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Biomedical subjects

F Kodama

Publications and source records attributed to F Kodama.

At least 55 records · Page 3Linked to original sources

Predicting relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation by bcr-abl mRNA and DNA fingerprinting.

Fourteen patients treated by allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr-abl-specific transcripts. Nine patients were transplanted in the first chronic phase, three in the second chronic phase, and two in the accelerated phase. All patients achieved a complete cytogenetic and hematologic remission after bone marrow transplantation. Twelve patients are alive (median, 18 months; range, 5-54 months) and two patients died early. bcr-abl mRNA was persistently detectable for 6 to 54 months in four patients (patients 1, 3, 4, 6). From two of them, DNA fingerprint analysis showed only donor type DNA although bcr-abl mRNA was detectable. bcr-abl mRNA was never detectable posttransplant in three patients (patients 2, 5, 13). Six patients had detectable bcr-abl mRNA (patients 8-12, 14): by 6 months, all of these patients were bcr-abl mRNA negative. One patient (patient 7) had detectable full bcr-abl mRNA again at 12 months, but was then negative at 20 months. Ten patients (patients 2, 4-8, 10-13) had never detectable Philadelphia (Ph1) chromosome t(9.22) translocation, whereas four patients had detectable Ph1 (patient 1, 3, 9, 14); by 6 months, three of four cases were negative. One patient (patient 1) had detectable Ph1 at 44 months, but was negative at 50 months. Three of six patients who initially had bcr-abl mRNA detectable posttransplant (patient 7-9) became negative for bcr-abl mRNA at the time of development of chronic graft-versus-host disease (GVHD). These results suggest that the detection of subclinical Ph1 positive cells by PCR is not associated with imminent clinical or cytogenetic relapse. Moreover, graft-versus-leukemia (GVL) activity may contribute to the treatment of minimal residual disease in CML after allogeneic bone marrow transplantation.

Adolescent↗

Accumulation of 123I-IMP in extrahepatic metastases of hepatocellular carcinoma.

Twenty patients with 58 extrahepatic metastases of hepatocellular carcinoma (HCC) (41 bone, 5 lung, 6 peritoneum, 4 adrenal glands, 1 brain, 1 lymph node) underwent 123I-iodoamphetamine (123I-IMP) and gallium-67 (67Ga) scintigraphy. The rate of positivity with 123I-IMP planar imaging was 44% above the level of the diaphragm and 76% below the diaphragm, with an overall sensitivity of 62%. The combination of 123I-IMP scintigraphy and single photon emission tomography enabled positive visualization of an additional six metastatic foci: three in the adrenal glands, one in the peritoneum, one in the cranium and one in a rib. The rate of positivity with 67Ga planar imaging was 75% above the level of the diaphragm and 45% below the diaphragm, with an overall sensitivity of 58%. Our findings suggest that 123I-IMP is effective for detecting extrahepatic metastases of HCC, particularly those below the diaphragm.

Adrenal Gland Neoplasms↗

[Autopsy cases of cytomegalovirus interstitial pneumonitis following bone marrow transplantation].

We investigated the relevance of cytomegalovirus (CMV) to interstitial pneumonitis (IP) using formalin-fixed and paraffin-embedded lung tissues obtained from 12 autopsy cases who died following bone marrow transplantation (BMT) from May 1985 to March in 1992. The lung tissues were examined by hematoxylin and eosin (H.E.) staining, immunohistochemistry with monoclonal antibodies (DDG9, CCH2) and polymerase chain reaction (PCR) for amplifying human CMV DNA. Eight of 12 cases were clinically diagnosed as IP. The 4 cases showed no signs of IP, and their tissues were used as controls. H.E. staining revealed inclusion bodies in two of the eight and only severe fibrosis in the other six. In 4 of the 6 cases, however, CMV was identified by immunohistochemistry or PCR. We concluded that the relevance of CMV in the genesis of IP is often overlooked by H.E. staining alone. Immunohistochemistry and PCR are useful in examining tissues which are suspected of CMV-IP.

Adolescent↗

Successful pregnancy after allogeneic bone marrow transplantation following conditioning with total body irradiation.

