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1.
2-Chlorodeoxyadenosine with or without daunorubicin in relapsed or refractory acute myeloid leukemia
E. Van Den Neste P. Martiat P. Mineur A. Delannoy C. Doyen A. Zenebergh J.-L. Michaux A. Ferrant 《Annals of hematology》1998,76(1):19-23
2-Chlorodeoxyadenosine (2-CdA) is a purine analogue which has proved to be active in acute myeloid leukemia (AML), especially
in children. In adults, results yielded by 2-CdA alone or with ara-C were less encouraging. Here we report on the efficacy
of 2-CdA with or without daunorubicin (DNR) in 19 relapsing or refractory adult AML patients, with a median age of 57 years.
2-CdA was administered as a continuous infusion to all patients at a dose of 0.1 mg/kg per day for 7 days. For 14 patients,
DNR was added at a dose of 50 mg/m2 per day on days 5, 6, and 7. Antileukemic activity was observed in all the patients, but no single complete remission was
achieved. One patient had a long-lasting partial response (response rate=5%). The remaining patients died of progressive AML
(n=7), uncontrollable infection with persistent disease (n=10), and cerebral hemorrhage (n=1). Median survival from start of 2-CdA therapy was 56 days. Long-lasting neutropenia and transfusion-dependent thrombopenia
were encountered in all 16 evaluable patients. Grade 4 hepatic toxicity occurred in one patient. Other side effects included
nausea in six, mucositis in three, and mental disturbances in three patients. Compared with 2-CdA alone, the addition of DNR
to 2-CdA changed neither the response rate nor the toxicities. In conclusion, our data do not support the use of 2-CdA ± DNR
for relapsing or refractory adult AML patients, at least as used in the present regimen.
Received: 21 July 1997 / Accepted: 18 November 1997 相似文献
2.
Clavio M Venturino C Pierri I Garrone A Miglino M Canepa L Balleari E Balocco M Michelis GL Ballerini F Gobbi M 《Annals of hematology》2004,83(11):696-703
Sixty-two patients with high-risk acute leukemia were treated with the FLAD regimen [3 days of treatment with fludarabine 30 mg/m2, cytarabine (AraC) 2 g/m2, and liposomal daunorubicin 80 mg/m2]. The acute myeloid leukemia (AML) patients were either refractory to standard induction regimens (8), were in first or second relapse (13), or received therapy as first-line treatment [21 patients, 16 were above 60 years of age and 5 had post-myelodysplastic syndrome (MDS) AML]. The acute lymphoblastic leukemia (ALL) patients were treated for relapsed (7) or refractory disease (10). Three patients had chronic myeloid leukemia (CML) in the blastic phase. FLAD was well tolerated by most patients. Ten major infectious complications were recorded while no signs of cardiac toxicity were observed. Five patients (8%) died before day 28 with hypocellular marrow, mainly of infection or hemorrhage, and response could not be evaluated. Complete response rate was 62% and 69% among AML patients treated at diagnosis or for relapsed disease, respectively, and 59% among the ALL patients. Furthermore, FLAD managed to overcome the negative impact of poor prognosis karyotype in ALL patients, since five of the seven patients with t(9;22) or complex karyotype achieved complete remission (CR). Nine patients underwent bone marrow transplantation (BMT). Among the AML patients who were treated at diagnosis or for relapse, the median duration of CR was 7 months (range: 2–18) and 8 months (range: 2–26), respectively. Median survival among these patients was 8 (range: 1–40) and 12 (range: 1–30) months, respectively. Similar values were found in ALL patients. In conclusion, FLAD may be an effective alternative treatment for patients with relapsed AML and for patients with ALL who failed first-line therapy. 相似文献
3.
4.
FLAG (fludarabine,cytosine arabinoside,G-CSF) for refractory and relapsed acute myeloid leukemia 总被引:2,自引:0,他引:2
I.-M. Huhmann H. H. Watzke K. Geissler H. Gisslinger U. Jäger P. Knöbl I. Pabinger L. Korninger C. Mannhalter G. Mitterbauer I. Schwarzinger P. Kalhs O. A. Haas K. Lechner 《Annals of hematology》1996,73(6):265-271
Twenty-two patients with refractory or relapsed AML were treated with FLAG [25 mg/m2 fludarabine daily (days 1–5), 2 g/m2 daily Ara-C (days 1–5) and 400 μg/m2 daily G-CSF (day -1 till the absolute neutrophil count was >500/μl)]. Median age was 46 years (range 24–63). Eight patients
had leukemia which was primarily refractory to conventional regimens, six were in first, seven were in second, and one was
in third relapse.
