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1.
Hofmann WK Heil G Zander C Wiebe S Ottmann OG Bergmann L Hoeffken K Fischer JT Knuth A Kolbe K Schmoll HJ Langer W Westerhausen M Koelbel CB Hoelzer D Ganser A 《Annals of hematology》2004,83(8):498-503
In an attempt to improve the complete remission (CR) rates and to prolong the remission duration especially in elderly patients >50 years of age, we have used a combination chemotherapy of idarubicin (10 mg/m2 IV×3 days), cytarabine (AraC, 100 mg/m2 CIVI×7d), and etoposide (100 mg/m2×5 days) in combination with granulocyte colony-stimulating factor (G-CSF) priming [5 mg/kg SQ day 1 until absolute neutrophil count (ANC) recovery] for remission induction. Responding patients received two consolidation courses of idarubicin, AraC, and etoposide, followed by a late consolidation course of intermediate-dose AraC (600 mg/m2 IV every 12 h×5 days) and amsacrine (60 mg/m2 IV×5 days). A total of 112 patients (57 male/55 female) with a median age of 58 years (range: 22–75) have been entered and are evaluable for response: 19 refractory anemia with excess of blast cells in transformation (RAEB-T), 84 acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS), and 9 secondary AML after chemotherapy/radiotherapy. The overall CR rate was 62%, partial remission (PR) rate 10%, treatment failure 16%, and early death rate 12%. The CR rate was higher in patients 60 years (68 vs 55%), mainly due to a lower early death rate (5 vs 21%, p<0.001). After a median follow-up of 58 months, the median overall survival is 14.5% and median duration of relapse-free survival 8 months. After 60 months, the probability of CR patients to still be in CR and alive is 16% (20% in patients 60 years and 13% in patients >60 years), while the probability of overall survival is 12% (15% in patients 60 years and 9% in patients >60 years). Compared to our previous trial (AML-MDS Study 01-92) which was done with identical chemotherapy but no G-CSF priming in 110 patients with RAEB-T, AML after MDS, or secondary AML (identical median age, age range, and distribution of subtypes), the CR rate in all patients, as well as CR rate, overall survival, and relapse-free survival in patients >60 years have significantly been improved. Thus, intensive chemotherapy with G-CSF priming is both well tolerated and highly effective for remission induction in these high-risk patients. 相似文献
2.
F. Ferrara L. Melillo M. Montillo F. Leoni A. Pinto G. Mele S. Mirto 《Annals of hematology》1999,78(8):380-384
Twenty-six patients affected by acute myeloid leukemia (AML) who relapsed after autologous stem cell transplantation (ASCT)
were treated with the FLAG regimen (fludarabine, cytarabine, and G-CSF). Their median age was 39 years (range 14–59). The
median interval from achievement of CR to ASCT was 4 months (2–8). The conditioning regimen was BAVC (BCNU, amsacrine, VP-16,
cytarabine) in eight patients, BuCy (busulfan, cyclophosphamide) in 13, and TBI-Cy (total body irradiation, cyclophosphamide)
in five. Relapse occurred after a median of 7 months (2–18). ASCT had been performed in CR1 for 23 patients and in CR2 for
three. Nineteen patients had been given bone marrow, seven peripheral blood stem cells collected following consolidation plus
G-CSF. Overall, CR was obtained by 13 patients (50%), all remitters requiring a single course. The median time for hematological
recovery of neutrophils >500/μl and platelets >20,000/μl was 24 and 30 days, respectively. The median duration of G-CSF administration
was 25 days, while the median hospitalization was 31 days. There were four deaths in induction (15%), while nine patients
(35%) were resistant. After achieving CR, two patients received allogeneic BMT, five a second ASCT, and four were consolidated
with HD-ARA-C. Only two patients were judged unable to receive any further therapy. There were 14 documented infections, while
nine patients experienced fever of unknown origin. WHO >2 nonhematological toxicity consisted of stomatitis (50%), hepatic
dysfunction (11%), diarrhea (11%), and lethargy (4%). Median overall survival and disease-free survival were 6 and 13 months,
respectively. Six patients are in CCR at present. We conclude that FLAG is effective in patients with AML who are relapsing
after ASCT. The toxicity is acceptable, enabling most patients to receive further treatment, including second transplantation
procedures.
