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J Mimaya

Publications and source records attributed to J Mimaya.

At least 19 recordsLinked to original sources
PubMed2000

Feasibility study of autologous peripheral blood stem cell transplantation for the treatment of childhood acute myelogenous leukemia.

BACKGROUND: The primary object of this study was to identify treatment-related variables that may predict relapse of acute myelogenous leukemia (AML) after autologous peripheral blood stem cell transplantation (PBSCT), which will be critical for the development of a suitable protocol for wider application. METHODS: A total of 28 children (age 0-18 years) with AML underwent PBSCT and have had a minimum follow-up of 25 months; including 24 patients in their first complete remission (CR) and four in their second CR. The patients were divided into two cohorts according to the study phase: 16 patients were treated in an early phase pilot study and 12 patients in their first CR were treated in a prospective trial. Fifteen of the first-CR patients had any of the cited high-risk features of high WBC count (>100x10(9)/l; n = 5), FAB M0/M4/M5/M7 subtypes (n = 11) or delayed achievement of CR (n = 9). Except in one patient, cytoreductive regimens did not include total body irradiation (TBI). RESULTS: After PBSCT, one patient died of veno-occulsive disease (VOD) and another patient relapsed early on day 43, but the remaining patients showed engraftment. Leukemic relapse was observed 1-29 months after PBSCT (median, 8 months); in all of the 4 children treated in their second CR and in 11 of the 24 patients (46%) treated in their first CR. The remaining patients have been disease-free for 24 to 97 months (median, 53 months). Using a multivariate analysis, the timing of apheresis was the most significant prognostic factor for those treated in their first CR (p = 0.03); 12 of the 16 patients whose PBSC were collected beyond 2.5 months of CR continue to remain in CR, while seven of the eight patients whose PBSC were harvested within 2.5 months of CR relapsed. CONCLUSION: Although the small number of patients studied does not allow firm conclusions to be drawn regarding the relative effectiveness of this therapy, the results do suggest the feasibility of further studies of PBSCT for the treatment of childhood AML with high-risk features including the assessment of minimum residual disease.

Adolescent↗
PubMed2000

Quantification of a very low level of serum human immunodeficiency virus type 1 (HIV-1) RNA using competitive PCR at intervals and the clinical course.

Quantification of human immunodeficiency virus type 1 (HIV-1) genomic RNA levels below the detection limit (400 copies/ml) of commercially available quantification kits is possible by increasing the amount of serum samples using competitive PCR conditions. We evaluated disease prognosis in patients without symptoms for a long period after infection (long-term non-progressors) and patients in whom the virus was controlled to a low level by administration of anti-HIV drugs. For 102 of the 414 serum samples stored at -80 degrees C which showed HIV-1 RNA below 400 copies/ml by competitive PCR using 100 to 200 microl sera, an increase in the sample volume to 500-2000 microl, extraction of HIV-1 RNA, and quantitative detection by competitive PCR was performed. Follow-up quantification of serum HIV-1 RNA from 4 patients indicated that this method is useful in assessing prognosis in the early stage of the disease in patients without symptoms for a long period after infection (long-term non-progressors) and patients in whom the virus in the serum was controlled by administration of anti-HIV drugs to below the detection limit of commercially available quantification kits. Quantification of low level serum HIV-1 RNA was also considered useful as a parameter of treatment.

HIV Infections↗
PubMed1999

Improvement in CNS protective treatment in non-high-risk childhood acute lymphoblastic leukemia: report from the Japanese Children's Cancer and Leukemia Study Group.

