Prior High Dose Chemotherapy and a Higher “Intensity” of the Preparative Regimen Can Influence Outcome after Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Acute Myeloid Leukemia (AML) in First Complete Remission (CR1).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2001-2001
Author(s):  
Mohamad Mohty ◽  
Xavier Cahu ◽  
Catherine Faucher ◽  
Patrice Chevallier ◽  
Norbert Vey ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Comprehensive Treatment ◽  
High Dose ◽  
Actual Performance ◽  
Gvhd Prophylaxis ◽  
Significant Difference ◽  
Preparative Regimen ◽  
Acute Myeloid

Abstract In the setting of AML, RIC regimens have emerged as an attractive modality to decrease toxicity. However, toxicity might represent only one aspect of the problem, since AML encompasses a group of chemosensitive diseases, raising concerns that significant reduction of the intensity of the preparative regimen, while increasing immunosuppression, may have a negative impact on long-term outcome. This report describes the comparative results of 31 AML patients in CR1 receiving RIC allo-SCT from an HLA-identical sibling in 2 institutions (Nantes, n=13; and Marseille, n=18) using 2 different “global” treatment approaches (Table below). After achievement of CR1, the “Nantes” approach included administration of one or two courses of consolidation with high-dose cytarabine (HDC), followed immediately by allo-SCT conditioned with a genuine nonmyeloablative, but highly immunosuppressive RIC regimen including fludarabine, low dose busulfan (4 mg/Kg), ATG (5 mg/Kg) and both CsA and corticosteroids for GVHD prophylaxis (“FB1A2” group). The “Marseille” program aimed to deliver after CR1, in addition to HDC, an autologous SCT followed by allo-SCT conditioned with fludarabine, an intermediate dose of busulfan (8 mg/Kg), low dose ATG (2.5 mg/Kg) and CsA alone for GVHD prophylaxis (“FB2A1” group). In the “FB2A1” group, 12 patients (67%) could actually receive the planned auto-SCT. With a median follow-up of 47 months, leukemia-free survival (LFS) in the whole study population was 56% at 5 years. However, the KM estimate of LFS was significantly higher in the “FB2A1” group as compared to the “FB1A2” group (P=0.01; 72% vs. 31% at 5 years). Overall, 8 patients (26%; 95%CI, 11–41%) had relapsed at a median of 320 (range, 241–707) days after diagnosis, and the significant difference between the 2 groups in terms of LFS was likely due to a higher risk of leukemia relapse in the “FB1A2” group (6/13, vs. 2/18; P=0.07). Five patients died from toxicity, for an overall incidence of TRM of 16% (95%CI, 6–34%), with this being comparable between the 2 groups (2/13 vs. 3/18; P=NS). Such comparable TRM despite a more “intensive” approach, translated towards a higher overall survival in the “FB2A1” group as compared to the “FB1A2” group (72% vs. 42% at 5 years; P=0.07). After controlling for relevant factors, in the multivariate analysis, actual performance of auto-SCT prior to RIC allo-SCT (P=0.04; RR=4.9; 95%CI, 1.1–22.4), was significantly predictive of an improved LFS. We conclude that RIC allo-SCT from an HLA-matched related donor represents a valid option for AML patients not eligible for standard allo-SCT. However, in order to achieve optimal results, a comprehensive treatment “package” including some form of high dose therapy prior to RIC allo-SCT and/or semi-intensive cytoreduction/myeloablation incorporated within the RIC regimen is likely necessary to allow sufficient time for the GVL effect. Table. Patients’ characteristics and acute myeloid leukemia features