A 23-year-old woman had a normal full-term delivery 78 months after BMT for ALL. Conditioning therapy was Ara C 1.4 g/m2 x 4, CY 60 mg/kg x 2 and TBI 2.5 Gy x 5 at a dose rate of 3.5 cGy/min. Despite GVHD prophylaxis with short-term MTX and CsA, she developed grade I acute GVHD, but showed no evidence of chronic GVHD. Following amenorrhea for 4 years, menstruation recommenced spontaneously. She had a normal pregnancy 6 years after BMT resulting in a healthy infant with simple hypospadias. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 10 Gy.

Acute Disease↗

[Hypoplastic leukemia achieved long-term remission with low-dose cytosine arabinoside].

A 74-year-old woman was admitted in October 1988 with anemia and leukocytopenia. Hematologic investigations established a diagnosis of hypoplastic acute leukemia. She received a low dose of cytosine arabinoside (LDAC: 10 mg/m2 every 12 hours) subcutaneously for 21 days and achieved complete remission (CR) one month later. After one course of LDAC of 14 days, she received LDAC of 21 days every 5 to 6 months as maintenance therapy till April 1993. She has been in remission for 6 years. Intensification therapy with LDAC every 5 to 6 months might be useful in maintaining remission for hypoplastic acute leukemia.

Aged↗

[Treatment for elderly patients with acute non-lymphocytic leukemia].

A retrospective analysis was performed on forty nine elderly (34 males and 15 females) patients aged 65 years or more (median age 73, range 65-82) with acute non-lymphocytic leukemia (ANLL). Patients were studied to examine factors according to age group (65-69 years, 70-74, 75-79 and 80 or over), respectively. Patients were treated with either low dose Ara-C therapy or BHAC-DMP therapy according of the choice of their attending physicians. Complete remission (CR) was obtained in 20 of 49 patients (43%), and in 6 of 14 patients (43%) aged 65-69, in 8 of 18 (44%) aged 70-74, in 5 of 12 (42%) aged 75-79 years and in 1 of 3 (33%) aged 80 or over, respectively. The median survivals of these groups were 263, 298, 260, 168.5 and 38.5 days, respectively. Multivariate analysis revealed that the achievement of CR was associated with normal karyotype, and serum GOT level < or = 30 mu/ml and GPT < or = 40 mu/ml. Prolonged survival was related to the achievement of CR. The results indicated that liver function before chemotherapy was an important prognostic factor.

Age Factors↗

Correlation between chondroitin sulfate iron colloid-enhanced MR imaging and the histological grade of hepatocellular carcinoma.

The association between contrast enhancement by chondroitin sulfate iron colloid (CSIC) and the histological grade of hepatocellular carcinoma (HCC) was evaluated in 24 patients diagnosed by histological examination of surgical specimens (26 nodules: 11 well-differentiated and 15 poorly-moderately-differentiated nodules). In the well-differentiated HCC nodules, the tumor-liver contrast to noise ratio (CNR) was not significantly increased after i.v. CSIC injection on both T1-weighted and T2-weighted images. In the moderately-poorly-differentiated HCC, CNR was significantly increased after CSIC administration on both T1-weighted and T2-weighted images (p < 0.01). MR imaging using CSIC may be useful for diagnosing the degree of HCC differentiation.

Carcinoma, Hepatocellular↗

[Therapy related leukemia].

Eleven therapy related leukemias (TRL) who were hospitalized in the Department of Hematology and Chemotherapy, Kanagawa Cancer Center between October 1983 and December 1993 were identified. Six of the patients were males and five were females. Their median age was 62 years (range from 14 to 75). Three patients had previously received treatment for breast cancer and two patients for malignant lymphoma. The other patients had received treatment for lung cancer, urinary bladder cancer, gastric cancer, brain tumor, maxillary sinus cancer and macroglobulinemia, respectively. Seven patients had been treated with chemotherapy and four patients had been treated with chemotherapy and irradiation for the primary tumor. The TRL cases consisted of 8 acute non-lymphoid leukemias, two acute lymphoid leukemias and one hypoplastic leukemia, respectively. The status of primary tumors at the development of TRL was complete remission in ten patients and partial remission in one patient. Three of the 10 patients who received anti-leukemic therapy entered complete remission and the median survival time was 36 days (from 7 days to 489 days). One patient expired of pneumonia before he received anti-leukemic therapy. TRL patients showed poor response to chemotherapy and had poor prognosis. These data suggest that the use of reduced doses of carcinogenic drugs for primary tumors might be required to prevent the development of TRL.

