[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Relapse in acute myeloid leukemia (AML) after chemotherapy reflects the persistence of resistant leukemia stem cells (LSCs). These cells have been described in the CD34(+)CD38(-) cell fraction. Leukapheresis products were harvested in 123 patients in morphological complete remission and analyzed by multi-parameter flow cytometry. The CD34(+)CD38(-) cell population showed a prognostic impact on survival. Median event-free survival (EFS) was 8.2 months (3-year EFS: 29%) for those with higher percentage of CD34(+)CD38(-) vs 91.9 months (3-year EFS: 62%) for those with lower percentage for the entire cohort. These differences were confirmed in patients undergoing autologous SCT with median EFS of 7.3 months vs 91.1 months (3-year EFS: 31% vs 70%). Higher proportions of CD34(+)CD38(-) cells were associated with adverse cytogenetics and with earlier relapses. Higher percentages of CD34(+)CD38(-) cells in apheresis products reflect inadequate in vivo purging and reliably distinguish samples enriched in LSCs from those involving mainly normal cells.
[Show abstract][Hide abstract] ABSTRACT: To evaluate quantitatively and qualitatively the different CD34(+) cell subsets after priming by chemotherapy granulocyte colony-stimulating factor (± G-CSF) in patients with acute myeloid leukemia.
Peripheral blood and bone marrow samples were harvested in 8 acute myeloid leukemia patients during and after induction chemotherapy. The CD34/CD38 cell profile was analyzed by multi-parameter flow cytometry. Adhesion profile was made using CXC chemokine receptor 4 (CXCR4) (CD184), VLA-4 (CD49d/CD29) and CD47.
Chemotherapy ± G-CSF mobilized immature cells (CD34(+)CD38(-) population), while the more mature cells (CD34(+)CD38(low) and CD34(+)CD38(+) populations) decreased progressively after treatment. Circulating CD34(+) cells tended to be more sensitive to chemotherapy after priming with G-CSF. CD34(+) cell mobilization was correlated with a gradual increase in CXCR4 and CD47 expression, suggesting a role in cell protection and the capacity of homing back to the marrow.
Chemotherapy ± G-CSF mobilizes into the circulation CD34(+) bone marrow cells, of which, the immature CD34(+)CD38(-) cell population. Further manipulations of these interactions may be a means with which to control the trafficking of leukemia stem cells to improve patients' outcomes.
World journal of stem cells. 10/2013; 5(4):196-204.
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT The absolute lymphocyte count (ALC) at presentation has been associated to survival in various malignancies. However its prognostic value in acute myeloid leukemia (AML) has not been established. In a series of 1702 newly diagnosed AML patients, we evaluated the prognostic value of ALC at diagnosis with regards to induction chemotherapy response, disease-free survival (DFS) and overall survival (OS). Low initial ALC (< 1 x 10(9)/l) appeared as a poor prognostic factor for DFS (P = 0.01) and OS (P = 0.02), while higher ALC (> 4.5 x 10(9)/l ) showed a lower response rate after one (P = 0.004) or two induction chemotherapy courses (P = 0.01). However, ALC did not appear as an independent predictor of outcome in a multivariate analysis model also including age, cytogenetics, and WBC count. Examination of lymphocyte subsets is warranted to specify the relationship between ALC at diagnosis and clinical outcome in AML.
[Show abstract][Hide abstract] ABSTRACT: Forty-seven percent of adults with acute myeloid leukemia (AML) who entered the ALFA-9802 trial and achieved a first complete remission (CR) experienced a first relapse. We examined the outcome of these 190 adult patients. Eighty-four patients (44%) achieved a second CR. The median overall survival (OS) after relapse was 8.9 months with a 2-year OS at 25%. Factors predicting a better outcome after relapse were stem cell transplant (SCT) performed in second CR and a first CR duration >1 year. Risk groups defined at the time of diagnosis and treatment received in first CR also influenced the outcome after relapse. The best results were obtained in patients with core binding factor (CBF)-AML, while patients initially defined as favorable intermediate risk showed a similar outcome after relapse than those initially entering the poor risk group. We conclude that most adult patients with recurring AML could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option at this stage of the disease.
