Kazuyuki Naito

Reconstitution of peripheral blood lymphocyte subsets in the long-term disease-free survivors of patients with acute myeloblastic leukemia

The number of long-term survivors of patients with acute myeloblastic leukemia (AML) has increased as a result of the progress of chemotherapy. We examined the recovery of peripheral blood lymphocytes (PBL) subset after chemotherapy to clarify the reconstitution of the immune system in AML. Thirty patients with AML in complete remission (CR) were entered into the study. There were 12 males and 18 females; one M0, six M1, 14 M2, three M3, two M4 and four M5 according to FAB classification. The age ranged from 21 to 78 years (median age, 46 years) and the duration of disease-free survival after completion of chemotherapy ranged from 5 to 122 months (median, 35 months). The chemotherapy was performed according to the protocol designed by the Japan Adult Leukemia Study Group (JALSG). PBL subsets were analyzed by flow cytometry with the use of monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD16, CD20, CD45RA, CD56, CD57 and HLA-DR. There was a significant positive relationship between the absolute number of CD4+, CD45RA+ CD4+ cells and the duration of time post-therapy and a significant negative relationship between %CD5+ B, CD56+ cells and the duration of time post-therapy. The appearance of autoantibodies (rheumatoid factor and anti-DNA antibody) tended to increase after 2 years, however, there was no relationship between CD5+ B cells and the frequency of rheumatoid factor. These findings demonstrate that patients in CR have a low number of CD4+ and CD45RA+ CD4+ T cells at an early period after chemotherapy and that each subset recovered to a normal level in 2 years. %CD5+ B and CD56+ cells gradually decreased and returned to their normal level after 4 years. There were high numbers of DR+ T cells and NK cells for a long time, suggesting that activated T cells and NK cells may play a role in the immune surveillance system after chemotherapy.

Characterization of the immunoglobulin light chain variable region gene expressed in multiple myeloma

We studied the organization, diversification and clinical significance of the immunoglobulin light chain (IgL) variable region genes expressed in 17 κ-chain and 16 λ-chain producing multiple myeloma (MM) samples. The V genes from 31 MM samples had over 84.9% homology to the known germline Vκ/λ genes, whereas one Vκ and one Vλ gene had only 75.5% and 65.9% homology, respectively. While all five Jκ segments were equally used, only Jλ-1 or Jλ-2/3 was used among seven Jλ segments. N nucleotide addition was found at two Vκ-Jκ and five Vλ-Jλ junctions. The λ-chain complementarity determining region (CDR)-3 was longer and more variable than the κ-chain CDR-3 mainly due to junctional flexibility of Vλ and Jλ segments. Somatic mutations were more frequent in the Jλ than the Jκ segments, and were distributed in the CDR-3 as well as the frame work region (FWR)-4. Those of the Jκ segments, however, were limited to FWR-4. In FWR-4, replacement mutations were clustered at codon 106 of κ-chain and 103 of λ-chain. Thus nucleotide mutation or conservation was dependent on position, indicating a structural necessity of IgL for the development of myeloma cells in addition to a non-random distribution of mutations. There was no characteristic IgL sequence according to the isotype of M-protein, clinical stage or renal complication.

A case of cALL relapse after allogeneic BMT: recurrence of recipient cell origin, initially determined as being that of donor cell origin by sex chromosome analysis.

Fig 1. Left: Clinical picture of the lesions on the right leg. Right: Skin biopsy showing marked vascular changes in the dermis: the endothelial cells are swollen. A cellular infiltrate around and focally in the vessel wall consists of neutrophils and some eosinophils. There also are nuclear fragments (nuclear dust) as a result of disintegration of neutrophils. Some vessels showed fibrinoid degeneration of the wall with occlusion of the lumina. The epidermis was intact.

Chromosomal assignments of genes coding for human leukocyte common antigen, T-200, and lymphocyte function-associated antigen 1, LFA-1 beta subunit.

Five hybrids reactive with monoclonal antibodies against human leukocyte common antigen (T-200) and/or lymphocyte function-associated antigen 1 (LFA-1) β subunit were obtained from the fusion of human blood lymphocytes or T-cell chronic lymphocytic leukemia cells with BW5147 mouse T-cell leukemia cells. Chromosome analyses of 20 clones showed concordance between the presence of human chromosomes 1 and 21 and the expression of T-200 and LFA-1 β subunit, respectively. Confirmation of human chromosomes in the hybrids was made by the electrophoretic analyses of phosphoglucomutase 1 for chromosome1and Superoxide dismutaseAfor chromosome 21. The results suggested that the presence of human chromosomes 1 and 21 was essential for the expression of T-200 and LFA-1 β subunit, respectively.

A randomized study comparing VMCP and MMPP in the treatment of multiple myeloma.

Abstract Purpose: To compare VMCP, a multidrug combination chemotherapy comprising vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as induction, to elucidate the value of alternating combination chemotherapy, and to search for an appropriate maintenance therapy in multiple myeloma. Methods: At 16 institutions in the Nagoya City area, we carried out a randomized trial of VMCP versus MMPP as the initial treatment. Patients who were refractory or resistant to the initial therapy were crossed over into the other arm (crossover trial). For patients who achieved a partial response (PR) or a minor response (MR) and in whom the paraprotein level ceased to decrease, the maintenance therapy was randomized either to an MPH/PSL combination (MP) or to alternating combination therapy (AT) with VMCP and MMPP. Results: In the 94 evaluable patients of the 111 enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7% (21/47) in the MMPP arm (P=0.0859). The crossover trial resulted in a PR rate of 15.8% (3/19) for the VMCP→MMPP crossover and 14.3% (2/14) for the MMPP→VMCP crossover. The median survival time was 23.4 months for those initially begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a tendency for better survival during a follow-up of 2–6 years with MMPP treatment, but without statistical significance. The survival time of patients with progressive disease was significantly shorter than that of patients with PR, MR or no change (NC). However, there was no significant difference in the survival rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there was no significant difference in survival between MP therapy and AT. Patients who reached a plateau phase survived significantly longer than those who did not. Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no significant difference in the hematologic or gastrointestinal toxicity between the two arms. Conclusions: We conclude that VMCP is less effective for myeloma than MMPP as the induction treatment, that alternating noncrossresistant chemotherapeutic combinations do not offer an advantage in multiple myeloma, and that patients who reach a plateau phase have a significantly longer survival time.

Gene encoding human p250 T-cell activation antigen maps to human chromosome 11

Human p250 T-cell activation antigen detected by a monoclonal antibody, B1.19.2, is a single peptide antigen with a molecular weight of 250 kilodaltons and is classified serologically into cluster of differentiation, CDw26. Concordance between the presence of human chromosome 11 and the reactivity with B1.19.2 was demonstrated by chromosomal analysis of 23 clones derived from three hybrid series obtained from the fusion of human activated lymphocytes or T-cell chronic lymphocytic leukemia cells and BW5147 mouse T-cell leukemic cells. The results indicated that the presence of chromosome 11 was essential for the expression of p250 T-cell activation antigen. Moreover, the gene for this antigen was assigned to chromosome 11pter→p11.2 by analysis of the hybrid clones retaining the translocated chromosome of 11.