Overall, 11 of 22 (50%) patients achieved complete remission (CR), three had a partial response (PR), and seven did not respond
(NR). One patient died of an early cerebral hemorrhage. The median remission duration from achievement of CR after FLAG was
9.9 months and median survival was 13.0 months. One patient is alive in CR at 31.9 months. Hematological toxicity of the regimen
was severe. The median time to neutrophil recovery (ANC >500/μl) was 21 days (range 18–33). A median of seven red cell units
(range 0–22) and of six platelet concentrate units (range 3–28) had to be given. Median duration of febrile neutropenia was
2 days (range 0–20 days) and patients were on i.v. antibiotics for a median of 16 days (range 0–51). There was no death from
infection. Nonhematological toxicity was remarkably low, with almost no neurotoxicity and no major hepatotoxicity. In conclusion,
FLAG seems to be an efficient and well tolerated regimen. It may be particularly useful for patients who have a sibling or
unrelated donor for subsequent allogeneic bone marrow transplantation.
Received: 27 August 1996 / Accepted: 17 September 1996 相似文献
5.
Specchia G Pastore D Carluccio P Spinosa G Giannoccaro M Rizzi R Mestice A Liso V 《Annals of hematology》2007,86(6):425-428
We analyzed the safety and efficacy of gemtuzumab ozogamicin (GO) combined with cytarabine and mitoxantrone in the treatment
of 21 patients with acute myeloid leukemia (11 refractory and 10 in second relapse). Patients’ median age was 52 years (range
36–68); all patients had previously been treated with anthracycline-containing regimens (daunorubicin and idarubicin). GO
at a dosage of 3 mg/m2 was administered as a 2-h intravenous infusion on days 1 and 14, cytarabine at 100 mg/m2 on days 1–7, and mitoxantrone at 12 mg/m2 on days 1–3. Infusion-related events were observed in 15 of 21 (71.4%) patients. The incidence of grade 1 or 2 elevations
of bilirubin and hepatic transaminases was 4 of 21 (19%) and 3 of 21 (14.2%). In response to chemotherapy, 2 of 21 (9.5%)
achieved complete remission and 2 of 21 (9.5%) achieved complete remission with incomplete platelet recovery, with an overall
remission rate of 4 of 21(19%); median survival of these 4 patients was 7 months. Four of 21 patients (19%) died during aplasia
after chemotherapy; no veno-occlusive disease occurred. No treatment-related cardiotoxicity or cerebellar toxicity was observed.
In our experience, the addition of GO to mitoxantrone and cytarabine is feasible in refractory or second relapse acute myeloid
leukemia patients but yields a low response rate when used as a third-line treatment. 相似文献
6.
Andrius Zucenka Regina Pileckyte Igoris Trociukas Valdas Peceliunas Vilmante Vaitekenaite Kazimieras Maneikis Linas Davainis Tadas Zvirblis Mindaugas Stoskus Egle Gineikiene Rimvydas Norvilas Vaidas Dirse Agne Surauciute Emile Zucenkiene Laimonas Griskevicius 《European journal of haematology》2021,106(1):105-113
7.
