scholarly journals Addition of Cladribine: Improving Standard of Care in Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3988-3988
Author(s):  
Shahram Mori ◽  
Nahir Rivera ◽  
Mohammed Wazir ◽  
Rushang D. Patel ◽  
Juan Carlos Varela ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Standard Of Care ◽  
The United States ◽  
Phase Iii ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Risk Patients ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) continues to be one of the most common myeloid malignancies in the United States. Achieving a complete response (CR) after induction with standard daunorubicin and cytarabine (7+3) remains suboptimal, occurring in 55-65% of patients. No significant advances have improved these outcomes in the last decade. A recent phase III randomized clinical trial by the Polish Adult Leukemia Group (PALG), showed that adding cladribine 5mg/m2 to standard 7+3 (Daunorubicin 60mg/m2, Ara-C 200mg/m2) improved CR rates to 68% vs 56% with standard 7+3 alone. Achieving a higher CR is important in the outcome of high-risk patients who require allogeneic stem cell transplantation (Allo-SCT) as a curative measure. At our center, we conducted a retrospective analysis evaluating the addition of cladribine to the current standard of care treatment in newly diagnosed AML. We hypothesized an improvement in CR rates in all-risk patients will allow more patients to proceed to Allo-SCT. Adult patients 18 years of age or older with newly diagnosed AML who received remission induction chemotherapy between May 2012 and May 2018 were included in the study. A total of 118 AML patients were screened and those who did not complete induction or did not have bone marrow biopsy at end of induction chemotherapy were excluded. A total of 100 patients were evaluable of which 26 (26%) received DAC and 74 (74%) received 7+3. Within the 7+3 group, 29 (39%) received a Daunorubicin dose of 60mg/m2 (D60) and 45 (61%) received a dose of 90mg/m2 (D90). A higher absolute CR rate was noted after one induction in the DAC group as compared to the combined 7+3 group (21 [80.7%] vs. 49 [66.2%], respectively). The improvement in CR between DAC and D60 reached statistical significance (p=0.043) but there was no statistically significance difference in CR rates between DAC vs D90 (p=0.48). It is interesting to note that more patients in D60 (39%) and D90 (26%) group required re-induction as compared with DAC (12%) (p=0.067). Median overall survival (OS) for the DAC group was not reached, while median OS for D60 was 10 (DAC vs D60 p=0.076) and for D90 was 28 months (DAC vs D90 p=0.97). In the subgroup of patients who underwent Allo-SCT, median OS in the D90 group was 30 months (DAC vs D90 p=0.43) while not reached in the DAC and D60 group (DAC vs D60 p=0.84). For all patients, the median relapse-free survival (RFS) for the DAC cohort was not reached. Median RFS was 12 months for D60 (DAC vs D60 p=0.047) and 25 months for D90 (DAC vs D90 p=0.166) groups. There was no difference in OS and RFS between all three groups who were transplanted in first CR (CR1). In conclusion CR rates following induction chemotherapy were higher in DAC vs Daunorubicin groups, however only statistically significant with respect to D60. Additionally a statistically significant improvement in RFS and a trend towards improved OS was noted in favour of DAC vs D60. Regardless of the induction chemotherapy, there was no difference in OS and RFS of patients who were transplanted in CR1. These results have encouraged us to perform a prospective comparison of standard 7+3 with Dauno 90mg/m2 and DAC. Disclosures No relevant conflicts of interest to declare.

On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group.

