Postremission therapy with two different dose regimens of cytarabine in adults with acute myelogenous leukemia

Sixty-seven out of 105 (64%) adults with de novo acute myelogenous leukemia (AML), achieving complete remission after induction chemotherapy, entered two successive postremission treatment protocols. Between 1987 and 1989, 35 patients received an intermediate dose of cytarabine (IDAC) along with other drugs. Between 1990 and 1993, 32 patients received high dose cytarabine (HIDAC) with similar other drugs. Patients treated with IDAC had a median survival of 13.8 months (95% Cl 11.2–23.1 months) and a 2 year survival of 34.3 ± 8.0%. Patients receiving HIDAC had a median survival of 35.5 months (95% Cl, lower limit 29.8 months) and a 2 year survival of 71.6 ± 9.4% (P < 0.002). The 2 year actuarial leukemia-free survival (LFS) was 17.8 ± 6.6% in the IDAC group and 67.3 ± 10.0% months in the HIDAC group (P = 0.004). The HIDAC group had a significant 2 year survival advantage over the IDAC group only in patients younger than 45 years. The 2 year survival in the first group was 83.3 ± 10.8% versus 23.5 ± 10.3% in the IDAC group (P = 0.0001). In patients older than 45 years, no significant differences in 2 year survival was noticed (52.9 ± 15.78 versus 44.4 ± 11.7, P = 0.8). Censoring the 21 patients who underwent bone marrow transplantation (BMT) at BMT did not change significantly the survival analysis of the patients in each group. This study is consistent with previous reports favoring HIDAC intensification in the postremission treatment of young patients with AML.     

High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia.

BACKGROUND: Liposomal encapsulation of daunorubicin (DaunoXome, DNX; Nexstar Pharmaceutical, Boulder, CO) changes the pharmacology profile to increase delivery to tumor sites and decrease toxicity. The authors investigated the effect of daunorubicin in combination with ara-C in patients with refractory or recurring acute myelogenous leukemia (AML). PATIENTS AND METHODS Sixty-two patients with refractory or recurring AML received escalating doses of daunorubicin of 75, 100, 125, or 135 mg/m(2) daily for 3 days together with ara-C 1 g/m(2) intravenous continuous infusion daily for 4 days. RESULTS: Eighteen patients (29%) achieved a complete remission (CR) and 7 (11%) a hematologic improvement (i.e., met all criteria for CR except for platelet count < 100 x 10(9)/L) for an overall response rate of 40%. The dose-limiting toxicity was mucositis in 4 in 9 (44%) patients treated at the 150 mg/m(2) dose level, but minimal at 125 mg/m(2) (2 of 32, 6%) or 135 mg/m(2) (1 of 13, 8%). Cardiotoxicity Grade 2 was observed in 4 patients (6%) and Grade 3 or higher in 4 patients (6%). The median CR duration was 63 weeks, and overall survival rate was 25 weeks, with 28% patients alive after 1 year. CONCLUSIONS: The combination of DNX (or liposomal daunorubicin) and ara-C has significant antileukemia activity with acceptable toxicity. Further studies are warranted to investigate the role of high-dose anthracyclines in frontline AML therapy.     

Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission.

PURPOSE: Despite substantial progress in the treatment of acute myeloid leukemia (AML), fewer than 25% of patients survive free of leukemia for more than 5 years without allogeneic bone marrow transplantation (BMT). In this study we analyzed the results of one or more cycles of high-dose cytarabine-based consolidation chemotherapy as compared with allogeneic BMT in first remission. PATIENTS AND METHODS: The results in 28 adult patients, aged 16 to 45 years, who underwent a closely HLA-matched BMT for AML in first remission were compared with those in 54 consecutive, age-matched, adult patients treated with one or more cycles of high-dose, cytarabine-based consolidation chemotherapy. RESULTS: After a median follow-up of 4 years, the actuarial risk of leukemic relapse was considerably lower in the transplant group than in the group treated with consolidation chemotherapy (32% +/- 26% v 60% +/- 14%; P = .05). Treatment-related mortality, however, was much higher in the group treated with BMT (32% v 6%, P = .002). The actuarial disease-free survival at 5 years was not significantly different for the two groups (45% +/- 24% v 38% +/- 14%). CONCLUSIONS: Our results show that BMT in first remission AML did not offer a disease-free survival advantage over intensive postremission consolidation chemotherapy. Larger studies are needed to identify patients who might benefit most from BMT.     

