Priming with Granulocyte Colony-Stimulating Factor (G-CSF) Has No Impact on Treatment Outcome but Impairs Mobilization of Peripheral Blood Stem Cells (PBSC) in Elderly Patients with Acute Myeloid Leukemia: Results of a Randomized Oligocenter Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 867-867
Author(s):  
Gesine Bug ◽  
Steffen Koschmieder ◽  
S. Wiebe ◽  
Gerd Heil ◽  
Carla Delfs ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Secondary Aml ◽  
Remission Duration ◽  
Cd34 Cells ◽  
Acute Myeloid

Abstract Treatment of elderly patients with acute myeloid leukemia (AML) is characterized by a low complete remission (CR) rate of less than 50% and short remission duration with a median disease-free survival (DFS) of less than one year (Rowe et al., Blood 2004). Sensitization of leukemic cells with growth factors may enhance the efficacy of chemotherapy in AML patients. Aims of this randomized prospective, oligocenter study were 1) to assess whether induction chemotherapy given simultaneously with and followed by G-CSF (G-CSFpriming) was superior to G-CSF following induction (G-CSFpost) with regard to CR rate and DFS in pts aged older than 60 yrs with previously untreated de novo and secondary AML and 2) to examine the feasibility of an early consolidation therapy followed by autologous stem cell transplantation (ASCT) as late consolidation. Between 01/00 and 04/04, a total of 116 eligible patients (median age 67 yrs) were randomly assigned to receive G-CSFpriming (n=57) or G-CSFpost (n=59) during two remission-induction cycles consisting of idarubicin, cytarabine and etoposide (IdAV) with daily application of 5μg/kg G-CSF (Neupogen®, Amgen). Pts achieving a CR received early consolidation using fludarabine, cytarabine, idarubicin, G-CSF (mini-FlagIda) and PBSC harvest, followed by ASCT. Pts lacking PBSC due to mobilization failure were optionally treated with a second cycle of mini-FlagIda. After induction chemotherapy, 74 out of 116 pts (63.8%) achieved CR. Response was not significantly different in the G-CSFpost vs. G-CSFpriming group (67.8 vs. 59.6%), nor was recovery of neutrophils. Of 74 complete responders, 44 have relapsed and 3 died in CR. Median remission duration was 15.2 and 14.7 months in the G-CSFpost and G-CSFpriming group, resp. Median DFS was 16.5 months and the probability of DFS at 4 yrs 21.2%, with no significant difference between the treatment groups and a median follow-up of 22 months at the time of this interim analysis. Mini-FlagIda consolidation was administered to 51 out of 74 CR patients (68.9%). The number of circulating CD34+ cells was monitored in 43 patients. The probability of mobilizing at least 1x106/kg CD34+ cells was significantly lower in the G-CSFpriming compared to the G-CSFpost group with 29.4% (5/17 pts) and 59.2% (16/26 pts), resp (p<0.05). ASCT was performed in 10 pts resulting in a significantly better 4-yr DFS (55%) compared to 10 pts treated with a second course of mini-FlagIda (22%, p<0.05). The major reason for not being autografted in spite of efficient collecting of CD34+ cells was early relapse. Conclusion: In elderly pts with de novo or secondary AML, G-CSF priming did not enhance the antileukemic efficacy of induction chemotherapy and had no significant impact on overall treatment outcome compared with G-CSF administered after induction. As ASCT proved to be an effective consolidation modality for CR patients mobilizing sufficient amounts of CD34+ cells, the detrimental effect of G-CSF priming on the collection of PBSC is clinically relevant.>

Impact of CRi on the Outcome of Elderly Patients with Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4384-4384 ◽  
Author(s):  
Anne Etienne ◽  
Aude Charbonnier ◽  
Thomas Prebet ◽  
Diane Coso ◽  
Anne-Marie Stoppa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
New Drugs ◽  
Response Criteria ◽  
Remission Induction ◽  
Remission Duration ◽  
Acute Myeloid