1989 ◽  
Vol 7 (9) ◽  
pp. 1268-1274 ◽  
Author(s):  
B Löwenberg ◽  
R Zittoun ◽  
H Kerkhofs ◽  
U Jehn ◽  
J Abels ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Supportive Care ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Survival Outcome ◽  
Phase Iii ◽  
Survival Duration ◽  
Remission Induction ◽  
Wait And See ◽  
Acute Myeloid

We report the results of a prospective study in patients more than 65 years of age in whom two different therapeutic strategies were compared: immediate intensive-induction chemotherapy (arm A) versus "wait and see" and supportive care and mild cytoreductive chemotherapy only for relief of progressive acute myeloid leukemia (AML)-related symptoms (arm B). The major objective of the study was to compare survival outcome of both regimens. Thirty-one patients on arm A received one or two courses of daunorubicin, vincristine, and cytarabine for remission induction followed by one additional cycle for consolidation in case of complete remission (CR). Among 29 patients on arm B, cytoreductive chemotherapy (hydroxyurea, cytarabine) had to be initiated for palliation of leukemia-associated complications in 21 patients at a median of 9 days after diagnosis. Overall survival duration for patients treated on arm A was significantly (P = .015) longer than the survival in arm B (median survival, 21 weeks v 11 weeks; projected survival at 2.5 years, 13% v 0%). Eighteen (58%) of arm A patients and none (0%) of arm B patients entered CR. Of the first group, projected disease-free survival at 2 years is 17%. The median percentages of days spent in the hospital by arm A and B patients were 55% and 50%, respectively. This study shows that a strategy based on modern supportive care and a wait and see approach yields extremely poor results. It is not superior in regard to the frequency of hospital admission and is inferior regarding survival outcome.

Acute Myeloid Leukemia: Challenges and Real World Data from India

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3685-3685
Author(s):  
Chepsy C Philip ◽  
Biju Geoge ◽  
Abhijeet Ganapule ◽  
Kavitha M Lakshmi ◽  
Fouzia N Abubacker ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Fungal Infection ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
Duration Of Symptoms ◽  
Npm1 Mutation ◽  
The Cost ◽  
Acute Myeloid

Abstract Management of acute myeloid leukemia (AML) in India remains a challenge. With a human development index rank of 134, a per capita gross net income of US$3500 and a government expenditure of only 1.2% of GDP allocated for health (http://indiabudget.nic.in) a major constraint to treatment of AML remains the cost of therapy. In the majority (>80%), in the absence of a universal and comprehensive health insurance, most payments are out of pocket (Karan et al. Health Policy and Planning 2008). We undertook a two year prospective study to evaluate the clinical characteristics and outcome of patients with a diagnosis of AML (AML-M3 excluded) referred to our tertiary care center. The study was conducted from July 2012 till June 2014 and was approved by the institutional ethics committee. In addition to standard of care diagnostic tests and therapy a detailed questionnaire was administered to patients at diagnosis and on follow up. A total of 427 patients were diagnosed with AML during this period. Of these 380 (89%) were newly diagnosed. Of the newly diagnosed 47 (12.3%) were ≤ 15 years and 62 (16.3%) were ≥ 60 years old. The age distribution of newly diagnosed cases is illustrated in Figure 1A. The median age of newly diagnosed patients was 40 years (range: 1-79) and there were 244 (64.2%) males. The median duration of symptoms prior to first presentation at our hospital was 4 weeks (range: 1-52). ECOG performance score at presentation was ≤ 2 in 94.7%. Cytogenetic data was available in 281 and of these 33 (11.7%), 197 (70.1%) and 51 (18.2%) were in the good, intermediate and adverse risk groups respectively. FLT3 and NPM1 mutation status was available in 143 and of these 22 (15.8%) and 5 (3.4%) were FLT3-/NPM+ and FLT3+/NPM- respectively. The median distance from home to hospital was 580km (range: 6-3200) and 27 patients were from another country. 348 (91.6%) patients were self paying with all expenses being out of pocket (data was not available in 7). Of the newly diagnosed patients only 109 (28.7%) opted for standard of care and were admitted for induction chemotherapy (Figure 1B). The comparison of the 109 that took treatment and the 271 (71.3%) that did not revealed that these two groups were comparable for the above baseline characteristics with the following exceptions; those that did not take treatment resided significantly further away from the hospital, had significantly longer duration of symptoms prior to reaching our hospital and were significantly less likely to be ≤15 years. Of the 271 that did not take treatment the major reason was lack of financial support in 219 (80.8%), lack of social support in 46 (17.6%) and a combination of denial, choice of alternative medicines, apathy and fatalistic attitude in 39 (14.9%). 220 (81%) of those that did not receive treatment were ≤ 60 years old. Induction chemotherapy consisted of standard induction as in the BFM98 protocol for patients ≤15 years, conventional 7/3 in adults and hypomethylating agents in older patients or in young adults with significant co morbidities at the discretion of the treating physician (n=12(11%) and of these 6 were ≥60 years). Following induction chemotherapy 100% developed febrile neutropenia. Blood cultures detected an organism in 71 (65%) on at least one occasion and the organism was a Gram negative bacilli (GNB) in 45 (42%), Gram positive in 18 (16%) and mixed/ alternate infection in 8 (7%). Of the GNB 19 (42%) were carbapenem resistance organisms (CRO) (Figure 1C). 30 (27.5%) had a fungal infection in induction which was proven (EORTC/MSG criteria) in 4 (Figure 1D). There were 27 (24.7%) inductions deaths and of these 18 (67%) were due to sepsis related to GNB of which in 12(67%) the organism was a CRO. Among the patients that had an induction death in 12 (52%) there was evidence of a fungal infection which was proven in one case. The overall survival at one year was 70.4%±10.7%, 55.6%±6.8% and 42.4%±15.6% in patients ≤ 15 years, >15to <60 years and in ≥ 60 years age groups respectively. In conclusion there are significant challenges in the management of AML in India. The major reason for not proceeding with treatment is the absence of financial resources. Induction deaths are related to a high incidence of multi-drug resistant organisms and fungal infections. The biggest constraint is the cost of the treatment and the absence of a health security net to treat all patients with this diagnosis. Disclosures Srivastava: Octapharma: Consultancy, Other.