Received: October 19, 1998 / Accepted: March 30, 1999 相似文献
3.
Long-term survival after induction therapy with idarubicin and cytosine arabinoside for de novo acute myeloid leukemia 总被引:8,自引:1,他引:8
Flasshove M Meusers P Schütte J Noppeney R Beelen DW Sohrab S Roggenbuck U Kemmeries G Brittinger G Seeber S Scheulen ME 《Annals of hematology》2000,79(10):533-542
We treated 153 patients with de novo acute myeloid leukemia (AML) with two induction courses of conventional-dose cytosine
arabinoside (ara-C) and idarubicin (AIDA) followed by either a third course of AIDA, high-dose ara-C or bone-marrow transplantation.
The complete remission (CR) rate for all patients was 63.4%, with a higher CR rate for patients with a normal (versus unfavorable)
karyotype (73.2% vs 52.5%;P=0.038). The probability of overall survival (OS) was 30.7% after 5 years (26.3% after 7 years). Improved OS at 5 years could
be observed for patients up to 50 years old versus patients older than 50 years of age (37.6% vs 19.9%;P=0.001) and patients with a normal (versus unfavorable) karyotype (42.9% vs 14.1%;P=0.0016). Disease-free survival (DFS) after 5 years was 33.2% for all 97 CR patients and was significantly better for patients
with a normal (versus unfavorable) karyotype (44.3% vs 12.3%;P=0.003). Multivariate analysis revealed that the age for OS (P<0.02) and the karyotype for both OS (P<0.03) and DFS (P<0.05) were independent prognostic factors. In conclusion, AIDA is an effective and well-tolerated induction regimen (even
in elderly patients) with a 5-year survival of more than 30% when combined with ara-C-containing postremission therapy. The
karyotype is the most powerful prognostic factor for predicting the outcome of patients treated with this protocol.
Received: 10 December 1999 / Accepted: 25 February 2000 相似文献
4.
Idarubicin, cytarabine, and topotecan in patients with refractory or relapsed acute myelogenous leukemia and high-risk myelodysplastic syndrome. 总被引:8,自引:0,他引:8
In an effort to develop more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of a combination chemotherapy consisting of idarubicin, cytarabine, and topotecan. Twenty-seven patients were treated: four with primary refractory AML, nine with AML in first relapse, four with AML in second relapse, and 10 with MDS-RAEB/RAEBT. Patients received as salvage therapy a single course of idarubicin 12 mg/m(2) IV bolus on days 1-3, cytarabine 1 g/m(2) over two hours q 12 hr on days 1-5, and topotecan 1.25 mg/m(2) over 24 hr on days 1-5. Median age was 42 years (range 17-65 years). All patients were evaluable for response: 14 (51.9%) achieved complete remission, 10 with AML (59%) and four with MDS (40%), respectively. Thirteen AML patients (excluding four relapsed after autologous stem cell transplantation) were grouped into four categories to stratify the probability of achieving complete remission (CR): group 1, first CR duration > or = 2 years and receiving first salvage treatment (S1); group 2, first CR duration 1-2 years and receiving S1; group 3, first CR duration 0-1 years and receiving S1; and group 4, first CR duration 0-1 years and receiving S2, S3, or S4 after failing S1. The response rate of each group was as follows: group 1, one of two (50%); group 2, one of one (100%); group 3, four of four (100%); group 4, two of six (33.3%). The median remission duration and survival of patients with AML were six and 12 months, respectively. Median duration of survival in 10 MDS patients was 15 months, and all four MDS patients achieving a CR maintained continuous CR with a median follow-up of 11 months. Severe myelosuppression was observed in all patients, resulting in fever or documented infections in 89% of patients. Median time to recovery of neutrophils > or =0.5 x 10(9)/l was 22 days (11-34) and for platelets > 20 x 10(9)/l 35 days (11-58). Reversible grade 3-4 toxicities included diarrhea (two patients) and mucositis (seven patients). We conclude that combination chemotherapy with intermediate dose cytarabine, idarubicin, and topotecan has significant antileukemic activity and acceptable toxicity in salvage AML and high-risk MDS. 相似文献
5.
