E-cadherin expression in lymph nodes of three patients with non-Hodgkin's lymphoma

The E-cadherins are a family of cell-cell adhesion molecules. These molecules exhibit Ca2+ dependent cell adhesion and are expressed on epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. We determined serum E-cadherin levels in 30 patients with non-Hodgkin's lymphoma (NHL) using an enzyme immunoassay and then investigated whether E-cadherin is expressed on lymphoma cells in lymph nodes of three cases selected to analyze from 15 cases of serum E-cadherin levels over mean + 2SD with monoclonal antibody immunohistochemistry. Results indicated that E-cadherin antigen is expressed on the lymphoma cells in these three patients with NHL, and that soluble E-cadherin might be released into blood from lymphoma cells. Expression of E-cadherin may contribute to the morphological appearance of some malignant lymphoma, although no conclusion can be drawn based on such small number of patients analyzed.     

Analysis of IL-18 bioactivity and IL-18 mRNA in three patients with adult T-cell leukaemia, acute mixed lineage leukaemia, and acute lymphocytic leukaemia accompanied with high serum IL-18 levels

Interleukin-18 (IL-18) bioactivity in sera and IL-18 mRNA expression in leukaemia cells of three patients with adult T-cell leukaemia (ATL), acute mixed lineage leukaemia (AMLL) and acute lymphocytic leukaemia (ALL) accompanied with high serum IL-18 levels have been analysed. There was little serum IL-18 bioactivity in the three patients with ATL, AMLL and ALL, while IL-18 mRNA expression was detected in leukaemia cells of all three patients.     

Nodal gamma/delta T cell lymphoma in complete remission following allogeneic bone marrow transplantation from an HLA-matched unrelated donor

Gamma/delta T cell lymphoma is very rare, and usually occurs as an extranodal tumor. We describe the case of a 16-year-old Japanese man with an unusual nodal gamma/delta T cell lymphoma with generalized lymphadenopathy and bone marrow involvement. No tumor involvement was observed in the liver, spleen, or nasal cavity. Examination for surface antigens on lymphoma cells revealed a unique phenotype, positive for CD3 and T cell receptor (TCR) gamma/delta, but negative for CD2. Genotypic analysis revealed the tumor to be of monoclonal origin and characterized by TCR gamma-chain gene rearrangement, but there was no rearrangement of the TCR beta-chain gene. Our patient's tumor responded to combination chemotherapy and subsequent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. He has remained well and free of disease for 35 months.     

Chronic GVHD with polymyositis after non-myeloablative stem cell transplantation

A 57-year-old man underwent an autologous hematopoietic stem cell transplant for mantle cell lymphoma in August 1999. Anemia and thrombocytopenia appeared in November 2001. He was diagnosed with further hematological examination as having acute myeloid leukemia with multilineage dysplasia following secondary myelodysplastic syndrome. He received the allogeneic hematopoietic stem cell transplant from his HLA DRB1 locus mismatched brother in May 2002. The nonmyeloablative preparative regimen consisted of fludarabine 30mg/m2 for 6 days and busulfan 4mg/kg for 2 days. Eosinophilia, decrease of lacrimal fluid and liver dysfunction appeared on Day 104. We diagnosed this as chronic GVHD and treated the patient with prednisolone 10 mg/day. Thereafter, his chronic GVHD gradually improved. He had fever and myalgia in the extremities and lumbar region with elevated serum CPK and aldolase in January 2003. Histological examination led to a diagnosis of polymyositis simultaneously with chronic GVHD. Prednisolone 50 mg/day as an initial dose was started for the polymyositis following which the prednisolone dose was gradually tapered off. The polymyositis improved promptly after the administration of prednisolone and remains in remission with a current maintenance program of prednisolone 5 mg/day.     