BACKGROUND: Prevention of central nervous system (CNS) leukemia by early introduction of therapy to this sanctuary site is an essential component of modern treatment strategy for acute lymphoblastic leukemia (ALL). However, the optimal form of preventive CNS therapy remains debatable. PROCEDURE: To address this issue, we evaluated the efficacy of CNS preventive therapy for 572 children with ALL who achieved complete remission in the Children's Cancer and Leukemia Study Group (CCLSG) ALL874 (1987-1990) and ALL911 (1991-1993) studies. They received risk-directed therapy based on age and leukocyte count. In the ALL 874 study, the non-high-risk (low-risk [LR] + intermediate risk [IR]) patients were randomly assigned to the conventional cranial irradiation (CRT) regimen (L874A and I874A) and the high-dose methotrexate (HDMTX) regimen without CRT (L874B and I874B). The former patients received 18-Gy CRT plus 3 doses of intrathecal (i.t.) MTX and the latter patients received 3 courses of HDMTX at 2 g/m2 plus 13 doses of ITMTX (L874B) or 4 courses of HDMTX at 4.5 g/m2 plus 1 dose of ITMTX (I874B). RESULTS: The 7-year probabilities (+/- SE) of CNS relapse-free survival were 97.3% +/- 2.6% (L874A, n = 41) vs. 90.3% +/- 5.3% (L874B, n = 39) (P = 0.25) in the LR patients, and 100% (I874A, n = 55) vs. 78.5% +/- 6.5% (I874B, n = 54) (P = 0.002) in the IR patients. The corresponding disease-free survival (DFS) rates were 79.4% +/- 6.5% vs. 74.4% +/- 7.3% (P = 0.62) in the LR group and 63.3% +/- 6.8% vs. 58.3% +/- 7.2% (P = 0.66) in the IR group. Thus, the HDMTX regimen could not provide better protection of CNS relapse as compared with the CRT regimen, although their overall efficacy was not significantly different. In the ALL 911 study, intensive systemic chemotherapy with extended i,t, injections of MTX plus cytarabine achieved a high CNS relapse-free survival (98% +/- 1.9% at 7 years) and a favorable DFS (85.5% +/- 5% at 7 years) in the IR patients. The patients in the high-risk (HR) group in both ALL874 and ALL911 studies received the 18-Gy or 24-Gy CRT with intensive systemic chemotherapy. Their 7-year probabilities of CNS relapse-free survival ranged from 88% to 95%, among which the T-ALL patients had a risk of CNS leukemia, which was 3-4 times higher compared with B-precursor ALL patients. CONCLUSIONS: These results indicate that long-term intrathecal CNS prophylaxis as well as appropriate systemic therapy for the non-high-risk patients can provide protection against CNS relapse equivalent to that provided by cranial irradiation.

Adolescent↗
PubMed1999

Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan.

We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.

Acute Disease↗
PubMed1999

Long-term survivors of advanced neuroblastoma with MYCN amplification: A report of 19 patients surviving disease-free for more than 66 months.

PURPOSE: According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN proto-oncogene developed progressive disease within 8 months. The prognosis for such patients, however, should now be reevaluated in light of recent results achieved with up-to-date combination chemotherapy. PATIENTS AND METHODS: Patients with stage 3, 4, and 4S neuroblastoma and more than 10 copies of MYCN received induction chemotherapy, which from January 1985 to February 1991 consisted of regimen A(1 )(cyclophosphamide 1,200 mg/m(2) on day 1, vincristine 1.5 mg/m(2) on day 1, pirarubicin 40 mg/m(2) on day 3, and cisplatin 90 mg/m(2) on day 5) and from March 1991 to September 1993 consisted of regimen A(3 )(cyclophosphamide 1,200 mg/m(2) on days 1 and 2, pirarubicin 40 mg/m(2) on day 3, etoposide 100 mg/m(2) on days 1 through 5, and continuous infusion cisplatin 25 mg/m(2) on days 1 through 5). Most of these patients underwent radical surgery to remove the original tumor and local metastases, irradiation, and supralethal preconditioning regimens, followed by blood stem-cell transplantation (SCT). Data on the patients were collected in December 1998, and the factors contributing to disease-free survival were analyzed. RESULTS: During the study period, 66 patients with more than 10 copies of MYCN were treated. Five of nine patients with stage 3 disease, 13 of 55 with stage 4, and one of two with stage 4S survived for at least 66 months. It is interesting that all but one patient who survived for more than 66 months underwent SCT, in contrast with only five of 45 patients who died. CONCLUSION: Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Effects of granisetron in children undergoing high-dose chemotherapy: a multi-institutional, cross-over study.

The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy. Granisetron controlled the onset of vomiting in 17 of 23 patients (73.9%) who were given 40 microg/kg of granisetron, while 8 of 21 patients (38.1%) were free of vomiting in the 20 microg/kg group. The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose. No safety problems were associated with either dose. The 40 microg/kg dose of granisetron appears to be more optimal.

