Low Doses Of Cytarabine Research Articles

Budget impact analysis of venetoclax for the management of acute myeloid leukemia from the perspective of the social security and the private sector in Argentina.

This study aimed to estimate the budget impact of the incorporation of venetoclax for the treatment of patients with Acute Myeloid Leukemia (AML) over 75 years of age or those with comorbidities and contraindications for the use of intensive chemotherapy, from the perspective of the social security and the private third-party payers in Argentina. A budget impact model was adapted to estimate the cost difference between the current scenario (azacitidine, decitabine and low doses of cytarabine) and the new scenario (incorporation of venetoclax) for a third-party payer over a time horizon of three years. Input parameters were obtained from a literature review, validated or complemented by expert opinion using a modified Panel Delphi approach. All direct medical costs were estimated by the micro-costing approach and were expressed in US dollars (USD) as of September 2020 (1 USD = 76.18 Argentine pesos). For a third-party payer with a cohort of 1,000,000 individuals covered, incorporating venetoclax was associated with an average budget impact per-member per-month (PMPM) of $0.11 USD for the social security sector and $0.07 USD for the private sector. The duration of treatment with venetoclax was the most influential parameter in the budget impact results. The introduction of venetoclax was associated with a positive and slight budget impact. These findings are informative to support policy decisions aimed to expand the current treatment landscape of AML.

Real World Data Venetoclax Based Therapies in a Single Center in Latin America

Introduction: Venetoclax-based therapies have changed the outcomes of acute myeloid leukemia, in combination with hypomethylating agents, low-dose cytarabine or in older patients not eligible for intensive regimens. Combinations with venetoclax with target therapy and with standard chemotherapy are being tested to improve outcomes in specific subgroups. In Latin America, the lack of clinical trials increases prescriptions not yet approved in international guidelines (off-label use). In this paper, we present data from a private reference center in Latin America for the treatment of acute myeloid leukemia and high-risk myelodysplasia. Methods: This is a unicentric, retrospective, and non-interventional cohort study performed at Brazilian Hospital Albert Einstein. Inclusion criteria were adult patients (aged ≥18 years) diagnosed with AML between May 2019 and January 2023, who were treated with a venetoclax-based regimen. Independent variables analyzed were age, gender, prognostic risk according to ELN 2022, indication of bone marrow transplantation, and molecular and cytogenetic risk at diagnosis. Results: Sixty-three (N= 63) patients were included, with a median age of 63.1 years old. Forty-eight patients received a combination of venetoclax and a hypomethylating agent, two were associated with low doses of cytarabine, eight were associated with target therapy (inhibitor of FLT3), and five with intensive chemotherapy. The median follow-up was 303 days, and the median use of venetoclax in those who did not suspend treatment was 352 days. The main cause of suspension was hematological toxicity. In the univariate analysis, the following onco-hematological karyotype variables, age, type of regimen combined with venetoclax, and decision for transplant did not show statistical significance. Conclusion: Real-world data show that venetoclax-based therapies are effective in patients with AML, and their combinations have been increasingly explored.

P1612: ACUTE MYELOID LEUKEMIA IN ADULT PATIENTS: FEATURES OF TREATMENT IN CONTEXT OF THE COVID-19 PANDEMIC.

