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Biomedical subjects

Y Horikoshi

Publications and source records attributed to Y Horikoshi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Correlation of chromosome abnormalities with presence or absence of WT1 deletions/mutations in Wilms tumor.

Of 40 Wilms tumors with chromosome abnormalities, 6 were hypodiploid, 10 were pseudodiploid, 7 were hyperdiploid with 47 to 49 chromosomes, and 17 were hyperdiploid with 50 or more chromosomes, mostly including +12. WT1 deletions/mutations were found in one hypodiploid, eight pseudodiploid, and one hyperdiploid (47-49 chromosomes) tumor, but in none of the hyperdiploid (> or =50 chromosomes) tumors. Of the 10 tumors with WT1 abnormalities, 6 had a homozygous WT1 deletion, 1 had a nonsense WT1 mutation and loss of heterozygosity at 11p, 1 had an intragenic hemizygous WT1 deletion without detectable WT1 mutation, and 2, which occurred in Wilms tumor-aniridia-genitourinary abnormalities-mental retardation syndrome patients, had a hemizygous deletion and a missense or frameshift mutation of WT1. Six of the nine tumors with homozygous or hemizygous WT1 deletions had chromosome aberrations involving chromosome band 11p13 in one of the two chromosomes 11. While one hypodiploid and one pseudodiploid patient died of the disease, and one hyperdiploid (47-49 chromosomes) patient was alive in nonremission, all hyperdiploid (> or =50 chromosomes) patients had no evidence of disease at the last follow-up. Our data show that chromosome aberrations are closely correlated to WT1 abnormalities and suggest that hyperdiploid (> or =50 chromosomes) Wilms tumors may be characterized by the absence of WT1 abnormalities and possibly also by a favorable prognosis.

Aneuploidy↗
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

Chromosome abnormalities and MLL rearrangements in acute myeloid leukemia of infants.

Of 29 infants with acute myeloid leukemia (AML), 14 (48%) had various 11q23 translocations. MLL rearrangements were examined in 21 of the 29 patients, and 11 (52%) showed the rearrangements. 11q23 translocations and/or MLL rearrangements were found in 17 (58%) of the 29 patients. While all but one of the 17 patients with 11q23/MLL rearrangements had M4 or M5 type of the FAB classification, the 12 patients without such rearrangements had various FAB types, including M2, M4, M4EO, M6 and M7. Of the 12 patients with other chromosome abnormalities or normal karyotypes, two had inv(16) ort(16;16), one had t(1;22)(p13;q13), and two had a novel translocation, t(7;12)(q32;p13). The breakpoint on 12p of the t(7;12) was assigned to intron 1 or the region just upstream of exon 1 of the TEL/ETV6 gene by fluorescence in situ hybridization. The event-free survival at 5 years for the 17 patients with 11q23/MLL rearrangements was 42.2%, and that for the 12 patients without such rearrangements was 31.3% (P = 0.5544). 11q231MLL rearrangements have been frequently reported and a poor prognosis in infant acute lymphoblastic leukemia implied. Our study showed that while 11q23/MLL rearrangements were also common in infant AML, AML infants with such rearrangements had a clinical outcome similar to that of AML infants without such rearrangements.

Acute Disease↗
PubMed1999

Swelling and ketoprofen release characteristics of thermo- and pH-responsive copolymer gels.

Swelling-controlled drug delivery copolymer gels were newly synthesized by introducing thermo- and pH-responsive methacryloyl-glycine (MA-Gly) or pH-responsive methacrylic acid (MA-Ac) for comparison with thermoresponsive acryloyl-L-proline ethyl ester (A-ProOEt). A homopolymer gel of A-ProOEt was kept at degrees of swelling that were less than 0.5 at a pH from 2.5 to 7.5 at 37 degrees C. The thresholds of swelling for copolymer gels consisting of A-ProOEt/MA-Gly and A-ProOEt/MA-Ac with a composition of 40/60 mol% were found to be pH 3.0 and pH 5.5, respectively, in buffer solutions at 37 degrees C. The diffusion characteristics of 2-(3-benzoylphenyl)propionic acid (ketoprofen) from such copolymer gels was evaluated in buffer solutions at pH's more than 5.5, and it was found that A-ProOEt/MA-Gly gel possesses a case II transport mechanism that is completely linear time dependent in both the amount diffused and the penetrating swelling front position. On the other hand, A-ProOEt/MA-Ac gel exhibited a non-Fickian (or anomalous) diffusion behavior under the same conditions.

Diffusion↗
PubMed1999

Biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia.