Adolescent↗
PubMed1998

Marginal benefit/disadvantage of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in children: results of a prospective randomized trial. The Japanese Cooperative Study Group of PBSCT.

In this prospective trial, a total of 74 children who were scheduled to undergo high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) were prospectively randomized at diagnosis to evaluate the effectiveness of exogenous granulocyte colony-stimulating factor (G-CSF) treatment in accelerating hematopoietic recovery after PBSCT. The diagnosis included acute lymphoblastic leukemia (ALL) (n = 27), neuroblastoma (n = 29), and miscellaneous solid tumors (n = 18). Eligibility criteria included (1) primary PBSCT, (2) chemotherapy-responsive disease, and (3) collected cell number >1 x 10(5) colony-forming unit-granulocyte-macrophage (CFU-GM)/kg and >1 x 10(6) CD34(+) cells/kg patient's body weight. After applying the above criteria, 11 patients were excluded due to disease progression before PBSCT (n = 6) or a low number of harvested cells (n = 5), leaving 63 patients for analysis; 32 patients in the treatment group (300 microg/m2 of G-CSF intravenously over 1 hour from day 1 of PBSCT) and 31 in the control group without treatment. Two distinct disease-oriented high-dose regimens without total body irradiation consisted of the MCVAC regimen using ranimustine (MCNU, 450 mg/m2), cytosine arabinoside (16 g/m2), etoposide (1.6 g/m2), and cyclophosphamide (100 mg/kg) for patients with ALL, and the Hi-MEC regimen using melphalan (180 mg/m2), etoposide (1.6 g/m2), and carboplatinum (1.6 g/m2) for those with solid tumors. Five patients (two in the treatment group and three in the control group) were subsequently removed due to protocol violations. All patients survived PBSCT. The median numbers of transfused mononuclear cells (MNC), CD34(+) cells, and CFU-GM were, respectively, 4.5 (range, 1 to 19) x 10(8)/kg, 8.0 (1.1 to 25) x 10(6)/kg, and 3.7 (1.2 to 23) x 10(5)/kg in the treatment group (n = 30) and 2.9 (0.8 to 21) x 10(8)/kg, 6.3 (1.1 to 34) x 10(6)/kg, and 5.5 (1.3 to 37) x 10(5)/kg, respectively, in the control group (n = 28), with no significant difference. After PBSCT, the time to achieve an absolute neutrophil count (ANC) of >0.5 x 10(9)/L in the treatment group was less than that in the control group (median, 11 v 12 days; the log-rank test, P =.046), although the last day of red blood cell (RBC) transfusion (day 11 v day 10) and the duration of febrile days (>38 degrees C) after PBSCT (4 v 4 days) were identical in both groups. However, platelet recovery to >20 x 10(9)/L was significantly longer in treatment group than control group (26 v 16 days; P =.009) and >50 x 10(9)/L tended to take longer in the treatment group (29 v 26 days; P =.126), with significantly more platelet transfusion-dependent days (27 v 13 days; t-test, P =.037). When patients were divided into two different disease cohorts, ALL patients showed no difference in engraftment kinetics between the G-CSF treatment and control groups, while differences were seen in those with solid tumors. We concluded that the marginal clinical benefit of 1 day earlier recovery of granulocytes could be offset by the delayed recovery of platelets. We recommend that the routine application of costly G-CSF therapy in children undergoing PBSCT should be seriously reconsidered.

Adolescent↗
PubMed1998

Frequent aberration of FHIT gene expression in acute leukemias.