Mycosis fungoides terminating in acute myelocytic leukemia

A 57-year-old woman was admitted to our hospital with suspected leukemia in September 1999. In 1990, systemic erythema had occurred, and mycosis fungoides (MF) had been diagnosed by skin biopsy. Interferon-gamma therapy had not been effective, and the erythema had disappeared after treatment with psoralen and ultraviolet A (PUVA) therapy (1.46 J/cm2). The patient had subsequently done well with a course of topical steroids. On admission this time, the WBC count was 1,600/microliter with 6% blasts. The total nucleated cell count in a bone marrow aspirate was 43.1 x 10(4)/microliter, of which 86.2% were peroxidase-positive blasts. Acute myelocytic leukemia (AML) was diagnosed. Chromosomal analysis demonstrated abnormalities of 48, XX, +4, +8, +add(10)(p11), add(11)(q23) in 10 of 20 cells, and 51, idem, +6, +8, +21, +mar in 8 cells with mixed-lineage leukemia gene rearrangement. Therapies (radiation, chemotherapy and PUVA) for MF, and the altered immune response seen in patients with this disease, especially in the more advanced stages, collectively termed cutaneous T-cell lymphoma (CTCL), suggest that such patients may be at increased risk of a second primary malignancy. To our knowledge, AML has been reported in 8 MF patients including the present one. Attention should be given to the possibility of MF terminating in AML.     

Successful treatment with reduced-intensity stem cell transplantation in a case of relapsed refractory central nervous system lymphoma

A 33-year-old male with refractory relapsed central nervous system lymphoma underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-identical sibling after reduced-intensity conditioning chemotherapy. The preparative regimen for allo-HSCT consisted of fludarabine and busulfan. Cyclosporine (CsA) and short-term methotrexate were used as prophylaxis for acute graft-versus-host disease (GVHD). Although CsA was quickly reduced to induce a graft-versus-lymphoma (GVL) effect, no symptoms of GVHD and GVL effect were evident. Donor lymphocyte infusion (DLI) was performed on day +40 following transplantation. The patient developed acute GVHD (grade III) after DLI, and lymphoma regression was observed after the occurrence of GVHD. Four months after transplantation, complete remission was achieved with extensive chronic GVHD, and the patient continues to be disease free at 15 months after transplantation.     

Intensified conditioning regimens improved disease-free survival and engraftment after unrelated single-unit cord blood transplantation but not after matched sibling or matched unrelated donor allogeneic hematopoietic cell transplantation

The impact of conditioning intensity on different donor groups has been unclear in allogeneic transplantation. The objective of this study was to clarify the effect of conditioning intensity on disease-free survival (DFS), relapse, non-relapse mortality (NRM), neutrophil engraftment, and graft-versus-host disease for each donor type. We retrospectively evaluated the effect of conditioning intensity on transplant outcomes for patients with acute leukemia or myelodysplastic syndrome aged between 16 and 60 years in Japan using the transplant conditioning intensity (TCI) scoring system. A total of 8526 patients who received first allogeneic transplantation from 6/6 antigen-matched sibling donor (MSD, n = 2768), 8/8 allele-matched unrelated donor (MUD, n = 2357), and unrelated single-cord blood (UCB, n = 3401) were eligible for the analyses. Compared to conditioning with TCI score 4.0, which was corresponds to conventional myeloablative conditioning, including cyclophosphamide with total body irradiation 12 Gy or busulfan 12.8 mg, and was considered as the reference group in the multivariate analyses, intensified conditioning with TCI score ≥4.5 improved DFS (hazard ratio [HR],0.81, P < 0.001) and relapse rate (HR, 0.70, P < 0.001) but only after UCB transplants and not MSD and MUD transplants. In contrast, NRM was higher after intensified conditioning with TCI score ≥4.5 for MSD (HR, 1.39, P = 0.008) and MUD (HR, 1.47, P = 0.002) transplants but not UCB transplants (HR, 1.12, P = 0.240). Neutrophil engraftment was also significantly higher after intensified conditioning with TCI score ≥4.5 but only for UCB transplants (HR, 1.24, P < 0.001), whereas it was significantly lower after reduced-intensity conditioning with TCI score ≤3.5 for MSD transplants only (HR, 0.82, P < 0.001). These data demonstrated that an intensified conditioning regimen improved survival and engraftment rate only after a UCB transplants. Therefore, TCI scoring system could enable the optimization of conditioning intensity according to donor type, particularly in terms of survival and engraftment.