Sequential Combination of Gemtuzumab Ozogamicin and Standard Chemotherapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia: Results of a Randomized Phase III Trial by the EORTC and GIMEMA Consortium (AML-17)

2013 ◽  
Vol 31 (35) ◽  
pp. 4424-4430 ◽  
Author(s):  
Sergio Amadori ◽  
Stefan Suciu ◽  
Roberto Stasi ◽  
Helmut R. Salih ◽  
Dominik Selleslag ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Sequential Combination ◽  
Grade 3 ◽  
Acute Myeloid

Purpose This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML). Patients and Methods Patients (n = 472) age 61 to 75 years were randomly assigned to induction chemotherapy with mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6 mg/m2 on days 1 and 15). In remission, patients received two consolidation courses with or without GO (3 mg/m2 on day 0). The primary end point was overall survival (OS). Results The overall response rate was comparable between the two arms (GO, 45%; no GO, 49%), but induction and 60-day mortality rates were higher in the GO arm (17% v 12% and 22% v 18%, respectively). With median follow-up of 5.2 years, median OS was 7.1 months in the GO arm and 10 months in the no-GO arm (hazard ratio, 1.20; 95% CI, 0.99 to 1.45; P = .07). Other survival end points were similar in both arms. Grade 3 to 4 hematologic and liver toxicities were greater in the GO arm. Treatment with GO provided no benefit in any prognostic subgroup, with the possible exception of patients age < 70 years with secondary AML, but outcomes were significantly worse in the oldest age subgroup because of a higher risk of early mortality. Conclusion As used in this trial, the sequential combination of GO and standard chemotherapy provides no benefit for older patients with AML and is too toxic for those age ≥ 70 years.

scholarly journals The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

2021 ◽  
Vol 10 ◽  
pp. e2288
Author(s):  
Mahdiyar Iravani Saadi ◽  
Mani Ramzi ◽  
Aliasghar Karimi ◽  
Maryam Owjfard ◽  
Mahmoud Torkamani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Quantitative Polymerase Chain Reaction ◽  
Remission Induction ◽  
Response To Chemotherapy ◽  
Before And After ◽  
Acute Myeloid

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

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