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  • 1
    In: The American Journal of Cardiology, Elsevier BV, Vol. 118, No. 9 ( 2016-11), p. 1386-1389
    Type of Medium: Online Resource
    ISSN: 0002-9149
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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  • 2
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5288-5288
    Abstract: Background Azacitidine (AZA) and intensive chemotherapy (IC) are respectively effective for MDS-MRC to some extent. However, their median overall survivals (OS) are within 1 year in the previous reports. Aims The remission induction therapy is performed with AZA for patients with the bone marrow (BM) blast of 〈 30% and with IC for patients with the BMblast of 〉 30% to improve CR rate. The patients who reached CR with AZA or IC, maintenance therapy by sequential AZA and IC were performed to prolong the OS. Patients and methods Sixty-six patients,who were diagnosed as AML-MRC from December, 2011 to March, 2014 in our institution were included. AZA was administered by drip infusion at a dose of 75 mg/m2 for 5 days every 26 day. As the IC, IBMP (idarubicin,behenoyl-ara-C (enocitabine), mercaptopurine, and prednisolone) was administered for 10 days. The patients ,who reached CR with AZA or IBMP, then sequential therapy of AZA for 5 days and mini-IBMP for 5 days/or BAMP (A; acularubicin) for 6 days were treated by establishing the withdrawal period for 21 to 35 days. When possible, the high-dose ara-C (HDAC) for 5 days was included. Among the patients with the BMblast of 〉 30%, 4 patients underwent allogeneic stem cell transplantation (allo-SCT). OS was evaluated using Kaplan-Meier estimates. Results Twenty four patients, whose BM blast 〈 30% (20 - 29%, median23%) treated with AZA as the first treatment. Six secondary AML were included. Fourteen patients were male (58%), the median age was 75-years (51-90), the IPSS cytogenetic risk was good in 5 patients (21%), intermediate in 6 (25%) and poor in 13 (54%). The median cycle of AZA was 12 (3-29). By the IWG criteria, CR was achieved by 10 patients (42%), marrow CR by 2 (8%), PR by 1 (4%), SD by 5 (21%) and PD by 6 (25%). The median number of cycle by CR was 3 (2 -10). Forty two patients, whose BM blast 〉 30% (32-95%, median 56%) treated with the remission induction therapy by IBMP. One secondary AML was included. Thirty patients were male (73%), the median age was 73-years (36-86), the cytogenetic risk was good in 8 patients (19%), intermediate in 14 (33%) and poor in 20 (48%). CR was achieved by 34 patients (81%), PR by 4 (10%) and failure by 4 (10%). The median follow up was 13 M in the BM blast 〈 30% group and 12 M in the BM blast 〉 30% group. The median OS in the BM blast 〈 30% was 23 M.The median OS in the BM blast 〉 30% group have not reached and 1year survival was 67%, 2 years survival 51% on the basis of Kaplan-Meier estimates. In both groups, there were 51 patients with CR+PR, 9 of which were treated with AZA only after CR, and 42 (82%) of which received sequential AZA treatment and IC. HDAC was included in chemotherapy by 24 patients (57%). Thirty eight patients, other than 4 patients who underwent Allo-SCT, have not reached the median OS, and 2 years survival was 55%. As concerns cytogenetic risk, the median OS in 33 patients with poor risk was 17 M, and 33 patients with good + intermediate risk have not reached the median OS, and 2years survival was 55%. Summary/Conclusion There was only one death of chemotherapy and AZA and IC for AML-MRC is very safe and good remission induction therapy. We have not described this time, but the measures for infection by such as fungi have contributed largely. In spite of the interim analysis of small sample size as 66 patients and short observation period, the median OS is approximately 2 years, so that the sequential therapy of AZA and IC is a feasible and useful therapy which realizes prolongation of OS. Particularly, the median OS of 17 M in the cytogenetic poor risk group can be mentioned as great progress. Because before introduction of AZA, when we treated more than 200 patients with AML-MRC only by almost similar chemotherapy, the median OS in the poor risk group was only 6M. Currently, we are following up 6 patients, who stopped the treatment,alive more than 6 M without any treatments. SinceAML-MRC is a disease in elderly people, it is important to devise therapeutic methods to prolong the untreatment period with CR in many patients in the future. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 3
