Effective Remission Induction for AML Using Two Days of Chemotherapy: Older Patients Tolerate and Respond Equally Well

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4004-4004
Author(s):  
Neel B. Shah ◽  
Melissa L. Larson ◽  
Nitin Goyal ◽  
Ann M. Thomas ◽  
Jamile M. Shammo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Older Patients ◽  
Response Rates ◽  
Remission Induction ◽  
High Dose ◽  
Refractory Disease ◽  
Toxicity Profile ◽  
Induction Regimen ◽  
High Dose Cytarabine

Abstract Background: The remission induction regimen used for treatment of adult AML has traditionally been the “7+3” regimen, which has not changed significantly since 1981. CR rates have been in the 55–60% range, historically. We present a single institution, retrospective analysis of a regimen consisting of two pulses of chemotherapy 96 hours apart with high-dose cytarabine and mitoxantrone. It is based on the concept of timed sequential therapy where the first pulse of chemotherapy recruits leukemic cells into the cell cycle and is followed by the second pulse at the time of peak cell recruitment. Cytarabine is a cell cycle-specific drug, and mitoxantrone was chosen because of its resistance to the effects of the gene MDR1, which is commonly expressed in adult leukemia, as well as its favorable cardiac toxicity profile. Patients and Methods: One hundred four patients with AML were treated with timed sequential chemotherapy from April 1997 to April 2008. Each pulse of chemotherapy consisted of 2 doses of cytarabine 2gm/m2 given 12 hours apart (at t=0 and t=12) followed by one dose of mitoxantrone 30 mg/m2 administered after the second cytarabine dose (t=15) given on days 1 and 5. Bone marrow biopsies were performed to assess for leukemia free-state (day 14) and subsequently for remission documentation. Responses were defined per the Revised IWG Recommendations (Cheson, J Clin Onc21: 4642, 2003). Toxicities, response rates, relapse rates, and preexisting conditions were also recorded. Results: Median age of the 104 patients was 57 y [range 17–79]. There were 47 males and 57 females. Forty-two patients (40%) were 60 years of age or older with 17 (16%) of them older than 70 years. Forty patients (38%) had preexisting MDS. Five patients (4.8%) had favorable cytogenetics, 61 (58.7%) had intermediate cytogenetics, and 38 (36.5%) had unfavorable cytogenetics. Seventy-four patients (71%) achieved a leukemia free state based on the day 14 bone marrow biopsy. At the time of the remission documentation bone marrow biopsy, the IWG-defined responses seen are the following: 56 CR (53.8%), 9 CRi (8.6%), and 10 CRp (9.6%). Three additional patients (2.9%) had a return to MDS (RMDS). Twenty patients (19.2%) had refractory disease. Overall, 78 patients had a response, (ORR=75%). The 30-day mortality rate was 2.8% (3/104). In the 62 patients under 60 years of age, 51 (82%) responded to chemotherapy. In the 42 patients age 60 and older, 27 had a response (64%). Thirteen of the seventeen patients age 70 and older had a response (10 CR, 2 CRp, 1 CRi) for an ORR of 76.4%. The remaining 4 patients in this age group had refractory disease. Conclusion: This remission induction regimen of high dose cytarabine and mitoxantrone produces very high response rates, even in the older AML patients. The response rates in both younger patients and older patients compare favorably with the rates historically seen with the standard 7 + 3 regimen. The 30-day mortality rate of less than 3% is less than that previously reported with the 7 + 3 regimen. This may be attributable to improvements in supportive care; although, this could also represent the favorable toxicity profile of this effective, novel regimen.