Background: Acute myeloid leukemia (AML) is a disease with a poor prognosis and a high mortality rate, while patients with acute myeloid leukemia are at increased risk of complications from COVID-19 infection. Aims: To investigate the treatment effectiveness and survival of patients with AML who had the COVID-19 diagnosis confirmed, as well as evaluating predictors of hospital mortality among this group of patients. Methods: From April 2020 to November 2021, Moscow City Clinical Hospital 52 treated 149 patients with AML who had the COVID-19 diagnosis confirmed, with a median age of 61 years (range 18-91), while 56% of patients were over 60 years old. An equal ratio of men and women was performed, 70 and 79 respectively. 13% were diagnosed with APL, while the remaining 87% had other variants of AML. At the time of hospitalization the most of the patients admitted had first- or second-degree pulmonary lesions (28 and 35%, respectively), while 31% of patients performed more severe lesions and the other 6% had no pulmonary damage detected, but they had a positive PCR. At the time of hospitalization, 10 out of 149 patients (7%) achieved complete remissions (CR) and were withdrawn from therapy; 41 patients (28%) were diagnosed with AML for the first time in our clinic; and 98 patients (65%) were already in process of AML treatment in other clinics. The effectiveness of treatment was assessed by the frequency of CR, as well as by the amount of cases of lethality and in-hospital survival rates. The analysis of treatment results was performed as at 01 November 2021. Results: 60 patients (38%) with AML (excluding APL) and confirmed COVID19 received anti-tumor treatment. Palliative care was received by 23 patients (38%), these were predominantly elderly patients with a median age of 71 years (range 45-91 years), with severe COVID-19. 19 patients (32%) with a median age of 38 years (range 21-61 years) received the 7 + 3 treatment protocol. While 18 elderly patients (30%) with a median age of 70 years (range 60-85 years) received the low intensity therapy (low doses of cytarabine, hypomethylation therapy and venetoclax containing regimens). As a result of COVID-19, 79 patients (54%) died. The main factor determining the high mortality rate in our study was the absence of AML CR. The Survival of patients in CR was 96.3±3.6%, which means almost all patients have recovered from COVID-19 and were discharged to continue their treatment in other medical institutions. For patients out of remission and primary patients with AML the survival rate was 38.0±6.5% and 33.7±8.7%, respectively. For the purposes of analyzes of predictors of survival, we divided our patients into 2 groups, due to a great variety of prognosis. Remission status essentially outweighs all other factors, including presence of significant comorbidities, AML variants, isolated cytopenias, severity of COVID-19 (CT, CRP, D-dimer, etc.), nature of AML therapy and other factors. In the group of patients out of AML remission the negative predictive value for hospital survival was shown by age over 60 years, as well as by agranulocytosis, CT 3-4, the use of GCS and transfer to the ICU. Summary/Conclusion: The diagnosis of COVID-19 in patients with AML greatly worsens their life prognosis. The leading predictor of mortality becomes the lack of remission of AML. Thus, antitumor treatment allows achieving CR, which in turn reduces the risk of developing a severe course of coronavirus infection.

Current State of Diagnosis and Treatment of Acute Myeloid Leukemias in Adult Patients in the Republic of Kazakhstan

Background. In recent years, the incidence of acute myeloid leukemias (AML) globally has continued to increase. Current approaches to AML treatment remain a challenge for the healthcare in many countries. There are only single studies on the analysis of AML state in adult patients in Kazakhstan. Over the last 10 years in Kazakhstan, no results of AML monitoring in adult patients have been available. Aim. To study the characteristics of clinical course and treatment outcomes in AML in the Central Kazakhstan and in the city of Ust-Kamenogorsk, East Kazakhstan Region. Materials & Methods. The study enrolled 86 AML patients (46 men and 40 women), the median age was 60.5 years (range 19-86 years); 64 (74.4 %) patients were from Karaganda Region, 15 (17.4 %) patients were from Ust-Kamenogorsk, and 7 (8.1 %) patients were from other regions of Kazakhstan. The analysis covered the structure and treatment outcomes in newly diagnosed AML patients within the period from 2018 to June, 2021. Statistical analysis of data was made using SPSS Statistics 23.0. Results. The analysis of diagnostic techniques showed that myelogram and immunophenotyping were used in 98.8 %, cytogenetic assay was made in 18 %, and molecular analysis was performed in 59.3 % of patients. The “7+3” remission induction was administered in 54.6 % of patients, 20.9 % of patients were treated with hypomethylating agents and low doses of cytarabine, and 24.4 % of patients were on palliative and supportive therapy. Out of 47 patients treated with the “7+3” remission induction, complete clinical hematological remission was reached in 29 (61.7 %) patients. Primary resistance was reported in 21.3 % of patients. Early mortality (death within 30 days from the start of induction) rate was 17 %. High-dose cytarabine consolidation (1.5-3 g/m<sup>2</sup> twice every other day, 2-3 courses) was administered to 75.8 % of patients. All the allogeneic bone marrow transplantations (n = 7) were performed at the National Research Center for Oncology and Transplantology in Nur-Sultan. The median overall survival in the group of standard “7+3” chemotherapy recipients was 11 months (range 1-83 months), and the median disease-free survival was 9 months (range 2-79 months). Conclusion. The study presents the characteristics and short-term outcomes of treatment of adult AML patients in Kazakhstan. The study limitations were a short follow-up period and enrollment of patients only from two regions of Kazakhstan. It is necessary to continue improving the current standards of AML diagnosis and treatment of adult patients.