Abstract New international recommendations of response for treatment of acute myeloid leukemia (AML) include morphologic complete remission with incomplete blood count recovery (CRi). This response criteria was defined following evaluation of new drugs used for the treatment of AML in first relapse (Sievers et al., JCO2001;19:3244–3254). The objective of our study was to determine the outcome of elderly patients with newly diagnosed AML achieving CRi. Between 1995 and 2006, 240 patients aged 65 years or older with previously untreated acute non promyelocytic leukemia received a conventional anthracycline and cytarabine induction chemotherapy at a single institution. Median age was 71 years (range, 65–85). One hundred and nineteen patients achieved a complete response (CR) (50%), 15 patients achieved CRi (6%), 69 patients had persisting leukemia (29%), and 37 died during remission induction therapy (15%). Patients who reached a CR or CRi after 1 or 2 cycles of induction chemotherapy proceeded to consolidation. Only 9 patients in CRi received this consolidation chemotherapy course (60%) and none had intensification (intermediate-dose cytarabine and/or autologous stem cell transplantation) whereas for patients achieving CR, 88% (n=104) and 69% (n=82) had consolidation and intensification, respectively (p=0,01 and p=0,03). The median overall survival (OS) was respectively 9 and 18 months for patients in CRi and CR (p=0,08). OS was significantly lower for patients in CRi younger than 70 years (5 versus 17 months for CR, p=0,02). By landmark analysis, there was no difference in OS between patients in CRi and a group of 67 patients with induction failure surviving at less 40 days (p=0,14). Disease-free survival (DFS) and remission duration were not significantly different between patients in CRi and CR overall (5 and 8 months, and 5 and 7 months, respectively), but we found a difference for patients younger than 70 years (p=0,004 and p=0,009 for DFS and remission duration, respectively). There was significantly more multilineage dysplasia in patients achieving CRi (8 versus 33, p=0,009) and platelet count at diagnosis were lower (44 G/L versus 82 G/L). Cytogenetic did not differ between the two groups. Our results show that the outcome of elderly patients who achieved CRi is inferior to patients in CR, especially for patients younger than 70 years. Although this response criteria seems to indicate activity, we were not able to found a difference with patients who did not achieve CR. This result will be revaluated in a larger study. Our data also suggest that patients with CRi have different initial disease characteristics. Figure Figure

scholarly journals Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia

2005 ◽  
Vol 16 (8) ◽  
pp. 1366-1373 ◽  
Author(s):  
C.-C. Chen ◽  
C.-F. Yang ◽  
M.-H. Yang ◽  
K.-D. Lee ◽  
W.-K. Kwang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Acute Myeloid

Gemtuzumab Ozogamicin (MylotargR) as Primary Induction Therapy for Elderly Patients with Acute Myeloid Leukemia: A Phase II Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4508-4508
Author(s):  
Lisa A. Kujawski ◽  
Elaina M. Gartner ◽  
Irene Ryan ◽  
Kent Griffith ◽  
Harry P. Erba
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Average Duration ◽  
Single Agent ◽  
Gemtuzumab Ozogamicin ◽  
Secondary Aml ◽  
Grade Iii ◽  
Acute Myeloid

Abstract The prognosis of older adults with acute myeloid leukemia (AML) remains poor. Cytotoxic chemotherapy has been associated with low complete remission rates (30–50%), short relapse free survival and excessive toxicity in elderly patients with AML. There is a need for development of more effective and tolerable therapies for this population. Gemtuzumab ozogamicin (GO) is a humanized murine anti-CD33 monoclonal antibody, covalently linked to the antitumor antibiotic, calicheamicin. GO has been shown to be effective in patients with relapsed CD33+ AML, with an overall response rate of 26% in patients older than 60 years. From May 2001 to December 2003, 16 patients &gt; 60 years of age with newly diagnosed CD33+ AML were treated with single-agent GO as induction chemotherapy. A two-stage design was employed; if fewer than 5 of the first 16 patients achieved CR, the study would be terminated. Treatment regimen: GO 9mg/m2 was given on day #1. Hydroxyurea could be used to control hyperleukocytosis prior to the first dose of GO. A bone marrow biopsy was performed on day #8. If a response to GO was seen, then patients continued on study and received GO 6mg/m2 IV on day #10. If progressive disease or no response was noted by day #8, patients were removed from the study. Post-remission therapy was at the discretion of the physician. Supportive care included GM-CSF and interleukin-11 beginning day #11, allopurinol, acyclovir, norfloxacin, IV hydration, and antiemetics. Patients received dexamethasone 8mg 12-18 hours prior to each dose of GO, as well as 30 minutes prior along with acetaminophen and diphenhydramine to help prevent infusion reactions. Patient characteristics: median age 69 (60–84); 9 patients with secondary AML; 8 patients with poor risk karyotypes and 8 with intermediate risk; performance status of 2 or less. Results: 4/16 patients achieved a CR (25%), 2 patients had no response, 9 progressed on therapy, and one patient died from sepsis and ARDS prior to a response evaluation. Therefore, the study was terminated after accrual of 16 patients. Two responders have relapsed, within 0.6 month and 9.7 months of CR. These two patients were ages 76 and 78, both with high risk karyotypes, and with de novo and secondary AML, respectively. The remaining two responders remain in CR for 27 months. These 2 patients were ages 65 and 79 at the time of treatment, both with de novo AML-M2 and normal karyotypes. Treatment-related toxicities included grade III-IV neutropenia (average duration 30 days) and thrombocytopenia (average duration 36 days), grade I-III infusion reaction in 5 patients, and grade III GI hemorrhage in 4 patients. Grade III-IV neutropenic fever occurred in 10 patients, of which there was only 1 patient with a life-threatening infection (VRE sepsis). There were 2 patients with grade III-IV elevation of hepatic transaminases, but hepatic veno-occlusive disease was not observed. 3/16 patients were able to receive the therapy as an outpatient. Conclusion: When used as induction chemotherapy for elderly patients with CD33+ AML, single agent GO produces response rates inferior to standard anthracycline-based induction regimens, with a comparable safety profile. However, two patients have had prolonged responses with single-agent GO, suggesting a possible role for this agent in a subset of elderly AML patients, yet to be defined.

