["Hetero to homo" allogeneic bone marrow transplantation from a related donor with two HLA loci mismatch].

We describe a 46-year-old HLA-homozygous female patient with CML who received a bone marrow transplant from her son, who had two HLA (A, B) loci mismatch. After conditioning with total body irradiation plus cyclophosphamide, the patient received 4.8 x 10(8) bone marrow cells/kg. Cyclosporin and short-term methotrexate were used for GVHD prophylaxis. She successfully established rapid engraftment with no acute GVHD, and later developed chronic but mild GVHD. Family members with two HLA loci mismatch may be considered as candidate donors for "hetero to homo" bone marrow transplantation.

[Adult acute lymphoblastic leukemia presenting a near haploid karyotype].

Thirty cases of childhood acute lymphoblastic leukemia (ALL) with a near haploid karyotype (< 30 chromosomes) have been reported so far. However, despite a few cases of severely hypodiploid (30-39 chromosomes) ALL, no near haploid cases have been reported in adult patients. Here, we describe a 64-year-old woman with ALL (L2, CD10+ 19+ 34+ HLA-DR+) presenting a near haploid karyotype of 27, X, +X, +6, +10, +21/54, idem x 2. She died of septic shock during complete remission 6.5 months after the diagnosis.

Cytotoxic T-cell lymphoma diffusely involving the entire gastrointestinal tract associated with Epstein-Barr virus and tubercle bacilli infection.

We describe a rare case of cytotoxic gastrointestinal T-cell lymphoma with protein-losing enteropathy. Initial examination revealed the coexistence of T-cell lymphoma and tuberculosis in the mesenteric lymph node and liver. Despite anti-tuberculosis and anti-cancer treatment, the patient experienced chronic diarrhea and malabsorption and died approximately 3 years after onset. Autopsy specimens revealed medium-sized lymphoma cells, with a phenotype of CD3+, CD4-, CD7+, CD8+, CD30-, CD56-, CD103 (HML-1)-, TIA-1+, and granzyme B+, proliferating primarily and consistently in the mucosa of the entire bowel tract from esophagus to rectum. Interestingly, Epstein-Barr virus (EBV)-encoded small nuclear RNAs were detected in the tumors by in situ hybridization. Southern blot analysis revealed monoclonal proliferation in the EBV-infected T cells. Although the present case can possibly be categorized as an intestinal T-cell lymphoma according to the Revised European-American Lymphoma Classification, the case showed a unique clinical course and distribution of lymphoma cells. We present here an interesting case of gastrointestinal cytotoxic T-cell lymphoma and examine the possible association with infectious agents.

Primary macroglobulinemia with t(11;18)(q21;q21).

These are the first cases of primary macroglobulinemia (PMG) with t(11;18)(q21;q21) reported in the literature. The first case was a 77-year-old man with macroglobulinemia (serum IgM: 8.36 g/dL). Abnormal lymphoid cells were detected in the blood and bone marrow. Immunologic and karyotypic analyses revealed that abnormal cells were positive for surface IgM-k, CD19, and CD20, negative for CD5 and CD10, and all had a t(11;18)(q21;q21). The second case was a 57-year-old woman with macroglobulinemia (serum IgM: 12.0 g/dL). Abnormal lymphoid cells were detected in blood and marrow, and cells were positive for surface IgM-lambda, CD19, and CD20, and negative for CD5 and CD10. Plasma cells bearing cytoplasmic IgM-lambda were increased in pleural fluid. Karyotyping demonstrated t(2;11;18)(q21-23;q21;q21). Rearrangements within BCL2 and YES genes located at 18q21 were not detected. Sixteen other cases with t(11;18)(q21;q21) have been reported in marginal zone B-cell lymphoma. Therefore, our report is in agreement with the finding that part of primary macroglobulinemia is a variant of marginal zone B-cell lymphoma.

Epstein-Barr virus-associated T cell lymphoproliferative disorder following autologous blood stem cell transplantation for relapsed Hodgkin's disease.

Post-transplant lymphoproliferative disorders (PTLD) of T cell type are a rare complication of solid organ and allogeneic hematopoietic cell transplantation (HCT), and usually are not associated with Epstein-Barr virus (EBV) infection. EBV-associated T cell PTLD has not been reported to occur after autologous HCT. We report an unusual case of T cell lymphoproliferation after autologous blood stem cell transplantation (ABSCT). A patient with relapsed Hodgkin's disease developed abdominal lymphadenopathy followed by atypical CD8+ lymphocytosis in the peripheral blood 30 months following ABSCT. DNA studies of the atypical lymphocytes demonstrated rearrangements of the T cell receptor beta gene and a clonal proliferation of EBV.