We analyzed the mRNA expression of the FHIT gene by reverse transcription-PCR (RT-PCR) in 54 cases of acute lymphoblastic leukemia (ALL; 11 cases of T-cell ALL [T-ALL] and 43 cases of non-T-ALL) and 40 cases of acute myeloid leukemia (AML). In 46% of the ALL cases and 55% of the AML cases, FHIT expression was absent or markedly decreased. Only abnormal short bands were detected in 30% of the ALL cases and 5% of the AML cases. Eighteen of 19 abnormal transcripts had the same fusion of exons 2-7, and all lacked the starting codon in exon 5. No obvious normal-sized PCR products were detected in cases exhibiting abnormal transcripts. These findings suggest that the expression of functional FHIT protein was lost in the majority of ALL (76%) and AML (60%) cases. Differential quantitative PCR of exons 3-9 of the FHIT gene and RT-PCR of the PTPRG gene, which is centromeric to the FHIT gene, showed the presence of the target sequences. Fluorescence in situ hybridization analysis using probes covering exons 5 and 8 revealed no difference in the signal patterns between leukemia and normal cells, showing one or two signal doublets in more than 90% of nuclei, and indicated that gross segments of the FHIT gene were not homozygously deleted in these cases. A small number of transcripts with an aberrant fusion between exons 2 and 7 were detected by RT-PCR in the bone marrow cells from four healthy individuals. Granulocytes, lymphocytes, and monocytes in the bone marrow cells of a healthy individual contained transcripts with the same fusion. This unique fusion of exons 2 and 7 might be preferentially seen in either neoplastic or normal hematopoietic cells, regardless of their lineage. The finding that FHIT expression was abolished in the majority of leukemia cases might support the hypothesis that the FHIT gene acts as a tumor suppressor, at least in leukemia.

Acid Anhydride Hydrolases↗
PubMed1998

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗
PubMed1998

Analysis of clinical AIDS-free interval after CD4+ cell counts fall below 200 x 10(6) L-1 in Japanese haemophiliacs infected with HIV-1.

We analysed the time from the date CD4+ cell counts fell below 200 x 10(6) L-1, defined as ti, to the onset of clinical AIDS, according to the 1987 Centers for Disease Control and Prevention case definition, in 129 Japanese haemophilia patients infected with HIV-1. The cumulative onset of clinical AIDS was analysed by the Kaplan-Meier method and proportional hazard model. Incorporated covariates were age of each patient at time ti, as well as CD4+ and CD8+ cell counts, serum levels of IgG, IgA, IgM, GOT and GPT at ti. The time of antiretroviral treatment initiation was also considered. The 50% AIDS-free interval after ti was 3.00 years (95% confidence interval (CI), range 0.49-5.51) and 1.71 years (95% CI, range 0.66-2.76) for the patients at CDC stage II and stage III, respectively (significantly different, P = 0.0013). Among the patients at CDC stage II at ti, higher levels of IgA were tightly associated with a shorter period from ti to onset of clinical AIDS (P < 0.0001), and relative hazard was 1.35 (95% CI, 1.11-1.64) with increase of IgA level by 1.0 g L-1. Thus there is a broad distribution in the time to onset of clinical AIDS in Japanese haemophiliacs even after CD4+ cell counts fall below 200 x 10(6) L-1. This should be taken into consideration in deciding upon the therapy and care of HIV-1 infected people.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Infantile hemangioendothelioma of the thymus with massive pleural effusion and Kasabach--Merritt syndrome: histopathological, flow cytometrical analysis of the tumor.

Infantile hemangioendothelioma of the thymus is a rare disease. We describe a patient who developed a large anterior mediastinal mass, severe thrombocytopenia and massive pleural effusion at 1 month of age. Glucocorticosteroid and irradiation therapy had no effect on either the tumor size or clinical symptoms and the tumor was resected subtotally. Three months after the subtotal resection, the remaining tumor had almost disappeared and the symptoms had resolved. The patient has now been well for 1 year after surgery without evidence of recurrence. The tumor tissue was characterized by prominent vascular endothelial proliferation intermixed with a normal thymic structure, producing a picture consistent with that of an infantile hemangioendothelioma in the thymus. Immunohistochemically, the tumor cells showed positive staining for vimentin, factor VIII and CD34. The DNA stemline and proliferative activity were examined by flow cytometry, which revealed a diploid stemline with a low growth fraction. DNA content and cell cycle analyses of the tumor tissue may be useful for predicting the biological behavior of the tumor.

DNA, Neoplasm↗
PubMed1998

Qualitative and quantitative detection of cytomegalovirus DNA in sera by PCR as a clinical marker.