Favorable Outcome In Patients with Poor Prognosis Acute Myeloid Leukemia (AML) Using a 2-Day Induction Regimen Incorporating High Dose Cytarabine and Mitoxantrone.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1069-1069
Author(s):  
Melissa L Larson ◽  
Sheena Sahota ◽  
Margaret C Keller ◽  
Bharathi Muthusamy ◽  
Allison Zindell ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Induction Therapy ◽  
Older Patients ◽  
Overall Response Rate ◽  
Response Rate ◽  
Remission Induction ◽  
High Dose ◽  
Younger Patients ◽  
Induction Regimen ◽  
High Dose Cytarabine

Abstract Abstract 1069 Background: Cytogenetic data plays an important role in assessing prognosis and determining choice of therapy for AML. Traditionally, patients with AML are treated with infusional cytarabine and an anthracycline. CR rates with this regimen have been reported at 50–60%. Evaluation of novel treatment regimens for AML should include determination of the impact of the regimen on intermediate and unfavorable cytogenetics. We present a retrospective analysis of a 2-day remission induction regimen, based on the concept of timed sequential therapy. The regimen combines high dose cytarabine, which has been shown to improve remission rates when used in induction therapy, and dose intensified anthracycline therapy, which has been shown to improve outcome in younger patients. The cycling cells are eradicated during an initial pulse of therapy, then, previously quiescent cells are targeted during the second pulse of therapy. Here we present the analysis of the study regimen and the response rates of patients with intermediate and unfavorable cytogenetic profiles. Patients and Methods: One hundred fifty five patients categorized as having intermediate or unfavorable cytogenetics were treated with timed sequential chemotherapy from 1998–2009. The treatment regimen consisted of two doses of cytarabine 2 gm/m2 IVPB given over 3 hours, administered 12 hours apart. This was followed by one dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Pre-therapy cytogenetic data was collected for each patient. Responses to therapy were determined based on IWG response criteria for AML. Results: One hundred fifty five patients with intermediate and unfavorable karyotypes received high dose cytarabine and mitoxantrone for remission induction therapy. Median age of patients was 55 years (ranged from 17–85). Sixty patients were 60 years or older. Eighty three patients (53.5%) had intermediate and 72 (46.5%) had unfavorable karyotypes. The younger patients (under 60 years of age) with intermediate cytogenetics achieved the following responses: 34 CR, 6 CRi, and 2 CRp. The overall response rate (ORR) was 80.8% for these younger patients, while the ORR for the older patients (over 60 years of age) with intermediate cytogenetics was 77.4% (15 CR, 4 CRi, 5 CRp). In the unfavorable cytogenetic category, the ORR of the younger patients (under 60 years of age) was 60.5% with 13CR, 8 CRi, and 5 CRp, while an ORR of 44.8% was shown in the older patients (over 60 years of age) with 9 CR, 1 CRi, and 3 CRp. Overall, twenty two out of seventy two (30.5%) had CR in the unfavorable group, 9 (12.5%) had CRi, and 8 (11%) had CRp for an overall response rate of 54%. The 30 day mortality rate was 3.8% (6/155). The 60 day mortality rate was 11.6%. The most common adverse events were Grade 3/4 hematologic toxicities. Conclusion: This convenient, 2-day induction regimen leads to high response rates with low treatment-related mortality in older patients and patients with unfavorable cytogenetic characteristics. Based on the tolerability and effectiveness, this regimen could potentially be useful in high risk transplant-eligible patients for remission induction. It appears that this regimen would also be appropriate for initial cytoreduction in elderly patients with AML prior to introduction of novel therapeutic strategies, such as hypomethylating agents or oral clofarabine for consolidation and maintenance. Disclosures: No relevant conflicts of interest to declare.

Tolerability of An Effective Two Day Induction Regimen for Newly Diagnosed AML

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4035-4035
Author(s):  
Melissa L. Larson ◽  
Nitin Goyal ◽  
Ann M. Thomas ◽  
Jamile M. Shammo ◽  
John J. Maciejewski ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Induction Therapy ◽  
Dose Intensity ◽  
Remission Induction ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Refractory Disease ◽  
Induction Regimen ◽  
High Dose Cytarabine ◽  
Grade 3

