Biomedical subjects

R Sobue

Publications and source records attributed to R Sobue.

At least 19 recordsLinked to original sources

PubMed1999

Cytotoxic large T-cell lymphoma with fulminant clinical course, CD8+ and CD56- phenotype, and its relation to Epstein-Barr virus: a report of two cases.

Currently, the immunohistochemical evaluation of cytotoxic granule-associated proteins such as TIA-1 and granzyme B can be carried out on paraffin sections. This procedure has broadened our knowledge of cytotoxic lymphoid neoplasms. Their detection is now regarded as a useful adjunctive in some characterizations of cytotoxic T- or natural killer (NK)-cell lymphoma, mostly in lymphoma of extranodal origin. We report two cases of nodal cytotoxic large T-cell lymphoma with identical biologic properties. Both cases presented with systemic lymphadenopathy, lymphomatous bone marrow involvement, and thrombocytopenia. The clinical course was fulminant, and both patients died within 1 week of presentation. The cells had a characteristic immunophenotype of CD2+, CD3+, CD4-, CD5-, CD8+, CD30 -/+, CD56-, CD57-, TCR alpha/beta+, and TCR gamma/delta-. They also expressed the cytotoxic granule-associated proteins of TIA-1 and granzyme B, and exhibited clonal rearrangements of the T-cell receptor beta chain gene. Monoclonal integration of Epstein-Barr virus was also detected. The present cases exhibited clinicopathological features that were distinct from other types of malignant lymphoma expressing cytotoxic granule-associated proteins.

Adult↗

PubMed1997

Functional expression of Fas (CD95) in acute myeloid leukemia cells in the context of CD34 and CD38 expression: possible correlation with sensitivity to chemotherapy.

Clinical studies of bone marrow transplantation (BMT) suggest that the immune system contributes to the eradication of acute myeloid leukemia (AML). A recent study also showed that the Fas (CD95/APO1) mediates apoptotic signal from cytotoxic T lymphocytes. Sixty-four patients with AML were studied for the expression of Fas in the context of CD34 and CD38 coexpression. The clinical relevance of Fas expression and function on AML was also investigated. Fas was expressed on 2% to 98% of AML cells (2% to 20% in 11 patients, 20% to 50% in 20 patients, 50% to 80% in 24 patients, and 80% to 98% in nine patients). Only 44.4% of patients with AML M1 (French-American-British [FAB] classification) were Fas+ (>/=20% of leukemia cells expressed Fas), whereas 89.1% of patients with AML M2, M3, M4, M5 were Fas+ (P < .01). Among 43 CD34+ patients (>/=20% leukemia cells were CD34+), 34 were Fas+, and 19 of 21 CD34- patients were Fas+ (P = NS). Thirteen cases were studied for their expression of Fas in the context of CD34 and CD38 using three-color analysis. Fas is expressed at a high level in the gated CD34+CD38+/- and CD34+CD38+ population. In 10 AML samples, Fas was expressed at a higher level in CD34+/CD38+ population than in CD34+/CD38+/- or CD34- cell populations. Fas-induced apoptosis by anti-Fas monoclonal antibody (MoAb) was determined by morphologic features and colorimetric DNA fragmentation assay. Induction of apoptosis was found in 14 of 24 cases. However, no statistically significant correlation was observed between Fas expression and induction of apoptosis. Leukemia colony-forming unit assays suggested that in some cases, Fas-induced apoptosis occurred in the clonogenic cell populations. Parameters such as laboratory and clinical data at initial diagnosis were correlated with Fas expression and only response to initial induction chemotherapy showed significant correlation with Fas expression (P < .05). We conclude that the majority of AML cells exhibit variable expression of Fas, and apoptosis could be induced by anti-Fas MoAb in some cases. Our results suggest the Fas-mediated apoptosis may be clinically relevant, whereas the issue of clonogenic leukemia cells and Fas expression needs further studies.

ADP-ribosyl Cyclase↗

PubMed1995

Interleukin-1 beta (IL-1 beta) and acute leukemia: in vitro proliferative response to IL-1 beta, IL-1 beta content of leukemic cells and treatment outcome.