Leukemia research 05/2012; 36(9):1112-8. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infections are a major complication in patients with acute myeloid leukemia undergoing intensive chemotherapy. They remain a major cause of therapy-associated morbidity and mortality, and represent a frequent cause of treatment withdrawal. An analysis of the medical charts of 459 younger adults included in the multicenter Acute Leukemia French Association (ALFA)-9802 trial showed that 1369 febrile episodes occurred among the 459 registered patients, including fever without identifiable source (23%) and clinically or microbiologically documented infections (77%). Bloodstream infections occurred in 314 episodes, including 129 documented episodes with Gram-positive and 96 with Gram-negative pathogens. Pulmonary infection was diagnosed in 144/1054 documented infectious episodes (14%). Invasive fungal infection was probable or proven in 116 patients. In all, 15 patients died of infection-associated complications, of whom seven died during early induction therapy, one during salvage therapy and seven during consolidation therapy. Better supportive care strategies may improve overall survival in patients undergoing chemotherapy for acute myeloid leukemia.
[Show abstract][Hide abstract] ABSTRACT: The treatment of older adults with acute myeloid leukemia (AML) is associated with unsatisfactory rates of response and overall survival. Identification of valuable factors that can facilitate therapeutic decision-making between intensive chemotherapy and investigational treatment strategies is warranted.
Analysis of proliferative (white blood cell [WBC] count) and invasive (percentage of blast cells in peripheral blood) characteristics of leukemic blasts at diagnosis is presented in a population of 432 promyelocytic leukemia AML patients who are older than than 60 years and have been selected for entering onto five successive clinical trials combining an anthracycline and cytarabine.
Five groups of patients were defined according to these two relevant parameters used in clinical practice. Response rates were lower for the hyperproliferative groups (47% and 46%, respectively) and the nonproliferative groups displaying circulating blasts (56% and 59%, respectively) compared with those for the nonproliferative and noninvasive group (77%) (P = .0003). Median overall survivals were shorter for the hyperproliferative groups (5.7 and 5.8 months, respectively) compared with those observed for the nonproliferative groups (8.9 and12.6 months, respectively).
This combination of basic characteristics helps estimate the outcome of elderly AML patients who are usually selected for intensive chemotherapy. Although these factors remain valuable for identifying leukemia behavior, our study demonstrated that results of intensive chemotherapy in elderly patients remained poor, whatever the prognostic group. Comparison with recent data from the literature requires investigators to study results differently and to consider investigational therapy as being the most appropriate treatment even for this highly selected population.
[Show abstract][Hide abstract] ABSTRACT: To assess the value of administering timed-sequential chemotherapy (TSC; 2 therapeutic sequences separated by a 4-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in consolidation therapy for acute myeloid leukemia (AML), 459 patients 15 to 50 years of age were enrolled in the prospective randomized Acute Leukemia French Association-9802 trial. Complete remission was achieved in 89%. A total of 237 patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the 2 consolidation arms (5-year event-free survival [EFS]: 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML NPM1(+) or CEBPA(+) and FLT3-ITD(-) had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; P = .02), especially cytogenetically normal AML (5-year EFS: 48% vs 31%; P = .04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243.
[Show abstract][Hide abstract] ABSTRACT: Data from 42 adult patients with newly diagnosed minimally differentiated (M0) acute myeloid leukemia (AML) were reported. Clinical and biological characteristics at diagnosis were heterogenous. All patients received induction chemotherapy combining an anthracycline with cytarabine. Complete remission (CR) was achieved in 22 cases (52%). Most patients received continuation chemotherapy. Median disease-free survival (DFS) was 13.6 months with a 2-year survival rate of 28%. As post-remission therapy, 7 patients could be allografted and showed an encouraging outcome. Overall, 14 patients have relapsed (63%) after a median time of 10.2 months. Median overall survival (OS) was 20.5 months with a 5-year survival rate of 18%. This retrospective analysis points to a somewhat heterogenous group of AML in terms of biological features and outcome, and warrants a larger multicenter study with study in molecular biology to clarify treatment effects further.
