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1.
Anna Candoni Cristina Papayannidis Giovanni Martinelli Erica Simeone Michele Gottardi Ilaria Iacobucci Filippo Gherlinzoni Giuseppe Visani Michele Baccarani Renato Fanin 《American journal of hematology》2018,93(5):655-663
The aim of this prospective clinical trial was to evaluate the efficacy and safety of a combination of Gemtuzumab‐Ozogamicin (GO) and FLAI scheme (fludarabine, cytarabine, idarubicin) as a first‐line therapy in CD33 positive AML. We treated 130 patients, aged <65, with a median age of 52 years. FLAI‐GO induction regimen included fludarabine (30 mg/sqm) and cytarabine (2 g/sqm) on days 1–5; idarubicin (10 mg/sqm) on days 1, 3, and 5; and GO (3 mg/sqm) on day 6. SCT was planned for all high‐risk AML patients, after consolidation with intermediate doses of cytarabine and idarubicin and a high dose of cytarabine. CD33 expression exceeded 20% in all cases. Primary endpoints of the study included feasibility, overall response rate (ORR) and toxicity. Secondary endpoints included the evaluation of MRD by WT1 expression, feasibility and outcome of consolidation with SCT, overall survival (OS) and disease‐free survival (DFS). After induction with FLAI‐GO, complete remission (CR) rate was 82%. Four patients achieved partial remission (PR) and 12% were resistant (ORR 85%); death during induction (DDI) was 3%. The hematological and extra hematological toxicity of FLAI‐GO was manageable; 45% of patients experienced transient and reversible GO infusion related adverse events. In the setting of patients who achieved a cytological CR after FLAI‐GO, the mean of WT1 copies dropped from 8337±9936 copies/104ABL (diagnosis) to 182 ± 436 copies after induction therapy (p = 0.0001) showing a very good disease debulking. After a median follow‐up of 54 months, 67/130 (52%) patients were alive. The probability of 1, 2, and 5‐year OS was 80%, 63%, and 52%, respectively. The probability of 1, 2, and 5‐year DFS was 77%, 58%, and 52%, respectively. Allogeneic and autologous SCT was performed in 60 (46%) and 23 (18%) patients, respectively. In summary, the final results of this trial confirm that FLAI‐GO is an active and safe treatment strategy for CD33‐positive AML patients aged ≤ 65 years, allowing a high ORR, a good disease debulking, favorable safety profile, low DDI, and subsequent high SCT rate. The encouraging results of this trial, consolidated by a long follow‐up, support the reintroduction of GO in clinical practice. 相似文献
2.
High feasibility and antileukemic efficacy of fludarabine,cytarabine, and idarubicin (FLAI) induction followed by risk‐oriented consolidation: A critical review of a 10‐year,single‐center experience in younger,non M3 AML patients
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Fabio Guolo Paola Minetto Marino Clavio Maurizio Miglino Carmen Di Grazia Filippo Ballerini Giordana Pastori Daniela Guardo Nicoletta Colombo Annalisa Kunkl Giuseppina Fugazza Barbara Rebesco Mario Sessarego Roberto Massimo Lemoli Andrea Bacigalupo Marco Gobbi 《American journal of hematology》2016,91(8):755-762
About 105 consecutive acute myeloid leukemia (AML) patients treated with the same induction‐consolidation program between 2004 and 2013 were retrospectively analyzed. Median age was 47 years. The first induction course included fludarabine (Flu) and high‐dose cytarabine (Ara‐C) plus idarubicin (Ida), with or without gemtuzumab‐ozogamicin (GO) 3 mg/m2 (FLAI‐5). Patients achieving complete remission (CR) received a second course without fludarabine but with higher dose of idarubicin. Patients not achieving CR received an intensified second course. Patients not scheduled for early allogeneic bone marrow transplantation (HSCT) where planned to receive at least two courses of consolidation therapy with Ara‐C. Our double induction strategy significantly differs from described fludarabine‐containing regimens, as patients achieving CR receive a second course without fludarabine, to avoid excess toxicity, and Ara‐C consolidation is administrated at the reduced cumulative dose of 8 g/m2 per cycle. Toxicity is a major concern in fludarabine containing induction, including the recent Medical Research Council AML15 fludarabine, cytarabine, idaraubicin and G‐CSF (FLAG‐Ida) arm, and, despite higher anti‐leukemic efficacy, only a minority of patients is able to complete the full planned program. In this article, we show that our therapeutic program is generally well tolerated, as most patients were able to receive subsequent therapy at full dose and in a timely manner, with a 30‐day mortality of 4.8%. The omission of fludarabine in the second course did not reduce efficacy, as a CR rate of 83% was achieved and 3‐year disease‐free survival and overall survival (OS) were 49.6% and 50.9%, respectively. Our experience shows that FLAI‐5/Ara‐C + Ida double induction followed by risk‐oriented consolidation therapy can result in good overall outcome with acceptable toxicity. Am. J. Hematol. 91:755–762, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
3.