scholarly journals The Efficacy and Safety of Decitabine in Combination with ATRA, G-CSF and Low Dose Cytarabine(Dlaag Regimen)in Relapsed/Refractory Acute Myeloid Leukemia Not Suitable for Strong Chemotherapy : A Phase 2, Prospective, Single-Arm, Multicenter Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5108-5108
Author(s):  
Li Yang ◽  
Ligen Liu ◽  
Limin Zhao ◽  
Yingting Lu ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multicenter Study ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Response Rate ◽  
Intensive Therapy ◽  
Significant Difference ◽  
Refractory Acute Myeloid Leukemia ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Background. Patients with relapsed or refractory acute myeloid leukemia (R/R AML)who are intolerant of strong regimen chemotherapy have poor responsibility to chemotherapy and clinic remission is lower. The DNMT is depleted to reactivate the silencing tumor suppressor gene to exert anti-tumor effects. Vitro experiments confirmed that ATRA has an anti-leukemia effect on non-M3-AML cell lines. We perform the 2 phase, single-arm, multicenter study of Decitabine in Combination with ATRA, G-CSF and low dose cytarabine(DLAAG Regimen)in R/R AML not suitable for strong chemotherapy (NCT03356080). Methods. R/R AML patients aged more than 18 years not suitable for strong chemotherapy were eligible to enroll on this study. The objective was to assess the responses and safety of this therapy. All patients received subcutaneous decitabine injection 0.1-0.2mg/kg on days 1-3 ,8-10,15-17 .ATRA was taken orally at 45mg/m2 on day 4-6 and 15mg/m2on days 7-20. Subcutaneous injection cytarabine 15mg/m2 every 12 hours on days 1-10 and G-CSF 300ug/d on day 0 until disease remission or absolute neutrophils count ≥ 0.5×109/L were administered. The FLT3 inhibitor, arsenious acid, and the JAK-2 inhibitor, rotectinib, were allowed to be combined.All patients received one or two courses of induction treatments. Results. During the period from December 1, 2017 to July 2019, a total of 33 patients were recruited, including 17 women and 16 men. The median age is 64 years (range 46-82). In 33 patients, the overall response rate (ORR = CR + PR) was 36.3%, and the complete response rate (CRR = CR + CRi) was 33.3%. The early treatment-related mortality rate was 6.0%. One died of infection and one died of organ bleeding. Of the 26 patients with karyotype data, 11 received CR. Seven patients (63.6%) in CR showed normal karyotype, 2 patients (18.1%) in CR, and 1 patient (9.0%) in PR showed other moderate karyotypes. One case (9.0%) of the CR group had a poor karyotype. Statistical analysis showed that there was a statistically significant difference between the different karyotype groups (P < 0.05). Only 2 of the 10 FLT3 mutant patients achieved CR (20%). Two patients with abnormal MLL gene did not receive CR. Conclusions DLAAG regimen is effective and tolerated in patients with R/R AML who are not suitable for intensive therapy and could be as a bridging therapy regimen followed by HSCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Retrospective Observation of Treatment Outcomes Using Decitabine-Combined Standard Conditioning Regimens Before Transplantation in Patients With Relapsed or Refractory Acute Myeloid Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuhang Li ◽  
Longcan Cheng ◽  
Chen Xu ◽  
Jianlin Chen ◽  
Jiangwei Hu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Hematopoietic Reconstitution ◽  
Conditioning Regimens ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid ◽  
Refractory Aml

Hypomethylating agents, decitabine (DAC) and azacitidine, can act as prophylactic and pre-emptive approaches after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a non-intensive bridging approach before allo-HSCT. However, they are rarely used as a part of conditioning regimens in patients with relapsed or refractory acute myeloid leukemia (AML). This retrospectively study included a total of 65 patients (median, 37; range, 13–63) with relapsed or refractory AML who were treated by allo-HSCT after myeloablative conditioning regimens without or with DAC (high-dose DAC schedule, 75 mg/m2 on day −9 and 50 mg/m2 on day −8; low-dose DAC schedule, 25 mg/m2/day on day −10 to −8). DAC exerted no impact on hematopoietic reconstitution. However, patients who were treated with the high-dose DAC schedule had significantly higher incidence of overall survival (OS, 50.0%) and leukemia-free survival (LFS, 35.0%), and lower incidence of relapse (41.1%) and grade II–IV acute graft versus host disease (aGVHD, 10.0%) at 3 years, when compared with those treated with standard conditioning regimens or with the low-dose DAC schedule. In conclusion, high-dose DAC combined with standard conditioning regimens before allo-HSCT is feasible and efficient and might improve outcomes of patients with relapsed or refractory AML, which provides a potential approach to treat these patients.