Leukemia research 03/2011; 35(8):1027-31. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dose intensity has been demonstrated to be one determinant for treatment efficacy in younger adults with high-risk (relapsed and refractory) acute myelogenous leukemia. Between 2000 and 2006, 56 patients entered the EMA 2000 study and received timed sequential reinduction chemotherapy. From 2004, chemotherapy was also followed by one subcutaneous dose of pegfilgrastim. Thirty-six patients reached a complete remission, while nine obtained a partial remission. Median time to granulocyte and platelet recovery was 34 and 38 days respectively. The major non-hematologic toxicities were severe infections but despite this 23 remitters could proceed to their post-remission treatment, although 13 did not because of severe toxicity or early relapse. The median overall survival was 9.3 months. The EMA 2000 regimen is a highly effective treatment with a response rate of 64% and a low early death rate. The period of critical neutropenia was relatively short in both phases and the supportive use of pegfilgrastim, although showing a trend toward reduced neutropenic period, did not appear to reduce the risk of infection in this group and may not be a critical requirement for reducing the risk of treatment-related toxicity.
[Show abstract][Hide abstract] ABSTRACT: Clofarabine, a next-generation deoxyadenosine analog, has demonstrated significant activity in patients with acute myeloid leukemia (AML). The single-agent activity compares favorably with that demonstrated by the current standard antileukemia agents. Clofarabine has been safely and effectively combined with other agents and will probably become an integral part of induction and/or consolidation regimens in AML. Current studies are underway to better define the role of clofarabine in younger and elderly patients with AML, and also explore development strategies for an oral formulation.
[Show abstract][Hide abstract] ABSTRACT: The poor prognosis for elderly patients with acute myeloid leukemia (AML) raises questions regarding the benefit of treating them with intensive chemotherapy. The impact of initial characteristics on prognosis has been addressed previously in elderly patients; however, very few data are available regarding the prognostic value of immunophenotypic characteristics in this setting.
The authors investigated expression of the membrane antigens CD13, CD15, CD33, and CD34 by flow cytometry in elderly patients with newly diagnosed AML and analyzed whether these parameters had clinical or prognostic relevance to help physicians in their choice of therapy.
Immunophenotyping was performed in 273 patients aged > or =60 years (median age, 69 years). CD13 was expressed in 73% of patients, CD15 was expressed in 43% of patients, CD33 was expressed in 64% of patients, and CD34 was expressed in 66% of patients. Complete remission was obtained in 157 patients (58%). The median overall survival was 8.1 months, and the 3-year survival rate was 14%. Three risk groups were defined based on CD34 and CD33 antigen expression: The poor-risk group included patients with CD34-positive/CD33-positive or CD34-negative/CD33-negative disease, the intermediate-risk group included patients with CD34-positive/CD33-negative disease, and the favorable-risk group included patients with CD34-negative/CD33-positive disease. After cytogenetic analyses, immunophenotype was the most significant prognostic factor in terms of survival in a multivariate analysis (P = .03 and P < .0001, respectively). When immunophenotypic and cytogenetic parameters were combined, patients were classified into 4 prognostic groups: Group A (3-year survival rate, 33%) included patients with favorable and normal karyotypes who had a favorable immunophenotype, Group B (3-year survival rte, 28%) included patients with normal karyotypes who had an intermediate immunophenotype, Group C (3-year survival rate, 8%) included patients with intermediate or normal karyotypes who had an unfavorable immunophenotype, and Group D (3-year survival rate, 2%) included all patients who had unfavorable cytogenetics.
Immunophenotypic characteristics appeared to be a major prognostic factor in this population of elderly patients with AML. By using 2 simple parameters assessed at the time of diagnosis, the authors devised a prognostic system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.