Idarubicin,cytarabine, and pravastatin as induction therapy for untreated acute myeloid leukemia and high‐risk myelodysplastic syndrome
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Carol Dean Tara L. Chen Kathleen Shannon‐Dorcy Vicky Sandhu Paul C. Hendrie Bart L. Scott Rol B. Walter Pamela S. Becker John M. Pagel Elihu H. Estey 《American journal of hematology》2015,90(6):483-486
Previous studies suggest that idarubicin/cytarabine(ara‐C)/pravastatin (IAP) is an active salvage regimen for patients with AML. We therefore investigated this regimen in patients with newly‐diagnosed AML or MDS (≥10% blasts). Patients were eligible if the anticipated treatment‐related mortality (TRM) was <10%. Patients received pravastatin (1,280 mg/day po; days 1–8), cytarabine (1.5 g/m2/day; days 4–7), and idarubicin (12 mg/m2/day, days 4–6). Up to 3 cycles of consolidation with a shortened course was permitted. The primary endpoints were “good CR” rate (CR on day 35 without minimal residual disease) and TRM in the first 28 days. The study was to stop if after each cohort of 5 patients (a) the Bayesian posterior probability was < 5% that the true “good CR rate” was ≥ 70% or (b) the posterior probability was >25% that the TRM rate was ≥5%. Twenty‐four patients were included. Conventional CR was achieved in 15 (63%) patients but only 12 (50%) achieved “good CR”. 4 of 12 (33%) patients with “good CR” relapsed at median of 16 weeks (10.5–19). Five (21%) patients had refractory disease. Survival probability at 1 year was 72% (48.7–64). Two (8.3%) patients died within 28 days from multiorgan failure. The most common grade 3–4 adverse effects were febrile neutropenia (75%) and diarrhea (25%). Based on the stopping rules accrual ceased after entry of these 24 patients. IAP did not meet the predefined efficacy criteria for success. Therefore, we would not recommend this regimen for phase three testing in this patient subset. Am. J. Hematol. 90:483–486, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
4.
Aziz Nazha Hagop Kantarjian Farhad Ravandi Xuelin Huang Sangbum Choi Guillermo Garcia‐Manero Elias Jabbour Gautam Borthakur Tapan Kadia Marina Konopleva Jorge Cortes Alessandra Ferrajoli Steve Kornblau Naval Daver Naveen Pemmaraju Michael Andreeff Zeev Estrov Min Du Mark Brandt Stefan Faderl 《American journal of hematology》2013,88(11):961-966
Clofarabine is a second generation nucleoside analogue with activity in adults with acute myeloid leukemia (AML). A phase I trial of clofarabine, idarubicin, and cytarabine (CIA) in relapsed and refractory AML had shown an overall response rate (ORR) of 48%. To explore this combination further, we conducted a phase II study of (CIA) in patients with newly diagnosed AML ≤60 years. Patients ≥18–60 years with AML and adequate organ function were enrolled. Induction therapy consisted of clofarabine (C) 20 mg m?2 IV daily (days 1–5), idarubicin (I) 10 mg m?2 IV daily (days 1–3), and cytarabine (A) 1 g m?2 IV daily (days 1–5). Patients in remission received up to six consolidation cycles (C 15 mg m?2 × 3, I 8 mg m?2 × 2, and A 0.75 g m?2 × 3). Fifty‐seven patients were evaluable. ORR was 79%. With a median follow up of 10.9 months, the median overall survival (OS) was not reached, the median event‐free survival (EFS) was 13.5 months. Most toxicities were ≤grade 2. Four week mortality was 2%. In subgroup analysis, patients ≤40 years had better OS (P = 0.04) and EFS (P = 0.04) compared to patients >40 years. Compared to historical patients treated with idarubicin and cyarabine (IA), the OS and EFS were significantly longer for CIA treated patients. In multivariate analysis, CIA retained its favorable impact on OS compared to IA. Thus, CIA is an effective and safe therapy for patients ≤60 years with newly diagnosed AML. Am. J. Heamtol. 88:961–966, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
5.
