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1.
A two-step timed sequential treatment for acute myelocytic leukemia   总被引:1,自引:1,他引:1  
Since 1980, adults with acute myelocytic leukemia (AML) have been treated on two clinical studies using intensive timed sequential therapy. All patients ages 16 to 80, including those with secondary AML (SAML) and those with AML preceded by a hematologic disorder (AHD), were treated, regardless of medical complications at the time of diagnosis. The first study combined high doses of cytarabine (ara-C, AC) and daunorubicin (DRN, D) in sequence (Ac2-D-Ac) and resulted in a complete remission rate of 55%. A group of these patients selected by functional status was able to receive a second course of therapy in remission, which resulted in a disease-free survival (DFS) of greater than 40% at 7 years. Because of toxicity in that study, 114 patients were entered on a second trial initiated 4 years ago, using a less aggressive first course, with amsacrine, to achieve a stable remission (Ac2-D-Amsa). This first treatment was followed by a more intensive second course (Ac6-D-Ac). With this two-step approach, a higher complete remission (CR) rate (76% for de novo AML and 54% for SAML-AHD) was achieved, and more patients were able to receive the second course of therapy. At the current median follow-up of 26 months, the median duration of DFS and overall survival are 11 and 14 months for patients with de novo AML. Age less than or equal to 55 is the most significant prognostic factor for both prolonged DFS and overall survival, with median durations of 17 and 18 months, respectively, for these younger patients. Patients with SAML-AHD remain relatively refractory to treatment despite aggressive chemotherapy, with median durations of DFS and overall survival of 9 months and 5 months, respectively.  相似文献   

2.
Cytogenetic analysis was successfully performed at diagnosis in 283 patients with de novo acute myeloid leukaemia (AML), including eight children aged 6-15 and 275 adults. Mean age was 50.3 (range 6-86) and the M/F ratio was 1.23. 214 patients were treated by intensive chemotherapy and 75.2% achieved complete remission. Patients with inv(16) and t(8;21) had very high CR rates whereas those with complex cytogenetic abnormalities (with or without involvement of chromosomes 5 and/or 7) had a poor response to therapy. Other karyotypic abnormalities and normal karyotypes were associated with intermediate CR rates. In a multivariate analysis, cytogenetics were the best prognostic factor of the achievement of CR, followed by age and platelet count. Median actuarial disease-free survival (DFS) of the patients who achieved CR was 19 months. No significant differences in actuarial DFS were found according to karyotype. However, no relapses were seen in patients with inv(16) and t(9;11) or its variants. Conversely, the median DFS was only 12.5 months in patients with t(15;17). Median actuarial DFS was 24 months in patients with t(8;21), but a high incidence of early relapses were seen, and the actuarial DFS was only 54% at 12 months. Patients with trisomy 8 also had a median actuarial DFS of 24 months. Our findings do not support the previously reported 'favourable' prognosis of t(15;17) translocations. They suggest that, although it is characterized by a high CR rate, t(8;21) might be associated with a high incidence of early relapses and that, finally, inv(16) might be the only 'favourable' cytogenetic rearrangement in AML. Furthermore, the prognosis associated with t(9;11) or its variants (at least in adults), and trisomy 8 might be less severe than suggested in other studies.  相似文献   

3.
OBJECTIVES: Preliminary reports have suggested that autologous stem-cell transplantation (ASCT) is feasible in elderly patients with acute myeloid leukemia (AML). The objective of this study was to describe the disease characteristics and treatment results from a series of 22 elderly AML patients undergoing ASCT. METHODS: The median age was 64 yr (range 61-71). Twenty patients were in first complete remission (CR1), two in CR2, and all were in performance status 0-1. The median interval between CR achievement and ACST was 3 months (range 2-5). In 20 cases peripheral blood stem cells were infused, in two bone marrow. RESULTS: All patients had a successful engrafment. One patient (5%) died from transplant-related complications. The median number of days to granulocytes > 500 mm-3 and platelets > 20 000 mm-3 was 11(range 9-15) and 13 (range 9-20), respectively. Non-hematologic toxicity included WHO grade III-IV stomatitis in 32% patients and grade IV nausea and vomiting in one (4.5%). Seven patients had fever of unknown origin, while in 14 a documented infection was diagnosed. Median duration of hospitalization was 31 d (range 16-60). CONCLUSIONS: After a median follow-up of 12 months from ASCT, nine patients are alive in continuous CR and 13 died from AML relapse. Median survival from diagnosis and disease-free survival (DFS) was 19 and 14 months, respectively. Our data show that ASCT with a standard conditioning regimen is feasible in AML patients aged more than 60 yr. Toxicity and hemopoietic recovery do not substantially differ from those observed in young adults. DFS and overall survival (OS) duration are encouraging, but a longer follow up is needed on a larger series of patients.  相似文献   