The amount of human cytomegalovirus (CMV) DNA in sera is considered to be a direct marker for CMV infection. We established conditions for nested PCR that detected one copy of CMV DNA, and for competitive PCR, which detected five or more copies of CMV DNA quantitatively. We tested 50 microl each of 16 freeze-stored and 5 fresh sera from patients, for CMV DNA. In sera obtained from the same patient at different time points, small amounts of CMV DNA were detected before the onset of CMV pneumonia. In sera from certain CMV-infected patients who were treated with the anti-CMV agent, ganciclovir, CMV DNA was not detected. Quantitative PCR detection of CMV DNA seems to be suitable for predicting early recurrent CMV infection and monitoring the efficacy of antiviral therapy. The qualitative nested PCR examination of CMV DNA in 40 cord blood plasma samples was carried out for the purpose of preventing CMV infection by cord blood stem cell transplantation, and they were all negative for CMV DNA.

AIDS-Related Opportunistic Infections↗
PubMed1998

[Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children's Cancer and Leukemia Study group (CCLSG)].

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Correlation of titer of antibody to principal neutralizing domain of HIVMN strain with disease progression in Japanese hemophiliacs seropositive for HIV type 1.

With the use of the principal neutralizing determinant (PND) peptide-based ELISA to measure anti-PND antibodies that specifically bound synthetic peptides derived from HIVIIIB, HIVMN, HIVRF, HIVSC, HIVWJM-2, HIVAf1l.con, or HIVAf2.con, type-specific antibodies to the HIVMN peptide were studied in 350 serum specimens from Japanese with hemophilia A who had been injected with known unheated factor VIII concentrates until 1985 and had been infected with HIV-1 subtype B. These antibodies were not found in any of the seronegative sera of hemophiliacs, patients with autoimmune diseases, or normal healthy controls. Further, all hemophiliacs rapidly progressing to AIDS and death among the 95 hemophiliacs in a restricted Nara area had antibody titers of less than 20 and their low levels preceded the rapid progression to the disease state. In contrast, slowly progressing hemophiliacs maintained an antibody titer of more than 100 from the initial stages of viral infection and remained asymptomatic. Sequence analysis of the V3 regions of HIV-1 indicated that the hemophiliacs who maintained a high anti-PNDMN antibody level showed a conserved MN sequence. In contrast, the HIV-infected hemophiliacs with nonreactivity in the ELISA showed sequence changes in the neutralizing epitopes of HIVMN. The dynamic of the serum anti-PNDMN antibody titer appear to be a characteristic indicator of the progression of the HIV-infected status in Japanese hemophiliacs seropositive for HIV-1.

Adult↗
PubMed1997

Treatment outcome and prognostic factors in childhood acute myeloblastic leukemia: a report from the Japanese Children's Cancer and Leukemia Study Group (CCLSG)

Treatment outcome and prognostic factors were evaluated in 152 children with acute myeloblastic leukemia (AML) treated on three consecutive protocols (ANLL 861, 8912, 9205) of the Children's Cancer Leukemia Study Group (CCLSG, Japan). In the ANLL 9205 protocol, anthracycline was used with a continuous infusion of cytosine arabinoside, followed by an intensive sequential post remission chemotherapy of short duration. Forty-two of these 46 patients (91.3%) achieved complete remission, and 58.8% of these patients projected a 3-year disease-free survival. These results were apparently superior to those obtained with the ANLL 861 and 8912 protocols, which used conventional doses of multiple drugs followed by a moderate post remission chemotherapy of long duration. This favorable response with the ANLL 9205 protocol was attributed mainly to the high induction rate of patients with the M4 and M5 FAB subtypes, as compared to those in the previous two protocols (93.3% in ANLL 9205 vs. 57.9% in ANLL 861 + 8912; P < 0.05). The ANLL 861 and 8912 protocols, an older age (> or = 8 years), higher WBC counts (> or = 10 x 10(9)/1) and all predicted an increased risk of relapse and decreased the survival following univariate analysis (P < 0.05). An older age and high WBC count continued to predict an increased risk of relapse in multivariate analyses: patients with an age > 8 years and WBC counts > 10 x 10(9)/1 had a 4.5 times higher risk of relapse than patients without these adverse features.

Adolescent↗