Hawk Kim Jae‐Hoo Park Je‐Hwan Lee Jung‐Hee Lee Young‐Don Joo Won‐Sik Lee Sung‐Hwa Bae Hun Mo Ryoo Kyoo‐Hyung Lee 《American journal of hematology》2009,84(3):161-166
We assessed continuous infusion (CI) of fludarabine and cytarabine (FLAG) plus idarubicin for patients under 60‐years old with resistant acute myeloid leukemia (AML). Induction chemotherapy consisted of idarubicin (12 mg/m2 iv infusion over 30 min on Days 1–3), plus fludarabine (30 mg/m2/day) and cytarabine (1,000 mg/m2/day) on Days 1–5 as a 24‐hr CI. G‐CSF was added on Days 1–5. The 29 patients enrolled were of median age 40 years (range, 18–57 years); of these, 8 (27.6%) had primary refractory disease, 19 (65.5%) were in early relapse, and 1 each (3.4%) was in multiple relapse and relapse after SCT. In response to induction, 8 patients (27.6%) achieved CR, 2 (6.9%) achieved CRp, and 19 (65.5%) failed treatment; of the latter, 14 had aplasia, three had an indeterminate course, and two showed resistance. Seven patients remain alive, while two were lost to follow‐up. Nineteen patients died, 14 of infection, one of toxicity during consolidation, three of relapse after SCT, and two of persistent disease. These findings indicate that although CI of FLAG plus idarubicin was effective for eradicating blasts, it carried a high risk of toxicity. Reduced doses are recommended for CI of FLAG plus idarubicin. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc. 相似文献
6.
Mike G. Martin Kristan M. Augustin Geoffrey L. Uy John S. Welch Lindsay Hladnik Sagun Goyal Divya Tiwari Ryan S. Monahan Richard M. Reichley Amanda F. Cashen Keith Stockerl‐Goldstein Peter Westervelt Camille N. Abboud John F. DiPersio Ravi Vij 《American journal of hematology》2009,84(11):733-737
The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG‐IM) or without gemtuzumab ozogamicin (GO) (9 mg/m2 on Day 8) (FLAG‐I) in relapsed/refractory AML. Three‐quarters of patients also received concurrent G‐CSF. Seventy‐one patients were treated, 23 with FLAG‐I and 48 with FLAG‐IM. The median duration of follow‐up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18–70) and 47 years (range 20–68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG‐I and FLAG‐IM. The complete remission (CR) rate in the FLAG‐I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG‐IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event‐free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG‐I over FLAG‐IM. The patients who received G‐CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G‐CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG‐I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G‐CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc. 相似文献
7.