4.
Seventeen consecutively admitted poor risk acute myeloid leukaemia (AML) patients and 4 patients with myelodysplastic syndrome (MDS) were treated with a remission-induction regimen consisting of a 7-day continuous intravenous infusion of conventional doses of cytarabine and of three 24-h constant rate infusions of daunorubicin administered intermittently on days 1, 3 and 5. The diagnoses were: relapsed primary AML in 6 patients, secondary AML in 11 patients (9 untreated, 2 relapsed) and MDS in 4 patients. The median age was 50 yr. Five of 6 patients with relapsed primary AML, 3 of 11 patients with secondary AML and 2 of 4 patients with MDS achieved complete remission (CR). The overall CR rate was 48% with a median remission duration of 5 months (range: 0.25-20 months). Few acute toxic side effects were observed thanks to the constant rate of infusion of daunorubicin.  相似文献   

5.
Twenty one adult patients with previously untreated acute myeloblastic leukemia (AML) were treated with sequential mitoxantrone and standard dose cytosine arabinoside remission induction therapy. The median age was 33 years (range 17-56 years). Complete remission (CR) was achieved in 80% (17/21 cases) and 76% (16/21 cases) achieved CR after one course of induction therapy. The median duration of disease free survival was 9 months with an actuarial disease free survival of 22% at 43 months. The non-hematological toxicity was acceptable. We conclude that sequential mitoxantrone and cytosine arabinoside combination therapy is an effective antileukemic regimen which produces high CR rates in previously untreated adult patients with AML.  相似文献   

6.
Thirty adult patients with acute myelogenous leukemia (AML) in remission were treated with hyperfractionated total body irradiation, VP-16, and cyclophosphamide followed by infusion of autologous bone marrow purged with 4-hydroperoxycyclophosphamide and VP-16. Fifteen patients were transplanted in first remission (R1), 13 in second remission (R2), and two in third remission (R3). All patients had hematopoietic engraftment. The median time to achieve a white blood cell count of 1.0 x 10(9)/l and a neutrophil count of 500 x 10(6)/l was 32 days. The median time to achieve an unsupported platelet count of 50 x 10(9)/l was 70 days. There were four transplant-related deaths, all in patients in R2. Ten patients have relapsed, including both patients transplanted in R3. The disease-free survival (DFS) of all patients is 52%, median follow-up not yet reached. Although the number of patients in each group is small and follow-up is limited, there is a trend toward improved actuarial DFS in patients transplanted in R1 compared with patients transplanted in R2 (72 vs 39%; p = 0.081). Use of VP-16 in the conditioning regimen as well as in the purging procedure is feasible in the treatment of patients with AML.  相似文献   

7.
We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML. Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T. Ten of 22 (45%) patients > or = 65 years old achieved CR. The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies. The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T. Myelosuppression was mild to moderate, and other than fever, severe nonhematologic toxicity was rare. CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.  相似文献   

8.
Linker  CA; Ries  CA; Damon  LE; Rugo  HS; Wolf  JL 《Blood》1993,81(2):311-318
We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.  相似文献   

9.
The GIMEMA ALL 0183 trial: analysis of 10-year follow-up   总被引:12,自引:0,他引:12  
We report the 10-year follow-up of the GIMEMA ALL 0183 trial.
From 1983 to 1987, 358 adults with acute lymphoblastic leukaemia (ALL) were entered into this trial, which included a mild induction, an early intensive consolidation, a post-consolidation phase randomized in conventional maintenance (arm A) and in more intensive regimen (arm B). CNS prophylaxis did not include CNS irradiation. The overall complete remission (CR) rate was 79.3% (284/358); 212 patients were randomized (110 in arm A and 102 in arm B).
The median overall CR duration was 20 months and the median overall survival (OS) 21 months; both curves reach a plateau after 6 years; at 10 years 25% of patients were projected to be in long-term remission and survivors. The median disease-free survival (DFS) was 17 months, at 10 years 27% and 28% of patients were DFSs in arm A and in arm B respectively.
In multivariate analysis age, WBC count and L2 FAB subtype were found to significantly influence OS and DFS. With regard to our previous report OS appears to linearly correlate with initial WBC count and age (P=0.0002 and P=0.042 respectively).
195 (68.7%) patients relapsed (only 25 had isolated CNS). The overall second CR rate was 56.5%; 23 patients underwent transplantation (12 BMT and 11 ABMT). Post-relapse survival was found to be influenced by the duration of first CR.  相似文献   