FLAG-IDA in the treatment of refractory/relapsed adult acute lymphoblastic leukemia 总被引:14,自引:0,他引:14
Specchia G Pastore D Carluccio P Liso A Mestice A Rizzi R Ciuffreda L Pietrantuono G Liso V 《Annals of hematology》2005,84(12):792-795
Relapsed or refractory adult acute lymphoblastic leukemias (ALL) have poor prognosis. The strategy for treating these patients
is through reinduction chemotherapy followed by allogeneic stem cell transplantation, provided that the toxicity of the salvage
regimen is acceptable. Twenty three patients with relapsed/refractory adult ALL were treated with fludarabine, cytarabine,
granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA). Five patients had primary refractory disease, and 18 were
in first relapse. Nine (39.1%) patients achieved complete remission (CR) following salvage therapy, whereas 13 (56.5%) patients
were refractory, and one patient died in aplasia due to infection. In patients achieving remission, the median time to reach
absolute neutrophil count (ANC) more than 0.5×109/l and 1×109/l was 20 (range 16–25) and 24 (range 20–28) days from the start of chemotherapy, respectively. Platelet levels of more than
20×109/l and 100×109/l were achieved in a median time of 23 (range 19–25) and 33 (range 28–39) days, respectively. Fever more than 38.5°C was
observed in 18 of 23 patients (78.2%), 13 had fever of unknown origin, and 5 had documented infections. Nonhematological side
effects, consisting mainly of mucositis (18/23 or 78.2%) and transient liver toxicity increase (10/23 or 43.4%), were generally
tolerated. All nine patients who achieved CR received a second course with FLAG-IDA, and seven patients underwent allogeneic
stem cell transplantation (four from a matched donor, one from a mismatched donor, and two from an unrelated donor), while
two did not reach that stage due to early relapse from CR. The median overall survival (OS) for all 23 patients was 4.5 (range
1–38) months; for the nine responders, the disease-free survival (DFS) and the OS were 6 (range 3–38) and 9 (7–38) months,
respectively; the seven patients who received allogeneic stem cell transplantation had a DFS of 10 (range 7–38) months. In
our experience, FLAG-IDA is a well-tolerated regimen in relapsed/refractory ALL patients; the toxicity is acceptable, enabling
patients who have achieved CR to receive allogeneic transplantation. 相似文献
8.
9.
Single agent thalidomide in patients with relapsed or refractory acute myeloid leukaemia 总被引:3,自引:0,他引:3
Thomas DA Estey E Giles FJ Faderl S Cortes J Keating M O'Brien S Albitar M Kantarjian H 《British journal of haematology》2003,123(3):436-441
Thalidomide is a putative anti-angiogenesis agent that has significant anti-tumour activity in haematological malignancies with increased bone marrow angiogenesis, including multiple myeloma (MM) and myelodysplastic syndromes (MDS). Increased levels of the mitogen for angiogenesis, vascular endothelial growth factor (VEGF), correlate with worse survival in acute myeloid leukaemia (AML). A phase II trial of thalidomide was conducted in patients with relapsed- or refractory-AML previously treated with cytarabine-containing regimens. A total of 16 patients with refractory- or relapsed-AML were treated with thalidomide 200-800 mg orally daily (median dose 400 mg daily) for a median of 27 d (range, 3-94 d). Overall, one patient (6%) achieved complete remission (CR) lasting for 36 months, and two patients had a transient reduction in marrow blasts from 8% and 7% to less than 5% in both cases. There was no correlation between reduction in levels of angiogenesis markers and response. Toxicities related to thalidomide were significant, and precluded dose escalation beyond 400 mg orally daily in most patients. Although there appears to be some evidence of biological activity, single agent thalidomide is not an optimal choice of therapy for salvaging patients with relapsed- or refractory-AML. Thalidomide analogues with more potent immunomodulatory activities and more favourable toxicity profiles may offer more promise as anti-AML therapy. 相似文献
10.
Enrico De Astis Marino Clavio Anna Maria Raiola Anna Ghiso Fabio Guolo Paola Minetto Federica Galaverna Maurizio Miglino Carmen Di Grazia Filippo Ballerini Carlo Marani Giordana Pastori Laura Mitscheunig Fabio Cruciani Davide Lovera Riccardo Varaldo Chiara Ghiggi Roberto Massimo Lemoli Andrea Bacigalupo Marco Gobbi 《Annals of hematology》2014,93(12):2011-2018
Therapeutic options for patients with relapsed or refractory acute leukemia are still undefined and often unsatisfactory. We report the outcome of 79 patients with relapsed-refractory acute leukemia treated with fludarabine, cytarabine, and liposomal daunorubicin (FLAD regimen) followed by hematopoietic stem cell transplantation (HSCT), when clinically indicated, between May 2000 and January 2013. Forty-one patients had acute myeloid leukemia (AML), and 38 had acute lymphoblastic leukemia (ALL). Two patients with myeloid blast crises of CML and three with lymphoid blast crises were included in the AML and ALL subgroups, respectively. Median age was 48 years (range 13–77). FLAD was well tolerated with negligible, nonhematological toxicity. Six patients (7.5 %) died before response evaluation. Forty-seven patients achieved hematologic complete response (CR). Complete remission rate was 53 and 65 % among AML and ALL patients, respectively. No CR was recorded among 11 refractory AML patients. Twenty-four patients (30 %) underwent HSCT. Nine patients received stem cells from an HLA identical sibling, and 15 from an alternative donor (3 unrelated matched, 12 haploidentical sibling). Median overall survival in AML and ALL patients receiving FLAD therapy was 9 and 8 months, respectively. A 5-year projected OS for patients receiving the whole program (FLAD + HSCT) was 24 % for AML patients (median survival 43 months), 28 % for ALL patients treated in relapse (median survival 15 months), and 0 % for ALL patients treated for refractory disease. In this paper, we show that FLAD seems to be an effective bridge therapy to HSCT for a part of poor prognosis acute leukemia patients. However, prospective studies are needed to confirm our results. 相似文献
11.