大剂量阿糖胞苷强化疗对急性髓性白血病长期生存的影响

目的探讨应用大剂量阿糖胞苷治疗缓解后急性髓细胞白血病（AML）的疗效及安全性。方法采用回顾性分析方法,对初次治疗完全缓解的AML患者给予4个大剂量阿糖胞苷强化化疗,治疗后对长期存活者进行随访观察。结果24例患者中存活2年以上者15例（62．5％）,其中8例（33．3％）已无病生存5年以上。结论大剂量阿糖胞苷强化疗安全有效,是AML患者获得长期无病生存的重要治疗方法,其治疗效果值得更大规模临床应用。     

急性髓系白血病患者巩固化疗过程中未成熟网织红细胞分数检测的临床意义

 目的　探讨急性髓系白血病（AML）患者在接受大剂量阿糖胞苷巩固化疗后骨髓抑制和恢复过程中包括未成熟网织红细胞分数（IRF）在内的外周血各参数的变化及其临床意义。方法　采用全自动血细胞分析仪动态检测30例AML患者接受大剂量阿糖胞苷巩固化疗前后外周血中性粒细胞绝对计数（ANC）、血小板计数（Plt）和IRF,并对各个参数的变化进行分析比较。结果　患者巩固化疗后,ANC、Plt和IRF平均恢复时间分别为（9.2±2.5）d、（11.3±3.7）d和（5.0±2.6）d,IRF恢复时间短于ANC和Plt回升时间（P＜0.05）,而ANC恢复时间短于Plt回升时间（P＜0.05）。不同FAB分型患者间及基于细胞遗传学和分子生物学危险因素分层患者间ANC、Plt和IRF平均恢复时间差异均无统计学意义（P＞0.05）。结论　IRF是AML患者接受大剂量阿糖胞苷巩固化疗后提示骨髓造血功能恢复的早期指标,对于评估疗效具有重要临床意义。     

Transplantation of autologous peripheral blood progenitor cells procured after high-dose cytarabine-based consolidation chemotherapy for adults with secondary acute myelogenous leukemia in first remission.

Patients with acute myelogenous leukemia secondary to an antecedent hematologic disturbance or cytotoxic chemotherapy are considered to have a very low likelihood of leukemia-free survival regardless of the form of post-remission therapy. The purpose of this study is to evaluate, on the basis of intention to treat, the feasibility and efficacy of high-dose cytarabine/anthracycline consolidation chemotherapy followed by autologous transplantation of chemotherapy/rHuG-CSF-mobilized peripheral blood progenitor cells for seventeen adult patients (median age 63, range 27 to 68) with secondary acute myelogenous leukemia in first remission. Ten eligible patients underwent autologous transplantation of peripheral blood progenitor cells procured following high-dose cytarabine/mitoxantrone consolidation chemotherapy used as a method of in vivo purging. A median of 5 collections (range 2 to 13) were required to procure a median of 9.27 x 10(8) total mononuclear cells/kg (range 2.35 to 21.44 x 10(8) per kg). The median number of CD34-positive progenitor cells was 1.18 x 10(6) kg (range 0.34 to 30.9 x 10(6) kg). After preparative conditioning with 11.25 Gy total body radiation and cyclophosphamide (120 mg/kg) and autologous transplantation, the median time to neutrophil and platelet recovery were 18 days (range 12 to 29 days) and 25 days (range 8 to 158+ days), respectively. After a median follow-up for surviving patients of 33.4 months (range 7.5 to 54 months), 9 of 17 patients (53%) remain alive with 7 in continued first remission. The median remission duration is 13 months (3 to 53 months) and actuarial leukemia-free survival at 3 years is 51+/-25%. Toxicity of autologous peripheral blood progenitor cell transplant included serious liver and pulmonary toxicity in 2 and 1 patient, respectively. Our results demonstrate that a postremission program of high-dose cytarabine-based consolidation chemotherapy followed by autologous transplantation of chemotherapy-mobilized peripheral blood progenitor cells is feasible for patients with secondary acute myelogenous leukemia producing prolonged leukemia-free survival with minimal toxicity.     