G‐CSF Priming,clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia,advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm
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Pamela S. Becker Bruno C. Medeiros Anthony S. Stein Megan Othus Frederick R. Appelbaum Stephen J. Forman Bart L. Scott Paul C. Hendrie Kelda M. Gardner John M. Pagel Roland B. Walter Cynthia Parks Brent L. Wood Janis L. Abkowitz Elihu H. Estey 《American journal of hematology》2015,90(4):295-300
Prior study of the combination of clofarabine and high dose cytarabine with granulocyte colony‐stimulating factor (G‐CSF) priming (GCLAC) in relapsed or refractory acute myeloid leukemia resulted in a 46% rate of complete remission despite unfavorable risk cytogenetics. A multivariate analysis demonstrated that the remission rate and survival with GCLAC were superior to FLAG (fludarabine, cytarabine, G‐CSF) in the relapsed setting. We therefore initiated a study of the GCLAC regimen in the upfront setting in a multicenter trial. The objectives were to evaluate the rates of complete remission (CR), overall and relapse‐free survival (OS and RFS), and toxicity of GCLAC. Clofarabine was administered at 30 mg m?2 day?1 × 5 and cytarabine at 2 g m?2 day?1 × 5 after G‐CSF priming in 50 newly‐diagnosed patients ages 18–64 with AML or advanced myelodysplastic syndrome (MDS) or advanced myeloproliferative neoplasm (MPN). Responses were assessed in the different cytogenetic risk groups and in patients with antecedent hematologic disorder. The overall CR rate was 76% (95% confidence interval [CI] 64–88%) and the CR + CRp (CR with incomplete platelet count recovery) was 82% (95% CI 71–93%). The CR rate was 100% for patients with favorable, 84% for those with intermediate, and 62% for those with unfavorable risk cytogenetics. For patients with an antecedent hematologic disorder (AHD), the CR rate was 65%, compared to 85% for those without an AHD. The 60 day mortality was 2%. Thus, front line GCLAC is a well‐tolerated, effective induction regimen for AML and advanced myelodysplastic or myeloproliferative disorders. Am. J. Hematol. 90:295–300, 2015. © 2014 Wiley Periodicals, Inc. 相似文献
8.
Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation 总被引:9,自引:5,他引:9
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de Lima M Anagnostopoulos A Munsell M Shahjahan M Ueno N Ippoliti C Andersson BS Gajewski J Couriel D Cortes J Donato M Neumann J Champlin R Giralt S 《Blood》2004,104(3):865-872
Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P =.006), patients in first CR (28% versus 3%, P =.008), and HLA-matched sibling donors (81% versus 40%, P =.001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P =.036), and lower cumulative incidence of relapse-related mortality (P =.029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after FAI and 35% following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity. 相似文献
9.
Russo D Malagola M de Vivo A Fiacchini M Martinelli G Piccaluga PP Damiani D Candoni A Michielutti A Castelli M Testoni N Ottaviani E Rondoni M Pricolo G Mazza P Zuffa E Zaccaria A Raspadori D Bocchia M Lauria F Bonini A Avanzini P Gugliotta L Visani G Fanin R Baccarani M 《British journal of haematology》2005,131(2):172-179
Fludarabine plus cytarabine (Ara-C) and idarubicin (FLAI) is an effective and well-tolerated induction regimen for the treatment of acute myeloid leukaemia (AML). This phase III trial compared the efficacy and toxicity of FLAI versus idarubicin plus Ara-C and etoposide (ICE) in 112 newly diagnosed AML patients <60 years. Fifty-seven patients received FLAI, as the first induction-remission course, and 55 patients received ICE. Post-induction treatment consisted of high-dose Ara-C (HDAC). After HDAC, patients in complete remission (CR) received a second consolidation course (mitoxantrone, etoposide, Ara-C) and autologous stem cell transplantation (auto-SCT) or allogeneic (allo)-SCT, according to the age, disease risk and donor availability. After a single induction course, CR rate was 74% in the FLAI arm and 51% in the ICE arm (P = 0.01), while death during induction was 2% and 9% respectively. Both haematological (P = 0.002) and non-haematological (P = 0.0001) toxicities, especially gastrointestinal (i.e. nausea, vomiting, mucositis and diarrhoea), were significantly lower in FLAI arm. In both arms, relapses were more frequent in patients who were not submitted to allo-SCT. After a median follow-up of 17 months, 30% and 38% of the patients are in continuous CR in FLAI and ICE arm respectively. Our prospective randomised study confirmed the anti-leukaemic effect and the low toxic profile of FLAI as induction treatment for newly diagnosed AML patients. 相似文献
10.