Real Life Study on Allogeneic Hematopoietic Cell Transplantation Practice According to International Guidelines and Its Impact on Survival in Acute Myeloid Leukemia French Population

IntroductionAllogeneic Hematopoietic Cell Transplantation (allo-HCT) has proved its efficiency in reducing Acute Myeloid Leukemia (AML) recurrence, although it was associated with high rates of complications especially in older patients. The worldwide number of allo-HCT has increased within 35 years, from 10.000 transplantations before 1985 to over a million in 2012. The decision to perform transplantation depends on the estimated risk-benefit ratio. High-risk prognostic factors include cytogenetics, age at diagnosis, presence of comorbidities and the response to treatment. By using combination of risk factors, international recommendations have been published to harmonize AML care and maximize the benefit of using allo-HCT. The principal aim of this study is to describe real life AML care management in all consecutive patients diagnosed and registered on 3 regional cancer registries in France, to analyze their outcome after different therapeutic strategies, following or not the international recommendations.MethodThis retrospective study included all AML patients diagnosed between January 2012 and December 2016 reported to the French population data-based of regional cancer registries specialized in hematological malignancies. Allo-HCT data were extracted from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) registry. Two groups of patients were defined according to the treatment received: i) group 1, patients who have received the best recommended care including allo-HCT considering HLA compatibility and best donor choice or best conventional treatment according to therapeutic guidelines based on individuals and clinical characteristics from The American Society for Blood and Marrow Transplantation guidance; ii) group 2, patients who received a treatment outside the recommendations.To study the impact of therapeutic decision on overall survival, a case-control study was performed using a one for one matching between group 1 and group 2. An exact matching on individual and disease characteristics (cytogenetic risk, Charlson score class, age group at diagnosis, subtype AML and response to treatment) allowed to pair-match patients following or not the international recommendations for therapeutic strategy. Net survival was estimated until five-year using non-parametric Pohar-Perme estimator (survival distribution compared using Grafféo test).ResultsA total of 1039 AML patients diagnosed from 2012 to 2016 were identified, 449 (43 %) received a curative treatment and 540 patients a non-curative treatment (hypomethylating agents, low dose of cytarabine or other palliative treatment, best supportive care combined to no effective treatment). Based on available clinical data, 430 patients were included in the study.Group 1 included 296 patients (68%), 167 males and 129 females with 54 receiving allo-HCT (32 geno-identical and 22 unrelated). Group 2 included 134 patients (31%), 72 males and 62 females with 94 receiving allo-HCT (14 geno-identical, 50 unrelated and 30 mismatched).In patients for whom allo-HCT represented the best option according to the recommendations (Figure B, n = 44), a very significant lower survival was observed in patients who did not receive allo-HCT when they were compared to patients who received allo-HCT, with a 5 year-overall survival probability of 7 % and 50 % respectively (p= 0.019). In patients for whom allo-HCT was not recommended (Figure A, n = 42), we did not observe any significant difference of survival between patients transplanted or not.ConclusionThis analysis shows the importance of allo-HCT decision in AML patients, especially when following international guidelines. Although individual risks factors have been previously studied, our analysis sums up theses factors and allow to understand the importance of integrating allo-HCT in the therapeutic strategy of AML and to re-evaluate current practices and its impact on patient outcome. [Display omitted] DisclosuresPigneux: Roche: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Amgen: Consultancy; Novartis: Consultancy, Research Funding. Forcade: Novartis: Other: travel grant. Mohty: Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Sanofi: Honoraria, Research Funding; Adaptive Biotechnologies: Honoraria. Dulery: Novartis: Honoraria; Takeda: Consultancy; Gilead: Other: Travel support and registration fees for scientific meetings .

