No abstract

Summary.  This study aimed to identify which graft product subset of cells might be the most predictive of late haematopoietic recovery (three to 12 months) following autologous peripheral blood stem cell transplantation (PBSCT). The relationships between the numbers of reinfused CD34+ cells and their immature subsets such as CD34+/CD90+, CD34+/AC133+, CD34+/CD38– and CD34+/HLA‐DR– cells, and haemoglobin, white blood cell (WBC) and platelet counts at 3, 6, 9 and 12 months after PBSCT, were studied in 25 patients with haematological and solid malignancies. The total CD34+ cell number, as well as CD34+/CD90+ and CD34+/AC133+ cell numbers, correlated with platelet counts at 3, 6, 9 and 12 months after PBSCT, but the CD34+/CD90+ cells infused best predicted platelet recovery during the first 12 months after PBSCT (P < 0·0238 at any time‐point). The CD34+/AC133+ cell dose also correlated with WBC counts at 3 months post PBSCT. In addition, all patients receiving more than 80 × 104 CD34+/CD90+ cells/kg showed platelet counts greater than 100 × 109/l at all points after PBSCT, suggesting that this value of the CD34+/CD90+ cells infused was a threshold dose for durable haematopoietic engraftment after PBSCT.

Ras gene mutations occur in 30% to 40% of patients with multiple myeloma (MM), and farnesylation is the first and most important step in the posttranslational modification of Ras proteins. R115777 is a newly synthesized potent farnesyl transferase inhibitor (FTI) and has recently demonstrated significant antitumor activities in vitro and in vivo. Therefore, we examined the effect of R115777 on the growth of fresh and cloned myeloma cells in vitro. R115777 inhibited the growth of fresh and cloned myeloma cells dose dependently, and effects were not dependent on the status of N-Ras mutation in fresh myeloma cells. Flow cytometric analysis using annexin V and 7-aminoactinomycin D (7AAD) showed that R115777 induced apoptosis of 2 of 3 myeloma cell lines at a concentration of 1.0 ؋ 10 ؊8 M. R115777 appears to be a potent inducer of apoptosis, and its effects depend on the status of Ras mutation in cloned myeloma cells but not on IntroductionMultiple myeloma (MM) is a malignancy of B cells characterized by the monoclonal proliferation of malignant plasma cells and osteolytic bone destruction. Several chemotherapeutic regimens have been used to improve the survival of patients with MM. Although high-dose melphalan supported by autologous stem cell transplantation (auto-SCT) has improved the survival of patients with MM, many patients were found to relapse during a long follow-up period. 1,2 Allogeneic stem cell transplantation (allo-SCT) is possibly the only genuinely curative therapy for MM, and a graft-versus-myeloma effect by immunocompetent donor lymphocytes has been demonstrated but the treatment-related mortality is high. 3,4 Recently, nonmyeloablative SCT has been reported to provide a stable engraftment of allogeneic stem cells and tolerable toxicity in patients with MM, but a longer follow-up period is necessary to evaluate late mortality. 5,6 Therefore, there is an obvious need for new therapeutic strategies.Ras proteins are prototypical G proteins that have been shown to play a key role in signal transduction, cell proliferation, and malignant transformation. Ligand-stimulated activation of the cell-surface receptor, receptor-associated tyrosine kinase, or agonist mediated through G protein-coupled receptors results in the activation of Ras protein. The Ras gene family consists of 3 functional genes, H-Ras, N-Ras, and K-Ras. Activating point mutations in all 3 Ras genes have been detected in a wide variety of human malignancies and are one of the most common alternations in hematologic malignancies. [7][8][9] In MM, Ras gene activation is observed in 30% to 40% of cases and one of the most frequent point mutations. [10][11][12][13] Although Ras protein undergoes several steps of posttranslational modification, farnesylation is the first and most important step for its membrane localization and cell-transforming activity. Thus, farnesyltransferase (FTase) is a very attractive target for the development of anticancer agents. R115777 (Zarnestra, Johnson & Johnson, Raritan, NJ), a potent and selective farnesy...

A 42-year-old female underwent hysterectomy because of a huge uterine mass. Histologically, she was diagnosed as having intravascular lymphoma co-existing with myoma uteri. Lymphoma cells were large in size and were positive for CD5, CD20, CD45, CD79a, lambda light chain, and EBV but were negative for CD3 and cyclin D1. No other organs except for the adjoining bilateral ovaries seemed to be affected by the lymphoma cells. She received the combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) together with rituximab and has been well without definite disease progression. So far, this is the first case of CD5 + EBV + intravascular large B-cell lymphoma (CD5 + EBV + IVLBL) in the uterus of a patient who was incidentally diagnosed and successfully treated. Am.

A 17-year-old male with chronic myelogenous leukemia in blast crisis received a non-T cell-depleted (TCD) HLA haplo-identical three-loci mismatched hematopoietic stem cell transplant (HSCT) from his mother. Long-term feto-maternal microchimerism was detected by nested polymerase chain reaction with sequence-specific primer typing. The post-transplantation prophylaxis against graft-versus-host disease (GVHD) was tacrolimus with minidose methotrexate. Sustained engraftment was obtained. Acute GVHD (grade 2) developed, but improved rapidly. Bone marrow aspiration on day 120 showed complete remission. Non-TCD HLA haplo-identical HSCT based on feto-maternal microchimerism might be feasible and has important implications in the selection of alternative family donors in HSCT.