Treatment of relapsed and refractory acute myeloid leukemia with diaziquone and mitoxantrone: a CALGB phase I study 总被引:1,自引:0,他引:1
Twenty-one patients with relapsed or refractory acute myeloid leukemia (AML) were treated with mitoxantrone (12 mg/m2/day, days 1-3) and diaziquone (continuous infusion days 1-5). The dosage of diaziquone was increased for sequential cohorts of seven patients from 20 mg/m2/day to 24 mg/m2/day, and finally to 28 mg/m2/day to determine the maximum tolerated dose for this chemotherapy combination. Myelosuppression was the dose-limiting toxicity. The median time to recovery of blood counts was greater at the highest dose of diaziquone (48 days) than at the lower two doses (31 and 28 days). Other toxic effects were minimal. Overall, 9/21 (43%, 95% confidence interval, 0.22 to 0.66) patients achieved complete remission. We conclude that this combination of drugs shows sufficient antileukemic activity with acceptable toxicity to warrant further trials. 相似文献
12.
Ferrara F Palmieri S Pocali B Pollio F Viola A Annunziata S Sebastio L Schiavone EM Mele G Gianfaldoni G Leoni F 《European journal of haematology》2002,68(4):203-209
OBJECTIVES: To evaluate therapeutic results and prognostic factors from a series of 44 patients affected by de novo acute myeloid leukemia with multilineage dysplasia (MD-AML), treated with the combination of fludarabine, cytarabine and G-CSF (FLAG). METHODS: Forty-four patients with de novo MD-AML were treated with the FLAG regimen. The median age was 61 yr (range 31-75 yr). Induction therapy consisted of the FLAG regimen; consolidation included idarubicin plus cytarabine. Patients with a compatible donor and aged less than 55 yr were programmed to receive allogeneic bone marrow transplantation (BMT), while in those without a donor and aged less than 65 yr autologous transplantation with peripheral blood stem cells mobilized by a consolidation regimen plus G-CSF was planned. Bone marrow harvest was performed in poor mobilizers. RESULTS: Complete remission (CR) was achieved in 28 out of 44 patients (64%). Death in induction occurred in four patients (9%), while 12 patients (27%) were resistant to FLAG. Toxicity of consolidation was negligible. Most patients aged less than 60 yr and achieving CR were eligible for transplantation procedures, the main reason of exclusion being early relapse. Median overall survival and disease free survival were 16 and 22 months, respectively. Unfavorable cytogenetics was the only parameter significantly related to inferior clinical outcome following multivariate analysis. CONCLUSION: Multilineage dysplasia per se is not an adverse prognostic factor in AML patients treated with the FLAG regimen. Favorable results are obtained in patients with intermediate karyotype, while in those with adverse cytogenetics new approaches are clearly needed. The toxicity of the regimen is also acceptable in the elderly, and following induction/consolidation, most patients may be submitted to transplantation procedures. 相似文献
13.