10.
Autologous peripheral blood stem cell transplantation (APBSCT) after intensifying conditioning is one of the post-remission therapeutic options in childhood acute myeloid leukemia (AML) patients without a matched family donor, but the optimal conditioning regimen has not been defined. This study was performed to evaluate the efficacy of a novel conditioning regimen without busulfan or total body irradiation. In total, 28 children with AML underwent APBSCT with BCVAC (BCNU, etoposide, cytosine arabinoside and cyclophosphamide) conditioning regimen during first remission. The event-free survival rate was 71.43% for all patients and the only cause of treatment failure was relapse. Eight male patients recurred at 1-11 months (median 5 months) after APBSCT. One patient remains alive with salvage therapy after relapse. With the exception of fever, mucositis and diarrhea, no serious complications occurred during APBSCT, including veno-occlusive disease (VOD), and there was no transplantation-related mortality. One patient developed secondary MDS after APBSCT but recovered hematologically on medication. APBSCT with BCVAC conditioning was found to be a safe and effective alternative option for patients with childhood AML in first remission, without a matched family donor.  相似文献   

11.
To improve long‐term outcome of de novo acute myeloid leukemia (AML) patients by intermediate dose of cytarabine integrated in induction therapy and to explore the impact of cytogenetic abnormalities on the prognosis. Eighty‐seven AML patients were treated with HAD regimen containing intermediate dose cytarabine (IDAra‐C) as induction therapy, 83 from which with karyotype results were divided into three cytogenetic groups according to SWOG criteria. Complete remission (CR) rate, disease‐free survival (DFS), and overall survival (OS) among different groups were evaluated. The CR rate of the 87 cases was 80/87 (92%). Median DFS and OS have not reached (NR). DFS rates at 1 and 3 years were 76.3% and 63.4%, respectively. OS rates at 1 and 3 years were 86.0% and 58.7%, respectively. According to SWOG criteria, CR rate, median DFS, and OS were 100%, NR and NR for the favorable group; 88.9%, NR, and 16 months for the intermediate group; 83.3%, 4.5 months, and 7.5 months for the adverse group. The differences among the three groups were statistically significant excepting for CR rate between adverse and intermediate groups. HAD regimen containing IDAra‐C as induction chemotherapy regimen is effective in de novo AML of adult patients and can achieve higher CR rate and longer survival than standard dose of cytarabine (SDAra‐C) regimen. Most of the patients were able to endure the therapy. Cytogenetics is still an important prognostic factor despite of the incorporation of IDAra‐C in induction chemotherapy. The differences among the three groups were statistically significant. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.  相似文献   

12.
Between 1969 and 1999, 420 patients (age > 60 years) with newly diagnosed AML were managed at St Bartholomew's Hospital (SBH), London, UK. Sixty-nine percent of patients received therapy with curative intent Eighty-eight patients (31%) of the latter achieved complete remission (CR), representing an overall CR rate of 21%. Treatment failure due to early death (ED) and resistant disease (RD) occurred in 50 and 19%, respectively. With median follow up of 11 years, actuarial survivals at 1,3 and 5 years were 20, 7 and 4%, respectively, the median survival of the entire cohort was 2 months. For patients who achieved CR, median survival was significantly better than that of patients in whom treatment failed (14 vs. 6 months). Over the 30 years, CR rate and the relative incidence of RD both increased from 13 to 45%, and 3 to 27%, respectively, whilst ED rate reduced from 84 to 27%. Multivariate analysis showed that treatment era, hepatosplenomegaly and increasing age predicted for reduced CR rate and OS. Although elderly patients with AML are characterised by a poor response to intensive chemotherapy, significant improvements in supportive care and the delivery of intensive treatment have led to improved CR rates and OS. New therapeutic strategies and a greater awareness of prognostic factors may further improve clinical outcome in this important group of patients.  相似文献   