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1571-1571
    Abstract: Introduction Azacitidine (AZA) has emerged as the standard of care for treatment of higher risk myelodysplastic syndromes (MDS) based upon results of several studies. However, the rate and duration of response are insufficient and the focus of research will shift towards further optimization of clinical outcome. Studies for a dosing schedule and a combination therapy with other drugs are important. In general, there are some difficulties to fix the dosing schedule of AZA due to its side effects (infection etc.) and complications. We had carried out the strict managements for protection of infection and bleeding to keep a fixed dosing schedule of 75mg/m2/day for 5 days, followed by 21 days drug-off. Methods Data from consecutive 62 patients with higher risk MDS treated with AZA at our institute between May 2011 and April 2013 were reviewed. AZA was strictly administered at a dosage of 75mg/m2/day intravenously for 5 days, followed by 21 days drug-off, every 26 days. Patients, whose neutropenia (≤500/mm3) were sustained, were hospitalized in clean rooms. Prophylaxis of antibiotics and the administration of G-CSF were carried out if necessary. When patients in poor risk cytogenetics achieved complete remission (CR) by AZA alone, they were subsequently received a sequential combination therapy with 5-day AZA, followed by 21 days drug-off and chemotherapy (including idarubicine or aclarubicine), followed by 35 days drug-off to maintain CR. Results A total of 62 patients were classified as RA 2, RAEB-1 14, RAEB-2 32, and RAEB-T 14. There were 40 male patients and 22 female. Median age was 73 years (range, 40-90). At the time of AZA treatment, 40 patients were stratified as Int-2 and 22 as High by IPSS. Sixteen patients had good risk cytogenetics, 17 intermediate, and 29 poor. Fourteen patients had 20-29% of bone marrow blasts, 32 10-19% , and 16 2-9%. Forty-seven patients were de novo MDS and 15 therapy-ralated MDS (t-MDS). Forty-five patients had the time from MDS diagnosis to AZA treatment within two month, 4 2-12 months, and 13 13-102 months. The median time of follow up was 11 months (3-27) and the median cycle of a 5-day AZA treatment was 8 (2-29). Totally, 537 cycles had been done. Days of drug-off within 21 days/cycle were 435 cycles(81%), 22-28 days/cycle 82 cycles (15%), and over 29 days/cycle 20 cycles (4%). The IWG2006 responses to AZA included 29 CR (47%), 10 marrow CR (16%), 9 stable disease (SD) with hematological improvement (HI) (15%), 6 SD without HI (10%), 3 progressive disease (PD) (5%), and 1 failure (2%). The overall response rate (ORR) was 78%. HI includes 35 HI-E (57%), 37 HI-P (59%), and 26 HI-N (42%). The CR/mCR rate in Int-2 was 23/40 (58%), High 16/22 (73%), good risk cytogenetics 11/16 (69%), intermediate 9/17 (53%), poor 19/29 (66%), 20-29% bone marrow blasts at initial diagnosis 9/14 (64%), 10-19% 21/32 (66%), and ≤9% 9/16 (56%). About the time to AZA from MDS diagnosis, the CR/mCR rates were 29/45 (64%) in 0-2 months and 10/17 (59%) in 3-102 months. Among t- MDS, 8/15 (53%) achieved to CR/mCR and among de novo MDS, 31/47 (66%) achieved to CR/mCR. Cytogenetic responses, excluding 9 normal karyotype patients, were 15/28 (54%) CR and 12/28 (42%) PR. Among 62 patients, 10 patients died and 12 received bone marrow transplantation (BTM) including 7 CR, 2 SD, and 3 PD. The median time to death from the initiation of AZA treatment was 11 months (3-23). The causes of death were 3 BMT-related, 3 PD, and 4 infection. Eight patients, including 4 CR and 4 SD, progressed to AML. They were immediately treated with chemotherapy, and 7 are still alive. Ten patients in poor risk cytogenetics, who achieved CR by AZA alone, subsequently switched to a sequential combination therapy with AZA and chemotherapy from March 2013. No relapse have been seen at present and they have been followed up. Conclusions The AZA regimen fixed dosing schedule of 75mg/m2 for 5 days, followed by 21 days drug-off showed promising efficacy for higher risk MDS (ORR; 78%). Based upon our results, the response rates of AZA against Int-2 vs High and de novo MDS vs t-MDS were almost the same. When patients with poor risk cytogenetics achieved CR by AZA treatment alone, the following sequential combination therapy with AZA and chemotherapy was effective to maintain CR. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 4