[Detection of t(3 ; 21) (q26 ; q22) with AML1/EVI1 mRNA during progression of myelodysplastic syndrome to acute myeloid leukemia].

A 74-year-old woman had myelodysplastic syndrome (MDS) in 1986. In June 1994, she suffered exacerbation of pancytopenia with no chromosomal abnormalities, but AML1/EVI1 chimeric mRNA was detected by RT-PCR. Two months later, an increase in bone marrow blasts (5%) was noted, and chromosomal analysis detected t(3 ; 21) (q26 ; 22), del(7) (q22), del(11) (q23). In 1995, the marrow blasts increased to 30% and the patient died of disease progression. The AML1/EVI1 gene has been shown to cause blast crisis in chronic myelogenous leukemia. This case suggested that the AML1/EVI1 gene may be involved in the progression of MDS together with del(7) (q22) and del(11) (q23).

A new multiple myeloma cell line, MEF-1, possesses cyclin D1 overexpression and the p53 mutation.

BACKGROUND: The t(11;14)(q13;q32) translocation with cyclin D1 overexpression commonly is found in multiple myeloma (MM) and in mantle cell lymphoma (MCL). Several reports have shown that p53 mutations in MCL lead to blastoid transformation and a worse prognosis; however, the role of p53 mutations in MM with t(11;14) is unclear. METHODS: In this study the authors describe a patient with MM with t(11;14) and a p53 mutation at presentation and characterized a cell line, MEF-1, established from this patient. Immunohistochemical analysis of p53 and cyclin D1 proteins was performed. The p53 gene was analyzed by polymerase chain reaction-single strand conformation polymorphism and direct sequencing. The expression of cyclin D1 mRNA was examined by Northern blot analysis. RESULTS: MEF-1 had t(11;14) with overexpression of cyclin D1 mRNA and produced immunoglobulin kappa-light chain. MEF-1 had a mutation in exon 7 (codon 255-257) of the p53 gene, which was noted in the patient's myeloma cells. CONCLUSIONS: p53 mutations may be important genetic events in disease progression of MM with t(11;14). The MEF-1 cell line may be a useful tool to study mechanisms of progression in MM based on abnormalities of the cyclin D1 gene.

Gene expression of erythropoietin in renal cell carcinoma.

A 57-year-old man with renal cell carcinoma and erythrocytosis showed a high serum level of erythropoietin (EPO). High EPO signal was observed on Northern blot analysis and RT-PCR in the total RNA extracted from the renal tumor. Immunohistochemical staining also demonstrated tumor tissue with high immunostaining of EPO. Nucleotide sequences of EPO cDNA in the tumor were normal. To date, only one report has discussed the nucleotide sequences of a tumor's EPO gene; it showed mutant EPO cDNA in hepatocellular carcinoma tissue. This is the first demonstration of normal EPO cDNA in renal cell carcinoma.

Successful treatment of a patient with cardiac lymphoma who presented with a complete atrioventricular block.

A patient with primary cardiac lymphoma, which is very rare, generally is regarded to have a poor prognosis. We herein report a patient with cardiac lymphoma who was treated successfully by systemic chemotherapy and radiotherapy using a pacemaker to control the complete atrioventricular (A-V) block. A 70-year-old man had a syncope caused by a complete A-V block. An echocardiogram, a computed tomographic scan, and magnetic resonance imaging of his chest showed a cardiac tumor. At this time, a biopsy of the cardiac tumor disclosed malignant lymphoma (diffuse large cell type, B cell type). The patient was thus treated with systemic chemotherapy and radiotherapy and, as a result, achieved a complete remission with a disappearance of the A-V block. Recently, several successful outcomes involving primary cardiac lymphoma have been reported because of the progress in diagnostic techniques including echocardiography, computed tomographic scanning, and magnetic resonance imaging, as well as improvement in the therapy of malignant lymphoma. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate therapy can thus help in obtaining a long survival in patients with primary cardiac lymphoma.

Soluble Fas in the serum of patients with non-Hodgkin's lymphoma: higher concentrations in angioimmunoblastic T-cell lymphoma.

The soluble form of Fas (sFas) can block apoptosis induced by the Fas ligand in vitro. A recent report demonstrated that mice injected with sFas displayed autoimmune features. Therefore, an elevated serum concentration of sFas may be associated with lymphoproliferation and autoimmune diseases. We measured the serum concentrations of sFas in 77 patients with non-Hodgkin's lymphoma (NHL) [8 angioimmunoblastic T-cell lymphoma (AIL), 12 T-cell NHL, 53 B-cell NHL, and 4 natural killer-cell NHL]. Elevated concentrations of sFas were detected only in AIL, which is frequently accompanied by autoimmune diseases (P < 0.005 compared with age-matched controls). A possible association of sFas and autoimmune features in AIL is discussed.

