using lenalidomide may be effective in the treatment of Japanese patients with MM.

Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides.

Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.

[Concurrent chemo-radiotherapy for localized refractory non-Hodgkin's lymphoma--report of two cases].

Localized refractory diffuse large B-cell lymphomas (DLBCL) were treated with concurrent chemo-radiotherapy. Case 1 had right cervical lymphadenopathy. Lymphoma enlarged even after the fourth courses of chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The second case had a pharyngeal tumor and bilateral cervical lymphadenopathy. A lymphoma enlarged after eighth courses of CHOP. Both cases were treated with concurrent chemo-radiotherapy. Chemotherapy consisted of mitoxantrone, methotrexate, ifosfamide,and prednisolone (MMIP). The dose of radiation to the involved sites was 40 Gy. The first case received chemotherapy three days after radiotherapy was started. The second case was treated with chemotherapy, and radiotherapy was begun one day after. Both cases show mucositis and leukopenia. One case received two courses of chemotherapy after chemo-radiotherapy, and the other received no additional chemotherapy. Both cases achieved complete remission after the combined therapy, however, lymphoma in one case recurred three months after the therapy. It is possible that this concurrent chemo-radiotherapy is effective for localized DLBCL which did not disappear after standard chemotherapy.