Greinix HT Loidolt H Rabitsch W Schulenburg A Keil F Mitterbauer M Laczika K Lechner K Dieckmann K Fischer G Jäger U Rosenmayr A Knöbl P Schwarzinger I Höcker P Mannhalter C Hinterberger W Haas OA Fonatsch C Kalhs P 《Annals of hematology》2000,79(4):206-213
Between February 1982 and 1999, 118 consecutive patients (65 male, 53 female) with acute myelogenous leukemia (AML), with
a median age of 35 years (range 17–56 years), received stem-cell grafts from a human leukocyte antigen-identical sibling (n=71), one-antigen-mismatched family member (n=2), matched unrelated donor (n=15), one-antigen-mismatched unrelated donor (n=4) or an autologous (n=26) graft. At the time of transplant, 56 patients were in the first complete remission (CR), 27 in the second CR, 6 in untreated
relapse, 17 in primary refractory, and 12 in refractory relapse. The French-American-British classification (FAB) subtypes
were as follows: M1 (n=25), M2 (n=28), M3 (n=11), M4 (n=32), M5 (n=16), M6 (n=6). For conditioning, most patients underwent total body irradiation-containing regimens. As of 28 February, 1999, probability
of leukemia-free survival (LFS) is 58% for patients after related and 45% after unrelated stem-cell transplantation (SCT).
The probability of LFS is 70% for patients given allogeneic transplants in the first CR compared with 33% for those beyond
the first CR at SCT. In autologous stem-cell graft recipients, the probability of LFS is 37%. Transplant-related mortality
was 28% after related, 20% after unrelated, and 4% after autologous SCT. Probability of relapse for patients given related-donor
stem-cell grafts in the first CR and beyond the first CR is 30% and 67%, 55% after unrelated and 63% after autologous stem-cell
grafting. Thus, myeloablative therapy followed by allogeneic stem-cell infusion has a high curative potential for patients
with AML in remission and offers substantial benefits to patients in advanced disease.
Received: 26 May 1999 / Accepted: 20 August 1999 相似文献
6.
Impact of pre-induction therapy leukapheresis on treatment outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis 总被引:6,自引:0,他引:6
9 /l were scheduled to undergo leukapheresis. This represented 53 patients (median age 59 years, range 16–78 years) who underwent
from 1 to 4 sets of leukapheresis (median 1). The median initial WBC count was 160×109/l (range 100–480×109/l). Morphologic subtypes, according to the French–American–British classification, showed 3 M0, 16 M1, 6 M2, 10 M4, 16 M5,
and 2 unclassified cases of AML. In 21 patients (40%), leukapheresis did not reduce their WBC counts significantly, while
32 patients (60%) achieved a WBC count of less than 100×109/l (median 71×109/l) after leukapheresis. Analysis of cell cycle was performed on bone marrow (BM) and peripheral blood leukemic cells before
and after leukapheresis in three cases. In two of those cases, a recruitment of BM leukemic cells in the S phase was observed
after leukapheresis. The median WBC count at the time of starting chemotherapy was 85×109/l (range 23–264×109/l). Complete remission was achieved in 55% (95% confidence interval 40–68%). Early death occurred in two cases. Median disease-free
survival was 10 months, while median overall survival was 8 months. In this study, early death rate is lower than data previously
published in the literature and almost all patients could receive chemotherapy. This might suggest a benefit of initial leukapheresis
in the treatment of AML presenting with hyperleukocytosis.
Received: 23 November 1999 / Accepted: 8 March 2000 相似文献
7.
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
8.