Abstract Background: The standard remission induction regimen for treating Acute Myeloid Leukemia consists of seven days of continuous infusion cytarabine and three days of an anthracycline, the “7 + 3” regimen. We present a single institution, retrospective analysis of toxicity associated with a regimen that requires only two days of chemotherapy using high dose cytarabine and mitoxantrone. The regimen is based on the timed sequential therapy concept where two pulses of chemotherapy are given. The first pulse recruits cells into the cell cycle, while the second pulse is given at the time of peak recruitment. Methods: One hundred four patients with AML were treated with two days of chemotherapy given 96 hours apart from April 1997 to April 2008. Each day of chemotherapy consisted of two doses of cytarabine 2gm/m2 (at t=0 and t=12) followed by one dose of mitoxantrone 30 mg/m2 administered after the second cytarabine dose (t=15). Each patient’s chart and electronic record were thoroughly reviewed, and toxicities associated with induction therapy were analyzed and graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events v3.0. Responses were defined per the Revised IWG Recommendations (Cheson, J Clin Onc21: 4642, 2003). Results: One hundred four patients were eligible for toxicity evaluation. Hematologic toxicities were the most common toxicities seen with this induction therapy. Overall, all patients experienced hematologic toxicity of some grade with 98% of patients having one or more Grade 3/4 hematologic toxicity. The incidences of grade 3/4 hematologic toxicities are the following: Hemoglobin 65.3% (Gr 3 59.6%, Gr 4 5.7%), thrombocytopenia 93.2% (Gr 3 9.6%, Gr 4 83.6%), and neutropenia 89.4% (Gr 3 1.9%, Gr 4 87.5%). Febrile neutropenia occurred in 64% of the patients, and grade 3 and 4 infections occurred in 25%. Common non-hematologic toxicities included fatigue, nausea, vomiting, diarrhea, and electrolyte abnormalities. The vast majority of non-hematologic toxicities were grade 1 and 2. Three patients (2.9%) died within the first 30 days of induction therapy. One patient died before completing therapy due to massive hemoptysis. One died from complications of refractory disease, and the third patient died from disseminated fungal infection. An additional 10 patients (6 TF-RD, 1 TF-aplasia, 1 CR, 1 CRi, 1 CRp) died within the first 60 days. Of the 6 patients with refractory disease, 4 received re-induction therapy to which 3 did not have a response and the fourth died of sepsis while aplastic. Two patients had intracerebral hemorrhage (TF-aplasia and CRp). One patient died suddenly in CR of unknown causes and one patient (CRi) died from complications of pneumonia/ARDS. Conclusion: Although this regimen incorporating high dose cytarabine into remission induction presents a significantly higher dose intensity of cytarabine and mitoxantrone compared to that of the “7+3” regimen, the toxicity profile and 30-day mortality rate compare favorably to the “7 + 3” regimen. This regimen has been shown to produce a CR rate comparable to that of the “7+3” regimen with equal efficacy and better tolerance in elderly patients with AML. We conclude that this regimen effectively administers a high yet apt dosage of chemotherapy, and it can even be used for remission induction in elderly patients. This induction regimen could serve as a platform for future studies of maintenance and biologic therapies in the elderly AML patients.

Timed Sequential Induction Therapy with Cytarabine and Mitoxantrone In Acute Myeloid Leukemia (AML): A Well-Tolerated Regimen with High Response Rates In Older Patients and Transformed AML.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1068-1068
Author(s):  
Sheena Sahota ◽  
Melissa L Larson ◽  
Margaret C Keller ◽  
Jamile M. Shammo ◽  
Allison Zindell ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Older Patients ◽  
De Novo ◽  
Response Rates ◽  
High Response ◽  
Remission Induction ◽  
High Dose ◽  
Remission Duration ◽  
Induction Regimen ◽  
De Novo Aml