Adult Langerhans cell histiocytosis presenting with multisystem involvement and sarcomatoid features: a case report

BackgroundLangerhans cell tumors are rare clonal disorders characterized by neoplastic proliferation of dendritic cells that can be further classified into the subtypes Langerhans cell histiocytosis and Langerhans cell sarcoma, which are rare neoplasms exhibiting aggressive features and a poor prognosis. In addition to illustrating the refractoriness and poor outcomes of multisystem Langerhans cell histiocytosis in adults, specific events in this case highlight important characteristics of disease biology that warrant detailed discussion and exposition to a wider audience.Case presentationWe describe the case of a 42-year-old Caucasian man with Langerhans cell histiocytosis diagnosed from a lesion on the left arm that presented with constitutional symptoms, early satiety, and weight loss. Esophagogastroduodenoscopy showed extensive esophageal and duodenal involvement by Langerhans cell histiocytosis with features of Langerhans cell sarcoma. He was initially treated for Langerhans cell histiocytosis with low doses of cytarabine until he eventually presented clear transformation to acute monoblastic leukemia with complex karyotype that could not be properly controlled, leading eventually to death.ConclusionsLangerhans cell histiocytosis remains an exceedingly rare entity in adults, frequently presenting as multisystem disease with risk organ involvement. Langerhans cell sarcoma represents an aggressive subtype with extremely poor prognosis for which intensive acute myeloid leukemia induction should be strongly considered.

The Use of Venetoclax for Acute Myeloid Leukemia in a Real-Life Setting: A Multicenter National Experience

The Use of Venetoclax for Acute Myeloid Leukemia in a Real-Life Setting: A Multicenter National Experience