Treatment with JNJ-26483327 (Pan Her/Src/VEGFR-3 kinase inhibitor) Prolongs Survival of Mice Engrafted with Systemic Human Acute Myeloid Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4026-4026
Author(s):  
Nathaniel C. Doro ◽  
Deepika Lal ◽  
Peter King ◽  
Eddy Freyne ◽  
Tim Perera ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Single Agent ◽  
Antibody Therapy ◽  
Tumor Burden ◽  
High Dose ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid ◽  
Daily Total

Abstract JNJ-26483327 is a novel oral Pan Her/Src/VEGFR-3 inhibitor which has previously been shown in preclinical models to cross the blood-brain barrier and to reach high levels in brain, solid tumor, and bone marrow sites. JNJ-26483327 is not an active substrate for P-glycoprotein pumps and has been well tolerated to date in an ongoing phase I trial. VEGF-C signaling through the VEGFR-3 (FLT-4) receptor has been shown to promote growth of acute myeloid leukemia (AML) cells and to mediate resistance to multiple chemotherapy drugs in vitro. Anti-VEGFR-3 antibody therapy decreased angiogenesis, increased hypoxia and necrosis, and reduced lymph node metastases in solid tumor xenografts. To date, however, VEGF-C/VEGFR-3 inhibition has not been actively been investigated for treatment of hematological malignancies. We hypothesized that JNJ- 26483327 treatment of VEGFR-3 expressing systemic AML would limit tumor growth and lymphatic spread via VEGF-C/VEGFR-3 mechanisms. An initial dose-finding pilot experiment was performed using SCID mice engrafted via tail vein with ten million HELluc cells, human acute myeloid leukemia cells with known expression of VEGF-A/C and VEGFR-2/3 and stably transfected with luciferase constructs to facilitate small animal imaging. Mice were treated with PBS, vehicle (200 mL by mouth twice daily), low dose JNJ-26483327 (75 mg/kg by mouth twice daily, total 150 mg/kg/day) and high dose JNJ- 26483327 (125 mg/kg by mouth daily, total 250 mg/kg/day) for 10 consecutive days. We found that low dose JNJ-26483327 therapy significantly improved the median survival of HELluc systemic xenografts by 46% (26 days longer than vehicle-treated controls) (p&lt;0.05). Although high dose JNJ-26483327 prolonged median survival over vehicletreated controls, the difference was not statistically significant. Moreover, although JNJ- 26483327 improved survival, HELluc leukemia burden (as measured by bioluminescent imaging) was not significantly reduced or eradicated as compared to control, consistent with cytostatic but not cytotoxic anti-tumor effects. VEGFR-3 signaling has also been shown to mediate leukemia cell proliferation, survival, and resistance to chemotherapy. Based on preclinical and clinical data demonstrating improved anti-tumor activity of VEGF inhibitors when combined with chemotherapy, we hypothesized that combining JNJ-26483327 with chemotherapy used in conventional AML therapy may result in additive synergistic anti-tumor effects. To determine if JNJ-26483327 inhibition enhanced the effects of cytotoxic chemotherapy, systemic HELluc tumor bearing mice were treated with low dose JNJ-26483327 (150 mg/kg/day for 10 days) and a single maximally tolerated dose of doxorubicin (1.5mg/kg). Both single agent doxorubicin and single agent JNJ-26483327 treatment resulted in significant reduction of HELluc tumor burden. However, no significant decrease in leukemia burden was observed after combination JNJ-26483327+doxorubicin treatment when compared to single agent groups. Lastly we postulated that combination therapies of JNJ-26483327 with other anti-VEGF therapies directed at inhibition of VEGF-A, VEGFR-1, or VEGFR-2 would result in inhibition of all known VEGFR signaling pathways and result in improved anti-leukemic effects of JNJ-26483327 therapy. Systemic HELluc bearing mice were treated with PBS, vehicle, low dose JNJ-26483327, an anti-hVEGF-A antibody BV (bevacizumab, Genentech) or combination JNJ-26483327+ BV. Results showed that single agent low dose JNJ- 26483327 or single agent BV significantly reduced HELluc tumor burden up until day 20. Combination JNJ-26483327+BV treatment, however, did not result in additive/synergistic anti-leukemic effects as compared to single agent therapy and may in fact have resulted in possible antagonistic effects. Conclusions: Single agent JNJ-26483327 therapy prolongs survival of mice engrafted with VEGFR-3+ HEL AML cells. Limitations of the above studies include the short duration of JNJ-26483327 administration (10 days only) and lack of synergistic effects of JNJ-26483327 when combined with doxorubicin and anti-hVEGF-A antibody therapy. Future studies will address the effects of long-term JNJ-26483327 administration on AML stem cell growth using NOD/SCID mouse models engrafted with patient samples and combination JNJ-26483327+ cytarabine/anthracycline chemotherapy.