Patient-specific dose rate for continuous infusion high-dose cytarabine in relapsed acute myelogenous leukemia

We hypothesized that the steady-state concentration of intracellular cytarabine 5'-triphosphate (ara-CTPss) in leukemia cells is proportional to the dose rate of cytarabine (ara-C) during continuous infusion. To evaluate this possibility, patients with acute myelogenous leukemia in relapse were treated with two sequential schedules of serially increasing ara-C dose rates over a total of 36 hours. Schedule I consisted of serial infusions of 250, 500, and 750 mg/m2 each over 12 hours. Subsequently, patients entered on schedule II received 500, 1,000, and 1,500 mg/m2 serially, each over 12 hours. Steady-state levels of ara-CTP were achieved within four hours after beginning ara-C infusion and, in separate studies of a single ara-C dose rate, were shown to be maintained beyond 36 hours. Four patients treated with schedule I and two patients treated with schedule II showed a linear dose rate-dependent increase-of ara-CTPss at all three dose rates. The cells of one patient on schedule I and two patients on schedule II had a dose rate-dependent ara-CTPss increase only over the first two dose levels, while no increase or lower ara-CTPss was observed at the third dose rate. The ara-CTPss of one patient on schedule II did not change. These results suggest that there is a proportionality between the continuous infusion dose rate of ara-C and the ara-CTPss in circulating leukemia cells within the dose range of 250 to 1,000 mg/m2 over 12 hours. This opens the possibility that pharmacologic determinations may be used to redirect the ara-C dose rate to achieve a desired ara-CTPss level in leukemia blasts during therapy.     

中剂量阿糖胞苷用于老年急性髓系白血病患者巩固强化治疗的临床观察

目的 分析初治老年急性髓系白血病(AML)患者诱导缓解后应用中剂量阿糖胞苷(MDAC)巩固治疗的临床效果及不良反应.方法 61例2个疗程内达完全缓解(CR)的老年AML(M3除外)患者,分别应用MDAC和常规剂量阿糖胞苷(SDAC)进行巩固强化治疗,对其临床资料进行回顾性分析.结果 MDAC组26例,SDAC组35例,MDAC组与SDAC组的无复发生存(RFS)时间分别为42.7和16.0个月(P=0.002),总生存(OS)时间分别为44.6和18.2个月(P=0.004),累积复发率分别为26.9%(7/26)和54.3%(19/35)(x2=4.567,P=0.033),3年生存率分别为23.1%(6/26)和8.6%(3/35)(x2=2.496,P=0.114).两组不良反应发生率差异均无统计学意义(均P>0.05).结论 老年AML患者应用MDAC巩固强化治疗,可延长早期达CR患者的RFS及OS时间,不良反应发生率与SDAC相似.     

Treatment of chronic myelogenous leukemia in accelerated and blastic phases with daunorubicin, high-dose cytarabine, and granulocyte-macrophage colony-stimulating factor.