Using HSP90 Inhibitors to Target DNA Repair Proteins in AML

Acute myeloid leukemia (AML) is a disease of proliferative and abnormally differentiated myeloid cells(Döhner, Weisdorf, & Bloomfield, 2015) that is characterized by chromosomal aberrations and gene mutations that influence outcome(De Kouchkovsky & Abdul-Hay, 2016). Despite the approval of targeted therapies, induction therapy with cytarabine (Ara-C) and anthracycline has remained the standard of care for AML(Dombret & Gardin, 2016; Showel & Levis, 2014). Newer chemotherapeutics such as Sapacitabine have shown comparable clinical outcomes to Ara-C in older patients(Burnett et al., 2015). Ara-C is a nucleoside analog which incorporates during DNA replication and stalls replication(Liu et al., 2010) while Sapacitabine induces single stranded nicks in the DNA leading to double stranded breaks which are repaired by Homologous Recombination (HR)(Burnett et al., 2015; Lim & Jamieson, 2014). However, eventually patients develop resistance to chemotherapy leading to poor prognosis after relapse(Wu, Duan, Chen, & Chen, 2017). One aspect of this is due to upregulation of DNA damage repair proteins leading to increased repair of any DNA lesions primarily through HR. We therefore are interested in developing a way to target DNA repair to extend nucleoside analog therapy in AML.HSP90 is a molecular chaperone that is critical for the folding and proper function of multiple key proteins of various DNA repair pathways(Dote, Burgan, Camphausen, & Tofilon, 2006). Relevant to such repair, ATM and Chk1 become recruited to DNA double strand breaks to activate defined downstream signaling cascades that result in cell cycle arrest and DNA repair(Ceccaldi, Rondinelli, & D'Andrea, 2016). Of these,γ-H2AX acts a sensor of DNA damage and repair by forming foci at the sites of damaged DNA that get resolved upon successful repair(Sharma, Singh, & Almasan, 2012). Similarly, the Rad51 helicase plays a key role in HR repair and the presence of Rad51 foci can be used as a marker for successful HR(Gachechiladze, Škarda, Soltermann, & Joerger, 2017). To determine whether inhibiting HSP90 compromised DNA repair, we treated both AML cell lines OCI-AML3 and MV4-11 with HSP90 inhibitor, onalespib. OCI-AML3 cells show a time dependent decrease in DNA damage repair proteins Chk1 and Rad51 by western blotting. Furthermore, primary patient samples treated with onalespib for 24 and 36 hours also show a depletion of Chk1 and Rad51. We then used ionizing radiation (IR) to induce dsbreaks and induce signaling and repair(Ceccaldi et al., 2016). Using immunofluorescence, we found that in OCI-AML3 after exposure to IR there was a significant increase in number of Rad51 foci after 6 hours. The large number of γ-H2AX foci formed at .5 hour after IR decrease by 6 hours post-IR. This suggests that there is a successful HR repair occurring in this AML cell line. When OCI-AML3 cells were pretreated with onalespib, Rad51 foci are no longer present and γ-H2AX foci remained present at 6 hours suggesting unrepaired dsbreaks. Using the colony forming assay we see that there is a slight decrease in viability of OCI-AML3 cells exposed to onalespib however, in MV4-11 cells there is a steep decline which could be due to the differential expression of genes such as FLT3-ITD, a client protein of HSP90. Low doses of cytarabine or sapacitabine modestly decreased colony growth of OCI-AML3 and MV4-11 cells but exposing cells to onalespib for 24 hours sensitized the cells to both cytarabine and sapacitabine. Finally, we have also evaluated effects of onalespib in an in-vivo MOLM13 driven mouse model of AML and have shown that treatment with onalespib extended survival in this mouse model. DisclosuresMims:Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy.

Molecular Screening of 28 Genes in Mexican Patients with Acute Myeloid Leukemia a Series of 70 Patients from the Instituto Nacional De Cancerologia, Mexico