We evaluated the in vitro proliferative response to exogenous IL-1 beta in terms of tritiated thymidine (3H-TdR) incorporation in leukemic cells obtained from 119 patients with various types of acute leukemia. The content of IL-1 beta in leukemic cells was measured by enzyme-amplified sensitivity immunoassay. We observed a significant proliferative response to exogenous IL-1 beta in leukemic cells from 27/66 patients with de novo AML, 1/29 patients with ALL, 2/3 patients with AUL, 8/12 patients with AML arising from MDS, 4/7 patients with myeloid crisis of CML, and 0/4 patients with lymphoid crisis of CML. Proliferation was marked in myeloid leukemic cells of a more premature stem cell origin. There were no significant differences in proliferative responses among the different FAB classes of de novo AML. The IL-1 beta content of leukemic cells was low in patients with lymphoid leukemia, but there was no significant difference among the various types of myeloid leukemia. There was no correlation between the proliferative response to exogenous IL-1 beta and the IL-1 beta content of leukemic cells. When we correlated the proliferative response to exogenous IL-1 beta with treatment outcome in patients with de novo AML, we found the rate of complete remission (CR) to be lower in those with a high proliferative response. We noted a longer duration of CR (p = 0.07) and of survival (p < 0.05) in patients with a low proliferative response. Thus, a high proliferative response to IL-1 beta in the cells of AML patients may indicate a poor prognosis.

Acute Disease↗

PubMed1994

Translocation (3;21)(q26;q22) in treatment-related acute leukemia secondary to acute promyelocytic leukemia.

We performed cytogenetic studies in a patient with treatment-related acute leukemia (t-AL) to identify the associated chromosomal changes. Metaphase analysis revealed a t(3;21)(q26;q22) translocation. Acute promyelocytic leukemia (APL) had been diagnosed 4 years earlier and the patient had received intensive induction chemotherapy and sequential post-induction therapy that included agents that targeted DNA-topoisomerase II (topo II). This case suggests an association between previous therapy with topo II inhibitors and development of t-AL associated with a balanced aberration involving the 3q26 and 21q22 bands.

Acute Disease↗

PubMed1994

[CAMBO-VIP for advanced diffuse large cell lymphoma (LSG classification)--a long-term follow-up study].

Twenty-two patients with advanced diffuse large cell lymphoma (LSG classification) were treated with the combination chemotherapy of cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide and prednisolone (CAMBO-VIP) from Oct. 1987 to Sept. 1989. Eighteen (90%) of 20 evaluable patients achieved complete remission and 2 patients had partial remission. With a median follow-up of 52 mos, 3 patients relapsed (17%), and 2 patients died. The actuarial overall survival and relapse-free survival at 4 years were estimated to be 90% and 83%, respectively. Myelosuppression was severe, but transient. No serious infection was seen, and no platelet transfusion was required. Oral mucositis and liver damage (Grade 3 in WHO grading) was seen in one patient each, but no treatment-related fatalities were observed. CAMBO-VIP is a well tolerated, effective treatment regimen for advanced diffuse large cell lymphoma.

Adolescent↗

PubMed1994

[Increased blood cell destruction during vigorous regeneration of bone marrow after CAMBO-VIP chemotherapy for non-Hodgkin's lymphoma].

Alternating non-cross-resistant chemotherapy has been induced for the treatment of non-Hodgkin's lymphoma (NHL) with the aim of cure, even in advanced cases. We formulated a new high dose regimen, CAMBO-VIP, which was a weekly treatment. They were administered during alternate weeks for a total period of 12 weeks. We obtained high response rate and prolonged disease-free survival with this regimen. We noticed the elevation of serum LDH level in some patients at or shortly after the completion of CAMBO-VIP treatment. LDH elevation was not associated with liver function abnormality in terms of elevation of GOT or total bilirubin. All of these patients were in complete or partial response with no evidence of tumor progression. An LDH isozyme study which was done at the time of LDH elevation showed elevation of both LDH1 and LDH2. Interestingly serum haptoglobin was undetectable in all 6 patients measured at the time of LDH elevation. Reticulocytosis and leukoerythroblastosis in peripheral blood were also observed in all of these patients. These abnormalities including LDH elevation returned to normal within a rather short period, usually within 1 to 3 weeks. From these observations, it is most likely that these abnormalities were due to excessive blood cell destruction, which was observed in association with rapid recovery from myelosuppression.

Adolescent↗

PubMed1994

[Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank].

One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.

Adolescent↗

PubMed1994

[Coordination of unrelated bone marrow donors in the Tokai Bone Marrow Bank--psychological reactions of donors to donation].