Abstract Abstract 1068 Background: Patients with AML who are eligible for chemotherapy are traditionally treated with infusional cytarabine and an anthracycline. CR rates with this combination have been approximately 50–60% with an induction mortality of 10–25%. However, this treatment is less effective in older patients in terms of CR attainment, remission duration, and overall survival. We present a retrospective analysis of an induction regimen that was designed based on the concept of timed sequential therapy. An initial pulse of chemotherapy is administered to eradicate cells in S phase. This is followed by a rest period during which previously quiescent cells that enter the cell cycle can be targeted by a second pulse of chemotherapy. The regimen incorporates high dose cytarabine, which has been shown to improve remission duration when used in induction, and dose-intensified anthracycline therapy, which has been shown to improve outcomes in younger patients. This report highlights the responses and tolerability of the study regimen, particularly in elderly patients and patients with prior myelodysplastic syndrome (MDS). Patients and Methods: One hundred sixty six patients were treated with timed sequential chemotherapy from 1998–2009. The treatment consisted of two doses of cytarabine 2 gm/m2 IVPB over 3 hours administered 12 hours apart followed by one dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Data on pre-therapy cytogenetics and MDS was collected for each patient. Remission status was assigned per the IWG response criteria for AML. Results: Median age of the patients was 54.5 years (range 17–85). There were eighty males and eighty-six females. Out of 166 patients, 11 (6.6%) patients had favorable, 83 (50%) had intermediate, and 72 (43.4%) had unfavorable karyotypes. One-third of the patients (57 pts) had AML transformed from MDS. The overall response rate (ORR: CR+CRi+CRp) for all patients was 69.9%. In patients who had de novo AML, the ORR was 79.8%, regardless of age. Patients over age 60 with de novo AML had an ORR of 74%. For those patients under the age of 60, the ORR was 82%. The ORR for patients with transformed AML was 52.6% (53% in pts over age 60, 52% in pts less than 60). The 30 day mortality rate was 3.4% (6/166). Five of the six patients who died had an unfavorable karyotype with 2 patients having therapy-related AML. The 30 day mortality for patients older than 60 was 3.3% (2/61) and for all patients was 3.6% (6/166). The 60 day mortality rate in all patients was 10.8% (18/166). Of the additional 12 patients, seven died from progressive disease and only 3 died of suspected therapy-related complications. Grade 3/4 hematologic toxicities were the most common adverse events seen. Conclusion: This is a convenient, 2-day induction regimen that is well-tolerated with comparatively low 30 and 60 day mortality and high response rates in older patients and those patients with AML transformed from MDS. This would be an excellent initial regimen for remission induction in a select population of patients in whom novel consolidation or maintenance therapies can be incorporated to further improve outcome. Disclosures: No relevant conflicts of interest to declare.

Efficacy of a Two Day Induction Regimen for De Novo and Secondary AML with Intermediate and Adverse Cytogenetic Profiles

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4027-4027
Author(s):  
Melissa L. Larson ◽  
Ann M. Thomas ◽  
Nitin Goyal ◽  
Jamile M. Shammo ◽  
John J. Maciejewski ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Complete Remission ◽  
De Novo ◽  
Response Rates ◽  
High Dose ◽  
Bone Marrow Biopsies ◽  
Secondary Aml ◽  
Number Of Patients ◽  
Induction Regimen ◽  
De Novo Aml