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1594-1594
    Abstract: Background: Imatinib (IMA), a first-generation tyrosine kinase inhibitor (TKI), has enabled safer, more successful treatment of chronic myeloid leukemia (CML). Moreover, second-generation TKIs such as nilotinib (NIL) and dasatinib (DAS) have enabled achievement of deeper molecular responses than IM. TKIs have improved prognosis for CML patients, but lifelong continuation of TKIs lowers quality of life and places an economic burden on patients. Whether administration of TKIs can be stopped is thus an important question. Trials including the STIM trial have suggested that IMA can be stopped in CML patients who maintain complete molecular response (CMR) for 〉 24 months, but little data is available regarding second-generation TKIs. Methods: Among adult CML patients in the chronic phase diagnosed at Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital from May 1995 to September 2010, we analyzed patients who achieved and maintained CMR for 〉 1 year on TKIs, and then stopped TKIs. We started TKI treatment with IMA in all patients and changed to NIL or DAS after March 2009, when second-generation TKIs became available in Japan. We continued each TKI for ³6 months, and for 〉 12 months in most cases. Molecular monitoring was performed with BCR-ABL1 real-time quantitative PCR (RQ-PCR) using bone marrow or peripheral blood samples. Sensitivity of this RQ-PCR was 0.004%, corresponding to MR4.4. Relapse was defined as a loss of CMR. We provided TKI therapy for relapsed patients. RQ-PCR was performed every three months after relapse. Results: Stopping TKI was possible in 51 patients (32 males, 19 females). Observations were continued until June 2015, and the median duration of observation was 147 months (range, 59-257 months). Interferon (IFN)-α was administered to 18 patients. Median age at diagnosis was 44 years (range, 22-83 years). Two deaths were observed, with neither due to CML. Median duration of TKI treatment was 91 months (range, 29-160 months). Median interval from starting TKIs until achieving CMR was 41 months (range, 6-144 months), and that from achieving CMR to stopping TKIs was 20 months (range, 10-91 months). Median duration of observation from stopping TKIs was 42 months (range, 4-135 months). TKI treatment comprised IMA alone in 10 patients, IMA → NIL in 8, and IMA →NIL → DAS in 33. Relapse after stopping TKIs was observed in 14 cases. The period from stopping TKIs to relapse was 3 months in 12 patients, and 6 months and 18 months in 1 patient each. We treated all relapse patients with TKIs as patients chose, and all achieved 2nd CMR. Median period from relapse to 2nd CMR was 20.5 months (range, 6-40 months). In univariate analysis by Fisher's exact test, no correlation was seen between relapse rate and sex (male, n=32 vs. female, n=19; p=0.106), history of IFN-α therapy (yes, n=18 vs. no, n=33; p=0.525), duration from achieving CMR to stopping TKI (³24 months, n=34 vs, 〈 24 months, n=17; p=0.183), and use of second-generation TKI (yes, n=34 vs. no, n=10; p=0.25). However, relapse rate was significantly lower in patients who received second-generation TKIs for ³24 months (n=23 vs. 〈 24 months, n=10; p=0.0425). Conclusions: In our cohort, the rate of relapse after stopping TKIs was lower among patients who received second-generation TKIs for a longer period. This suggests that achieving deeper molecular response may be more important than maintaining CMR for a long time when trying to stop TKIs. The fact that most relapses after stopping TKIs occurred 3 months after stopping TKIs implies a need for careful molecular monitoring, particularly just after stopping TKIs. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 5
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5272-5272