Efficacy Of Azacitidine Versus Low-Dose Cytarabine In Patients With Acute Myeloid Leukemia - A Retrospective Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3974-3974
Author(s):  
Aleksandar Radujkovic ◽  
Sascha Dietrich ◽  
Alwin Krämer ◽  
Tilmann Bochtler ◽  
Anthony D. Ho ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Cox Regression ◽  
Single Center ◽  
Treatment Groups ◽  
Significant Difference ◽  
Blast Count ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Abstract Introduction Azacitidine (AZA) treatment has been shown to be superior to conventional care regimens including low dose cytarabine (LD-Ara-C) in acute myeloid leukemia (AML) patients with low bone marrow (BM) blast counts (20-30%). In contrast, data on efficacy of AZA in patients with blast counts exceeding 30% are scarce. Here we present a retrospective, single center analysis, comparing the efficacy and toxicity of AZA versus LD-Ara-C in AML patients with high BM blast counts (≥30%) prior to treatment. Patients and Methods Twenty-seven patients receiving AZA and 38 patients receiving LD-Ara-C met the eligibility criteria for the analysis (age ≥18 years, documented BM blast count ≥30% prior to start of treatment and administration of at least one complete therapy cycle). Patients who underwent allogeneic transplantation following AZA treatment or received stem cell support following LD-Ara-C therapy were excluded from this analysis. Overall survival (OS) was estimated using the method of Kaplan and Meier. Comparison of OS between the AZA and LD-Ara-C group was done using the logrank test and by Cox regression adjusting for known confounders. Results Patient (age, ECOG status) and diseases characteristics (type of AML, cytogenetics, pretreatment, number of treatment cycles) did not differ significantly between the treatment groups, except for BM blast count (median 44% vs. 60% in the AZA and LD-Ara-C group, respectively; p=0.03) and peripheral blood blast count (median 6% vs. 56% in the AZA and LD-Ara-C group, respectively; p<0.01). Response rates to AZA treatment according to international working group (IWG) criteria were low with two patients achieving a complete remission (CR) and one patient showing partial remission (PR) after AZA treatment. In the LD-Ara-C cohort no CR was observed and two patients experienced a PR. Hematologic improvement (HI) rates according to IWG criteria did not differ between both treatment groups (any type of HI 33% vs. 24% in the AZA and LD-Ara-C group, respectively; p=0.41). In both cohorts, most common non-hematologic toxicities (CTCAE grade≥3) included febrile neutropenia, pneumonia and bleedings without significant differences regarding frequencies. As expected, skin involvement was more commonly observed in the AZA group (19% vs. 3%, p=0.04). One year survival rates were only 15% (95% CI 8-22%) and 13% (95% CI 7-19%) in the AZA and LD-Ara-C group, respectively. There was no statistically significant difference between the treatment groups (HR 1.2, p=0.41). Furthermore, there was no difference in hospitalization time (total days spent in hospital during treatment per patient-year of follow-up 29.4 vs. 27.2 in the AZA and LD-Ara-C group, respectively; RR 1.07 95% CI 0.95-1.21, p=0.23). In a multivariate analysis with OS as endpoint adverse cytogenetics (HR 2.24 95% CI 1.17-4.70, p<0.02) were significantly associated with inferior survival, whereas the treatment had no impact (AZA vs. LD-Ara-C HR 1.27 95% CI 0.67-2.40, p=0.46). Conclusion In our center, treatment with AZA showed limited efficacy and no superiority to LD-Ara-C treatment in AML patients with BM blasts ≥30%. Disclosures: Dreger: Riemser Pharma : Consultancy, Honoraria, Research Funding.

