Hiroyuki Kitajima

Transfer of autoimmune thyroiditis and resolution of palmoplantar pustular psoriasis following allogeneic bone marrow transplantation

We report an unusual case of a patient who was cured of one autoimmune disease (palmoplantar pustular psoriasis (PPP)) but developed another autoimmune disease (autoimmune thyroiditis) after allogeneic BMT. A 40-year-old man suffering from AML with PPP underwent allogeneic BMT from his HLA-identical sister for the treatment of AML. The patient experienced complete clearance of the cutaneous PPP despite the cessation of immunosuppressive therapy for over 2 years. However, he developed hyperthyroidism with anti-thyroglobulin antibodies 5 months after BMT, although he had showed normal thyroid functions without anti-thyroglobulin antibodies before BMT. The donor had no history of thyroid diseases and showed normal thyroid functions but was positive for anti-thyroglobulin antibodies. Thus, even when the donor is in a subclinical state, autoimmune thyroiditis may be transferred from donors to recipients by BMT.

CD3+CD4-CD8-TCR-αβ+ T-cell Lymphoma With Clinical Features of Primary Effusion Lymphoma: An Autopsy Case

We report an unusual case of T-cell lymphoma presenting as ascites. A 72-year-old HIV-negative woman was admitted to our hospital for abdominal discomfort associated with increasing abdominal girth over the course of 1 month. Physical examination showed a tense and distended abdomen and edema of the lower extremities. There was no hepatosplenomegaly or lymphadenopathy. A computed tomographic scan of the abdomen and chest showed massive ascites and pleural effusions, but there was no evidence of tumor masses or lymph node enlargement. The cytospin prepared from the peritoneal fluid was hypercellular and composed of a population of monotonous, large cells containing fine chromatin. No herpesvirus-8 (HHV-8) DNA was detected by polymerase chain reaction in the cells. Immunohistochemistry showed the neoplastic cells to be CD3+, CD4-, CD7+, CD8-, CD34-, CD56-, and TCR-αβ+. Repeated cytogenetic studies showed common abnormalities of del(1) (p11p22), +i(7)(q10), and t(11;14)(q23;q11). The morphologic and immunologic findings were suggestive of peripheral T-cell lymphoma (PTCL), unspecified. This case suggests that some PTCLs with clonal chromosomal aberrations can exhibit peculiar serosal spreading in the absence of HHV-8 infection.

Changes of immunological markers after autologous peripheral blood stem cell transplantation

Abstract Purpose: Recently high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. Methods: Immunological parameters were examined before and after PBSCT in 9 patients with lung cancer and 13 patients with malignant lymphoma. Findings were compared with those for bone marrow transplantation (BMT). Peripheral blood cells were analyzed for phenotype and the levels of cytokines and soluble factors were measured. Results: After PBSCT, activated T cells (CD3+HLA-DR+ cells, CD8+HLA-DR+ cells) and suppressor/cytotoxic T cells (CD8+CD11b− cells) were significantly higher in the patients with lung cancer than in those with malignant lymphoma. Serum levels of interleukin-4 and soluble interleukin-2 receptor were also significantly higher in the patients with lung cancer than in those with lymphoma. On the other hand, the serum levels of interferon γ, tumor necrosis factor α, interleukin-6, soluble human leukocyte antigen class 1, and soluble thrombomodulin were significantly increased after bone marrow transplantation. The transfused peripheral stem cells of lung cancer and lymphoma patients had a similar number of granulocyte/macrophage-colony-forming units, but lung cancer patients had significantly more CD34-positive cells. Conclusion: By reinfusing large numbers of autologous immune cells, PBSCT may accelerate immune reconstitution, with T cells being likely to have a marked therapeutic potential. The changes after PBSCT were greater in patients with lung cancer than in lymphoma patients. These blood cells are potent mediators of anticancer activity and could play an important role in the elimination of autologous malignant cells.

Acute myelomonocytic leukemia with marrow eosinophilia showing 5q− and 16q22 mosaicism

We report an 82-year-old Japanese female with acute myelomonocytic leukemia with dysplastic marrow eosinophilia (FAB M4Eo) exhibiting a partial deletion of the long arm of chromosome 5, del(5)(q13q31) and a derivative chromosome 16 with a breakpoint at band 16q22, in addition to 5q-. The patient had a history of a preleukemic phase for several months with marked dysplasia in trilineage marrow cells, in addition to leukemic features compatible with M4Eo. These findings strongly suggested that the leukemic cells in this case were derived from a preleukemic clone with a del(5q).

Platelet Procoagulant Activity During,Peripheral Blood Stem Cell Harvest

We used flow cytometry to measure platelet-derived microparticle levels in plasma obtained from 16 patients during peripheral blood stem cell harvest (PBSC) and in platelet concentrates prepared by apheresis from 10 normal controls. We also studied the binding of an anti-P-selectin antibody and annexin-V to platelets. When all 60 harvests were assessed, we noted a significant difference in microparticle levels between patients with a platelet count >10 x 104/μl and those with a platelet count <10 X 10 4/μl (12.3 ± 4.4 vs. 75 ± 3.9%). In both the first and total harvests, the percentage of platelets and microparticles positive for anti-P-selectin and annexin-V were significantly higher than the normal control levels. These results suggest that patients undergoing mobilization by granulocyte colony-stimulating factor (G-CSF) who have a platelet count >10 X 10 4/μl are at risk of increased procoagulant activity after retransfusion following PBSC harvest. Key Words: Platelet-derived microparticle— Peripheral blood stem cell harvest—Granulocyte colony-stimulating factor.

Effect of thrombopoietin on peroxidase activity of cryopreserved peripheral blood stem cells

Transplantation of mobilized peripheral blood stem cells is increasingly used to facilitate hematological recovery following high-dose chemotherapy. In general, peripheral blood stem cells can be maintained by cryopreservation, e.g., at −80°C, until the day of transplantation. We investigated the effect of thrombopoietin (c-Mpl ligand) on cryopreserved peripheral blood stem cells obtained from 10 patients with malignant disease by assessing peroxidase activity by ultrastructual technique. Leukocyte surface markers wre evaluated by flow cytometry. After peripheral blood stem cells had been purified by use of CD34 monoclonal antibody, cells whose size resembled that of monocytes showed low levels of positivity for CD7, CD41a, and CD42b, but high levels of positivity for CD13, CD14, and HLA-DR. The lymphocyte-size cells showed high levels of positivity for CD7 only. Recombinant human thrombopoietin, administered alone and in combination with various cytokines, promoted the expression of CD41a by CD34-positive progenitor cells. No increase in the expression of CD7, CD13, CD14, and HLA-DR was detected following exposure to cytokines. However, the expression of CD41a and CD42b was enhanced by thrombopoietin. Ultrastructural study of peroxidase activity detected CD41a-positive cells. as well as platelet peroxidase-positive cells, following stimulation with thrombopoietin. Stimulation by other cytokines failed to yield platelet peroxidase-positive cells. Results thus suggest that thrombopoietin may be useful for increasing the recovery of platelets following transplantation of cryopreserved peripheral blood stem cells.