PURPOSE: The study was undertaken to improve the results of intensive chemotherapy in chronic myelogenous leukemia (CML) in accelerated (CML-AP) and blastic phases (CML-BP) by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) as supportive therapy. PATIENTS AND METHODS: Forty-eight patients were treated with daunorubicin 120 mg/m2 intravenously on day 1, cytarabine (ara-C) 1.5 g/m2/d by continuous infusion over 24 hours for 4 days, and Solu-Medrol (methylprednisolone; The Upjohn Co, Kalamazoo, MI) 100 mg/d for 5 days, followed on day 5 by GM-CSF 125 micrograms/m2/d over 6 hours until recovery of granulocyte count above 2.0 x 10(3)/microliters. Twenty-four patients had CML-BP, and 24 had CML-AP. RESULTS: During remission induction, 45 patients (94%) developed febrile episodes (fever of unknown origin, 23 patients [48%]; documented infections, 22 patients [46%]). The median time to recovery of granulocyte count above 0.5 x 10(3)/microliters was 29 days and to platelet count above 30 x 10(3)/microliters, 28 days. Overall, 14 of 48 patients (29%) achieved a complete hematologic remission (CHR), and seven (15%) reverted to a second chronic phase. CHR was noted in eight of 24 patients with CML-BP (33%), and in six of 24 patients with CML-AP (25%). Cytogenetic responses were observed in 11 patients (23%), but were transient. Sixteen patients developed either fluid retention, hypotension, pleuropericardial effusions, or pericarditis, or a combination of these side effects. These side effects were severe in four patients and are likely to be disease-associated, as a similar regimen of intensive chemotherapy and GM-CSF at the same dose and schedule in acute lymphocytic leukemia was not associated with these side effects. CONCLUSIONS: The results pertinent to remission rates, induction mortality, myelosuppression profile and related complications, and overall survival were not significantly improved compared with previous experience. In summary, the results of intensive chemotherapy in CML-transformed phases remain poor, despite the addition of GM-CSF as a supportive measure.     

Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia

The potential mechanism of the chemotherapy resistance in acute myeloid leukemia (AML) is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is often overexpressed in myeloblasts from acute myeloid leukemia. In a multicenter clinical trial, 38 patients with poor risk forms of AML were treated with tetrandrine (TET), a potent inhibitor of the MDR-1 efflux pump, combined with daunorubicin (DNR), etoposide and cytarabine (TET-DEC). Overall, post-chemotherapy marrow hypoplasia was achieved in 36 patients. Sixteen patients (42%) achieved complete remission or restored chronic phase, 9 achieved partial remission (PR) and 13 failed therapy. Toxicities included infection, myelosuppression, stomatitis, mucositis, cerebellar toxicity and reversible cardiotoxicity. There was no significant difference in response for P-gp-positive and -negative patients. P-gp function was assessed in 26 patients by flow cytometric analysis, TET-contained plasma-augmented DNR accumulation relative to pretreatment plasma in K562/A02 cells by a median value of 88+/-101% (range, 11-501%). However, there was no difference in DNR uptake between responding and non-responding patients. Our data showed that TET-DEC was relatively well tolerated in these patients with poor risk AML, and had encouraging antileukemic effects.     

High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: long-term follow-up and results

In an effort to increase the proportion of patients with acute myeloid leukemia (AML) remaining in continued complete remission (CCR), we administered intensive postremission consolidation therapy with high-dose cytarabine (Ara-C) and daunorubicin. Eighty-seven patients, with a median age of 38 years (range, 7 to 71), received consolidation therapy after first complete remission was obtained with standard induction chemotherapy that included conventional doses of Ara-C. Consolidation therapy consisted of from one to three cycles of high-dose Ara-C (3 g/m2 intravenously [IV] over 1 hour every 12 hours for 12 doses) followed by daunorubicin (30 mg/m2/d IV bolus for 3 days). After completion of the high-dose Ara-C and daunorubicin, no further therapy was administered. Myelosuppression encountered with consolidation resulted in a median duration of neutropenia and thrombocytopenia of 3 weeks. Four patients (5%) died during consolidation due to infection and/or hemorrhage; 59% of patients experienced severe but nonfatal infectious or extramedullary organ toxicity. With a median follow-up of more than 3.5 years from diagnosis, the proportion of patients, by Kaplan-Meier product-limit estimate, remaining in CCR is 49% (95% confidence limits, 37% to 61%). In a Cox multivariate analysis, only age significantly (P less than .001) influenced the probability of remaining in CCR. The probability of remaining in CCR was 83%, 50%, and 23% for age groups of 25 or less, 26 to 45, and more than 45 years, respectively. These survival curves all have stable long-term plateaus, suggesting cure. In this study, the administration of brief, intensive nonmarrow ablative chemotherapy resulted in a large proportion of patients with AML remaining in CCR, results similar to those reported with allogeneic bone marrow transplantation. Relapse of acute leukemia was still the major reason for therapy failure, suggesting that more effective or additional postremission therapy will be required to further improve the likelihood of cure especially for older patients.     

