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Biomedical subjects

R Hanada

Publications and source records attributed to R Hanada.

At least 91 records · Page 5Linked to original sources
PubMed1992

11;13 translocation in acute nonlymphocytic leukemia.

In this paper, we report on a 9-year-old girl with acute nonlymphocytic leukemia (FAB-M5) with a rare chromosome abnormality, t(11;23)(q21;p11). Peripheral blood showed Hb 7.5 g/dl, WBC 3,600 cells/microliters (10% blasts), and platelet count 110 x 10(3) cells/microliters. The bone marrow aspirates showed normal cellularity with 36.7% blasts. On morphological characteristics, micromegakaryocytes were observed, and on chromosome examination the karyotype was shown to be 46,XX,t(11;13)(q21;p11) in all metaphases.

Bone Marrow↗
PubMed1992

Biology of neuroblastomas in Japan found by screening.

Between June 1983 and December 1990, cytogenetic analysis was performed on 82 neuroblastoma patients, including 41 patients found by mass screening. The N-myc copy number was determined in 77 of the 82 patients. Patients were classified into three groups: patients found by mass screening (group A) (n = 41), patients found clinically who were under 12 months of age (group B) (n = 12), and patients found clinically who were over 12 months of age (group C) (n = 29). All patients in group A had hyperdiploid (H-2n) or near-triploid (3n) karyotypes; they were all completely free of tumor for 4-84 months after diagnosis, although one patient relapsed and attained complete remission again. Among those in group B, one patient with a stage 4 tumor had a near-diploid Karyotype (2n) and N-myc amplification, and died 18 months after diagnosis. Another patient aged 2 days with a stage 4S tumor had near-diploid karyotype and N-myc amplification, and died 9 months after diagnosis. Tumors in the remaining 18 patients in group B had hyperdiploid or near-triploid karyotypes, they lacked N-myc amplification, and the patients were free of tumor for 12-89 months after diagnosis. All patients in group C except two have near-diploid or hypotetraploid karyotypes, and 21 of 29 patients died within 18 months. One 13-month-old patient (classified in stage 2) and another 7-year-old patient (stage 2) had near-triploid karyotypes and were alive at 74 and 72 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene Amplification↗
PubMed1991

Infant leukemia in Japan: clinical and biological analysis of 48 cases.

Forty-eight Japanese infants with acute lymphoid leukemia (ALL) (n = 24) and acute nonlymphoid leukemia (ANLL) (n = 24) were analyzed on the basis of clinical and laboratory data. Morphologically, 20 of the 24 infants with ALL were of the FAB L1 type, and 20 of the 24 infants with ANLL were of the M4 or M5 type. Markedly enlarged liver and spleen, and hyperleukocytosis (more than 50,000/microliters) were seen in 9, 12, and 14 infants with ALL and 10, 11, and 10 infants with ANLL, respectively. Initial CNS leukemia was evident in 2 infants. Chromosome studies of the leukemic cells showed abnormal karyotypes in 9 of the 21 infants with ALL and 19 of the 22 infants with ANLL, consisting mainly of translocation 11, 12, and inversion 16. By surface marker analysis, only 7 of the 22 infants with ALL (32%) were diagnosed as having common ALL (HLA-DR+, CD19+, CD10+). Of the 15 infants with ANLL, 12 and 5 infants also showed reactivity to HLA-DR and CD19, respectively. All of the 5 ANLL infants with lymphoid markers showed different leukemic cell features at the time of relapse. Twelve of the 19 infants with ALL (63%) who achieved a complete remission relapsed within the first 2 years; 8 of the 21 with ANLL (38%) relapsed within the first year. Analysis of event-free survival shows that the ALL infants with hyperleukocytosis have a poorer prognosis than those without hyperleukocytosis (p less than 0.05). Infant leukemia originates in a multipotent cell with lymphoid and myeloid features, and intensive multiagent chemotherapy is necessary for the treatment of infants with acute leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Chromosome abnormalities and prognosis in childhood acute leukemia.