目的:探讨标准剂量的去甲氧柔红霉素(IDA)联合阿糖胞苷(Ara-C)治疗急性髓细胞白血病(AML)的疗效和不良反应。方法:14例AML患者,年龄13~70岁(中位年龄36岁),男8例,女6例。初治AML10例,难治、复发AML4例。所有患者均在治疗前进行染色体核型分析,4例染色体异常。诱导方案为IDA 12 mg·m-2·d-1,第1~3天,Ara-C 100 mg·m-2·d-1,持续静脉点滴,第1~7天。结果:1个疗程结束后总有效率92.9%(13/14),完全缓解率85.7%(12/14),其中初治AML的CR率为90.0%(9/10),复发、难治AML的CR率为75.0%(3/4),3例染色体异常患者达细胞遗传学缓解,未发生早期死亡。化疗的不良反应主要为骨髓抑制和粒细胞缺乏所致感染,未见严重的非造血系统不良反应。结论:标准剂量的IDA联合Ara-C 24 h持续静脉点滴,为初治、复发难治AML的高效、安全的方案。 相似文献
14.
15.
Fassas A Buffels R Anagnostopoulos A Gacos E Vadikolia C Haloudis P Kaloyannidis P 《British journal of haematology》2002,116(2):308-315
We have conducted a phase I/II trial to determine the maximum tolerated dose, early safety and efficacy of single-agent liposomal daunorubicin in relapsed or refractory acute myeloid leukaemia (AML). Successive cohorts of six patients received escalated doses of 75, 100, 125 or 150 mg/m2 of DaunoXome for three consecutive days. Responding patients received a further consolidation cycle of DaunoXome at a dose identical to the one inducing complete or partial remission at the various dose levels. Twenty-eight patients with a median age of 50.5 years were enrolled. A maximum tolerated dose was determined at 150 mg/m2. Twelve patients received the second cycle. DaunoXome was well tolerated at all administered levels; dose-limiting toxicities included nausea and vomiting, mucositis and two episodes of cardiotoxicity resulting in the death of two patients. The overall response rate was 46% with a median duration of response of 180 d and a median duration of survival of 208 d. Ten patients demonstrated a complete response following cycle 1, and a further four entered partial response with the first cycle (marrow blasts between 5% and 10%). Of these, three attained complete response with the second cycle (total complete response 13/28). Our results indicate that DaunoXome at a dose of 150 mg/m2 displays acceptable toxicity in a 3-d regimen followed by a 3-d consolidation course at 100 mg/m2/d. At this dose schedule, interestingly high remission rates were achieved, justifying further evaluation of DaunoXome for the treatment of relapsed or refractory AML patients. 相似文献
16.
Giebel S Krawczyk-Kulis M Adamczyk-Cioch M Jakubas B Palynyczko G Lewandowski K Dmoszynska A Skotnicki A Nowak K Holowiecki J;Polish Adult Leukemia Group 《Annals of hematology》2006,85(10):717-722
Outcome of adults with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) or who relapse soon after initial response is poor. The goal of this phase II study by the Polish Adult Leukemia Group (PALG) was to evaluate safety and efficacy of a new salvage regimen (FLAM) consisting of sequential fludarabine, cytarabine, and mitoxantrone. Fifty patients were included with primary (n=13) or secondary (n=5) refractoriness, early (<12 months) first relapse (n=15), first relapse after hematopoietic cell transplantation (HCT) regardless CR duration (n=13), and second or subsequent relapse (n=4). Median age was 31(18–60) years, 28% of patients were bcr/abl-positive. CR rate equaled 50% and was significantly higher for patients in whom FLAM was administered as a second-line therapy compared to those more heavily pre-treated (66 vs 13%, p=0.02). Seventeen patients had leukemia regrowth after initial cytoreduction, whereas, eight patients died in aplasia. The incidence of early death was higher in patients aged ≥40 years compared to the younger subgroup (33 vs 8%, p=0.03). Septic infections were the most frequent severe complication. At 3 years, the probability of disease-free survival for patients who achieved CR equaled 16%. Seven patients underwent allogeneic HCT. FLAM regimen is feasible for relapsed and refractory adults with ALL and could be recommended in particular for younger patients as a second-line treatment. However, as the remission duration is short, allogeneic HCT (alloHCT) should be considered as soon as possible. 相似文献
17.