scholarly journals Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study

2015 ◽  
Vol 59 (4) ◽  
pp. 2078-2085 ◽  
Author(s):  
Oliver A. Cornely ◽  
Angelika Böhme ◽  
Anne Schmitt-Hoffmann ◽  
Andrew J. Ullmann
Keyword(s):  
Acute Myeloid Leukemia ◽  
Adverse Events ◽  
Dose Escalation ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
High Dose ◽  
Dose Escalation Study ◽  
Once Daily ◽  
Dose Cohort ◽  
Acute Myeloid

ABSTRACTIsavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort (n= 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort (n= 12). The mean ± standard deviation plasma isavuconazole areas under the concentration-time curves for the dosing period on day 7 were 60.1 ± 22.3 μg · h/ml and 113.1 ± 19.6 μg · h/ml for the patients in the low-dose and high-dose cohorts, respectively. The adverse events in five patients in the low-dose cohort and in eight patients in the high-dose cohort were considered to be drug related. Most were mild to moderate in severity, and the most common adverse events were headache and rash (n= 3 each). One patient in the high-dose cohort experienced a serious adverse event (unrelated to isavuconazole treatment), and two patients each in the low-dose and high-dose cohorts discontinued the study due to adverse events. Of the 20 patients who completed the study, 18 were classified as a treatment success. In summary, the results of this analysis support the safety and tolerability of isavuconazole administered at 200 mg and 400 mg once-daily as prophylaxis in immunosuppressed patients at high risk of fungal infections. (This study is registered at ClinicalTrials.gov under registration number NCT00413439.)

High-Dose Cytarabine Consolidation With or Without Additional Amsacrine and Mitoxantrone in Acute Myeloid Leukemia: Results of the Prospective Randomized AML2003 Trial