The purpose of this study was to investigate the biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia (ALL). We carried out in vitro tests with a 4-day culture and a methyl-thiazol-tetrazolium assay on bone marrow samples from 209 children newly diagnosed with ALL. After testing the resistance of leukemic cells to 14 drugs, we classified the patients into two groups according to their sensitivity to three drugs (prednisolone, L-asparaginase, and vincristine) used in remission induction therapy. The three-drug resistant group (RR: sensitive to no drugs or to one drug) correlated with both short-term and long-term treatment failure. Three-year event-free survival (95% confidence interval) for the sensitive group (SS: sensitive to two or three drugs) was 0.813 (0.773-0.853) and that of the RR group was 0.616 (0.569-0.669) (P = 0.0001). Univariate analysis showed that Philadelphia-chromosome (Ph1) positivity and immunophenotype of mixed lineage were also prognostic factors in the 209 patients. The prognosis of the SS/RR drug resistance profile within 14 Ph1 patients was marginally significant (P = 0.062). Multivariate Cox regression analysis showed that Ph1 was an overwhelmingly adverse factor in event-free survival, with a relative hazard of 5.37 (2.57-11.21, P < 0.0001), followed by RR, with a relative hazard of 2.98 (1.69-5.25, P = 0.0001). Furthermore, we clarified the characteristics of the RR group by examination of the pattern of drug resistance to other drugs in comparison with the SS group. The leukemic cells of RR patients were more resistant than those of SS patients (P < 0.0001) to all the drugs tested, with resistance ratios of 1.6 to 13.1 (mean 3.4). In conclusion, in vitro three-drug resistance at the initial stage is an important independent predictor of treatment failure for both induction response and long-term outcome in childhood ALL.

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

Peripheral blood stem cell autografts for the treatment of children over 1 year old with stage IV neuroblastoma: a long-term follow-up.

This is the first report of the long-term therapeutic results in 22 children more than 1 year old with stage IV neuroblastoma who were treated with autologous peripheral blood stem cell transplantation (PBSCT). The median age of the patients at PBSCT was 4 years (1 to 10 years) and seven of the 17 patients who were evaluated for N-myc amplification were positive. PBSC were collected by a median of four aphereses per patient. The patients underwent PBSCT from 6 to 21 months after the start of therapy (median 10.5 months) at which time 13 patients were in CR, seven were in PR, and two had refractory disease. Multi-drug therapy using the 'high-MEC' regimen consisting of carboplatinum (400 mg/m2) and VP-16 (200 mg/m2) on days -7 to -4, and melphalan (90 mg/m2) on days -3 and -2, was the primary cytoreductive regimen. The median number of infused MNC and CFU-GM was, respectively, 4.3 x 10(8)/kg and 2.4 x 10(5)/kg. After PBSCT, three patients died of regimen-related toxicities and one patient who was transplanted with refractory disease died of disease progression without any benefit from transplantation. Hematological recovery was evaluated in 21 patients, excluding one early death. The median number of days required to achieve an AGC of >0.5 x 10(9)/l and platelet count of >50 x 10(9)/l were, respectively, 11 and 46. Eleven patients relapsed 3 to 50 months after PBSCT, and currently seven patients (5/13 who were transplanted in CR and 2/7 in PR) are surviving disease-free at 52 to 84 months. Although the retrospective nature of this study and several variables prevent a meaningful analysis, the overall results still support the feasibility of developing a prospective study of PBSCT with a larger number of children with high-risk neuroblastoma.

Child↗
PubMed1998

Cloning, sequencing, and disruption of the Bacillus subtilis psd gene coding for phosphatidylserine decarboxylase.

The psd gene of Bacillus subtilis Marburg, encoding phosphatidylserine decarboxylase, has been cloned and sequenced. It encodes a polypeptide of 263 amino acid residues (deduced molecular weight of 29,689) and is located just downstream of pss, the structural gene for phosphatidylserine synthase that catalyzes the preceding reaction in phosphatidylethanolamine synthesis (M. Okada, H. Matsuzaki, I. Shibuya, and K. Matsumoto, J. Bacteriol. 176:7456-7461, 1994). Introduction of a plasmid containing the psd gene into temperature-sensitive Escherichia coli psd-2 mutant cells allowed growth at otherwise restrictive temperature. Phosphatidylserine was not detected in the psd-2 mutant cells harboring the plasmid; it accumulated in the mutant up to 29% of the total phospholipids without the plasmid. An enzyme activity that catalyzes decarboxylation of 14C-labeled phosphatidylserine to form phosphatidylethanolamine was detected in E. coli psd-2 cells harboring a Bacillus psd plasmid. E. coli cells harboring the psd plasmid, the expression of which was under the control of the T7phi10 promoter, produced proteins of 32 and 29 kDa upon induction. A pulse-labeling experiment suggested that the 32-kDa protein is the primary translation product and is processed into the 29-kDa protein. The psd gene, together with pss, was located by Southern hybridization to the 238- to 306-kb SfiI-NotI fragment of the chromosome. A B. subtilis strain harboring an interrupted psd allele, psd1::neo, was constructed. The null psd mutant contained no phosphatidylethanolamine and accumulated phosphatidylserine. It grew well without supplementation of divalent cations which are essential for the E. coli pssA null mutant lacking phosphatidylethanolamine. In both the B. subtilis null pss and psd mutants, glucosyldiacylglycerol content increased two- to fourfold. The results suggest that the lack of phosphatidylethanolamine in the B. subtilis membrane may be compensated for by the increases in the contents of glucosyldiacylglycerols by an unknown mechanism.