E. Archimbaud B. Anglaret X. Thomas J. Jaubert C. Sebban D. Guyotat D. Fiere 《Annals of hematology》1992,65(2):71-74
Summary Thirty-four patients with acute myeloid leukemia (AML) in complete remission (CR), 30 of them aged over 60, received maintenance therapy scheduling four courses of low-dose cytarabine (LDA) 20 mg/m2/day in two subcutaneous injections for 3 weeks every 6 weeks. Each course was stopped when hematologic toxicity occurred, and doses of LDA were subsequently reduced by 50% for the following courses. During the first course of LDA, 15 patients needed blood and four patients platelet transfusions. Overall, 28 patients received four courses of LDA: 11 did not require any dose reduction, while 14 required one dose reduction and three neeeded two successive dose reductions. Two patients were hospitalized during maintenance. Median disease-free survival (DFS) is 308 days, with 16% of patients surviving at 5 years. Seven patients relapsed during the 168 days of maintenance, while ten of the 27 patients remaining at risk on day 169 relapsed during the 168 days following maintenance. We conclude that in AML in CR, the maximal dose of LDA tolerated by ambulatory patients is 10 mg/m2/day for 3 weeks. LDA seemed to delay relapse; however, precise assessment of the efficacy of this approach would require a randomized trial. 相似文献
18.
Wierzbowska A Robak T Pluta A Wawrzyniak E Cebula B Hołowiecki J Kyrcz-Krzemień S Grosicki S Giebel S Skotnicki AB Piatkowska-Jakubas B Kuliczkowski K Kiełbiński M Zawilska K Kłoczko J Wrzesień-Kuś A;Polish Adult Leukemia Group 《European journal of haematology》2008,80(2):115-126
Objectives: Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients.
Methods: The induction chemotherapy consisted of 2-CdA 5 mg/m2 , Ara-C 2 g/m2 , MIT 10 mg/m2 , and granulocyte-colony stimulating factor. In the case of PR, a second CLAG-M was administered. Patients in CR received consolidation courses based on high doses of Ara-C and MIT with or without 2-CdA.
Results: One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4–23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11–49%). Poor karyotype was the only factor associated with decreased probability of DFS.
Conclusions: We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML. 相似文献
Methods: The induction chemotherapy consisted of 2-CdA 5 mg/m
Results: One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4–23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11–49%). Poor karyotype was the only factor associated with decreased probability of DFS.
Conclusions: We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML. 相似文献
19.
Walter Fiedler Joerg Chromik Stefanie Amberg Maxim Kebenko Felicitas Thol Vera Schlipfenbacher Anne Christine Wilke Franziska Modemann Melanie Janning Hubert Serve Arnold Ganser Carsten Bokemeyer Susann Theile Ute Deppermann Anne L. Kranich Michael Heuser 《British journal of haematology》2020,190(3):e169-e173
20.
Thomas R. Chauncey Holly Gundacker Mazyar Shadman Alan F. List Shaker R. Dakhil Harry P. Erba Marilyn L. Slovak I-Ming Chen Cheryl L. Willman Kenneth J. Kopecky Frederick R. Appelbaum 《British journal of haematology》2010,148(1):48-58
Attempts to overcome multi-drug resistance in acute myeloid leukaemia (AML) have been limited by toxicities. To investigate the effect of reducing peak drug levels, we performed sequential phase II studies using continuous infusion daunorubicin and cytarabine without (AD) and then with ciclosporin (ADC) in older patients with AML. Untreated patients (age 56+ years) received daunorubicin (45 mg/m2 per day for 3 d) and cytarabine (200 mg/m2 per day for 7 d), both by continuous infusion, without (S0112, 60 patients) and then with (S0301, 50 patients) the addition of ciclosporin. Complete response (CR) rates were 38% on S0112 and 44% on S0301. Fatal induction toxicities occurred in 17% and 12% respectively, arising primarily from infection and haemorrhage. Median overall and relapse-free survival was 7 and 8 months for AD respectively, and 6 and 14 months for ADC. Patients with phenotypic or functional P-glycoprotein had somewhat higher CR rates with ADC than AD, although confidence intervals overlapped. In these sequential trials, continuous infusion AD produced CR rates comparable to those with bolus daunorubicin. The addition of ciclosporin did not cause undue toxicities, produced a similar CR rate, and possibly improved relapse-free survival. Further correlate analyses did not identify a subpopulation specifically benefitting from the addition of ciclosporin. 相似文献