2013 ◽  
Vol 31 (17) ◽  
pp. 2094-2102 ◽  
Author(s):  
Markus Schaich ◽  
Stefani Parmentier ◽  
Michael Kramer ◽  
Thomas Illmer ◽  
Friedrich Stölzel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Purpose To assess the treatment outcome benefit of multiagent consolidation in young adults with acute myeloid leukemia (AML) in a prospective, randomized, multicenter trial. Patients and Methods Between December 2003 and November 2009, 1,179 patients (median age, 48 years; range, 16 to 60 years) with untreated AML were randomly assigned at diagnosis to receive either standard high-dose cytarabine consolidation with three cycles of 18 g/m2 (3× HD-AraC) or multiagent consolidation with two cycles of mitoxantrone (30 mg/m2) plus cytarabine (12 g/m2) and one cycle of amsacrine (500 mg/m2) plus cytarabine (10 g/m2; MAC/MAMAC/MAC). Allogeneic and autologous hematopoietic stem-cell transplantations were performed in a risk-adapted and priority-based manner. Results After double induction therapy using a 3 + 7 regimen including standard-dose cytarabine and daunorubicin, complete remission was achieved in 65% of patients. In the primary efficacy population of patients evaluable for consolidation outcomes, consolidation with either 3× HD-AraC or MAC/MAMC/MAC did not result in any significant difference in 3-year overall (69% v 64%; P = .18) or disease-free survival (46% v 48%; P = .99) according to the intention-to-treat analysis. Furthermore, MAC/MAMAC/MAC led to additional GI and hepatic toxicity and a higher rate of infection and bleeding, resulting in significantly shorter 3-year overall survival in the per-protocol analysis compared with 3× HD-AraC (63% v 72%; P = .04). Conclusion In younger adults with AML, multiagent consolidation using mitoxantrone and amsacrine in combination with high-dose cytarabine does not improve treatment outcome and confers additional toxicity.

International Randomized Phase III Study of Elacytarabine Versus Investigator Choice in Patients With Relapsed/Refractory Acute Myeloid Leukemia

2014 ◽  
Vol 32 (18) ◽  
pp. 1919-1926 ◽  
Author(s):  
Gail J. Roboz ◽  
Todd Rosenblat ◽  
Martha Arellano ◽  
Marco Gobbi ◽  
Jessica K. Altman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
Control Treatment ◽  
High Dose ◽  
Dismal Prognosis ◽  
Significant Difference ◽  
Acute Myeloid ◽  
Refractory Aml

Purpose Most patients with acute myeloid leukemia (AML) eventually experience relapse. Relapsed/refractory AML has a dismal prognosis and currently available treatment options are generally ineffective. The objective of this large, international, randomized clinical trial was to investigate the efficacy of elacytarabine, a novel elaidic acid ester of cytarabine, versus the investigator's choice of one of seven commonly used AML salvage regimens, including high-dose cytarabine, multiagent chemotherapy, hypomethylating agents, hydroxyurea, and supportive care. Patients and Methods A total of 381 patients with relapsed/refractory AML were treated in North America, Europe, and Australia. Investigators selected a control treatment for individual patients before random assignment. The primary end point was overall survival (OS). Results There were no significant differences in OS (3.5 v 3.3 months), response rate (23% v 21%), or relapse-free survival (5.1 v 3.7 months) between the elacytarabine and control arms, respectively. There was no significant difference in OS among any of the investigator's choice regimens. Prolonged survival was only achieved in a few patients in both study arms whose disease responded and who underwent allogeneic stem-cell transplantation. Conclusion Neither elacytarabine nor any of the seven alternative treatment regimens provided clinically meaningful benefit to these patients. OS in both study arms and for all treatments was extremely poor. Novel agents, novel clinical trial designs, and novel strategies of drug development are all desperately needed for this patient population.