We report here on the leukemic cell karyotypes of 134 children with acute nonlymphocytic leukemia (ANLL) examined at Saitama Children's Medical Center (SCMC), and of 88 children with acute lymphoblastic leukemia (ALL) referred to SCMC. The patients were mainly treated according to the protocol of the Tokyo Children's Cancer Study Group. Of 106 ANLL cases with adequate banding, 18% were normal, 34% had miscellaneous clonal abnormalities, and 48% were classified into known cytogenetic subgroups: t(8;21) (n = 21), 11q23 abnormalities (n = 14), -7/del(7q) (n = 6), inv (16)/del(16) (n = 5), and t(15;17) (n = 5). According to the FAB classification, M7 (21.7%) were more frequent than in previous reports because this study included a number of Down's Syndrome patients with M7 morphology. The present study confirmed the well-known association of t(15;17) with M3, t(8;21) with M2, 11q23 abnormalities with M4 and M5, and inv (16)/del(16) with M4. Patients with t(8;21) or inv (16)/del(16q) ANLL fared no better overall than the entire group. Of 51 ALL cases with adequate banding, 13.7% were normal, and 86.3% were classified into abnormal subgroups: translocation (n = 14), hyperdiploidy (greater than 50) (n = 13), and miscellaneous abnormalities (n = 17). Cases with hyperdiploidy (greater than 50) were restricted to a common phenotype and fared better overall than the entire group. Patients with translocation were found in all phenotypes, and had a poor prognosis. We concluded that childhood acute leukemia could be subgrouped according to karyotypic patterns, and that patients with translocations had a poor prognosis in ALL as well as ANLL.

Adolescent↗
PubMed1991

[Clinical evaluation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in autologous bone marrow transplantation].

We administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 5 micrograms/kg/day by intravenous drip infusion for 21 consecutive days in autologous bone marrow transplanted patients. The period of posttransplant neutropenia was markedly shortened by the rhG-CSF treatment; mean days required for neutrophil recovery (greater than 500/mm3) of 14.3 days in the rhG-CSF group (n = 21) versus 27.8 days in the historical control group (n = 11). More importantly, the numbers of febrile days between day 15 and day 28 were found to be fewer in the rG-CSF group than in control group. These effects were obtained without delay in the recovery of other blood cell series and without any side effect. We conclude that the posttransplant use of the rhG-CSF is beneficial for prevention and treatment of infectious complications after autologous bone marrow transplantation.

Adolescent↗
PubMed1990

Characterization of an embryonal rhabdomyosarcoma cell line showing amplification and over-expression of the N-myc oncogene.

A parent rhabdomyosarcoma cell line designated SCMC-RM2 was established from bone-marrow tumor cells taken from an 11-year-old girl with an embryonal rhabdomyosarcoma. Subsequently a cloned SCMC-RM2-1 cell line was isolated from a parent line. These cell lines grew as adherent monolayers in liquid culture with a doubling time of 50 and 52 hr, respectively. In addition, colonies were established in soft agar, which grew in a dose-dependent fashion with a cloning efficiency of 0.7 and 0.8%, respectively. Chromosomal analysis showed these cell lines had neither double minutes nor homogeneously staining regions. Chromosome number ranged from 61 to 93, translocation; t(9;13)(p22;q14) was identified, and no alteration of chromosome 2 was observed. Surface membrane antigen profile of parent and cloned lines by using a panel of 24 monoclonal antibodies (MAbs) excluded the possibility of these being neuroblastoma cell lines. In addition, MAbs to the cytoplasmic protein desmin, myoglobin, muscle actin (alpha and gamma) and alpha-sarcomeric actin reacted with these cell lines, SCMC-RM2 and SCMC-RM2-1 being thus identified as rhabdomyosarcoma. Southern blot analyses revealed 8- and 7-fold amplification of the N-myc gene in SCMC-RM2 and SCMC-RM2-1 as compared with the promyelocytic cell line HL60. Over-expression of the N-myc mRNA was noted over control cell lines.

Antigens, Neoplasm↗
PubMed1990

[Bone marrow transplantation for girls with aplastic anemia utilizing modified field of total lymphoid irradiation and cyclophosphamide: with emphasis on the field of pelvic cavity].

A preparative regimen for allogeneic bone marrow transplantation, consisting of total lymphoid irradiation (TLI) with 750 cGy and cyclophosphamide (CY), was used in five girls with aplastic anemia. All patients received bone marrow from HLA matched/mixed lymphocyte culture negative siblings. In our regimen the "inverted Y" field to irradiate the pelvic nodes was modified, which did not include the whole pelvic cavity in an attempt to protect the ovaries from irradiation. Although some of the pelvic nodes was supported not to be irradiated in order to protect the ovaries, engraftment occurred in all five patients including four who had been transfused prior to transplantation. All five are alive from 47 days to 1378 days (median 285 days) after transplantation without transplantation-associated complications. The calculated dose to the ovaries was sixteen percent of the entire dose of the regimen. Both of the two evaluable patients that had received transplantation just before or during the puberty are developing normal sex maturity including menstruation. This study suggests that our preparative regimen is effective not only for engraftment of the donor marrow but also for protecting the ovaries from irradiation.

Adolescent↗
PubMed1990

Karyotypic patterns in acute mixed lineage leukemia.