scholarly journals Survival and Prognostic Factors in Adults Acute Myeloid Leukemia: A Retrospective Analysis of 119 Cases

2013 ◽  
Vol 1 (2) ◽  
pp. 70-73
Author(s):  
Alina M Gridjac ◽  
Cristian Daniel Pirlog ◽  
Anca Simona Bojan
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Risk Groups ◽  
Developed Countries ◽  
Risk Level ◽  
Secondary Aml ◽  
Cytogenetic Testing ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a malignant disease with significant identified prognostic factors. Therefore our aim was to develop an Assessment Scheme of Prognosis in AML based on prognostic factors. In some counties, such as Romania or other less-highly developed countries, this scheme would be beneficial particularly when cytogenetic testing is unavailable or time-intensive. Methods: We analyzed 119 adult patients with AML during a five year-period from a single-center in Romania. We retrospectively collected and analyzed data with Epi Info and Excel using patient medical records. Results: According to age, the group A1 (<60 years) had a 40 months survival, in contrast with the group B1 (≥60 years) with a survival of 19 months (p=0,0063). The group A2 (secondary AML) survived 15 months, whereas the group B2 (AML de novo) survived 40 months (p=0.0021). Additionally, the group A3 (mild comorbidities) achieved a 40 months survival, the group B3 (moderate comorbidities) survived 19 months, whereas the group C3 (severe comorbidities) survived 7 months (p=0,0059). According to WBC and blast number, the group A4 (high levels) had a 25 months survival, whereas the group B4 (low levels) survived 40 months (p=0,0057). Conclusion: The prognostic factors studied are useful to identify the risk level of AML disease for each patient at diagnosis. We developed an assessment scheme of prognosis with three risk groups according to age, secondary AML, comorbidity, WBC and blasts and cytogenetic examination.

scholarly journals Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2464-2469 ◽  
Author(s):  
AF List ◽  
CS Spier ◽  
TM Grogan ◽  
C Johnson ◽  
DJ Roe ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Prognostic Significance ◽  
Secondary Aml ◽  
Lung Resistance Protein ◽  
Transporter Protein ◽  
Lung Resistance ◽  
Resistance Protein ◽  
Acute Myeloid

The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P =.0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.

Integrating resistance functions to predict response to induction chemotherapy in de novo acute myeloid leukemia

2019 ◽  
Vol 103 (4) ◽  
pp. 417-425 ◽  
Author(s):  
Yu‐Chiao Chiu ◽  
Tzu‐Hung Hsiao ◽  
Jia‐Rong Tsai ◽  
Li‐Ju Wang ◽  
Tzu‐Chieh Ho ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Acute Myeloid

scholarly journals Intensive induction chemotherapy with regimen containing intermediate dose cytarabine in the treatment of de novo acute myeloid leukemia

2009 ◽  
Vol 84 (7) ◽  
pp. 422-427 ◽  
Author(s):  
Jiazhuo Liu ◽  
Yingchang Mi ◽  
Mingwei Fu ◽  
Wenjuan Yu ◽  
Ying Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Acute Myeloid ◽  
Intermediate Dose