Results of conventional-dose cytosine arabinoside and idarubicin in elderly patients with acute myeloid leukemia 总被引:1,自引:0,他引:1
A. Heyll C. Aul F. Gogolin V. Runde D. Söhngen G. Meckenstock H. -H. Wolf J. Zahner M. Burk M. Winkelmann W. Schneider 《Annals of hematology》1994,68(6):279-283
Summary Conventional-dose Ara-C (200 mg/m2 d 1–5) combined with idarubicin (12 mg/m2 d 1–3) was employed as remission induction and consolidation therapy in 23 elderly AML patients with a median age of 66 years (range, 60–75) with AML according to the FAB criteria (M1n=3, M2n=10, M4n=6, M5n=2, M6n=2), eligible for the study. In seven patients earlier MDS had been documented by previous bone marrow aspirates. The CR rate after one induction course was 65% (15/23). Toxicity was acceptable, with four patients dying during the chemotherapy-induced hypoplasia (4/23). Although 80% of the CR patients received two additional cycles of Ara-C and idarubicin as consolidation therapy, only two patients are still in continuous complete remission more than 12 months after achieving CR. The median disease-free survival of the CR patients was 11.5 months and the median survival of the entire group was 10 months. We conclude that conventional dose Ara-C/idarubicin is an effective protocol for inducing complete remission in elderly patients with AML, but that consolidation therapy consisting of two courses of the same regimen does not produce a relevant rate of long-term disease-free survival. 相似文献
9.
E. Archimbaud V. Leblond P. Fenaux H. Dombret C. Cordonnier F. Dreyfus P. Cony-Makhoul H. Tilly X. Troussard G. Auzanneau X. Thomas M. Ffrench J.-P. Marie 《Hematology and Cell Therapy》1997,38(2):161-167
Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1–3, etoposide on days 8–10 and cytarabine on days 1–3 and 8–10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38–55%) of refractory patients and 78% (CI: 70–86%) of late first relapse patients (p < 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7–19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6–20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only. 相似文献
10.
Pegylated doxorubicin for primary cutaneous T-cell lymphoma: a report on ten patients with follow-up 总被引:1,自引:0,他引:1
Purpose: Pegylated liposomal doxorubicin (PEG-DOXO) was found to be effective in primary cutaneous T-cell lymphomas (CTCL). The present
observation reports on follow-up and relapse-free interval in patients with CTCL. Methods: Ten patients (one female, nine male) aged 50–78 years (mean 66.7 years) with relapsing or recalcitrant CTCL, stage I b (n=3), II a (2), II b (3), IV a (1), and IV b (1) were treated with PEG-DOXO 20 mg m−2 once a month with an upper limit of 400 mg or eight infusions to induce a clinical response. There was one drop out after
a single infusion because of a capillary leak syndrome. Results: In nine patients with PEG-DOXO the best response was a complete response (CR) in five patients and a partial response (PR)
in four patients. The final outcome was CR in six, PR in two, stable disease (SD) in one, and progressive disease (PD) in
another patient. The overall response rate (CR + PR) was 80% (of ten patients). The follow-up was 2–22 months (mean 12.8 ± 7.1 months).
The overall survival was calculated as 19.8 ± 7.4 months with eight out of ten patients still alive. Response duration was
15.2 ± 3.9 months, disease-free survival 13.3 ± 6.1 months, event-free survival 16.7 ± 9.0 months, and progression-free survival
18.2 ± 6.5 months. Four patients (stage I b and II b) achieved 12–19 months of disease-free survival. The follow-up after
the first course with PEG- DOXO was 2–22 months (mean 12.8 ± 7.1 months). The survival rate after 12 months of follow-up was
80% (n=5). One patient free of relapse died after 12 months because of pulmonary embolism not related to disease or treatment. Another
patient died 1 month after a second course of PEG-DOXO in an advanced tumor stage of CTCL. The most frequent side effects
of treatment were anemia and lymphopenia without the need of supportive treatment or dose-reduction. Only one patient developed
toxicity of grade 4 (anemia). Conclusions: These results indicate that patients with relapsing or recalcitrant CTCL can achieve an 80% response rate with PEG-DOXO and
long-term remissions.
Received: 26 April 2000 / Accepted: 9 June 2000 相似文献
11.