Peripheral neuropathy after high-dose cytosine arabinoside, daunorubicin, and asparaginase consolidation for acute nonlymphocytic leukemia

Two patients with acute nonlymphocytic leukemia (ANLL) developed peripheral motor and sensory neuropathies after consolidation chemotherapy with high-dose cytosine arabinoside (ara-C), daunorubicin, and asparaginase. Evidence for ara-C and daunorubicin-induced peripheral neuropathies is reported. Despite the frequent use of these agents, only two cases of peripheral neuropathy after systemic therapy have been previously described; neurotoxic effects may be potentiated and become clinically important when the three drugs are used in combination.     

Mitoxantrone and cytarabine versus daunorubicin and cytarabine in previously untreated patients with acute myeloid leukemia

Summary A total of 44 adults aged 18–78 years were allocated to an open randomized study whose aim was to compare the efficacy and toxicity of mitoxantrone with those of daunorubicin in previously untreated patients presenting with acute myeloid leukemia. In one arm, induction treatment consisted of mitoxantrone plus cytarabine given on a 3- plus 7-day schedule. Post-induction treatment consisted of two courses of mitoxantrone plus cytarabine given on a 2- plus 5-day schedule. In the control arm, mitoxantrone was replaced by daunorubicin. In all, 14 of 21 eligible and evaluable patients in the mitoxantrone arm achieved a complete remission (CR). In the control arm, 14 of 20 subjects attained a CR. The median survival was 365 days for patients randomized to mitoxantrone-cytarabine and 401 days for those given daunorubicin-cytarabine. The efficacy and toxicity of mitoxantrone were similar to those of daunorubicin.     

Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia

BACKGROUND:

Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease‐free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high‐dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis.

METHODS:

One hundred sixty‐one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged ≥60 years.

RESULTS:

One hundred twenty‐eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow‐up of 10.4 years for surviving patients, the 5‐year DFS rate was 25% (95% confidence interval, 18%‐33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%‐37%). Patients aged <60 years who received the 80 mg/m² dose of daunorubicin had a DFS of 33% (95% confidence interval, 22%‐44%) and an OS of 39% (95% confidence interval, 29%‐49%) at 5 years. Eighty‐four patients (52%) relapsed, including 9 patients (6%) who had isolated CNS relapses. The omission of cranial irradiation did not result in higher than historic CNS relapse rates.

CONCLUSIONS:

Intensive systemic, oral, and intrathecal methotrexate dosing permitted the omission of CNS irradiation in adult patients with ALL. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historic CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets. Cancer 2013. © 2012 American Cancer Society.     

Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival

BACKGROUND.

Acute myelogenous leukemia (AML) associated with core‐binding‐factor (CBF) abnormalities is the type of leukemia most responsive to cytarabine (ara‐C) therapy and is of relative favorable prognosis. In vitro and ex vivo observations suggest that increases in intracellular ara‐C levels influenced by administration of fludarabine and granulocyte colony‐stimulating factor (GCSF) increase the effect of ara‐C, prompting us to clinically evaluate the efficacy of such combinations.

METHODS.

We analyzed the event‐free survival of patients with newly diagnosed CBF AML treated with fludarabine and ara‐C (FA) (N = 45) or with FA and GCSF (FLAG) (N = 22) and compared results to patients treated with regimens consisting of idarubicin and ara‐C with or without GCSF (IA/IAG) (N = 47).

RESULTS.

After accounting for prognostic covariates other than treatment (including year in which treatment was administered), FA, and in particular FLAG, were associated with longer event‐free survival than IA/IAG.