Amino Acid Sequence↗
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

[International perspectives on the treatment of gastric cancer].

Our experience of treatment of gastric cancer in European and developing countries suggested the necessity of the establishment of both operative and chemotherapeutic modalities. These modalities should be first based on theoretically convincing data and secondarily well analyzed from the viewpoint of cost-effectiveness.

Cost-Benefit Analysis↗
PubMed1998

[Studies of childhood non-Hodgkin's lymphoma--treatment results with the CCLSG NHL 960 protocol. Children's Cancer and Leukemia Study Group (CCLSG)].

We report here on the preliminary treatment findings of a CCLSG NHL 960 study that was initiated in March 1996. In this study, 37 patients with non-Hodgkin's lymphoma were assigned to 4 different treatment groups according to disease stage and histology: (1) localized disease; (2) advanced disease, lymphoblastic type; (3) advanced disease, large cell type; and (4) advanced disease, Burkitt type. The first three groups received the modified protocols of the NHL 890 study. Groups 1 and 3 received COPADM induction therapy (CPM, VCR, PRD, ADR, and MTX). After achieving remission, Group 1 received only maintenance therapy consisting of alternate administration of 7 drugs, while Group 3 received additional intensification therapy with combination chemotherapy consisting of MTX and Ara-C, followed by a maintenance phase involving the administration of 9 drugs. Group 2 received COPADL induction therapy (CPM, VCR, PRD, ADR, and LASP) and consolidation/intensification therapies followed by a maintenance phase. Group 4 received short-term intensive COPADM polychemotherapy. Twelve patients with localized with localized disease (stage I-II) and 25 patients with advanced disease (stage III-IV) were enrolled in this study. Except for 2 patients in the advanced disease stages who died earlier in the course of the study, all patients remained in remission.

Adolescent↗
PubMed1997

In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia.

It is vital to develop effective therapy for children with acute lymphoblastic leukemia (ALL), in whom no remission occurs or who suffer relapse with current protocols. Cellular drug resistance is thought to be an important cause of induction failure and relapse. We performed in vitro tests of bone marrow samples in 196 children with newly diagnosed ALL with a 4-day culture and a methyl-thiazol-tetrazolium assay. We tested 16 drugs and calculated the 70% lethal dose (LD70) for 14 drugs and the leukemic cell survival (LCS) rate for dexamethasone and prednisolone. For each single drug, patients were classified into two groups, sensitive or resistant, by median concentration of LD70 or LCS. When patients were classified into three groups by sensitivity to four drugs of DPAV (dexamethasone, prednisolone, L-asparaginase, and vincristine), 3-year event-free survival (EFS; 95% confidence intervals) of the super sensitive group (SS; sensitive to all 4 drugs) was 0.833 (0.690 to 0.976), that of the intermediate sensitive group (IS; sensitive to 2 or 3 drugs) was 0.735 (0.609 to 0.863), and that of the relatively resistant group (RR; sensitive to no drugs or to 1 drug) was 0.541 (0.411 to 0.670; P = .0008). We then investigated the relationship between the above four-drug sensitivity and the time of relapse. The SS and IS patients tended to maintain continuous complete remission, and RR patients tended to undergo induction failure and early and late relapse (P = .004). Initial white blood cell count, immunologic classification, and age were also predictive factors, but the patient numbers showed no statistical correlation between these factors and the four-drug sensitivity groups (SS, IS, and RR). When we took three groups SS/IS/RR and investigated the EFS for various clinical groups, DPAV sensitivity strongly influenced EFS in the standard-risk ALL (P = .016). In vitro drug sensitivity testing provides additional prognostic information about childhood ALL, and early detection of drug resistance at the time chemotherapy commences may provide a successful strategy for individualizing treatment, as the results indicate de novo resistance to front-line drugs and suggest alternative, second-line drugs.

Aclarubicin↗
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↗
PubMed1997

Minimal residual disease with TEL-AML1 fusion transcript in childhood acute lymphoblastic leukaemia with t(12;21).