    Abstract: Introduction Chromosomal aberration is a powerful prognostic factor for acute myeloid leukemia (AML). On the other hand, age and high leukocyte counts at diagnosis are additional prognostic factors. In the case of high leukocyte counts, chemotherapy becomes difficult since there is a possibility of developing disseminated intravascular coagulation (DIC) and tumor lysis syndrome (TLS). In our hospital, we conducted leukapheresis for leukemia patients with high leukocyte counts at diagnosis who had not developed DIC, and then we performed the original intensive chemotherapy of our institution (see below). Therefore, we targeted AML patients with leukocyte counts high at diagnosis and analyzed the outcome of the chemotherapy retrospectively. Patient and methods We examined AML patients with leukocyte counts of 50000/ul or more who received their first treatment at our institution between April 2009 and December 2013. We conducted leukapheresis for patients with leukocyte counts of 50000/ul or more who had not developed DIC, followed by our original induction therapy. It consisted of four drugs; idarubicin (IDR) 12mg/m2 (10mg/m2 for 70 years of age or older) days 1, 3, 5, 8 and behenoyl cytosine arabinoside (BH-AC) 350mg/m2 (300mg/m2 for 70 years of age or older) days 1-10, merucaptopurine (6-MP) 70mg/m2 days 1-10, predonisolone (PSL) 20mg/person days 1-6. If the patient had developed DIC, we performed this induction therapy treating the DIC with recombinant human soluble thrombomodulin (rTM) and gabexate mesylsate (FOY). Since the release of rasburicase in April 2010, we used it to prevent TLS. After induction therapy, we performed consolidation therapy, which consisted of mitoxantrone + cytarabine, and then maintenance therapy. This consisted of two courses; BAMP therapy (BH-AC, Aclarcin, 6-MP, PSL) and miniIBMP + VCR therapy (IDR, BHAC, 6- MP, PSL) alternately. We performed hematopoietic stem cell transplantation (HSCT) for patients with relapse during suitable age and other eligible cases. Result A total of 33 patients with newly diagnosed AML were examined. There were 16 men and 17 women whose median age was 70 years (range, 17-93 years). The elderly patients over the age of 60 were 21/33 (63.6%). Median follow-time was 24 months (range 2-60 months). Leukocyte counts at the time of diagnosis were 50,400-445,900/ul (median 107,700/ul), 17 patients (15.5%) had counts of over 100,000/ul. Leukapheresis was performed on 7 patients and leukocyte reduction rate was 41.7%-75.4%. Serious complications were not observed during the procedure. Serum lactate dehydrogenase (LDH) value was 283-3645 U/L (median 1111 U/L) and serum uric acid value was 2-13.7 mg/dl (median 6.5 mg/dl). We administered rasbricase to 20/33 (60.6%) patients and three (9.1%) patients developed TLS. Seventeen patients (51.5%) underwent DIC, 9 patients were at diagnosis and the remaining 8 patients were after initiation of the induction therapy. We treated DIC with FOY single agent (5 patients), rTM single agent (4 patients) and combination of rTM and FOY (8 patients) and then all patients showed improvement. Karyotype was as follows: Good risk in 3 (9.1%) patients, two had t(15;17) and one had t(8;21); intermediate risk in 23 patients (69.7%), thirteen had normal karyotype, 3 patients had trisomy 8 and 4 patients had others; poor risk in 7 patients (21.2%), six patients had complex karyotype and one patient had monosomy 7. We performed bone marrow aspiration and examination of cerebrospinal fluid after the induction therapy. Twenty-seven (81.8%) patients achieved complete remission, one (3.0%) patient had partial remission and four (12.1%) patients were refractory. There were 10 (30.3%) patients who had central nerve invasion. One patient died of pulmonary hemorrhage and TLS during the induction therapy. One patient received HSCT during the first CR and the remaining 4 patients did so after relapse. Seventeen (51.5%) patients are alive and the median survival time was 13 months, the 3-year overall survival was 40%. Conclusion Intensive chemotherapy was feasible and effective with the supporting therapy if the patient was elderly and had high leukocyte counts. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 6
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2500-2500