Barbara Scappini Giacomo Gianfaldoni Francesco Caracciolo Francesco Mannelli Caterina Biagiotti Claudio Romani Enrico M. Pogliani Federico Simonetti Lorenza Borin Rosa Fanci Ilaria Cutini Giovanni Longo Maria Chiara Susini Emanuele Angelucci Alberto Bosi 《American journal of hematology》2012,87(12):1047-1051
Clofarabine has been shown to be effective in AML patients, either as single agent or, mainly, in association with intermediate dose cytarabine. Based on these reports, we conducted a preliminary study combining clofarabine and intermediate dose cytarabine in AML patients who relapsed or failed to respond to at least two induction therapies. We treated 47 patients affected by relapsed/refractory AML with a regimen including clofarabine at 22.5 mg/m2 daily on days 1–5, followed after 3 hr by cytarabine at 1 g/m2 daily on days 1–5. Ten patients received a further consolidation cycle with clofarabine at 22.5 mg/m2 and cytarabine at 1 g/m2 day 1–4. Among the 47 patients, 24/47 (51%) achieved a complete remission, 5/47 (10.5%) a partial response, 10/47 (21%) had a resistant disease, and 6/47 (13%) died of complications during the aplastic phase. The most frequent nonhematologic adverse events were vomiting, diarrhea, transient liver toxicity, febrile neutropenia, and infections microbiologically documented. Among the 24 patients who obtained a CR 13 underwent allogeneic bone marrow transplantation. In 14 patients, complete remission duration was shorter than 12 months, whereas 10 patients experienced longer complete remission duration. These very preliminary results suggest that clofarabine‐cytarabine regimen is effective in this particularly poor prognosis category of patients, representing a potential “bridge” toward bone marrow transplant procedures. Safety data were consistent with previously reported salvage therapies. Further studies and a longer follow up are warranted. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc. 相似文献
11.
Caner Saygin Karilyn Larkin James S. Blachly Shelley Orwick Apollinaire Ngankeu Charles T. Gregory Mitch A. Phelps Shylaja Mani Alison Walker Ramiro Garzon Sumithira Vasu Katherine J. Walsh Bhavana Bhatnagar Rebecca B. Klisovic Michael R. Grever Guido Marcucci John C. Byrd William Blum Alice S. Mims 《American journal of hematology》2020,95(12):1457-1465
Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) have poor outcomes and hematopoietic cell transplantation (HCT) is the only curative treatment. New targeted therapies improved survival in select patients with specific mutations, however management of patients without these molecular alterations is an unmet need. We conducted a phase one study of lenalidomide in combination with cytarabine/idarubicin salvage chemotherapy in patients with R/R AML and high-risk myelodysplastic syndromes. A total of 33 patients were enrolled in the study (30 AML, 3 MDS), and treated at three dose levels with 3 + 3 design. Dose-limiting toxicity (DLT) was seen in eight patients, including four hematologic DLTs. The most commonly observed non-hematologic serious adverse events were febrile neutropenia, rash, sepsis and renal injury. Dose level −1, consisting of 25 mg/d lenalidomide D1-21, 1 g/m2 cytarabine D5-8, and 8 mg/m2 idarubicin D5-7 was determined to be the maximum tolerated dose. Note, 15/33 (45%) of patients were able to receive pre-planned 21 days of lenalidomide. Overall, 18 patients achieved complete remission (CR) (n = 14) or CR with incomplete count recovery (CRi) (n = 4) with total CR/CRi rate of 56%. The 1-year and 2-year overall survival (OS) were 24% and 10%, respectively. Among responders, 10/18 underwent allogeneic HCT and had a 1-year OS of 40%. There was no molecular pattern associated with response. These data demonstrate that the combination had clinical activity in R/R AML. This regimen should be further investigated for patients who relapsed after HCT, and as a bridge therapy to HCT. ( ClinicalTrials.gov identifier: NCT01132586). 相似文献
12.