Cancer 02/2008; 112(3):572-80. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Farnesyltransferase inhibitors (FTIs) are a new class of biologically active anticancer drugs. The exact anti-tumorigenic mechanism is currently unknown. FTIs inhibit farnesylation of a wide range of target proteins. In preclinical models, tipifarnib (R115777, Zarnestra(R)), a non-peptidomimetic competitive FTI, showed great potency against leukemic cells. Although it has recently demonstrated clinical responses in adults with refractory and relapsed acute myeloid leukemia (AML), and in older adults with newly diagnosed poor-risk AML, its activity was far less than anticipated. However, it appears that tipifarnib as a single agent may be important in selected groups of patients. Much remains to be learned to optimize such therapy in patients with AML. To this end, trials that combine tipifarnib with cytotoxics are ongoing.
[Show abstract][Hide abstract] ABSTRACT: Background
The treatment of elderly adults with acute myeloid leukemia (AML) is associated with unsatisfactory rates of complete responses and long-term overall survival (OS). Therefore, a clinically useful prognostic index would facilitate therapeutic decision-making and evaluation of investigational treatment strategies in this patient population.Patients and MethodsA prognostic score is presented based on the multivariate analysis of 432 patients with non-M3 AML aged > 60 years, selected on the basis of their initial performance status and the absence of severe comorbid factors for entering into 5 successive clinical trials combining an anthracycline and cytarabine. Four clinically relevant parameters are included in this index: cytogenetics at diagnosis, history of previous hematologic disorder, hematologic features at diagnosis, and lactate dehydrogenase level at diagnosis.ResultsUsing this stratification system, 3 risk groups were defined: a favorable-risk group A (OS of 39% at 2 years and 21% at 5 years), an intermediate-risk group B (OS of 19% at 2 years and 8% at 5 years), and a poor-risk group C (OS of 5% at 2 years and 0 at 5 years).Conclusion
The prognostic index estimates the outcome of elderly patients with AML usually selected for intensive chemotherapy trials using 4 easily determined parameters and might identify patients who are really candidates for this treatment strategy from those for whom investigational therapy or palliation might be most appropriate.
[Show abstract][Hide abstract] ABSTRACT: In a multicenter trial, 259 young adults (15-49 years) with newly diagnosed acute myeloid leukemia (AML) were first randomized to receive a timed-sequential induction regimen given either alone (135 patients) or concomitantly with granulocyte-macrophage colony-stimulating factor (GM-CSF) (124 patients). Patients reaching complete remission (CR) were then randomized to compare a timed-sequential consolidation to a postremission chemotherapy including four cycles of high-dose cytarabine followed by maintenance courses. In the appropriate arm, GM-CSF was given concurrently with chemotherapy during all cycles of consolidation. CR rates were significantly better in the GM-CSF arm (88 vs 78%, P<0.04), but did not differ after salvage. Patients receiving GM-CSF had a higher 3-year event-free survival (EFS) estimate (42 vs 34%), but GM-CSF did not impact on overall survival. Patients with intermediate-risk cytogenetics benefited more from GM-CSF therapy (P=0.05) in terms of EFS than patients with other cytogenetics. This was also confirmed when considering only patients following the second randomization, or subgroups defined by a prognostic index based on cytogenetics and the number of courses required for achieving CR. Priming of leukemic cells with hematopoietic growth factors is a means of enhancing the efficacy of chemotherapy in younger adults with AML.
[Show abstract][Hide abstract] ABSTRACT: One hundred and fifty-four acute myeloid leukemia patients with trisomy 8 were studied for their clinical and biological characteristics, and treatment outcome. Forty-seven patients presented with trisomy 8 as the sole aberration, 107 with trisomy 8 associated with other cytogenetic abnormalities (13 with favorable, 54 with intermediate, and 40 with unfavorable risk cytogenetics). Overall complete remission (CR) proportion was 48%. Median disease-free survival (DFS) and overall survival (OS) were 7.8 and 8.3 months, respectively. In multivariate analysis, age >or=60 years (P<0.0001) and association with unfavorable karyotype (P=0.03) were of poor prognostic value for CR achievement. Age >or=60 years (P<0.0001) and antecedents of dysmyelopoiesis (P=0.02) were of poor prognostic value for OS. Patients with trisomy 8 alone did not show any difference in terms of outcome as compared with those in whom trisomy 8 was associated to intermediate risk cytogenetics (P=0.0002). Trisomy 8 in addition to favorable karyotype maintained a good clinical outcome, while trisomy 8 in addition to unfavorable cytogenetics showed the worst prognosis.