13.
Twenty-nine patients aged 62-82 years with acute myeloid leukemia (AML) were treated with a 21-day course of continuous infusion cytarabine, oral hydroxyurea, and 1,25-dihydroxyvitamin D3 (calcitriol). Ten patients had an antecedent myelodysplastic syndrome. Calcitriol was continued as the only postremission therapy. Thirteen patients (45%) obtained a complete remission, and 10 patients (34%) had a partial response for an overall 79% response rate. There were three early deaths. The median remission duration was 9.8 months. Overall median survival was 12 months for all patients and 14 months for responding patients. All responding patients had marked bone marrow hypoplasia. Twenty patients received part or all of their chemotherapy as outpatients. This regimen has acceptable toxicity and can result in prolonged remissions in elderly, high-risk patients with AML. The favorable results may be related to the synergistic effect of hydroxyurea, cytarabine, and calcitriol.  相似文献   

14.
We report analysis of all consecutive Hodgkins disease patients undergoing autologous hematopoietic stem cell transplant from September 1999 to December 2014. Out of total 38 patients 26 were males and 12 were females. 32 were adults and 6 were pediatric (<18 years). None were elderly. Median age was 28 years (9–61). All received BEAM protocol as conditioning regimen. Median engraftment time for granulocytes was 12 and 14 days for platelets. Thirty three (86.84 %) patients achieved complete remission out of which 8 (24.24 %) had further relapse. Transplant related mortality occurred in 4 (10 %) patients. Finally 26 (78.78 %) patients were disease free at median follow up of 60 months and median disease free survival (DFS) was 35 months. DFS was 66.66 and 65 %, respectively on 3 and 5 years. While overall survival was 70.83 and 70 % on 3 and 5 years, respectively.  相似文献   

15.
An alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The safety and efficacy of this new conditioning regimen has been investigated prospectively in patients with AML. A total number of 75 patients with AML in CR were treated with 3 × 14 g/m(2) treosulfan and 5 × 30 mg/m(2) fludarabine, followed by matched sibling or unrelated SCT. Patients were evaluated for engraftment, adverse events, GVHD, and for non-relapse mortality, relapse incidence, overall and disease-free survival (DFS). All patients showed primary engraftment of neutrophils after a median of 20 days. Non-hematological adverse events grade III-IV in severity included mainly infections (59%) and gastrointestinal symptoms (7%). Acute GVHD grade II-IV occurred in 21% and extensive chronic GVHD occurred in 16% of the patients. After a median follow-up of 715 days, the 2-year overall and DFS estimates were 61% and 55%, respectively. The 2-year incidences of relapse and non-relapse mortality reached 34% and 11%, respectively. In summary, our data confirm promising safety and efficacy of the treosulfan-based conditioning therapy in AML patients, ClinicalTrials.gov Identifier: NCT01063660.  相似文献   

16.
Outcomes of acute myeloid leukemia (AML) in elderly patients unfit for intensive chemotherapy is challenging. Hypomethylating agents (HMAs) can be effective in these patients but responses are usually short‐lived. The majority of patients will either have stable disease or progress through therapy. We hereby describe the outcome of these patients at our institution after they fail HMAs. The data on 56 AML patients at Mayo Clinic, Rochester were reviewed. Patients were considered for our study if they received HMA as frontline therapy for their AML. Out of 56 patients, 15 (27%) patients received azacitidine (AZA) and 41 (73%) received decitabine. Complete remission was found in 10 (18%), with overall response of 28% and median response duration of 10 months. Thirteen (81%) out of 16 responders relapsed. Therefore 53 patients were included in the primary or secondary failure analysis with a median overall survival (OS) of 2 months after the date of failure. Out of 53 patients, 12 (23%) received subsequent treatments. None of the 12 patients who got first salvage therapy achieved remission. Five out of the 12 patients received second salvage therapy, 2 (40%) of which achieved CR. Median OS for patients who received subsequent salvage therapies was better than those who did not receive any subsequent therapy after failing HMA (9.5 vs. 2 months, P = .0009). Outcome for patients who have primary or secondary failure is very poor. Our study provides important historical data for future novel therapies, which are sorely needed for these patients.  相似文献   