Karyotype plus NPM1 mutation status defines a group of elderly patients with AML (≥60 years) who benefit from intensive post‐induction consolidation therapy
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Wolfgang R. Sperr Otto Zach Iris Pöll Susanne Herndlhofer Paul Knoebl Ansgar Weltermann Berthold Streubel Ulrich Jaeger Michael Kundi Peter Valent 《American journal of hematology》2016,91(12):1239-1245
Although it is generally appreciated that a subset of elderly patients with acute myeloid leukemia (AML) may benefit from intensive consolidation, little is known about variables predicting such benefit. We analyzed 192 consecutive patients with de novo AML aged ≥60 years who were treated with intensive chemotherapy. About 115 patients (60%) achieved complete hematologic remission (CR). Among several parameters, the karyotype was the only independent variable predicting CR (P < 0.05). About 92% (105/115) of the CR‐patients received up to four consolidation cycles of intermediate dose ARA‐C. Median continuous CR (CCR) and disease‐free survival (DFS) were 1.3 and 1.1 years, respectively. CCR, DFS, and survival at 5 years were 23%, 18%, and 15%, respectively. Only karyotype and mutated NPM1 (NPM1mut) were independent predictors of survival. NPM1mut showed a particular prognostic impact in patients with normal (CN) or non‐monosomal (Mkneg) karyotype by Haemato‐Oncology Foundation for Adults in the Netherlands (HOVON)‐criteria, or intermediate karyotype by Southwest Oncology Group (SWOG)‐criteria. The median CCR was 0.94, 1.6, 0.9, and 0.5 years for core‐binding‐factor, CN/Mkneg‐NPM1mut, CN/Mkneg‐NPM1‐wild‐type AML, and AML with monosomal karyotype, respectively, and the 5‐year survival was 25%, 39%, 2%, and 0%, respectively (P < 0.05). Similar results (0.9, 1.5, 0.9, and 0.5 years) were obtained using modified SWOG criteria and NPM1 mutation status (P < 0.05). In summary, elderly patients with CN/Mkneg‐NPM1mut or CBF AML can achieve long term CCR when treated with intensive induction and consolidation therapy whereas most elderly patients with CN/Mkneg‐NPM1wt or Mkpos AML may not benefit from intensive chemotherapy. For these patients either hematopoietic‐stem‐cell‐transplantation or alternative treatments have to be considered. Am. J. Hematol. 91:1239–1245, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
12.
Autologous stem-cell transplantation for patients with acute myeloid leukemia aged over 60 yr 总被引:4,自引:0,他引:4
Ferrara F Venditti A Carellajr AM Cantore N Buccisano F Tamburini A Palmieri S Mele G Annunziata M Greco MM Amadori S 《European journal of haematology》2002,69(4):200-204
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
13.
Wedding U Röhrig B Klippstein A Fricke HJ Sayer HG Höffken K 《Journal of cancer research and clinical oncology》2006,132(10):665-671
Acute myeloid leukaemia (AML) is mainly affecting elderly patients. Elderly patients are increasingly affected by impairment of functional status (FS). FS is of prognostic relevance for survival in different tumours. Data for patients with AML are rare. Within a prospective trial we recruited patients with newly diagnosed AML and measured FS by two different methods: Karnofsky performance status (KPS) and instrumental activities of daily living (IADL). Sixty-three patients aged 19–85 years (median 61.1) were included. Twenty-three had prior myelodisplastic syndrome (MDS), 7 favourable, 17 unfavourable karyotype. Fifty received induction chemotherapy, 13 palliative chemotherapy. Median survival was 15.2 months (95% CI, 10.8–22.3) in all patients. Age, cytogenetic risk group, and impaired KPS and IADL significantly influenced median survival in univariate analysis. Impairment of IADL was the single most predictive variable. In multivariate analysis, impairment of IADL Score (HR:4.3, 95% CI 1.7–10.5, P = 0.001) and of KPS (HR:4.8, 95% CI 1.9–12.3, P = 0.001), and unfavourable cytogenetic risk group (HR:6.0, 95% CI 2.5–14.3, P < 0.001) significantly predicted median survival. In patients with AML, FS and not age is a major predictor of survival. The influence of FS is independent from cytogenetic risk group. IADL measurement adds information to KPS. The results have to be confirmed in a large sample of patients. 相似文献
14.