We performed cytogenetic and immunologic studies of blast cells from 13 children with acute mixed lineage leukemia (AMLL) to discern patterns of chromosome alteration and antigen expression that would assist in classification of this disease entity. Six patients with 11q23 translocations--including four with the t(11;19), one with the t(9;11), and one with the t(1;11)--were characterized by a young age and hyperleukocytosis. A B cell-associated antigen (CD19) and HLA-DR antigens were expressed by blast cells from all patients; only one case was positive for the common acute lymphocytic leukemia antigen (CALLA, CD10). A myeloid-associated antigen (CD13) was expressed by blast cells from one patient at diagnosis and from another at relapse; it was also expressed by cells from the remaining four patients after brief in vitro culture without addition of differentiating agents. Four patients with t(9;22)(q34;q11) were characterized by an older age and hyperleukocytosis. Each of these cases was positive for CD13, CD19, and HLA-DR, and three were positive for CALLA. The 11q23 translocation was associated with CALLA- ALL marked by a myeloid phenotype, whereas the t(9;22) occurred in cases of acute myeloid leukemia with a CALLA+ lymphoid phenotype. One case had a 7q35-q36 translocation, which involves the region of the T cell receptor beta-chain gene. Our results suggest that karyotypic alterations can be used to refine the classification of AMLL.

Antigens, CD↗
PubMed1990

[Relapsed stage I neuroblastoma successfully treated by allogeneic bone marrow transplantation in second remission: case report of a 7-year-old girl].

Stage I neuroblastoma in a seven-year-girl have had local recurrence with bone metastasis. Second surgery was performed after the aggressive chemotherapy including cisplatin, VP16, cyclophosphamide, vincristine and doxorubicin. She underwent allogeneic bone marrow transplantation from her HLA identical brother, following the preparative regimen consisting of high-dose melphalan and total body irradiation (12 Gy). Clinical course after the transplantation was uneventful. She is still alive with no evidence of disease for twenty-eight months after the transplantation. It is suggested that bone marrow transplantation is an effective way of therapy even in a patient with relapsed neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed1990

[Myelodysplastic syndrome in a child which developed into megakaryocytic leukemia with late appearing Ph1 chromosome and rearrangement of breakpoint cluster region].

A 3-year-old boy was referred to our hospital in September 1985, because of pancytopenia. His bone marrow was normocellular with 18% blasts, which had Auer rod and were positive for peroxidase staining. A diagnosis of refractory anemia with excess blasts in transformation was made according to FAB criteria. Chromosome analysis of bone marrow cells showed normal male karyotype. He attained complete remission with aclarubicin and BH-AC and continued it until August 1987 when pancytopenia and hypoplastic bone marrow developed. Chromosome analysis of bone marrow cells showed normal male karyotype and gene analysis revealed germ-line configuration of breakpoint cluster region (bcr). Overt leukemia developed in May 1988 when his WBC count increased to 60, 600/microliters with 91% blasts, which were negative for peroxidase staining, positive for anti-Ia and CDw 41 by cell surface analysis, and positive for ultrastructurally demonstrable platelet peroxidase. A diagnosis of megakaryocytic leukemia was made. Chromosome analysis of bone marrow cells showed 46, XY, t(9;22) (q34;q11) and gene analysis revealed rearrangement of bcr. He died in November 1988. Our results and review of literature suggest that late appearing ph1 chromosome and rearrangement of bcr may occur in a variety of hematologic malignancies and influence the course of disease.

Anemia, Refractory, with Excess of Blasts↗
PubMed1989

Cytogenetic findings and prognosis in neuroblastoma with emphasis on marker chromosome 1.

The relationship between cytogenetic findings and prognosis in 51 pediatric patients with neuroblastoma is described. Patients were classified into the following four groups based on karyotypic findings: (1) near diploidy, 42 to 47 chromosomes (n = 11); (2) hyperdiploidy, 50 to 56 chromosomes (n = 4); (3) near triploidy, 60 to 77 chromosomes (n = 33); and (4) hypotetraploidy, 80 to 83 chromosomes (n = 3). Patients with near diploid or hypotetraploid karyotypes also had several structural abnormalities including marker chromosome 1, with or without double minutes (DM) or homogeneously staining regions (HSR). Most of these patients were 1 year of age or older and had advanced tumors. The patients who were in the hyperdiploid or near triploid category had few structural abnormalities; all of them, except one, were younger than 1 year of age, had localized tumors, and are long-term, disease-free survivors. Kaplan-Meier analysis of survival rates disclosed a significant difference favoring the latter group (P less than 0.001). N-myc gene amplification was found in five patients of the former group but in no patients of the latter group. The presence or absence of DM or HSR in the former group had no statistically demonstrable effect on survival. However, the presence of marker chromosome 1 appears to indicate a poor prognosis. Five patients with Stage IV-S disease had near triploid abnormalities similar to findings in patients with localized tumors. We propose that localized and Stage IV-S neuroblastomas can be classified as one disease category, and that patients with near diploid or hypotetraploid karyotypes are clinically distinct from those having hyperdiploid or near triploid karyotypes. We consider that chromosomal pattern is a more influential prognostic factor than age, disease stage, or N-myc gene amplification.