Introduction:Acute Myeloid Leukemia is a clonal heterogeneous disease, where age is an important risk factor to develop theses disease, PCR studies and next generation sequence have proven the diversity of these disease. A lot of genes mutations have been identifying to play a role in the DNA metilation, epigenetics a transcription. We initiate a screening to all acute myeloid leukemias that where the novo or relapse with a 28 gene panel of HEMAVISION a 28q; DNA diagnostic, for the detection al ARN gene fusion and alternatives of the: PML-RAR ALFA (bcr2,V), CBF-MYH11, RUNX1-RUNX1T1, PML-RAR alfa(bcr1,L), KMT2A-MLT3, PML-RAR alfa (bcr3,S), KMT2A-ELL, FUS-ERG, ETV6-MN1, DEK-NUP214, KMT2A-EPS15, KMT2A-AFDN, TCF3-PBX1, ETV6-RUNX1, KMT2A-MLLT1, KMT2A-AFF1, TCF3-HLF, STIL-TAL1, BCR/ABL(p190), SET-NUP214, BCR/ABL(p210), BCR/ABL(p230), ZBTB16-RARalfa, ETV6-ABL1, ETV6-PDGFRB, KMT2A-MLLT10, KMT2A-MLLT11,KMT2A-FOXO4, KMT2A-MLLT6, RUNX1-MECON, NPM1-RAR alfa, NMP1-MLF1, RUNX1-MECON.FLT3 ITD mutation and D385 by PCR electrophoresis by Invivoscribe was also perform. And the regular cytogenetics and FISH mutations for BCR/ABL, PML/RAR alfa, Inv16, MLL, +8, ETO, BCR, ABL, monosomy 7, monosomy8ObjectivesThe main objective is the know the mutation in the Mexican population and the prognostic in these group of patientsResultsThese study was perform at Instituto Nacional de Cancerologia, Mexico, randomized patient from 2016-2018 where screen. A total of 70 patients, 37 females and 33 males, ages from 18-85years old, 54 patients where newly diagnosis of acute myeloid leukemia, 4 where relapses and 12 where secondary leukemias, the most frequent FAB morphologic classification where M4:22 cases, M2:15 cases, M3:8 cases, M1:4cases, M0 and M5:3 cases each.Of the 70 patients: 56 patients where negative to all of the panel screen, FLT3 where only perform in 14 patients 12 where negative and 2 where insufficient to perform the test, the most common FISH translocation was PML/RAR alfa, follow by MLL, ETO and +8.For the cytogenetics we had 21 cases that didn´t have enough metaphases, 7 normal, 28 cases with more than 2 cytogenetics alterations and 9 with only 1. With a Cytogenetics risk: high risk 44, intermedium:10 and low12.Of the 70 patient, 14 have some genes mutations +: t(9;11)(p22;q23) KMT2A-MLLT3, t(6;11)(q27;q23) KMT2A-AFDN, t(5;12)(q33;p13) ETV6-PDGFRB, t(8;21)(q22;q22) RUNX1RUNX1T1, inv16(p13q;22q) CBFB-MYH11, t(6;11)(q27;q23) KMT2A-AFDN, t(3;21)(q26:q22) RUNX1-MECOM, inv16(p13q;22q) CBFB-MYH11, t(15;17)(q24;q21) PML-RARA (bcr2,V) t(15;17)(q24;q21) PML-RARA (bcr1,L) t(15;17)(q24;q21) PML-RARA (bcr3,S), t(8;21)(q22;q22) RUNX1RUNX1T1, t(8;21)(q22;q22) RUNX1RUNX1T1, t(15;17)(q24;q21) PML-RARA (bcr3,S)Out of 70 patients: 38 receive 7+3 (cytarabine + Daunorubicin) for first line of treatment, 41 received high doses of cytarabine at 3g /m2. Our first option for relapse treatment is MEC (mitoxantrone, cytarabine and etoposide) because of costs and the second line of rescued treatment is Flag- Ida (idarubicin, fludarabine and cytarabine) and not all patient can afford it.For the elderly patients the first line of treatment is low dose of cytarabine and only in those who can pay azacytidine it is use.The correlation between high risk cytogenetics with mortality is 12 cases out 70. And genes with morality only 4 patients with: t(9;11)(p22;q23) KMT2A-MLLT3, t(6;11)(q27;q23) KMT2A-AFDN, t(5;12)(q33;p13) ETV6-PDGFRB, t(6;11)(q27;q23) KMT2A-AFDNConclusionWe need to know our population characteristics, we don´t have the incidence and prevalence of the gene mutation in the Mexican population. In the market there are several screening panels with different genes. We need to have more genes and more patient to be analyzed to learn our molecular risk, to have a better approach to these patients and better techniques.There is no paper publish with the genetics and gene alteration in the Mexican Population, it is important to continuing working and to use panels with genes as ASXL1, FLT-TKD, CEBPA, KIT, KRAS, IDH1,2, TET2 and others.And other important issue that we found is the high number of patient that abandon treatment 4 cases, because of money issues. And the time of these population 24 patient where death.The incidence of FLT3 mutation ITD and D385 is low in theses population but it was performed only 14/70 patients, we need a large number of patient to know the real incidence. DisclosuresNo relevant conflicts of interest to declare.