Leukemia Research 02/2007; 31(1):67-73. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We retrospectively assess the long-term outcome and determined prognostic factors correlated with outcomes in adults with acute myeloid leukemia (AML) undergoing autologous hematopoietic stem cell transplantation (HSCT) in our institution over a 19-year period. A total of 78 adults who received autologous HSCT for AML in first complete remission (CR) and of 21 adults in further CR were included in the study. Bone marrow (n = 14) or peripheral blood stem cells (PBSC) (n = 85) transplantation was performed at a median of 2.9 months from CR. Hematologic recovery was significantly reduced in the PBSC group. Five-year cumulative incidences of relapse were 56 and 49%, respectively. Corresponding 5-year probabilities of event-free survival (EFS) were 33 and 35%, while those of overall survival (OS) were 38 and 49%, respectively. In multivariate analyses, cytogenetics was the main prognostic factor for outcome. Treatment-related mortality (TRM) was of 15% at 5 years, but higher in females as compared to males (p = 0.04). We confirmed that long-term EFS can be achieved after autologous HSCT in adult patients with AML. Results in adults who experience a relapse after conventional chemotherapy support the use of autologous HSCT as salvage therapy if such patients achieve a subsequent CR.
[Show abstract][Hide abstract] ABSTRACT: Post-remission options were compared in a population of 262 relapsing and refractory acute myeloid leukemia patients achieving complete remission (CR) after the same re-induction according to etoposide - mitoxantrone - cytarabine (EMA) trials. The selection of post-remission therapy depended on trial recommendations, age, performance status, and availability of an HLA-identical sibling. One hundred and thirty patients received chemotherapy consolidation courses, 50 received autologous stem cell transplantation (SCT), and 43 underwent allogeneic bone marrow transplantation (BMT), while 39 did not receive any additional therapy. The preliminary analysis identified 3 favorable prognostic factors correlated with event-free survival (EFS): M3 subtype, previous CR duration > 1 year, and transplantation. Three year EFS was 68 vs. 23% with autologous SCT and allogeneic BMT in M3 patients and, respectively, 41 vs. 20% in non-M3 patients. Three year probabilities of treatment-related mortality were 11 and 47%, respectively. A statistical model was conceived with adjustment on prognostic factors and post-remission option. In the multivariate analysis, autologous SCT appeared significantly better than allogeneic BMT (P < 0.01) or chemotherapy (P = 0.001), while allogeneic BMT was not statistically different than chemotherapy. This indicates a high treatment-related toxicity with allogeneic BMT in patients re-induced by highly intensive chemotherapy, and therefore a tendency for a better outcome with autologous SCT as post-remission treatment in those patients.
Leukemia and Lymphoma 07/2005; 46(7):1007-16. · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Following a dose-escalation study performed to assess the maximally tolerated dose of high-dose mitoxantrone in a single injection combined with chemotherapy, a phase II trial (EMA 2000 regimen) was performed in patients with refractory or relapsed acute myelogenous leukemia (AML) between October 2000 and December 2003. Sixty-two patients entered the study and received mitoxantrone 45 mg/m(2) on day 1 in combination with cytarabine and etoposide. Overall, 39 patients (63%) achieved complete remission (CR). Four patients died during remission induction, and 19 patients had resistant disease. Median time to granulocyte and platelet recovery was 34 and 39 days, respectively. The predominant non-hematologic toxicity was infection, with 53% severe infections. Thirty-three of the 39 remitters received subsequent treatment consisting of maintenance chemotherapy courses in 17 patients, allogeneic stem cell transplantation (SCT) in 7 patients, and autologous SCT in 9 patients. The median overall survival of the entire cohort was 8.1 months, with 18% at 2.5 years. EMA chemotherapy using a single injection of mitoxantrone is effective in the treatment of high-risk AML. CR proportion was significantly higher in patients with a first CR duration > or =6 months when compared with those from a control trial using standard-dose mitoxantrone (90 vs 70%, p=0.03).