The Tokai Bone Marrow Bank was established in 1989 and coordinated 1,415 patients with 3,000 HLA-A, B-typed donors. Of the 1,415 patients, 757 patients had HLA-A, B-identical donors, 206 patients had HLA-DR-identical donors, and 80 patients had MLC-compatible donors. Finally, 55 unrelated donor bone marrow transplantations were done. The most frequent reason of interruption in coordination was disagreement of donor's family. We sent several questions by mail around 1 month after the donation to 55 donors to analyze the psychological reactions of unrelated bone marrow donors to donation. Donors were generally quite positive about the donation. 92% of the donors felt it was worthwhile and no one felt it was not at all worthwhile. 73% of the donors would be willing to donate again in the future. 79% of donors would like to know the clinical course of the patient after the bone marrow transplantation. We hope that these results may be helpful in the development of the Japan Marrow Donor Program.

Bone Marrow↗

PubMed1994

Severe rhabdomyolysis as a complication of peripheral blood stem cell transplantation.

We present a case of severe rhabdomyolysis developing after peripheral blood stem cell transplantation (PBSCT) in a 17-year-old woman with Ki-1 lymphoma. Severe muscle weakness, myoglobinemia and acute renal failure developed on day 23 following PBSCT associated with painful peripheral neuropathy. Cytomegalovirus infection may have been a contributory factor.

Acute Kidney Injury↗

PubMed1994

[Salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide and carboplatin].

Seventeen patients with refractory or relapsed, intermediate or high grade non-Hodgkin's lymphoma (NHL) were treated with the combination of dexamethasone (40 mg/body x 3d, iv) (DeVIC) between January and December 1992. The treatments were repeated every three weeks for a minimum of two courses unless the patient had PD. G-CSF (2 micrograms/kg, sc) was given during leukopenia in most cases. Of 16 evaluable patients 6 (38%) achieved a complete remission (CR) and 4 showed a partial remission. With median follow up of 15 (7-26) months (mos.) all CR patients were alive in CR, except for 1 patient who died of secondary AML. The actuarial 50% survival duration after DeVIC was 15+ mos. One patient died of sepsis but myelosuppression was generally moderate and no other serious toxicity was observed. Although this is a preliminary study, DeVIC regimen seems to be an effective salvage therapy for patients with refractory or relapsed NHL with acceptable toxicity.

Adolescent↗

PubMed1993

Autologous BMT in high risk patients with CALLA-positive ALL: possible efficacy of ex vivo marrow leukemia cell purging with monoclonal antibodies and complement.

Autologous BMT (auto-BMT) has been conducted for 17 high-risk common ALL antigen (CALLA)-positive non-T cell type ALL patients. Ex vivo purging of leukemia cells from infused BM cells was performed using complement and three kinds of mouse monoclonal antibodies reactive to CALLA-positive leukemia cells: NL-1 (IgG2a), NL-22 (IgM), and HL-47 (IgM). Minimal residual leukemia cells in BM were examined by PCR method in Philadelphia chromosome (Ph1)-positive ALL cases. BCR/ABL chimeric transcript, which was positive in BM samples before purging, was shown to be absent after ex vivo purging in all three cases tested. Among four Ph1-positive cases transplanted in first CR, three cases survived in CR remission 77, 29 and 26 months after BMT, and one case died without relapse 4 months after BMT. The other four Ph1-negative cases transplanted in the first CR also remained in CR except one who relapsed. The results of minimal residual leukemia cell studies and clinical data indicate the effectiveness of our ex vivo leukemia cell purging method and auto-BMT in the early stage of CR for patients with high risk ALL.

Adolescent↗

PubMed1993

[A study of toxicities and complications observed in alternating non-cross-resistant chemotherapy (CAMBO-VIP) for non-Hodgkin's lymphoma].