CONCLUSIONS.

Thus, our data lends clinical credence to the observed modulation of ara‐C by fludarabine and GCSF. Cancer 2008. © 2008 American Cancer Society.     

High-dose cytarabine and mitoxantrone in consolidation therapy for acute promyelocytic leukemia.

The objective of our study was to evaluate high-dose cytarabine in consolidation therapy in patients with newly diagnosed acute promyelocytic leukemia (APL). Patients (age 16-60 years) received induction therapy according to the AIDA protocol (all-trans retinoic acid, idarubicin) followed by one cycle of ICE (idarubicin, cytarabine, etoposide) and two cycles of HAM (cytarabine 3 g/m(2) q12h, days 1-3; mitoxantrone 10 mg/m(2), days 2 and 3). From 1995 to 2003, 82 patients were enrolled. In total, 72 patients (88%) achieved a complete remission, and 10 patients (12%) died from early/hypoplastic death (ED/HD). A total of 71 patients received at least one cycle of HAM. Relapse-free survival (RFS) and overall survival (OS) after 46 months were 83 and 82%, respectively. White blood cell count above 10.0 x 10(9)/l at diagnosis and additional chromosomal aberrations were unfavorable prognostic markers for OS, whereas no prognostic markers for RFS were identified including FLT3 mutations. In conclusion, high-dose cytarabine in consolidation therapy for patients with newly diagnosed APL is an effective treatment approach.     

A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study.

PURPOSE: A randomized clinical trial was undertaken to compare the therapeutic effectiveness of idarubicin (IDR) to daunorubicin (DNR), and both were given in combination with cytarabine (CA) in acute myelogenous leukemic (AML) patients. PATIENTS AND METHODS: Newly diagnosed patients were given a daily infusion of CA (100 mg/m2) for 7 days and were assigned randomly to receive DNR (45 mg/m2) or IDR (12 mg/m2) daily for the first 3 days. Those patients who achieved a complete remission (CR) were given three consolidation courses that consisted of CA (100 mg/m2 intravenously [IV]) and thioguanine (TG; 100 mg/m2 orally) every 12 hours for 5 days and either DNR (50 mg/m2) or IDR (15 mg/m2) on the first day of each cycle. After consolidation, patients received late intensification, which consisted of the same drugs used for induction except that the CA was given for 5 days and the anthracycline for 2 days. Four courses were planned at 13-week intervals. RESULTS: The CR rates were 75 of 105 (71%) on the IDR arm and 65 of 113 (58%) on the DNR arm (P = .03). The median survival and median remission durations were 297 and 433 days, respectively, on the IDR arm. The median survival and median remission durations were 277 and 328 days, respectively, on the DNR arm. Six deaths occurred during late intensification, five on IDR and one on DNR; this approach was abandoned after 47 patients were entered. The median survival was significantly longer for patients who received late intensification. CONCLUSION: This trial demonstrated that IDR was more effective than DNR in remission induction in AML.     

Pilot study of gemtuzumab ozogamicin,liposomal daunorubicin,cytarabine and cyclosporine regimen in patients with refractory acute myelogenous leukemia

Multi-drug resistance (MDR) protein expression is associated with reduced gemtuzumab ozogamicin (Mylotarg) activity. Both cyclosporine-A (CSA) and liposome-encapsulated daunorubicin, DaunoXome (DNX) may reduce the negative impact of MDR. A gemtuzumab ozogamicin, DNX, cytarabine (ara-C) and CSA (MDAC) regimen was piloted in patients with refractory acute myelogenous leukemia (AML) (relapsed 10, primary refractory 1) (median age 37 years (16-67)). One (9%) patient achieved a transient CR, one CRp. Grade 3/4 toxicities included sepsis (seven patients; 63%); hyperbilirubinemia (six patients; 54%), with transaminitis in one patient; mucositis (three patients; 27%). The inclusion of CSA in a gemtuzumab ozogamicin-containing regimen is feasible. The MDAC regimen was associated with significant toxicity in a cohort of patients with very advanced AML.