Abstract Background: Cytogenetic data remains one of the most powerful prognostic factors for predicting response and survival in adult AML patients. The relationship between cytogenetics and induction response to the standard “7+3” regimen has been analyzed in the past. In a CALGB study, patients with favorable cytogenetics achieved a complete remission (CR) rate of 88%, those with intermediate cytogenetics achieved a 67% CR rate and those with adverse cytogenetics had a 32% CR rate (Byrd et al. Blood100: 4325, 2002). We present a retrospective analysis of the correlation between the hierarchical cytogenetic groups and complete remission rate following induction of AML using a novel induction regimen. This regimen was developed based on the concept of timed sequential therapy. The first pulse of chemotherapy recruits leukemic cells into the cell cycle while the second pulse is given at a time of peak cell recruitment. It utilizes two highly active anti-leukemic drugs: cytarabine, a cell cycle-specific drug, and mitoxantrone, which has a favorable cardiac toxicity profile. Patients and Methods: One hundred four patients with AML were treated with two days of chemotherapy given 96 hours apart from April 1997 to April 2008. Each day consisted of two doses of cytarabine 2gm/m2 (at t=0 and t=12) followed by one dose of mitoxantrone 30 mg/m2 administered after the second cytarabine dose (t=15). Bone marrow biopsies were performed for assessment of leukemia-free state (day 14) and to document remission response. Cytogenetic results were classified into favorable, intermediate, and unfavorable categories based on CALGB data. Responses were defined per the Revised IWG Recommendations (Cheson et al, J Clin Onc21: 4642, 2003). Results: Median age of the 104 patients was 57 years [range 17–79]. There were 47 males and 57 females. Forty-two patients (40%) were 60 years of age and older, and the remaining 62 patients (60%) were younger than 60. Sixty-four patients (61.5%) had de novo AML. Five patients had favorable cytogenetics with 100% of them achieving CR. All of the patients with favorable cytogenetics were less than 60 years of age. For the 61 patients with intermediate cytogenetics, the ORR was 83.6% with a CR of 61%. In patients younger than 60, the ORR was 83.8%% (26 CR, 3 CRi, 2 CRp) with CR of 70%. For patients 60 years and older, the ORR was 83.3% (11 CR, 3 CRi, 5 CRp, 1 RMDS). In the 38 patients with unfavorable cytogenetics, the ORR was 57.9% with CR of 37%. For patients younger than 60 and 60 years and older, the overall responses were 75% and 38.8%, respectively. Of the 40 patients with secondary AML due to pre-existing MDS, the ORR was 65% with CR of 27.5%. In patients with de novo AML, the ORR was 81% with CR of 70%. Patients with prior MDS were more likely to have CRi (20% vs 1.5%), TF due to refractory disease (25% vs 15.6%) or aplasia (7.5% vs 1.5%) as compared to patients without MDS. The rates of CRp (10% vs 9%) were similar for both groups. MDS patients with intermediate cytogenetics had an ORR of 77.7% as compared to 54.5% in those with unfavorable cytogenetics. De novo patients with intermediate cytogenetics had ORR of 86% and those with unfavorable cytogenetics had ORR of 62.5%. Conclusion: Our data reflects the overall effectiveness of high dose cytarabine and mitoxantrone for induction therapy of AML. In the favorable cytogenetic group, the CR rate was higher than previously reported response rates; however, the number of patients was small. In the intermediate and unfavorable cytogenetic groups, the response rates for de novo AML compare favorably to historic controls. Patients with secondary AML respond equally well as compared to those with de novo AML; though, the influence of cytogenetics was similar to that seen in de novo AML. This regimen is very effective in producing a high response rates across cytogenetic categories.

scholarly journals Intensive chemotherapy is the treatment of choice for elderly patients with acute myelogenous leukemia

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 467-470 ◽  
Author(s):  
KA Foon ◽  
J Zighelboim ◽  
C Yale ◽  
RP Gale
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Older Patients ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Intensive Chemotherapy ◽  
Younger Patients ◽  
Remission Rates ◽  
Induction Regimen ◽  
Acute Myelogenous

Abstract One-hundred and seven patients with acute myelogenous leukemia (AML) ranging in age from 15 to 82 yr who were previously untreated, received a 70 day high-dose remission induction regimen consisting of daunorubicin, cytarabine, and thioguanine (TAD). Identical complete remission rates of 65% were observed for 33 patients 60 yr of age and older and for 74 patients age 15–59 yr. Median remission duration and survival were 14 mo and 22 mo for patients 60 yr and older, and 16 mo and 22 mo for patients 15–59 yr. These differences are not significant. These data indicate that older patients respond to intensive chemotherapy in a similar manner to younger patients with this disease.

scholarly journals Intensive chemotherapy is the treatment of choice for elderly patients with acute myelogenous leukemia

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 467-470 ◽  
Author(s):  
KA Foon ◽  
J Zighelboim ◽  
C Yale ◽  
RP Gale
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Older Patients ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Intensive Chemotherapy ◽  
Younger Patients ◽  
Remission Rates ◽  
Induction Regimen ◽  
Acute Myelogenous

One-hundred and seven patients with acute myelogenous leukemia (AML) ranging in age from 15 to 82 yr who were previously untreated, received a 70 day high-dose remission induction regimen consisting of daunorubicin, cytarabine, and thioguanine (TAD). Identical complete remission rates of 65% were observed for 33 patients 60 yr of age and older and for 74 patients age 15–59 yr. Median remission duration and survival were 14 mo and 22 mo for patients 60 yr and older, and 16 mo and 22 mo for patients 15–59 yr. These differences are not significant. These data indicate that older patients respond to intensive chemotherapy in a similar manner to younger patients with this disease.