17.
Twenty-five elderly patients with untreated indolent non-Hodgkin lymphoma were treated with oral fludarabine 25 mg/m(2)/d (40 mg total dose) and cyclophosphamide 150 mg/m(2)/d, both for four consecutive days, repeated every 28 d for four cycles. In all, 21 (84%) patients were responsive: 10 patients achieved complete remission while partial response was obtained in 11. During an observation period of 37 months, there was an overall survival rate of 70% and a median event-free survival of 20 months. Haematological and extra-haematological toxicity were mild. This reduced-dose Flu-based oral regimen showed good efficacy and was simple to administer on an outpatient basis.  相似文献   

18.
To assess the influence of graft-versus-host disease (GVHD) on the outcome of patients with advanced haematological malignancies (AHM) who received a primary, unmodified allogeneic peripheral blood progenitor cells transplant (allo-PBT) from a human leucocyte antigen (HLA) identical sibling donor, we analysed 136 patients with myeloid neoplasms (n = 70) or lymphoproliferative disorders (n = 66), transplanted at 19 Spanish institutions. Median age was 35 years (range 1-61). The cumulative incidence of relapse for all patients was 34% (95% CI, 26-42%), 41% (95% CI, 33-49) for patients without GVHD and 14% (95% CI, 3-25) (P = 0.001) for patients with acute and chronic GVHD. After a median follow-up of 11 months (range 2-49), 60 (44%) patients remained alive with an actuarial probability of overall survival and disease-free survival (DFS) at 30 months of 31% (95% CI, 21-41%) and 28% (95% CI, 17-39%) respectively. In patients surviving > 100 d, the low incidence of relapse in those with acute and chronic GVHD led to a DFS of 57% (95% CI, 38-76%) compared with a DFS of 34% (95% CI, 17-51%) in the remaining patients (P = 0.03). Our results indicate a reduced incidence of relapse for patients with AHM receiving an unmodified allo-PBT and developing acute and chronic GVHD, which results in an improved DFS.  相似文献   

19.
The Cancer and Leukemia Group B (CALGB) study 9222 tested the hypothesis that treatment intensification of acute myeloid leukemia (AML) in first remission with multiple chemotherapy agents is superior to high-dose cytarabine (HiDAC) alone. We enrolled 474 patients younger than 60 years old with untreated de novo AML. Daunorubicin and cytarabine resulted in complete remission (CR) in 342 patients (72%), and 309 of these patients were randomized to receive one of 2 different intensification regimens. The first regimen consisted of 3 courses of HiDAC. The second regimen consisted of one course of HiDAC, a second course with etoposide and cyclophosphamide, and a third course with diaziquone and mitoxantrone. After a median follow-up time of 8.3 years, the median survival for all randomized patients was 2.8 years (95% CI, 1.9-6.8 years). There was no difference in disease-free survival (DFS) between the 2 regimens (P = .66). The median DFS was 1.1 years (95% CI, 0.9-1.7 years) for patients receiving HiDAC and 1.0 year (95% CI, 0.9-1.3 years) for those receiving multiagent chemotherapy. Cytogenetics was the only pretreatment characteristic prognostic for DFS, but there was no evidence of a differential treatment effect within cytogenetic risk groups. Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens produced similar outcomes.  相似文献   

20.
We retrospectively analyzed the outcomes of 81 patients with non-M3 acute myelogenous leukemia (AML) in first complete remission (CR1) who were treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (Auto-PBSCT) by the Fukuoka Blood and Marrow Transplantation Group between 1989 and 2005. Cytogenetically, 16 patients were defined as good risk, 56 as intermediate risk, and nine as poor risk, following the Southwest Oncology Group criteria. The pre-transplant conditioning regimen consisted of high-dose busulfan, etoposide, and cytarabine (BEA regimen), combined with priming by granulocyte colony-stimulating factor (G-CSF). Disease-free survival (DFS) and overall survival at 5 years were 64.0 % (95 % CI 52.5–73.4) and 66.4 % (95 % CI 54.9–75.6) after Auto-PBSCT at a median follow-up time of 103 months (range 3–240 months), respectively. Two patients died of transplant-related pulmonary complications 6 months after Auto-PBSCT without relapse. The 5-year DFS rates of patients in the genetically good-, intermediate-, and poor-risk groups were 80.8, 64.3, and 33.3 %, respectively, but there was no significant difference statistically among the risk groups (log-rank p = 0.0579). These observations suggest that HDCT supported by Auto-PBSCT with the BEA regimen combined with G-CSF priming is a therapeutic option for postremission therapy of AML in CR1.  相似文献   

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