We analysed the TEL-AML1 transcript using reverse transcription-polymerase chain reaction (RT-PCR) in order to detect minimal residual disease (MRD) in seven children with t(12;21)-associated B-lineage ALL. Leukaemic cells with the TEL-AML1 transcript appear to be very sensitive to chemotherapy, and may be eradicated in most patients if adequate chemotherapy is given. However, a small number of patients with t(12;21) ALL may relapse under the currently used chemotherapy, and we believe that RT-PCR for detecting MRD with the transcript is a suitable tool for monitoring the efficacy of chemotherapy or impending relapse in these patients. We analysed the TEL-AML1 transcript using reverse transcription-polymerase chain reaction (RT-PCR) in order to detect minimal residual disease (MRD) in seven children with t(12;21)-associated B-lineage ALL. Two sets of primers, TEL exon 5 and AML1 exon 3 or 4, detected two types of transcript in four patients and two other types in two other patients. The two different translocation breakpoints in the AML1 gene with or without splicing out of AML1 exon 3 seemed to result in these four types of transcript in leukaemia samples.

Child↗
PubMed1997

Quantitative detection of human immunodeficiency virus type 1 (HIV-1) RNA by PCR and use as a prognostic marker and for evaluating antiretroviral therapy.

The amount of human immunodeficiency virus type 1 (HIV-1) genomic RNA in sera is considered to be one of the most direct markers for patient prognosis and monitoring the efficacy of antiretroviral therapy. Quantitative detection of HIV-1 RNA was performed by the dilution endpoint method and competitive PCR. Conditions for detecting one copy of HIV-1 control DNA were examined to decide the dilution endpoint exactly. PCR of the gag region by SK145/SK39 primer pair and seminested PCR by SK145/SK101 primer pair gave the best result. Conditions for competitive PCR of HIV-1 cDNA, which was reverse transcripted from HIV-1 control RNA, were also studied using a SK38/SK39 primer pair in the presence of HIV-PCR MIMIC as a competitor DNA. The detection limit of HIV-1 control DNA by competitive PCR was 10 copies but that of HIV-1 control RNA was 50 copies. Time-course quantitation of HIV-1 RNA in frozen-stored sera from an AIDS patient was carried out and traced back to 1993. The amount of serum HIV-1 RNA markedly decreased when the treatment was changed but increased again before deterioration of his clinical status. It is considered that the quantitation of serum HIV-1 RNA is useful for the prognosis of HIV-infection and the evaluation of the antiretroviral therapy.

Anti-HIV Agents↗
PubMed1997

[Myelogenous leukemia in children. ANLL9205 study by Children's Cancer and Leukemia Study Group (CCLSG)].

Treatment results were evaluated in 45 children with acute myeloblastic leukemia (AML) treated on the ANLL-9205 protocol of the Children's Cancer Leukemia Study Group (CCLSG, Japan). In this protocol, terarubicin (THP-ADR), vincristine and continuous infusion of cytosine arabinoside (Ara C) were applied for remission induction therapy (AVC), and VP16+ high dose Ara C were used sequentially for 32 or 48 weeks. Eleven patients received stem cell transplantation. Thirty-eight out of the 43 eligible patients (88.4%) achieved complete remission, and the overall 3-year event-free survival (EFS) was 55.6% (S.E.,10%). This favorable response was attributed mainly to the high induction rate of patients with the M5, M7 FAB subtypes and higher WBC counts (> or = 10 x 10(9)/L). There was no difference in the 3-year EFS of these patients who discontinued treatment between 32 weeks and 48 weeks. Serious toxicities were not observed in this study. These findings suggest that the ANLL-9205 protocol is an effective and safe treatment regimen for childhood AML. When comparing the treatment period of 32 or 48 weeks, the difference was not statistically significant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Treatment results in childhood acute myeloblastic leukemia--a report of clinical trials of a past decade from the Japanese children's Cancer and Leukemia Study Group (CCLSG)].

Treatment results were evaluated in 167 children with acute myeloblastic leukemia (AML) treated on four protocols (ANLL 861, 8912, 9205, APL-ATRA) of the Children's Cancer Leukemia Study Group. 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, 42/46 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 & 8912 protocols, which used conventional doses of multi 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 (91.3% in ANLL 9205 vs 57.9% in ANLL 861 + 8912; p < 0.05). No significant difference in the patients outcome was found between the chemotherapy group and allogenic bone marrow transplantation group in the ANLL 9205 study. The patients with the M3 FAB subtype treated with the APL-ATRA protocol which consisted of an alternative use of all-trans retinoic acid and chemotherapy significantly prolonged event free survival as compared with the patients treated with ANLL 861/8912 protocols without all-trans retinoic acid.

Anthracyclines↗