Adolescent↗

[Preliminary report on the usefulness of 123I-IMP scintigraphy in distant metastases from hepatocellular carcinoma: except for bone and lung metastases].

N-isopropyl-p-[123I] Iodoamphetamine (IMP) scintigraphy was performed in 10 lesions of metastatic hepatocellular carcinoma. Five of 10 lesions (50%) were detected with planar images, which was superior to the 2 of 8 lesions (25%) detected with 67Ga-citrate (Ga) scintigraphy. The positive ratio was increased to 83% (5/6) with SPECT. Thus our findings suggested that IMP could compensate for Ga scintigraphy in detecting distant metastases of hepatocellular carcinoma.

Adrenal Gland Neoplasms↗

[VEPA and ML-Y1 regimen for elderly non-Hodgkin's lymphoma].

A total of 32 previously untreated patients aged 65 years or older with non-Hodgkin's lymphoma (NHL) were treated with VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin) or ML-Y1 (doxorubicin, cyclophosphamide, vincristine, methotrexate, bleomycin, procarbazizin and prednisolone). The median age of the patients was 70 years (range 65-77), 19 males and 13 females. The outcome of 16 patients with VEPA and 16 patients with ML-Y1 was retrospectively evaluated. There were no significant differences in response or survival between VEPA and ML-Y1, complete remission rates were 37.5% vs. 31.3% and duration of 50% survival were 20 months and 13 months, respectively. Major side effects of both regimens were myelosuppression, hair loss, nausea, vomiting and peripheral neuropathy. There was no increased toxicity in ML-Y1 but this regimen seemed like VEPA, to be insufficient for NHL in elderly patients. A new intensive regimen should be designed to treat NHL in the elderly patients.

Aged↗

Double contrast MR imaging with iron colloid and Gd-DTPA in cholangiocellular carcinoma.

Double contrast MR imaging with combined use of chondroitin sulfate iron colloid (CSIC) and Gd-DTPA was attempted in 3 cases of cholangiocellular carcinoma (CCC). In all cases, nonenhanced spin echo T1- and T2-weighted images, and T1-weighted images after i.v. injection of Gd-DTPA were obtained. Within one week, the MR sequences were repeated one hour after i.v. injection of CSIC. Double contrast (CSIC/Gd-DTPA) T1-weighted imaging was evaluated and compared with the other sequences in terms of tumor detectability, tumor spreading and tumor characterization. Double contrast MR imaging was comparable in tumor detectability and superior as to the evaluation of spreading and characterization to the other MR imaging modalities.

Bile Duct Neoplasms↗

Phase IV group study of natural human interferon alpha (HLBI) on chronic myelogeneous leukaemia.

Under the control of Kanagawa CML/HLBI phase IV study group in Japan, 18 cases out of registered 30 cases of chronic myelogeneous leukaemia consisting of 17 chronic phase and 1 accelerated phase, during July, 1991 to January, 1992, were analyzed for their hematological responses and cytogentic responses preliminarily. Hematological response rate (PR + CR) was 83.3% including 50.0% of CR, as judged by Kimura's criteria after treatment with HLBI alone (16 cases) or/and with other chemotherapy (2 cases). The dosage and duration of HLBI therapy required to get into the complete remission ranged from 212 to 1272 millions IU and between 6 to 42 weeks (mean value was 20 weeks), respectively. The clonally proliferated leukocytes and decreased physiological hematopoiesis started to recover from 2 to 4 weeks and reached their normal ranges from 16 weeks after 6 millions IU of HLBI were administered every day. In the 4 cases examined, 3 cases showed minimal cytogenetic responses and a case showed no cytogenetic response. Slight and temporary adverse effects were observed in 15 out of 18 cases (83.3%) including fever, general malaise, appetite loss, eruption, diarrhea, glossitis, hypogustation, weight loss and local muscle pain.