Child↗
PubMed1989

Similar chromosomal patterns and lack of N-myc gene amplification in localized and IV-S stage neuroblastomas in infants.

Chromosome analysis was performed on 33 neuroblastomas in infants. Near triploid chromosome abnormalities (range, 60 to 77) were found in 29 patients with localized and IV-S stage neuroblastoma, and hyperdiploidy (range, 50 to 56) in 3 patients with localized neuroblastoma. No marker chromosome 1, homogeneously staining region (HSR), or double minutes (DMS) was observed in these patients, all of which have been previously reported in advanced neuroblastomas. N-myc gene amplification was not detected in any of these patients. All the patients were completely free of disease 4-45 months after diagnosis. Only one patient with stage IV neuroblastoma had a marker chromosome 1 (mode 46) and N-myc gene amplification and relapsed. Five patients with IV-S neuroblastoma lacking N-myc gene amplification had near triploid chromosomal abnormalities similar to those seen in localized neuroblastoma in infants. We consider that, cytogenetically, localized and IV-S neuroblastoma may be within the same disease category and different from advanced neuroblastoma.

Chromosome Aberrations↗
PubMed1989

Fatal infectious mononucleosis with staphylococcal pyoderma in a girl with hereditary immunological dysregulations.

We describe a 14-year-old girl with fatal infectious mononucleosis with high fever, pancytopenia, and multiple skin ulcers due to Staphylococcus aureus. Immunological studies revealed low serum IgM, low natural killer (NK) activity, and high CD4/CD8 ratio. Her father had also low NK activity and high CD4/CD8 ratio. It is suggested that she had a dominantly inherited immunodeficiency predisposing to severe Epstein-Barr virus infection.

Adolescent↗
PubMed1989

[Acute myelomonocytic leukemia (M4) with CD19 antigen expression, eosinophilia and basophilia in bone marrow].

A 12-year old boy was admitted to Saitama Children's Medical Center because of fever and epistaxis. He had leukocytosis (WBC 40,800/microliters, blast 75%), anemia, thrombocytopenia and high levels of serum LDH, lysozyme, Vitamin B12, and plasma histamine. Bone marrow aspiration revealed hypercellular marrow with 31.2% blasts, 15.2% eosinophils, and 14.2% basophils. Blasts had Auer rods and were positive for peroxidase and negative for alpha-naphthyl butyrate esterase and PAS stainings. Ia, CD13 (My7), and CD19 (B4) antigens were expressed on his leukemic cells. Chromosomal study showed 46, XY, t(7;8) (q35;q22), del(9) (q13q22). Southern blot analysis using immunoglobulin constant region (C) probes revealed germline patterns of C mu, C kappa, C lambda, and breakpoint cluster region. A diagnosis of acute myelomonocytic leukemia (AMMoL, M4) was made. He attained a complete remission with daunorubicin and cytarabine, and 6 months later he received bone marrow transplantation from HLA-identical sister. This case had the common breakpoint 8q22 with ANLL with t(8;21) (q22;q22), and was unique AMMoL with proliferation of eosinophils and basophils in bone marrow.

Antigens, CD19↗
PubMed1989

[Effect of high-dose cyclophosphamide plus high-dose etoposide in malignant brain tumors of children followed by autologous bone marrow rescue].

Four pediatric patients with malignant brain tumors were treated with very high-dose etoposide plus very high-dose cyclophosphamide (HD-VP 16/CPM) followed by autologous bone marrow rescue. There were two brain stem gliomas, which were refractory to radiation therapy, ACNC, and beta-interferon and two relapsed malignant brain tumors. Both of the two with brain stem gliomas achieved response, one with clinical improvement and decrease of tumor size on CT scanning, the other with clinical improvement. Overall response duration was three months and nine months. Two patients with relapsed brain tumors received HD-VP 16/CPM as adjuvant chemotherapy. Low but significant levels of VP 16 and CPM were detected in CSF. Further investigation of HD-VP 16/CPM is needed as a chemotherapy for malignant brain tumors in children.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Obstruction of nasolacrimal ducts closely related to graft-versus-host disease after bone marrow transplantation.

A 2-year-old boy underwent bone marrow transplantation for severe aplastic anemia. Eighteen months later he developed chronic lung disease and dryness of the eyes. Ophthalmologic examination revealed obstruction of the nasolacrimal ducts and marked dilatation of the lacrimal sacs bilaterally. It seems likely that the nasolacrimal duct obstruction was a manifestation of chronic graft-versus-host disease.

Anemia, Aplastic↗