    Abstract: Introduction Disseminated intravascular coagulation (DIC) occurs about 10% of adult patients with acute lymphoblastic leukemia (ALL) at presentation, and develops in approximately 30-40% of adult patients after starting induction therapy. Although reports of DIC developing with a high frequency in Philadelphia chromosome-positive (Ph+) ALL are scarce, we have experienced many cases of DIC in Ph+ ALL patients. We start chemotherapy and prednisolone (PSL) at the same time after diagnosis of ALL, and give imatinib (IM) at the time it is found to be Ph+. However, we have experienced cases of early death due to severe DIC and tumor lysis syndrome (TLS) when utilizing this approach. Therefore, we have tried mild tumor reduction via initiation of PSL, IM and chemotherapy at different times. We investigated the difference in the incidence of DIC between Ph+ ALL patients and Ph negative (Ph-) ALL patients and discuss the management of DIC and its effect. Patients and methods We examined ALL patients who received their first treatment at our institution between January 2012 and December 2014. We monitored for DIC by twice daily blood testing, and diagnosed DIC according to the diagnostic criteria for DIC of the Japanese Ministry of Health, Labour and Welfare. When DIC developed, the patients were encouraged to rest, and we treated DIC with recombinant human soluble thrombomodulin (rTM) and/or gabexate mesylsate (FOY). To prevent bleeding episodes, platelet (Plt) and fresh frozen plasma transfusion were given to maintain Plt count 〉 50,000/ul and fibrinogen (Fib) level 〉 100 mg/dl. For induction therapy, to avoid rapid development of DIC and TLS, we first administered PSL 60 mg/m2. While confirming a decrease in leukocyte counts and fibrin degradation products (FDP), we started IM followed by chemotherapy (daunorubicin + vincristine + cyclophosphamide + L-asparaginase) in Ph+ ALL patients. We began PSL followed by the same chemotherapy in Ph- ALL patients as well. We used rasburicase to prevent TLS. Results A total of 35 patients with newly diagnosed ALL were examined: 18 patients were Ph+ and 17 were Ph-. The incidence of DIC was 82.3% (14/17) in Ph+ patients and 38.9% (7/18) in Ph- patients. The group with Ph+ showed a significantly higher rate of DIC (p value = 0.015). Duration of the treatment of DIC was 4-14 days (median, 10 days) in Ph+ patients, and 3-10 days (median, 5 days) in Ph- patients. The group with Ph+ also showed significantly longer duration of treatment (p value = 0.02). Twelve Ph+ patients developed DIC (two patients were excluded because of treatment that was different from that described above); five were men and seven were women. Median age was 61 years (range, 34-78 years). Leukocyte counts at the time of diagnosis were 4400-542100 /ul (median 34400 /ul), hemoglobin value was 6.4-15.6 g/dl (median 11.6, g/dl), Plt counts were 6000-262000 /ul (median, 56000 /ul), Fib value was 199-707 mg/dl (median, 299 mg/dl), and FDP value was 3.4-45.7 ug/ml (median, 9.7 ug/ml). DIC occurred at 1-8 days (median, 3 days) from diagnosis. One patient (8%) had DIC at presentation, and the remaining 11 patients (92%) had DIC after the initiation of induction therapy. We started IM at day 3-6 (median, day 5), DIC developed in two patients starting IM, and chemotherapy was started at day 5-10 (median, day 7). Only one patient had slight elevation of FDP, and this value decreased in a progressive fashion in the remaining 11 patients. The maximum FDP value during the treatment of DIC was 32-1162.8 ug/ml (median, 140 ug/ml). We treated DIC with FOY single agent (one patient) or a combination of rTM and FOY (10 patients); all patients showed improvement. The period for improvement of DIC was 4-14 days (median, 8 days), and none of the patients had bleeding or organ damage. Only one patient had TLS, but it immediately improved. In these Ph+ patients, 11/12 patients (92%) achieved complete remission (CR), and one patient had partial remission. Further, 5/5 patients (100%) achieved CR, and none had TLS in the group with Ph-. Conclusion DIC occurred at a high incidence in Ph+ ALL patients. By starting PSL, IM, and chemotherapy at the right time, we can perform induction therapy without generating serious complication due to DIC. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 7
    Online Resource
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    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 1340-1340
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1340-1340