Wenjuan Yu Liping Mao Jiejing Qian Wenbin Qian Haitao Meng Wenyuan Mai Hongyan Tong Yin Tong Jie Jin 《Annals of hematology》2013,92(8):1091-1100
To assess the efficacy and toxicity of HAA regimen (Homoharringtonine 4 mg/m2/day, days 1–3; cytarabine 150 mg/m2/day, days 1–7; aclarubicin 12 mg/m2/day, days 1–7) as a salvage therapy in the treatment of refractory and/or relapsed acute myeloid leukemia (AML), 46 patients with refractory and/or relapsed AML, median age 37 (16–65) years, participated in this clinical study. The median follow-up was 41 (10–86) months. Eighty percent of patients achieved complete remission (CR), and the first single course of re-induction HAA regimen resulted in CR rate of 76.1 %. The study protocol allowed two courses of induction. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 90 %, 88.9 %, and 37.5 %, respectively. For all patients, the estimated 3-year overall survival (OS) rate was 42 %, and the estimated relapse free survival (RFS) at 3 years for the 36 CR cases was 49 %. The toxicities associated with HAA regimen were acceptable. HAA is a good choice in cases with refractory/relapsing AML for salvage chemotherapy, preferably with a high-efficacy and low-toxicity profile. 相似文献
13.
A phase II trial was designed to explore the potential feasibility and efficacy of a reinduction therapy consisting of fludarabine, cytarabine, idarubicin and granulocyte colony stimulating factor (G-CSF) for acute myelogenous leukaemia (AML) patients with poor prognosis.
Twenty-three patients aged 1.2–17.5 years with refractory ( n = 3), relapsed ( n = 19) or secondary ( n = 1) AML were treated with the IDA-FLAG regimen, a combination therapy of idarubicin (days 2–4, 12 mg/m2 /d), fludarabine (days 1–4, 30 mg/m2 /d), cytarabine (days 1–4, 2000 mg/m2 /d) and G-CSF (day 0 up to ANC > 1 × 109 /l, 400 μg/m2 /d). They received a total of 37 courses of IDA-FLAG and/or FLAG (IDA-FLAG without idarubicin). 17/23 patients achieved a complete remission (CR) with a median duration of 13.5 months (1–39 months), one patient showed a partial remission, and five were nonresponders while in CR, 11 patients underwent bone marrow or PBSC (peripheral blood stem cells) transplantation. Overall, nine patients remain in continuous complete remission with a median duration of 17.5 months (9.5–39 months). The toxicity of the IDA-FLAG courses was more severe than for the FLAG courses with marked neutropenia and thrombocytopenia (for IDA-FLAG: median 22.5 and 25 d respectively; for FLAG: median 10.5 and 14 d respectively). Pulmonary infections were the main nonhaematological toxicity. One patient died in CR from invasive aspergillosis.
The IDA-FLAG regimen produced a CR of >12 months in more than half of the patients and can be recommended as a therapeutic option prior to allogeneic or autologous bone marrow transplantation. 相似文献
Twenty-three patients aged 1.2–17.5 years with refractory ( n = 3), relapsed ( n = 19) or secondary ( n = 1) AML were treated with the IDA-FLAG regimen, a combination therapy of idarubicin (days 2–4, 12 mg/m
The IDA-FLAG regimen produced a CR of >12 months in more than half of the patients and can be recommended as a therapeutic option prior to allogeneic or autologous bone marrow transplantation. 相似文献
14.
Gemtuzumab ozogamicin with fludarabine,cytarabine, and granulocyte colony stimulating factor (FLAG‐GO) as front‐line regimen in patients with core binding factor acute myelogenous leukemia
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Gautam Borthakur Jorge E. Cortes Elihu E. Estey Elias Jabbour Stefan Faderl Susan O'Brien Guillermo Garcia‐Manero Tapan Mahendra Kadia Xuemei Wang Keyur Patel Rajyalakshmi Luthra Charles Koller Mark Brandt Farhad Ravandi Hagop Kantarjian 《American journal of hematology》2014,89(10):964-968
Despite being considered “good‐risk” acute myelogenous leukemia (AML), long term outcomes in core binding factor (CBF) AML suggest room for improvement. We report on a regimen consisting of fludarabine, cytarabine, granulocyte colony stimulating factor, and low dose gemtuzumab ozogamicin (FLAG‐GO) as front‐line therapy of patients with CBF AML. Forty‐five patients were enrolled (median age 48 years). Remission rate was 95% with 5% induction deaths. The overall survival (OS) and relapse free survival (RFS) probability at 3 years are 78% and 85%, respectively. FLAG‐GO regimen results in high rates of RFS and OS in CBF AML. Our data along with recent data from several large groups strongly argues in favor of incorporation of gemtuzumab ozogamicin in frontline regimens for CBF AML. Am. J. Hematol. 89:964–968, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
15.