Continuous High-Dose Idarubicin and Busulfan As Conditioning Regimen for Chinese Patients with Acute Myeloid Leukemia Undergoing Autologous Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4539-4539
Author(s):  
Hong Ming ◽  
Sixuan Qian ◽  
Liu Peng ◽  
Wu Hanxin ◽  
Qiu Hongxia ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Chinese Patients ◽  
High Dose ◽  
Significant Difference ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 4539 Objective: To investigate the efficacy and toxicity of continuous high-dose idarubicin and busulfan as conditioning regimen for Chinese patients with acute myeloid leukemia (AML) undergoing autologous stem cell transplantation (ASCT). Methods: A total of 27 patients with AML were enrolled in our prospective study, including 25 of first complete remission and 2 of second complete remission. Twelve patients were male, and 15 were female, with ages ranging from 14 to 56 (median, 31) years. All the patients were given induction and consolidation treatments and underwent ASCT receiving a continuous infusion of high-dose idarubicin (20 mg/m2 qd, days -13 to -11) and busulfan (oral busulfan 1 mg/kg q6h or intravenous busulfan 0.8 mg/kg q6h, d-5∼-2) as conditioning regimen. Results: All the patients acquired hematopoietic reconstitution. The median number of days to neutrophil (©ƒ0.5×109/l) and platelet (©ƒ20×109/l) recovery was 10 and 12, respectively. After a median follow-up of 23 months from diagnosis, the median overall survival (OS) and the median disease-free survival (DFS) were 19(7∼87) and 15(6∼85) months, respectively. A total of 18 patients (73.4%) are alive (17 in continuous complete remission) and 10 (37.4%) relapsed after transplant. Those who underwent standard dose of idarubicin (12 mg/m2 qd, days1–3) and cytarabine (100∼200 mg/m2 qd, days1–7) as induction treatment showed lower relapse rate and better OS and DFS as compared to other induction regimens without significant difference. Patients with favorable karyotypes and molecular biological types acquired better OS and DFS as compared to those with intermediate karyotypes and molecular biological types, but there was no significant difference. Myelosuppression and infections due to neutropenia was the most frequent adverse effects, severe nonhematologic toxicity was not observed in all patients. The patients in our study acquired similar OS and DFS compared to those with intermediate karyotypes and molecular biological types who underwent allogeneic transplantation (HLA identical sibling donor) in first complete remission, and the side effects were minor. Conclusion: Continuous high-dose idarubicin and busulfan as conditioning regimen for Chinese patients with AML undergoing ASCT was effect and well tolerable. Disclosures: No relevant conflicts of interest to declare.

Double intensive consolidation chemotherapy in adult acute myeloid leukemia.

1991 ◽  
Vol 9 (8) ◽  
pp. 1432-1437 ◽  
Author(s):  
J L Harousseau ◽  
N Milpied ◽  
J Briere ◽  
B Desablens ◽  
P Y Leprise ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Model ◽  
Univariate Analysis ◽  
Induction Treatment ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
Significant Difference ◽  
Wbc Count ◽  
Acute Myeloid

Of 115 adult patients with de novo acute myeloid leukemia (AML), 87 (75.5%) achieved complete remission (CR) after induction treatment with zorubicin and conventional doses of cytarabine (Ara-C). Patients under age 45 years with histocompatibility locus antigen-identical sibling underwent bone marrow transplantation (BMT). The others were treated with two courses of intensive consolidation chemotherapy (ICC): course 1 with 4 days of high-dose Ara-C and 3 days of amsacrine (m-AMSA); course 2 with carmustine (BCNU), Ara-C, cyclophosphamide, and etoposide. Forty-two patients received both planned courses, 15 received only the first, and 13 patients could only support conventional maintenance therapy. Four patients died during consolidation. With a median follow-up of 60 months, the disease-free survival (DFS) after ICC at 5 years is 40.3% (+/- 6.5%), with no statistically significant difference between patients receiving one or two courses. The DFS for the 17 transplanted patients is comparable (P = .72) and is lower for the 13 excluded patients (23% +/- 11.5%, P = .046). Age did not influence the probability of remaining in CR. In univariate analysis, three parameters had a negative impact on the 5-year DFS: a high initial WBC count (52% for patients with less than 30 x 10(9) WBC/L v 12% for patients with greater than 30 x 10(9) WBC/L, P = .01), a long delay between induction treatment and course 1 (+/- 60 days; 63% v 29%, P = .01), and a long delay between course 1 and course 2 (+/- 60 days, 61.5% v 28.5%, P = .05). In multivariate analysis (Cox model), only the WBC count remained significant. This study confirms the value of intensive postremission chemotherapy, which can be compared in AML with allogeneic or autologous BMT. It also demonstrates the prognostic value of the initial WBC count. The optimal modalities of ICC remain to be defined by further studies.

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