    Abstract: Introduction Patients with AML-MRC are almost older and highly resistant to chemotherapy, so that they are thought to be not eligible for intensive chemotherapy (IC) compared with de novo AML. Reduced intensity chemotherapy, such as low-dose cytarabine and azacitidine (AZA), are used for AML-MRC therapy, but their overall survival (OS) is not satisfactory. Although chemotherapies for AML (except for M3) have not improved for 30 years, several supportive cares for IC have shown a great progress. In this background, we have used IC as induction, consolidation, and maintenance therapies, including AZA, for elderly AML-MRC to avoid relapses and obtain longer survivals. For patients, whose age are under 65 years, hematopoietic stem cell transplantations (HSCT) were mainly considered after IC treatments. Methods Between March 2012 and April 2015, 62 newly diagnosed AML-MRC were treated with idarubicin (IDR) 12 mg/m2 on days 1, 3, 5, 8, and enocitabine (BH-AC) 350mg/m2 on days 1-10 as an induction chemotherapy (IDR+BH-AC). Over 70 years patients, IDR and BH-AC were reduced to 10 mg/m2 and 300 mg/m2, respectively. On day 15, if bone marrow blasts were over 5%, etoposide 100 mg/m2 was additionally treated on days 16-19. Some fit patients, who reached complete remission (CR), were received cytarabine (Ara-C) 1 g/m2 on days 1-5 (bid) and mitoxantrone (MIT) 7 mg/m2 on days 2-4, as a consolidation therapy (Ara-C+MIT). As a maintenance therapy, AZA 75mg/m2 days 1-5 (i.v.) and IDR day1 + BH-AC days 1-4 (or aclarubicine 14 mg/m2 days 1-6 + BH-AC days 1-4) were sequentially treated for one year. If a relapse was observed, mainly AZA was treated to keep a good quality of life. Results Total number of patients was 62 (44 were male) and median age at diagnosis was 71 years (range 36-86). Median WBC was 3,800 x 109/L (600-129,200), median peripheral blast count was 16% (0-96), and median bone marrow blast count was 57% (22-95). Thirty-five patients had intermediate cytogenetics and 27 adverse. Twenty-nine patients, who had 〉 5% bone marrow blasts on day 15, were additionally treated with etoposide. Median follow-up time was 25 months. After the induction therapy, 54 patients (87%) achieved CR, 5 (8%) partial remission, 2 (3%) were refractory, and 1 (2%) died. The CR rate of male was 82% (36/44) and female 100% (18/18). The CR rate of patients with intermediate cytogenetics was 86% (30/35), adverse 89% (24/27), 〈 70 years 83% (20/24), and ≥70 years 89% (34/38). There were no significant differences between CR rates and gender, cytogenetics, or age, respectively. The CR rate of patients treated with etoposide after IDR+BH-AC was 83% (24/29) and without etoposide 91% (30/33). There was no significant difference between the two groups. Among patients with adverse cytogenetics, 67% (18/27) patients treated with etoposide, and intermediate 31% (11/35) (p=0.00983), so that patients with adverse cytogenetics tended to be resistant to IDR+BH-AC and needed the additional etoposide treatment. By Kaplan-Meier method, two year survival of 62 patients was 50.1% (95% CI, 33.9-64.3) and 53.2% (95%CI, 35.0-68.4) in patients achieving CR (n=53, excluding one withdrawn patient). The rate of CR duration for 2 years was 48.2% (95% CI, 30.7-63.7). The median survival with adverse cytogenetics in CR was 18 months (95% CI, 11-25) and that of intermediate was not reached (95% CI, 18-NA). There was a significant difference between OS with adverse cytogenetics in CR and intermediate (p=0.00463). Thirty-two patients in CR received the consolidation therapy, median age was 70 years (range 36-82), 2 patients died due to fungal infection. On the other hand, 21 patients in CR, median age was 77 years (range 59-86), did not have the consolidation, but the maintenance therapy. The survival rate of two groups were almost the same. Ten patients underwent HSCT, 8 in CR and 2 in refractory or relapse, and 2 patients died due to HSCT-related events. HSCT did not influence on OS and CR duration. Conclusions Our intensive chemotherapy for AML-MRC showed a great efficacy and a good tolerability. The additional treatment with etoposide after IDR+BH-AC was especially effective for patients with adverse cytogenetics. Although the 2-years survival rate of elderly AML-MRC was 50% in our study, further efforts are needed to obtain a longer survival, especially for patients with adverse cytogenetics. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 8