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
16.
Hołowiecki J Grosicki S Kyrcz-Krzemien S Skotnicki AB Piatkowska-Jakubas B Warzocha K Seferynska I Zdziarska B 《Annals of hematology》2008,87(5):361-367
In 1992–1993, synergistic interaction of ribonucleotide reductase inhibitors (fludarabine, cladribine) and cytarabine (Ara-C)
increasing Ara-CTP concentration in myeloblasts was proved. Based on these findings and encouraging results of the addition
of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia
Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction
treatment of AML to assess tolerance, toxicity, and early outcome. The DAF regimen consisted of daunorubicine 60 mg m−2 day−1 iv on days 1–3 and fludarabine 25 mg m−2 day−1 iv on days 1–5 given before cytarabine 200 mg m−2 day−1 in ci on days 1–7. Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study
between September 2003 and August 2004. Achieved response rate in the whole study population was 56%; n = 16 patients with complete remission (CR), and n = 3 patients with partial remission (PR). Fifteen of 16 patients achieved CR after the first course of therapy. Only 9% of
total population died before the assessment of remission. All patients developed severe neutropenia. Serious infections were
observed in 47% of the cases. Severe thrombocytopenia was observed in 72% of the patients. All patients required substitution
of platelet concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis, vomiting were of low frequency. Liver,
kidney, or circulatory failure, diarrhea, or polyneuropathy were not observed. The probability of overall survival (OS) for
1 year for the whole study population (34 patients) and the group of 16 patients in CR was: 44% (95% confidence interval [CI]
36–52%) and 69% (95% CI 55–83%), respectively. The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI
22–54%). Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable
toxicity and early efficacy. 相似文献
17.
Wrzesień-Kuś A Robak T Wierzbowska A Lech-Marańda E Pluta A Wawrzyniak E Krawczyńska A Kuliczkowski K Mazur G Kiebiński M Dmoszyńska A Wach M Hellmann A Baran W Hołowiecki J Kyrcz-Krzemień S Grosicki S;Polish Adult Leukemia Group 《Annals of hematology》2005,84(9):557-564
Purine nucleoside analogues, cladribine (2-chlorodeoxyadenosine, 2-CdA) and fludarabine (FAMP) are active agents in acute myeloid leukemias (AMLs). Synergistic interaction between FAMP or 2-CdA with cytarabine (cytosine arabinoside, Ara-C) has been demonstrated in preclinical and clinical studies. The current multicenter phase II study was initiated to evaluate the efficacy and toxicity of induction treatment consisting of 2-CdA (5 mg/m2), Ara-C (2 g/m2), mitoxantrone (MIT, 10 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (CLAG-M) in refractory AML. In case of partial remission, a second CLAG-M was administered. Patients in complete remission (CR) received consolidation courses based on high-dose Ara-C and MIT with or without 2-CdA. Forty-three patients from five centers were registered: 25 primary resistant and 18 relapsed. CR was achieved in 21 (49%) patients, 20 (47%) were refractory and 2 (5%) died early. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS; 1 year) for the 42 patients as a whole and the 20 patients in CR were 43% and 73%, respectively. Disease-free survival (1 year) was 68.6%. None of the analyzed prognostic factors influenced the CR and OS probability significantly. We conclude that CLAG-M regimen has significant antileukemia activity in refractory AML, which seems to be better than the activity of many other regimens. The toxicity of the treatment is acceptable. 相似文献
18.
Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late first relapse
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Sylvain Pilorge Sophie Rigaudeau Florence Rabian Clémentine Sarkozy Anne L. Taksin Hassan Farhat Fathia Merabet Stéphanie Ghez Victoria Raggueneau Christine Terré Isabelle Garcia Aline Renneville Claude Preudhomme Sylvie Castaigne Philippe Rousselot 《American journal of hematology》2014,89(4):399-403
Gemtuzumab ozogamicin (fGO), a humanized anti‐CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m2, days 1, 4, 7) with standard‐dose cytarabine (200 mg/m2/day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty‐four patients (median age 68 years) received fGO with cytarabine. Median follow‐up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two‐year overall survival (OS) was 51% (95% CI: 28–69) and 2 years relapse‐free survival (RFS) was 51% (95%CI: 25–72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. Am. J. Hematol. 89:399–403, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
19.
Holbrook E. Kohrt Samit Patel Michelle Ho Terri Owen Daniel A. Pollyea Ravindra Majeti Jason Gotlib Steve Coutre Michaela Liedtke Caroline Berube Ash A. Alizadeh Bruno C. Medeiros 《American journal of hematology》2010,85(11):877-881
The majority of patients with acute myeloid leukemia (AML) will require second‐line chemotherapy for either relapsed or refractory disease. Currently, only allogeneic hematopoietic cell transplantation (HCT) offers a curative option in this setting and no preferred regimen has been established. The reported efficacy of second‐line regimens is widely disparate, thus limiting informed clinical decision making. A retrospective review of 77 patients receiving therapy between 2001 and 2008 with relapsed, 42, and refractory, 35, AML was performed to determine overall response rate and survival following mitoxantrone (8 mg/m2/day), etoposide (100 mg/m2/day), and cytarabine (1,000 mg/m2/day) chemotherapy administered over 5 days. Among 77 patients (median age of 54 years and 64% intermediate risk karyotype) with median follow‐up of 153 days, 18% achieved a complete response and 8% a morphologic leukemia‐free state. Fifty‐seven (74%) experienced treatment failure, 10 of whom achieved a remission after additional therapy. Median overall survival (OS) was 6.8 months. Among patients achieving a response, 50% received consolidation with allogeneic HCT, autologous HCT (5%), or consolidation chemotherapy alone (45%). A nonsignificant trend in overall response (50%, 27%, and 23.8%) and median OS (8.3, 6.8, and 4.7 months) was observed by cytogenetic stratification into favorable, intermediate, and unfavorable risk. Patients with refractory versus relapsed disease had similar overall responses (20% and 31%, P = 0.41) and median OS (5.3 and 7.6 months, P = 0.36). Despite risk stratification by the European Prognostic Index, our series demonstrates inferior rates of response and survival, illustrating the limited activity of this regimen in our cohort. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc. 相似文献
20.
Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS 总被引:7,自引:3,他引:7
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de Lima M Couriel D Thall PF Wang X Madden T Jones R Shpall EJ Shahjahan M Pierre B Giralt S Korbling M Russell JA Champlin RE Andersson BS 《Blood》2004,104(3):857-864
Postulating favorable antileukemic effect with improved safety, we used intravenous busulfan and fludarabine as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Fludarabine 40 mg/m2 and intravenous busulfan 130 mg/m2 were given once daily for 4 days, with tacrolimus-methotrexate as graft-versus-host disease (GVHD) prophylaxis. We treated 74 patients with AML and 22 patients with MDS; patients had a median age of 45 years (range, 19-66 years). Only 20% of the patients were in first complete remission (CR) at transplantation. Donors were HLA-compatible related (n = 60) or matched unrelated (n = 36). The CR rate for 54 patients with active disease was 85%. At a median follow-up of 12 months, 1-year regimen-related and treatment-related mortalities were 1% and 3%, respectively. Two patients had reversible hepatic veno-occlusive disease. Actuarial 1-year overall survival (OS) and event-free survival (EFS) were 65% and 52% for all patients, and 81% and 75% for patients receiving transplants in CR. Recipient age and donor type did not influence OS or EFS. Median busulfan clearance was 109 mL/min/m2 and median daily area-under-the-plasma-concentration-versus-time-curve was 4871 micromol-min, with negligible interdose variability in pharmacokinetic parameters. The results suggest that intravenous busulfan-fludarabine is an efficacious, reduced-toxicity, myeloablative-conditioning regimen for patients with AML or MDS undergoing HSCT. 相似文献