The priming induction regimen of HAG as a low dose chemotherapy strategy in AML clonal evolution.

Chemotherapy employs chemical substances to interfere with the growth of cancer cells, and is a major treatment strategy in human cancer including acute myeloid leukemia (AML). Although they often effectively kill fast-dividing tumor cells, chemotherapeutic drugs also profoundly affect mutation spectrum of the tumor genome. Each chemotherapeutic drug has a working concentration within an appropriate range. Concentrations beyond this range will increase drug toxicity without adding clinical benefit, while concentrations below the range will result in an insufficient drug effect. The conventional strategy in oncology is to give a patient drugs at the maximum tolerated dose (MTD) in order to kill as many tumor cells as possible. However, this inevitably causes a high rate of toxicity to normal tissue, as well as resulting in new mutations and genome instability which can lead to drug resistance and relapse. The priming induction regimen of HAG (low dose of cytarabine (Ara-C) and Homoharringtonine (HHT) with granulocyte colony-stimulating factor (G-CSF) priming), has proven to be effective in subgroup of AML patients in small scale clinical studies. It is of great medical significance to explore whether low dose chemotherapy can reduce the side effect of chemotherapeutic drugs while maintaining the therapeutic benefits, and whether such alternative therapeutic strategy is advantageous compared to conventional intensive treatment regarding the development of drug resistance by affecting leukemic genome mutation load and clonal evolution in subgroup of AMLs.

The Survival Of The Elderly Acute Myeloid Leukemia Patients Do Not Depend On The Intensity Of Induction Chemotherapy. Retrospective Study Results

The aims of this study were comparison of overall survival (OS) and complete remission rate (CR) in whole group of acute myeloid leukemia (AML) >60 patients, and in younger older (61 – 70) AML patients in dependency of qualification to risk group according to PALG stratification and a schedule of treatment.Patients with AML >60 after diagnosis were qualified into the risk groups according to PALG stratification for AML >60. The patients from group 1 patients were receiving intensive induction chemotherapy DAC (daunorubicin, cytarabine, cladribine) or DA (daunorubicin, cytarabine), those from group 2 were receiving cytarabine+thioguanine induction chemotherapy, and those from group 3 chemotherapy with low doses of cytarabine. Patients from first group, who reached CR after induction were receiving consolidation with mitoxantrone + standard dose of cytarabine, and next they were qualified to HSCT or maintenance phase. Patients from group 2 and 3 independently of results of induction were receiving successive cycles of chemotherapy like in first course every 4 weeks to 2 years with very intensive supportive care.One hundred sixteen patients with untreated AML treated In period 02.2009-12.2012, age 73 (61-89), men 50% were included to this study. Thirty three patients were qualified to group 1, 50 to second and 33 to third. After preliminary analysis, because of similar early and late outcomes of the therapy in group 2 and 3, those groups of patients were joint for next analysis. Disclosures:No relevant conflicts of interest to declare.In comparison of therapy outcomes in group 1 and in group 2+3 of patients with AML >60 significantly higher CR rate in group 1 vs. 2+3 48% vs. 2% (p<0,001) was confirmed but OS was not better after 2 years 10% vs. 8% (p=NS).The same results were stated In subgroup of age 61-70 of AML patients despite of significantly higher CR in group 1 vs. group 2/3 46% vs. 7% (p=0,01) we did not obtain a benefit in OS after 2 years 9% vs. 25% (p=NS) respectively.In conclusion we must underline, that in elderly AML patients proper qualification to favorable risk group and as a consequence more intensive induction chemotherapy is a main predictor of better CR rate, but overall survival do not depend on the intensity of the induction therapy.