Intensive consolidation with G‐CSF support: Tolerability,safety, reduced hospitalization,and efficacy in acute myeloid leukemia patients ≥60 years
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Wolfgang R. Sperr Susanne Herndlhofer Karoline Gleixner Michael Girschikofsky Ansgar Weltermann Sigrid Machherndl‐Spandl Thamer Sliwa Rainer Poehnl Veronika Buxhofer‐Ausch Karin Strecker Gregor Hoermann Paul Knoebl Ulrich Jaeger Klaus Geissler Michael Kundi Peter Valent 《American journal of hematology》2017,92(10):E567-E574
The aim of this study was to evaluate the efficacy and feasibility of intensified consolidation therapy employing fludarabine and ARA‐C in cycle 1 and intermediate‐dose ARA‐C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML) patients and to analyze the effects of pegfilgrastim on the duration of neutropenia, overall toxicity, and hospitalization‐time during consolidation in these patients. Thirty nine elderly patients with de novo AML (median age 69.9 years) who achieved complete remission (CR) after induction‐chemotherapy were analyzed. To examine the effect of pegfilgrastim on neutropenia and hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given routinely from day 6 (IDAC‐P) with cycle 3 where pegfilgrastim was only administered in case of severe infections and/or prolonged neutropenia. All four planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%) received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation‐cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC‐P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC‐P) (P < .05). Median overall survival was 1.1 years and differed significantly between patients aged <75 and ≥75 years (P < .05). The probability to be alive after 5 years was 32%. Together, intensified consolidation can be administered in AML patients ≥60, and those who are <75 may benefit from this therapy. Routine administration of pegfilgrastim during consolidation shortens the time of neutropenia and hospitalization in these patients. 相似文献
15.
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
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.
Michael Heuser Antonia Zapf Michael Morgan Jürgen Krauter Arnold Ganser 《Annals of hematology》2011,90(3):273-281
Randomized controlled trials (RCT) investigating administration of colony-stimulating factors (CSF) during or after chemotherapy
in acute myeloid leukemia (AML) patients have not been systematically reviewed. We performed a meta-analysis of all reported
RCTs comparing prophylactic or concurrent use of CSFs in adult AML patients. Two reviewers extracted data independently. Summary
estimates with 95% confidence intervals (CIs) were calculated using a fixed effects model. Fourteen RCTs (n = 4,069 patients) were identified investigating prophylactic CSF administration. Time to neutrophil recovery (>500/μl) was
significantly reduced in the CSF group (−4.13 days; 95% CI, −4.23 to −4.04) as was the length of hospitalization (−2.06 days;
95% CI, −2.36 to −1.76). However, no significant reduction in infection-related mortality was observed in CSF-treated compared
with control patients (odds ratio (OR) 0.94; 95% CI, 0.8 to 1.1). Prophylactic CSF administration did not impact complete
remission (CR) rate or survival. Fourteen RCTs (n = 4,518 patients) were identified investigating administration of CSFs during chemotherapy. Summary estimates of CR, disease/event-free,
or overall survival were not significantly different for CSF versus control patients. Prophylactic CSF administration reduces
the time to neutrophil recovery and length of hospitalization, but has no impact on documented infections or outcome. Economic
analyses of prophylactic CSF administration in AML patients are warranted. 相似文献
18.
Li JM Wang L Shen Y Xia ZG Chen Y Chen QS Chen Y Zeng XY You JH Qian Y Shen ZX 《Annals of hematology》2007,86(9):639-645
The objective of this study is to evaluate the long-term efficacy and safety of rituximab combined with cyclophosphamide,
doxorubicin, vincristine, and prednisone (CHOP) in Chinese patients with newly diagnosed diffuse large B cell lymphoma (DLBCL).