Priming with Granulocyte-Colony Stimulating Factor Did Not Improve Outcome in a Randomized Study of Elderly Acute Myeloid Leukemia but Increased Induction Mortality.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1980-1980 ◽  
Author(s):  
Gesine Bug ◽  
Steffen Koschmieder ◽  
Juergen Krauter ◽  
Stefanie Wiebe ◽  
Carla Hannig ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Randomized Study ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Secondary Aml ◽  
To Receive ◽  
Stimulating Factor ◽  
Acute Myeloid

Abstract Introduction: In acute myeloid leukemia (AML), granulocyte-colony stimulating factor (G-CSF) has been used in combination with induction chemotherapy to improve complete remission rates (CR) by sensitization of leukemic cells. This randomized prospective oligocenter study was designed to assess whether two induction cycles given simultaneously with and followed by G-CSF (G-CSFpriming) was superior to G-CSF administered only after induction (G-CSFpost) with regard to CR and disease-free survival (DFS) in patients older than 60 years. Secondary objectives were comparison of this concept in de novo versus secondary AML and to examine the feasibility of autologous stem cell transplantation (ASCT) as late consolidation. Methods: Overall, 183 eligible pts (median age 67 yrs) were randomly assigned to receive G-CSF starting on the day before (n=91) or after chemotherapy (n=92) during two induction cycles consisting of idarubicin, cytarabine and etoposide (IdAV). The two treatment groups were evenly matched with respect to age, diagnosis and cytogenetic risk factors. G-CSF was given as daily s.c. injection at 5μg/kg. Pts achieving a CR were scheduled to receive early consolidation chemotherapy with fludarabine, cytarabine, idarubicin plus G-CSF (mini-FlagIda) and peripheral blood stem cell (PBSC) harvest, followed by ASCT as late consolidation. Pts lacking PBSC due to mobilization failure were optionally treated with a second cycle of mini-FlagIda as late consolidation. Results: After induction chemotherapy, 118 out of 183 pts (64%) achieved CR. Response was not different in the G-CSFpost vs. G-CSFpriming group (70% vs. 59%, p=0.148). Recovery of neutrophils was similar in both groups after cycle 1 (21.8 vs. 20.5 days) and cycle 2 (14.9 vs. 16.3 days). Notably, G-CSF priming resulted in a significantly increased mortality in induction 1 (25% vs. 9%, p=0.003) associated with a higher rate of severe mucositis and infectious complications. The probability of OS and DFS at 5 years was 16% and 20%, resp., with no significant differences between the induction groups. With a median follow up of 26 months (range, 5–77), 77 out of 118 complete responders have relapsed and 7 died while in CR. Patients with de novo AML had a significantly better OS than those with secondary AML (17 vs. 11 months, p<0.001). Unfavorable cytogenetics were associated with a poor median OS (7 vs. 15 months, p<0.001). Following mini-FlagIda I, collection of at least 2x10E6 CD34+ PBSC/kg was feasible in 35 of 67 pts in whom mobilization of CD34+ cells was monitored. Late consolidation with ASCT (n=19) was not superior to mini-FlagIda II (n=16, DFS 24 vs. 27 months). Conclusions: In this randomized study with elderly AML patients, G-CSF priming did not result in an increased CR rate and was associated with higher induction mortality, but OS was not influenced. We demonstrated feasibility of ASCT in patients up to the age of 70 years, which was not superior to chemotherapy consolidation.

Prognostic Significance of NQO1 Polymorphism and GST-M1 Deletion in De Novo Acute Myeloid Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4846-4846
Author(s):  
Yeo-Kyeoung Kim ◽  
Hee-Je Kim ◽  
Woo-Sung Min ◽  
Jong- Ho Won ◽  
Deog-Yeon Jo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcomes ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Induction ◽  
Repair System ◽  
Significant Difference ◽  
Normal Cytogenetics ◽  
Acute Myeloid