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 3897-3897
    Abstract: There is little evidence to support the efficacy of dosage exceeding conventional high dose chemotherapy (HDC), referred to as super-HDC (SHDC) for Acute Leukemia (AL). However our hospital has been successfully conducting an original SHDC and has realized the highest complete remission rate and 10 years event free survival ratio for all generations with no selection bias. For example, de novo AML except M3 results are 91%, 59% for under 70 years old and 75%, 32% for over 70 years old respectively (51st ASH #1052, until 2010). The treatment of complications is the key to SHDC success, with fungal infection one of the major complications. With our unique preemptive approach, we have successfully eliminated fungal mortalities on all AML patients with no selection bias (53st ASH #1544). In this group using ITCZ as prophylaxis, pulmonary invasive aspergillosis (PIA) morbidity rate was still high, so we had to switch from ITCZ to VRCZ. Thus we theorized that VRCZ is more effective as prophylaxis. As there is little supporting data, we scheduled this prospective randomized study commencing 2011/4/23. This is the interim analysis of the first 100 of 200 patients as of 2012/9/26. All AL patients without a history of PIA who received induction chemotherapy were included. The patient number was dictated by our previous GM positive rate (30%). Either VRCZ or ITCZ were randomly assigned at admission and commenced from day 5. VRCZ as tablet at 400-600 mg/day, ITCZ as capsule at 150-200 mg/day. The primary end point is PIA morbidity rate and the secondary end points are all cause mortality, fungal infection mortality, non-PIA fungal infection, non-assigned antifungal drug use and PIA treatment efficiency using GM. This study is unique as diagnostic and treatment strategies are completely unified for all. We conducted GM twice a week with CT at the time of admission and weekly. Additional CT was conducted within 24 hours when pyrexia of ≥38.0°C occurred, without improvement CT was repeated every 3 days. Our concept is original preemptive therapy, we assumed PIA when GM ≥0.5, and VRCZ was automatically started. Combination therapy using Micafungin (MCFG) was routinely conducted when PIA continued to worsen. Per contra we assumed candida infection, and conducted MCFG treatment, when the results met our original twice weekly surveillance culture and ß-D glucan criteria. Table 1 shows patient characteristics. Excluding ALL and M3, all other characteristics were almost identical. Regarding PIA morbidity, Probable PIA rate was the same 22%, with no proven cases (EORTC/MSG criteria). However this result does not actually reflect the strength of these prophylactic drugs. As, in many cases, PIA existed from hospitalization (fig1). With our unique diagnostic strategy of regular CT and GM regardless of pyrexia from admission, we traced the onset more precisely to a much earlier stage than the theory that PIA appears from the latest phase of neutropenia. All cause mortality rate was identical, 6%. In VRCZ group (gp) AL progression was the sole cause. In addition to AL progression, 1 fungal infection caused by Cunninghamella was proved in ITCZ gp. Non-PIA fungal infections were only seen in ITCZ gp, Trichosporonemia, Candidemia or Cunninghamella pneumoniae were proved in three different patients. For non-assigned antifungal drug use, MCFG was comparable. VRCZ 60% (30/50), 17days (2-62), versus (vs) ITCZ 64% (32/50), 15 days (2-154). L-AmB was prescribed less in VRCZ gp (4% vs 8%) and VRCZ was prescribed to 18 ITCZ gp patients. The ITCZ gp required more drugs. Regarding PIA treatment efficacy using GM, was evaluated by max GM, number of days at max GM and final GM. All data median plus range. VRCZ was superior in every aspect, with 0.8 (0.5-3.1), 15 (9-53), 0.2 (0.1-1.5) results vs 2.35 (0.5-5.1), 28 (2-44), 0.65 (0.2-1.3) for ITCZ. Using our peerless fugal strategies, satisfactory results were realized for both gp. PIA onset was found to be much earlier, so morbidity appears comparable. However, VRCZ superior results including better PIA control appears to be achieved due to early PIA onset, and supports VRCZ prophylactic use. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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