The study comprised a retrospective analysis of patients treated at a single center. Patients received four to six infusions
of rituximab (375 mg/m2 per dose) on day 1 of each cycle of CHOP chemotherapy. CHOP was initiated on day 3 of each cycle; cycles were repeated at
21-day intervals. A total of 82 patients with a median age of 45 years (range 18–76 years) was included. The overall response
(OR) and complete response (CR) rates were 90.2 and 70.7%, respectively. The estimated 5-year progression-free survival (PFS)
and overall survival (OS) rates were 56.4 ± 8.3% and 74.1 ± 7.4%, respectively. Patients with International Prognostic Index
(IPI) scores ≤2 had significantly higher OR, CR, PFS, and OS rates (p = 0.01, p = 0.02, p = 0.01, p < 0.001, respectively) compared with patients with IPI scores >2. The hematologic toxicity was mild. Five patients with a
history of chronic hepatitis B experienced a reactivation of viral hepatitis. The rituximab–CHOP combination was effective
and well tolerated in Chinese patients with newly diagnosed DLBCL.
This study was conducted in accordance with the Chinese Good Clinical Practice (GCP), including ethical approval. 相似文献
19.
Summary Seventy-seven elderly patients (median age 72, range 59–85) with de novo AML were treated with lowdose Ara C (10 mg/m2/12 h over 21 days, for one or two courses). Thirteen (17%) achieved complete remission (CR), 16 (21%) partial remission (PR); 28 (35%) had resistant leukemia, and 20 (26%) early death or death during hypoplasia. Most (86%) of the patients had severe pancytopenia and 58% were hospitalized. Overall median survival was 3 months. Median duration of CR was 9 months. Five CR were longer than 1 year, and two were longer than 4 years. All but one PR were 9 months, and 12/16 were 4 months. Karnofsky index and karyotype (the latter performed for 52 patients) were the only significant prognostic factors of response to treatment (including CR + PR) and survival: poor response rate (8%) and survival (median 0.7 months) were found in patients with Karnofsky index < 60, compared with 44% and 4 months, respectively, in patients with Karnofsky index 60; likewise, patients with rearrangements of chromosome 5 and/or 7 or complex rearrangements had a response rate of 13% and median survival of 1.5 months, compared with 68% and 8 months, respectively, in patients with normal karyotype or single abnormalities (not involving chromosomes 5, 7, or 8). Patients with isolated trisomy 8 had a response rate of 37% but short median survival (2.5 months). Significantly longer survival was seen in responders. Our findings suggest that, overall, low-dose Ara C yields limited results in AML in the elderly. However, it could remain a useful option in elderly patients with AML who are not candidates for intensive chemotherapy (even with the support of growth factors), provided their general condition is not too altered and they do not have an unfavorable karyotype (i.e., rearrangements of chromosomes 5 or 7 or complex abnormalities). 相似文献
20.
Camera A Rinaldi CR Palmieri S Cantore N Mele G Mettivier V Miraglia E Mastrullo L Grimaldi F Luciano L Guerriero A Rotoli B Ferrara F 《Annals of hematology》2009,88(2):151-158
A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant
to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory
(n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous
infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and
relapsed patients, respectively, with an overall response rate of 52% (32 of 61). Twenty-two patients (36%) were resistant
to the salvage therapy. Seven patients (12%) died early during chemotherapy, four of them because of sepsis. Nineteen patients
in complete remission (CR) underwent a stem-cell transplant (SCT) procedure: five autologous, nine from a HL-A identical sibling,
and five from HL-A matched unrelated donors. Post-treatment aplasia and mucositis were major toxicities. Twenty patients (62.5%)
relapsed after this treatment in a median of 7.3 months; ten patients relapsed after a SCT procedure. Nine patients are alive
and disease free; three of them were rescued after a further cytotoxic treatment. The FLAD regimen proved to be an effective
and well-tolerated treatment, with acceptable toxicity in this group of high-risk patients. A better response rate was obtained
in the subgroup of relapsed patients, compared to patients treated for refractory disease. More then half (five of nine) of
long-surviving patients are those who were submitted to a transplant procedure; thus, the main indication for FLAD seems to
be to try to induce a rapid CR with minimum toxicity in order to perform a transplant as soon as possible. 相似文献