Annals of Hematology 06/2005; 84(6):376-82. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Farnesyltransferase inhibitors (FTIs) are small-molecule inhibitors that selectivly inhibit farnesylation of a number of intracellular substrate proteins such as Ras. Preclinical work has revealed their ability to effectively inhibit tumor growth in vitro and in vivo in animal models across a wide range of malignant phenotypes. Acute myeloid leukemias (AMLs) are appropriate disease targets in that they express relevant biologic targets such as Ras, MEK, AKT, and others that may depend upon farnesyl protein transferase activity to promote cell proliferation and survival. Indeed, different intracellular proteins are substrates for prenylation. Interruption of prenylation may prevent substrates from undergoing maturation which may result in the inhibition of cellular events that depend on the function of those substrates. Phase I trials in AML and myelodysplasia have demonstrated biologic and clinical activities as determined by target enzyme inhibition, low toxicity, and both complete and partial responses. As a result, phase II trials have been initiated in order to further validate clinical activity and to identify downstream signal transduction targets that may be modified by these agents. It is anticipated that these studies will serve to define the optimal roles of FTIs in patients with these hematologic malignancies and provide insight into effective methods by which to combine FTIs with other agents.
Bulletin du cancer 04/2005; 92(3):227-38. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary resistant acute myeloid leukemia (AML) has a very poor prognosis. Etoposide-mitoxantrone-cytarabine (EMA) timed sequential chemotherapy including a first sequence combining mitoxantrone (12 mg/m(2) per day over 3 days) with cytarabine (500 mg/m(2) per day over the same period), and a second sequence consisting in etoposide (200 mg/m(2) per day for 3 days) and cytarabine as in the first sequence, has been proposed as a salvage regimen. Over a 10-year period, 66 primary resistant AML patients have been treated by EMA salvage chemotherapy. All patients displayed intermediate- or high-risk karyotypic abnormalities. Of the 66 patients, 24 [36%, 95% confidence interval (CI): 25-49%] achieved complete remission (CR). Thirty-eight patients were resistant to EMA chemotherapy and four patients died from toxicity during aplasia. After CR achievement, 18 patients received consolidation therapy. Five patients with an HLA-identical sibling donor underwent allogeneic stem cell transplantation (SCT), one patient received autologous SCT, two patients received a second course of EMA chemotherapy, and ten were scheduled for 6-monthly maintenance courses (mini-EMA). Median follow-up was 7.3 years. At the time of analysis, 21 of the 24 patients (87%) who achieved CR have relapsed. Median disease-free survival (DFS) was 5 months (95% CI: 4.3-7.7 months). Median overall survival (OS) was 5 months (95% CI: 3.8-6.7 months). There were only two long-term remitters (3%). In the univariate analysis, CR achievement was mainly related to white blood cell (WBC) count at the time of starting salvage therapy with poorer outcome for patients with more aggressive leukemia (WBC count > or =10 x 10(9)/l) (CR rates: 50% vs 10%, p<0.001). Overall survival was also influence by WBC count (median OS: 7.2 months vs 2.8 months, respectively, for WBC or =10 x 10(9)/l, p<0.0001). Initial karyotype was not a significant prognostic factor either for CR achievement or for DFS or OS when comparing patients with normal karyotype and those with chromosomal abnormality. In multivariate analysis, WBC count less than 10 x 10(9)/l with the absence of circulating blasts at the time of starting salvage therapy appeared to be of favorable prognostic value for CR achievement ( p=0.002), while WBC count less than 10 x 10(9)/l appeared to be of favorable prognostic value for survival ( p<0.0001). Using these two objective parameters of proven significance, we devised a prognostic system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices. Patients with both factors (WBC count <10 x 10(9)/l and no circulating blasts) or with at least one at the time of starting salvage therapy had a CR rate of 50% and were therefore candidates for intensified post-remission therapy. All other patients displayed a very poor outcome and must be oriented after failure of first-line therapy to alternate therapeutic programs based on investigational drugs.
Annals of Hematology 11/2003; 82(11):684-90. · 2.87 Impact Factor