Adult T-cell leukemia-lymphoma successfully treated with 2-chlorodeoxyadenosine.

Adult T-cell leukemia-lymphoma (ATL) is resistant to currently available chemotherapy and has a poor prognosis. We describe here a patient with ATL successfully treated with 2-chlorodeoxyadenosine (2-CdA). A 75-year-old Japanese male with an acute type of ATL, who had become resistant to the initial cytotoxic chemotherapy, was treated with 2-CdA administered by continuous drip infusion of 0.09 mg/kg/d for seven consecutive days in one month (one cycle). After three cycles of treatment, partial remission (PR) was achieved. Surprisingly, 249 days after the administration of 2-CdA, ATL cells completely disappeared from the peripheral blood. PR was maintained during 10 weeks until evidence of a new lymphadenopathy. No remarkable toxicity of 2-CdA occurred.

Immunoglobulin class switch from IgA1 to IgG2 and simultaneous association with Bence Jones proteinuria in the escape phase in a myeloma patient treated with interferon alpha.

Immunoglobulin (Ig) class switch from alpha1 to gamma2 associated with kappa-type Bence Jones proteinuria was evident in the escape phase of an IgA1 myeloma patient treated with interferon alpha (IFN alpha). The additional M-protein, IgG2-kappa, level rapidly increased and was associated with Bence Jones proteinuria, whereas monoclonal IgA1-kappa progressively declined. The N-terminal 21 amino acid sequences of the kappa-chains of monoclonal IgA1, IgG2 and the Bence Jones protein were the same. The N-terminal 15 amino acid sequence of the gamma2-chain was identical to that of the alpha1-chain. Based on these findings, the IgA1 myeloma cells underwent a class switch in CH gene expression from alpha1 to gamma2 with cell differentiation in vivo. The mechanism of the Ig class switching is discussed from three points of view: (1) Increase in immature and plasmablastic myeloma cells in the escape phase is susceptible to Ig class switching by the T-cell-derived cytokines. (2) We presumed that administered IFN alpha increased the amounts of secreted IFN gamma from the Th1 cells. (3) Due to a large quantity of IFN gamma, an inducer of Cgamma2 germline transcript, Ig class switching occurred stepwise from the alpha1 constant region gene to the next 3'CH gamma2 gene.

Biphenotypic blast crisis of chronic myelogenous leukemia: abnormalities of p53 and retinoblastoma genes.

The molecular mechanisms responsible for progression of chronic myelogenous leukemia (CML) to blast crisis have not been well defined. Blast crisis may be partially related to inactivation of tumor suppressor genes/such as p53 or retinoblastoma (Rb) gene. There is evidence for an association of blast cell phenotypes in CML with alterations of these genes: a strong association of myeloid phenotypes with abnormalities of the p53 gene and a weaker association of lymphoid phenotypes with abnormalities of the Rb system. We found a marked decrease in Rb gene product and rearrangements of the p53 gene simultaneously in two cases of biphenotypic blast crisis of CML (myeloid and B-lymphoid). These results support the association of blast cell phenotypes with alterations in tumor suppressor genes in CML blast crisis.

Parvovirus B19-associated haemophagocytic syndrome with lymphadenopathy resembling histiocytic necrotizing lymphadenitis (Kikuchi's disease).

A 15-year-old girl developed a haemophagocytic syndrome caused by human parvovirus B19 (PVB19). The cervical lymph node histology, resembling that of histiocytic necrotizing lymphadenitis (HNL, Kikuchi's disease), included several transformed lymphocytes, numerous histocytes, and massive necrosis. We detected PVB19-positive cells in the lymph node by immunohistochemistry. Possible autoimmune mechanisms in HNL-like diseases triggered by PVB19 are discussed.

Interaction of BCR-ABL with the retinoblastoma protein in Philadelphia chromosome-positive cell lines.

The tyrosine kinase activity of BCR-ABL fusion proteins plays an important role in the pathogenesis of leukemia that is for the Philadelphia chromosome (Ph1). Because nuclear c-ABL is regulated during the cell cycle through a specific interaction with the retinoblastoma protein (pRB), the possible interaction of BCR-ABL with pRB in Ph1-positive cell lines was investigated. P145 c-ABL as well as P190 and P210 BCR-ABL proteins interacted with pRB. Furthermore, c-ABL and BCR-ABL associated with both phosphorylated and nonphosphorylated forms of pRB. These findings suggest that BCR-ABL interferes with pRB function and thereby regulates cell growth.