HPLC–MS/MS Method for the Determination of Cytarabine in Human Plasma

Cytarabine is an anti-tumor drug that is currently under investigation for treatment in combination with other anticancer drugs for the chemotherapy of leukemia. The quantitative determination of cytarabine in plasma is challenging due to the required sensitivity, its in vitro instability and the presence of an isobaric endogenous compound, cytidine. Owing to the polarity of cytarabine, conventional chromatography cannot provide adequate separation of the analyte and the interfering compounds. A few analytical methods have been reported for the determination of cytarabine in plasma, but their sensitivity was not sufficient since most of these methods apply spectrophotometric detection. In this article, an LC-MS/MS method is described for the determination of cytarabine in human plasma down to the sub ng/ml level. To prevent conversion of cytarabine by cytidine deaminase, whole blood samples were stabilized with tetrahydrouridine directly after the collection of whole blood at the clinical site. Cation-exchange SPE was employed to extract cytarabine from 50 µl human plasma. UHPLC on high strength silica T3 column (100 × 2.1 mm × 1.8 µm) was applied to achieve adequate separation of cytarabine from cytidine within a reasonable run time of 5 min. A triple quad mass spectrometer equipped with an ESI source was used for detection. The method was linear over the concentration ranges of 0.500-500 ng/ml. The intra- and inter-day relative standard deviation (precision) as well as the bias (accuracy) were well below 15%. In the presence of tetrahydrouridine, cytarabine was sufficiently stable under all relevant conditions. The method was successfully applied to support a clinical pharmacokinetic study with a low dose of cytarabine.

Acute Myeloid Leukemia in the Elderly, Intensive or Maintenance Therapy? Our Experience in Patients over 65 Years.

The treatment of acute myeloid leukemia in elderly with age > 65 years is still debated. Various reported studies have valued the feasibility of intensive chemotherapy in these setting of patients. The aim of the our study is to value the difference in DFS and OS among 2 groups of elderly patients with AML treated with intensive chemotherapy (IC) or maintenance (M). From June 2001 to May 2005 we have accepted in our Division 45 patients affected by AML aged up to 65 years. 25 were male and 20 were female, with a median age of 75 years (range 67–86 years). 22 patients (12 M and 10 F, median age: 71 years) received intensive chemotherapy (I.C. Flag and MICE) and 23 (13 M and 10 F, median age: 78 years) received or maintenance therapy (low dose cytarabine) or only support. In IC group 11 patients (50%) have obtained to complete remission (CR) with a DSF and OS media of 7,5 and 6,3 months respectively, and a TRM rate of 27%. In the M group the CR has been documented in 6 patients (35%) treated with low dose of cytarabine, with a DFS and OS media of 6,9 and 4,4 months respectively (graph 1–2). This results have shown, as expected, a better CR rate in the IC group, but without any advantage in terms of OS and DFS when compared with the M group. Difference is not statistically significant between the two groups (p: 0.5). Despite a good CR rate, Intensive chemotherapy do not improves survival in elderly patients. This is probably due to the combination of either a high TRM in patients treated with intensive chemotherapy or a high relapse rate. New therapeutics strategies are needed to improve DFS and OS in these patients. Interesting is the use of specific monoclonal antibodies (anti CD33) in this poor risk disease especially in maintenance after a CR obtainable with a low intensive or low dose chemotherapy. [Display omitted]

Successful treatment of a 93-year-old patient with hypoplastic acute monocytic leukemia using macrophage colony-stimulating factor

A 93-year-old patient with hypoplastic acute monocytic leukemia (AMoL) achieved a complete remission after macrophage colony-stimulating factor (M-CSF) therapy. Initially, the patient was treated with a low dose of cytarabine, but this treatment proved ineffective. M-CSF was administered for 14 days by drip intravenous infusion, 800 × 10 4 units per day. After a gradual decrease in the number of leukemic cells, a rapid increase in neutrophils was observed in the peripheral blood, and a bone marrow examination 22 days after discontinuation of M-CSF medication revealed a complete remission. These findings suggest that M-CSF may be useful in treating some elderly patients who have hypoplastic AMoL.