Thirty-nine patients with non-Hodgkin's lymphoma were treated with weekly alternating non-cross-resistant chemotherapy (CAMBO-VIP). We obtained a high response rate, and prolonged disease-free survival with side effects and complications of various severity were observed. Three patients were withdrawn from the study due to aggravation of liver cirrhosis, cerebral infarction, and poor tolerance. Thirty-six patients completed this 12-week intensive chemotherapy. The median treatment delay in all patients was 3 days (-4 to 29 days), and a delay of over 15 days was seen in 5 patients. The nadir of the neutrophil count was 0 to 2,100/microliters (median 140/microliters), and 15 patients were below 100/microliters. Two patients had pneumonia and 4 had herpes zoster infection. The platelet count nadir was 20,000 to 240,000/microliters (median 90,000/microliters). Ten patients were below 50,000/microliters, but none required platelet transfusion. Red cell transfusion was given in 6 patients. Elevation of transaminases was seen in 25 patients, but it was not serious except for a patient with liver cirrhosis. The elevation of serum LDH level and decrease of serum haptoglobin level seen shortly after completion of treatment seemed due to the increased blood cell destruction. Stomatitis was observed in 32 patients, 17 of whom showed more than grade 3 toxicity. Blister formation on palms and/or soles was noted in 6 patients. There was no treatment-related death observed.

Adolescent↗

PubMed1993

[Rearrangements of immunoglobulin light chain and heavy chain constant region genes in B-cell malignancies].

We analyzed immunoglobulin (Ig) gene rearrangements in 69 patients with B-cell malignancies by Southern hybridization. We used 5 probes which covered JH 5'S mu and S gamma 3 loci of the Ig heavy (IgH) chain gene, and C kappa and kappa de loci of the Ig light (IgL) chain kappa gene, respectively. DNA rearrangements were observed in 68 out of the 69 patients using the JH probe. In 97% (33/34) of patients with non-Hodgkin's lymphoma (NHL), 100% (5/5) of chronic lymphocytic leukemia (CLL), 42% (10/24) of non-T cell acute lymphoblastic leukemia (non-T ALL), and in 0% (0/4) of chronic myelogenous leukemia lymphoid crisis (CML-LBC), the rearrangements were detected by C kappa and/or kappa de probes. Furthermore, the genotype of the light chain was defined by rearrangement patterns of these 2 probes. The by using the 5'S mu-probe, class switch recombinations were detected in 76% (25/33) of NHL, 20% (1/5) of CLL, 17% (4/24) of non-T ALL, and in 0% (0/4) of CML-LBC. Among them, 1 case of IgM NHL and 3 cases of double bearer NHL had rearranged on both IgH alleles by the constant region. The results of this study indicate that genotypes correspond well to phenotypes of B-cell malignancies and that the determination of genotype will be useful for making an exact diagnosis of B-cell malignancies.

DNA, Neoplasm↗

PubMed1992

Alternating non-cross-resistant chemotherapy for non-Hodgkin's lymphoma of intermediate-grade and high-grade malignancy. A pilot study.

Thirty-two patients with advanced non-Hodgkin's lymphoma (NHL) with aggressive histologic findings were treated with cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide, and prednisolone (CAMBO-VIP), in which presumably non-cross-resistant myelosuppressive and nonmyelosuppressive agents were administered during alternate weeks for 12 weeks. To ensure the high-dose intensity of the protocol, dose reduction and delay in treatment were minimized. Three patients were treated inadequately. Twenty-six (89.7%) of 29 evaluable patients had a complete response, and three had a good partial response. Relapse occurred in four patients, with a median follow-up of 29 months. The actuarial overall survival and disease-free survival were estimated to be 87.6% and 75.9%, respectively. The CAMBO-VIP treatment was well tolerated; myelosuppression was severe but transient and caused no serious infections. Side effects that affected dose intensity were oral ulceration, occurring in 28 patients, and blister formation under the thickened skin of palms and/or soles, followed by desquamation (5 patients). Hepatic toxicity was generally mild to moderate; it was severe in one patient. A 12-week regimen of CAMBO-VIP was effective for advanced NHL with aggressive histologic findings.

Adolescent↗

PubMed1992

[High-dose adjuvant chemotherapy with peripheral blood stem cell transplantation for breast cancer with poor prognosis--a pilot study].