Adult↗

Evaluation of chimerism after bone marrow transplantation with single locus minisatellite DNA probes.

The origin of cells in almost all allogeneic donor-recipient pairs can be determined through the use of highly polymorphic minisatellite DNA probes. Single-locus probes were cloned from hypervariable fragments in a human DNA fingerprint detected with a multi-locus probe. While each probe is highly polymorphic and locus specific, they all contain repetitive sequences. The properties of single-locus probes have improved the sensitivity of detecting mixed chimerism in comparison with multi-locus probes. The use of single-locus probes permitted detection of mixed chimerism (MC) at levels as low as 0.625%, approaching that obtained by PCR methods. In the present study, five patients who received allogeneic BMT for hematologic malignancies were analyzed. Two patients exhibited MC after BMT. One developed acute GVHD and chronic GVHD and remained in CR while the second patient who had no signs of GVHD suffered a relapse.

Adult↗

Low-dose cytosine arabinoside for treating hypocellular acute leukemia in the elderly.

Ten previously untreated elderly patients with hypocellular acute leukemia received a low dose of cytosine arabinoside (Ara-C), 10 mg/m2 injected subcutaneously every 12 hours for 14-28 days. Six patients achieved a complete remission (CR) for periods ranging for 6-23 months (median 8.5 months) and the others had a partial remission (PR). Relapse has occurred in three patients to date. The median survival ranged from 10-24 months (median 14.5 months). Only two of the six patients, in whom bone marrow biopsy was performed at CR, had a normal cellularity. This change, however, did not appear to be a significant prognostic factor in those patients. In seven patients who achieved a CR or PR low-dose Ara-C was administrated as maintenance therapy at the same low dose for 10 days each month. Treatment was well tolerated in all patients despite for myelosuppression. There were no drug-related deaths. These observations suggest that low-dose Ara-C is effective in treating elderly patients with hypocellular acute leukemia.

Acute Disease↗

Case report: fulminant hepatitis C viral infection after allogeneic bone marrow transplantation.

The authors describe two patients with acute leukemia who died of fulminant hepatitis caused by hepatitis C virus (HCV) after an allogeneic bone marrow transplant, the first such cases reported in Japan. Both had developed posttransfusion hepatitis during chemotherapy to induce remission and for consolidation. Six months after blood transfusion, the blood serum of each patient was positive for HCV antibody and HCV RNA. In each case, there was a transient improvement in liver function after the transplant. However, within 5 months of receiving the transplant and coincident with the withdrawal of cyclosporin A, each patient developed an acute exacerbation of hepatitis. The fulminant hepatitis in our patients may, therefore, have been caused by the reactivation of HCV induced by the immunosuppressive therapy followed by a reconstitution of the immune system.

Adult↗

[Polycythemia vera terminating in chronic neutrophilic leukemia: studies on in vitro growth of hematopoietic progenitor cells].

A 57-year-old man, diagnosed as Polycythemia vera (PV), had been treated with administrations of Busulfan since 1984. Three years later, the number of neutrophils in peripheral blood increased to 50,000/microliters with progression of splenomegaly, and the case was diagnosed as Chronic neutrophilic leukemia (CNL) based on the criteria by Miura et al, in November, 1989. In spite of 6MP and Busulfan therapy, marked neutrophilia and splenomegaly progressed, and the patient died due to liver dysfunction in June of 1991. To clarify the pathophysiology of PV and CNL, we studied the in vitro growth kinetics of hematopoietic progenitor cells in bone marrow of this unique case and made a comparison with those of 4 cases of PV and 4 normal volunteers employing methylcellulose culture. As in other cases of PV, erythroid colonies were formed in culture of bone marrow from this patient without addition of erythropoietin. Furthermore, spontaneous colonies derived from CFU-GM and CFU-Mix increased remarkably in this case only. The results suggest that the hematopoietic abnormalities in this case involve the multipotent stem cells as well as erythroid and granuloid-macrophage progenitors.

Colony-Forming Units Assay↗