[Successful treatment with combination of all-trans retinoic acid (ATRA) and rhG-CSF a relapsed acute promyelocytic leukemia with umbilical tumor].

A 48-year-old female was admitted to our hospital because of pancytopenia and pneumonia in February, 1993. The increase of abnormal promyelocytes with t (15; 17) and PML-RAR mRNA was detected in bone marrow aspirate and a diagnosis of acute promyelocytic leukemia was made. She obtained complete remission after the administration of all-trans retinoic acid (ATRA) and following chemotherapy. Then she received peripheral blood stem cell transplantation in September, 1993. However she noticed a umbilical tumor in June, 1995. Abnormal promyelocytes were demonstrated not only in bone marrow aspirate but also in the umbilical tumor. Because of the poor response to ATRA and development of fever, a side effect of ATRA, G-CSF and prednisolone were administrated together with ATRA. After the combined therapy, umbilical tumor disappeared and she obtained complete remission again. These findings suggest that combined therapy of ATRA and G-CSF is effective to the low responder to ATRA and that combined use of ATRA and prednisolone reduces the side effect of ATRA without diminishing the favorable effect on differentiation.

[Comparison between monotherapy with imipenem/cilastatin sodium (IPM/CS) and combinations of IPM/CS and other drugs for treating bacterial infections in patients with hematopoietic disorders].

One hundred and nine patients with infections concurrent with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS combination therapy). The following results were obtained. 1. One hundred and nine patients were allocated at random to two groups: 53 patients to IPM/CS monotherapy and 56 patients to IPM/CS combination therapy. Fourteen patients (6 and 8 in the 2 groups, respectively) were excluded from the clinical evaluation. There were not significant differences between the two groups with respect to the background. 2. The efficacy rates of the 2 treatments against bacterial infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0% in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with FUO, 50.5% in 8 patients with pneumonia, and 67.4% in the 48 patients. The differences between the two groups were not significant. 3. Among the drugs used in combination with IPM/CS, antibiotics other than penicillins, cephalosporins, and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7% was obtained. 4. Bacteriologically, 19 and 17 strains were isolated from the IPM/CS monotherapy and combination therapy groups respectively, and the eradication rates were 100% and 88.9% respectively. 5. Side effects were noted in 2 patients in the IPM/CS monotherapy group and 7 in the combination therapy group, but all of these resolved after discontinuation or completion of the treatment. The efficacies against severe bacterial infections in the presence of hematopoietic disorders were not different between IPM/CS alone and IPM/CS in combination with other antibiotics. Adverse reactions were uncommon with the monotherapy.

Expression of EVI1 and the Retinoblastoma genes in acute myelogenous leukemia with t(3;13)(q26;q13-14).

The EVI1 DNA-binding protein gene on chromosome 3q26 has been reported to be activated in some leukemia cells with alterations in 3q26. We present an acute myelogenous leukemia (AML) patient with a rare chromosomal translocation, t(3;13)(q26.2;q13-14). By reverse transcription-polymerase chain reaction, we detected active transcription of the EVI1 gene in the patient's leukemia cells. The retinoblastoma susceptibility (Rb) gene, a tumor-suppressor gene, is located at chromosome 13ql4 and is within the other translocation breakpoint in this patient. The expression of the Rb gene product was found to be substantially decreased in the patient's leukemia cells by Western blotting. Southern blot analysis, however, revealed no gross abnormalities of the Rb gene. Although it is unlikely that the Rb gene is directly involved in this translocation, the loss of the Rb gene product combined with the activation of the EVI1 gene may have led to the development of leukemia.

Case report: primary splenic non-Hodgkin's B cell lymphoma in a patient with chronic hepatitis C.

A case of primary splenic lymphoma in a patient with chronic hepatitis C is reported. A 69-year-old man with chronic hepatitis C was admitted to Fukuoka City Hospital for evaluation of an enlarging splenic tumour. In the spleen, ultrasonographic examination revealed a hypoechoic tumour and computed tomography demonstrated a non-enhancing low density area measuring 7 cm in diameter; coeliac angiography revealed a hypovascular tumour. Gallium scintigraphy showed uptake of the radioisotope in the splenic tumour. A splenectomy was performed and the morphological and immunohistochemical findings of this tumour were compatible with those of non-Hodgin's B cell lymphoma. Recently, cases of malignant B cell lymphoma associated with hepatitis C virus infection have been reported. Lymphotropism of hepatitis C virus may play a pathological role in the development of non-Hodgkin's lymphoma. We emphasize the importance of considering lymphoma in the differential diagnosis of extrahepatic disorders during the course of chronic hepatitis C virus infections.