Three patients with breast cancer with poor prognosis were treated with high-dose chemotherapy (HD-CT) and peripheral blood stem cell transplantation (PBSCT) as adjuvant treatment. After radical mastectomy, the consolidation chemotherapy with Adriamycin 50 mg/m2, Cyclophosphamide 1,000 mg/m2, Vincristine 1.0 mg/m2 and Methotrexate 200 mg/m2 with Leucovorin rescue was started. Recombinant human granulocyte colony stimulating factor (rhG-CSF) was also added for early recovery from myelosuppression. This combination chemotherapy was given every 3 weeks for 3 courses, and after the 2nd and 3rd courses, peripheral blood stem cells (PBSC) were collected and cryopreserved. HD-CT with Cyclophosphamide 2,000 mg/m2/day, Thio-TEPA 200 mg/m2/day, and Etoposide 300 mg/m2/day, were administered for 3 consecutive days, and after 48 hours of last doses, frozen-thawed PBSC (6.4-8.9 x 10(4)/kg of CFU-GM) were administered. rhG-CSF was also added. HD-CT and PBSCT were well tolerated, recovery from myelosuppression of the HD-CT was very quick and no serious side effects were observed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

[Multiple hepatosplenic abscesses: successful treatment by continuous intraportal administration of amphotericin B in a case with acute promyelocytic leukemia].

A 40-year-old female was admitted in August 1989 with a diagnosis of acute promyelocytic leukemia (AML; M3). One course of modified-DCMP regimen induced complete remission in September, but she developed spiking fever at a nadir period of WBC after induction chemotherapy. CT revealed multiple hepato-splenic abscesses presumably due to candida infection. She was treated with intravenous administration of amphotericin B (AMPH-B) and other antifungal agents. Despite the hematological remission and prolonged use of these antifungal agents, high fever persisted. A catheter was inserted into the portal vein under ultrasonic-guidance. AMPH-B was administered through the catheter: the initial dose was 3 mg/day and was soon increased to 20 mg/day. Her fever subsided in 1 week, and the sizes of liver abscesses on CT reduced markedly. Chill and hypokalemia were observed during this therapy. The catheter was removed from the portal vein after 29 days. Partial portal vein thrombosis was noted around the catheter tip. This case suggests the usefulness of intraportal administration of AMPH-B in patients with hematological malignancy developing multiple liver abscesses.

Abscess↗

PubMed1992

[Rearrangement of immunoglobulin light chain and heavy chain constant region genes in multiple myeloma].

We analysed immunoglobulin (Ig) gene rearrangements in 28 patients with multiple myeloma by Southern hybridization method. We used 5 probes which cover C kappa and kappa de loci of Ig light chain kappa gene, and JH, 5'S mu and S gamma 3 loci of Ig heavy chain gene. In 11 out of 12 patients with kappa-producing myeloma, DNA rearrangements were observed using C kappa probe. Among them, kappa de region was rearranged in 7 patients and kept germline configuration in 4 patients. In all of 14 patients with lambda-producing myeloma, C kappa region was deleted and kappa de region was rearranged. 5'S mu-probe was very useful for detecting class switch recombination, and furthermore by using S gamma-probe together, S mu-S gamma joining could be detected. In all of 10 patients with gamma-producing myeloma, 5'S mu and S gamma-probes detected the rearranged band of the same size on at least 1 allele, which suggested the presence of S mu-S gamma joinings. In 8 of 10 patients with Bence-Jones myeloma, 5'S mu-probe detected rearranged bands and the presence of class switch recombinations were suggested as observed in other Ig secretory myelomas. In other 2 patients with Bence-Jones myeloma, non-functional class switch recombinations were detected. The results of this study indicated that genotypes corresponded well to phenotypes in multiple myeloma, and further analysis in other types of B cell malignancies will be interesting.

Gene Rearrangement, B-Lymphocyte, Heavy Chain↗

PubMed1991

Human herpesvirus-6 infection in bone marrow transplantation.

Twenty-five pediatric patients who received bone marrow transplantation (BMT) were studied prospectively to determine the relationship between BMT and human herpesvirus-6 (HHV-6) infection by the virus isolation from peripheral blood and/or bone marrow and by determining neutralizing antibodies to HHV-6 during the 2 months following BMT. All of the 25 donors and the recipients were immune to HHV-6 at the time of BMT and the virus was not isolated from them. HHV-6 was isolated from peripheral blood and/or bone marrow mononuclear cells in ten (40%) of the 25 recipients between day 14 and day 22 of BMT, but not from any other day. Two additional recipients showed a significant increase in the antibody titer. Thus, infection with HHV-6 was confirmed in 12 (48%) of the 25 recipients. Four of the 12 developed skin rashes; three of these four had a febrile episode when the virus was isolated, whereas none of the remaining 13 developed the skin rash. These results suggest a frequent infection with HHV-6 only a few weeks after BMT and a close association between the infection with the virus and the development of skin rashes.

Adolescent↗