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

1992 ◽  
Vol 10 (1) ◽  
pp. 41-46 ◽  
Author(s):  
G J Schiller ◽  
S D Nimer ◽  
M C Territo ◽  
W G Ho ◽  
R E Champlin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
First Remission ◽  
Disease Free

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.

scholarly journals Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia

2018 ◽  
Vol 2 (16) ◽  
pp. 2063-2071 ◽  
Author(s):  
Brian Ball ◽  
Rami S. Komrokji ◽  
Lionel Adès ◽  
Mikkael A. Sekeres ◽  
Amy E. DeZern ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Response Rates ◽  
High Dose ◽  
Hypomethylating Agent ◽  
Key Points ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Key Points Induction led to response in 41% and 32%, survival of 10.8 and 6 months, and transplant in 40% and 42% of responders in MDS and AML. Treatment with high-dose cytarabine improved response rates in MDS and an anthracycline-containing regimen increased survival in AML.

Optimizing Cardiovascular Care in Children With Acute Myeloid Leukemia to Improve Cancer-Related Outcomes

2019 ◽  
Vol 37 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Saro H. Armenian ◽  
Matthew J. Ehrhardt
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Systolic Function ◽  
Left Ventricular ◽  
Laboratory Evaluation ◽  
Remission Induction ◽  
High Dose ◽  
High Dose Cytarabine ◽  
Lv Systolic Function ◽  
Acute Myeloid

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 14-year-old African American female presented with fatigue, easy bruising, and fever. On examination, she had scattered bruising, lymphadenopathy, and hepatosplenomegaly. Laboratory evaluation revealed pancytopenia with peripheral blasts, and acute myeloid leukemia (AML; French-American-British M2, t[8;21][q22;q22.1]) was diagnosed on bone marrow biopsy. A baseline echocardiogram revealed normal left ventricular (LV) systolic function (ejection fraction [EF], 60%; shortening fraction [SF], 32%), and conventional chemotherapy was initiated that consisted of two cycles of remission induction (cytarabine, etoposide, and daunorubicin [50 mg/m2 × 3 days per cycle]) followed by intensification 1 (high-dose cytarabine and etoposide), intensification 2 (high-dose cytarabine and mitoxantrone [12 mg/m2/dose daily; four total doses]), and intensification 3 (high-dose cytarabine and l-asparaginase). Of note, an echocardiogram was not repeated before the start of intensification 1. During intensification 1, the patient developed Streptococcus viridans sepsis, which required 4 days in the intensive care unit with antimicrobial and inotropic support. Repeat echocardiogram after recovery from the sepsis episode demonstrated low-normal LV systolic function (EF, 53%; SF, 27%), and she subsequently began intensification 2. On day 3 of intensification 2, the patient developed afebrile tachypnea, tachycardia, and an increasing oxygen requirement. Chest x-ray revealed cardiomegaly and pulmonary vascular congestion. Cardiac troponins were normal, whereas N-terminal pro B-type natriuretic peptide was 10 times the upper limit of normal. Repeat echocardiogram showed an enlarged LV with moderate to severely depressed LV function (EF, 28%; SF, 14%). Day 4 mitoxantrone was omitted and a cardiology consult obtained.

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission.

1996 ◽  
Vol 14 (8) ◽  
pp. 2206-2216 ◽  
Author(s):  
A S Stein ◽  
M R O'Donnell ◽  
A Chai ◽  
G M Schmidt ◽  
A Nademanee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adult Patients ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
Acute Myelogenous ◽  
Intent To Treat ◽  
First Complete Remission

PURPOSE To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.

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