Abstract Background: Although the most powerful prognostic factor of acute myeloid leukemia (AML) patients is the karyotype of the leukemic blast, data have not been obtained almost entirely in patients with heterogeneous cytogenetics. Further, some patients with favorable cytogenetics may show the poor treatment outcomes. Previous reports suggested that the single nucleotide polymorphisms of genes coding drug detoxification enzymes such as cytochrome P450 family or DNA repair system may influence the treatment outcomes in the patients with AML. We evaluated the role of polymorphisms in XRCC1, XRCC4, CYP1A1, GST-T1, GST-M1, NOQ1, and NAT2*6A in predicting therapeutic outcomes of adults with AML. Methods: XRCC1 (rs25487), XRCC4 (rs1056503), NQO1 (rs1800566), CYP-4501A1*2B (rs1048943), NAT2*6A (rs1799930) gene polymorphisms and deletion of GST-M1/GST-T1 were evaluated in 460 bone marrow (BM) samples obtained at initial diagnosis from de novo AML patients. Genotyping method is pyrosequencing using genomic DNA from BM samples. Homozygous deletions of GST-M1 and GST-T1 genes were detected with a multiplex PCR technique. All patients except APL (acute promyelocytic leukemia) received one or two rounds of intensive induction chemotherapy consisting of 3 days of idarubicin and 7 days of cytarabine. APL patients treated with AIDA regimen consisting of 45 days of ATRA (all-trans retinoic acid) and 3 days of idarubicin. Results: Of total 460 patients, ninety-nine patients (21.5%) were APL. Seventy-one (15.4%) were AML with t(8;21), twenty-three (5%) were AML with inv(16), and 179 patients (38.9%) showed normal cytogenetics. The median age of patients was 44 years (range, 14–75 years). In all cytogenetic risk group, the patients carrying homozygous NQO1 gene polymorphism (TT) showed significantly lower rate of complete remission (CR) than in those with negative or heterogyzous polymorphisms (TT: 72.7% vs. CC/CT: 85.9%, p=0.03). There was no significant difference in relapse rate, leukemia-free survival (LFS) and overall survival between homo- and heterozygote groups in these polymorphsims. In subgroup analysis, APL patients carrying TT genotype in NQO1 also showed lower rate of CR (TT: 77.8% vs. CC/CT: 95.4%, p=0.04). In AML patients except APL, NQO1 homozygous polymorphsim (TT) was also associated with lower CR rate (TT: 69.6% vs. CC/CT: 84.2%, p=0.005). In normal cytogenetics, the patients with del GST-M1 showed shorter LFS compared with those carrying GST-M1 (18.0 ± 5.7ms. vs. 34.6 ± NA. p=0.04). Conclusions: This study revealed an association between NQO1 polymorphism and GST-M1 deletion and the treatment outcomes for AML patients. Further study and larger sample size are needed to reach the definite conclusion on these associations. However, a stratified treatment plan in remission induction chemotherapy such as augmentation or addition of other chemotherapeutic agents may be warranted for AML patients harvoring homozygous NQO1 polymorphism (TT) or del GST-M1.

High Response Rate in Patients with De-Novo or Relapsed/Refractory Acute Myeloid Leukemia Using a Novel Strategy of Low-Dose, Prolonged Administration of Cytarabine and Thioguanine in Combination with Filgrastim in the Ambulatory Setting: A Single-Center, Retrospective Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2624-2624
Author(s):  
Christopher K Arthur ◽  
Brandon Aubrey ◽  
Matthew Greenwood ◽  
Keith Fay ◽  
Luke Coyle ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
De Novo ◽  
Single Center ◽  
Novel Strategy ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Abstract Abstract 2624 The incidence of acute myeloid leukemia (AML) increases with age and outcomes for elderly patients remain poor. Furthermore, intensive induction chemotherapy is often unsuitable for elderly patients and can result in significant periods of inpatient care. Recent understanding of leukemia stem cell cycling suggests that prolonged cytotoxic exposure, e.g. >14–21 days, could provide a more effective anti-leukemic effect than the typical 5–7 days schedules during which time very few leukemic stem cells would be likely to undergo cell division. We have been using prolonged low-dose cytarabine schedules as reported 20 years ago (Hellstrom-Lindberg, Brit J Haem,1992;81:503), however we have combined this with oral thioguanine, a purine analogue that may synergize with cytarabine. Concomitant filgrastim or pegfilgrastim was given to minimize neutropenia and for its possible synergizing anti-leukemic effect when combined with cytotoxic agents. Encouraging experience with this schedule in a few relapsed/refractory elderly AML patients prompted us to use this strategy in elderly de-novo patients unsuitable for standard induction. Surprisingly good results prompted us to report our preliminary experience with this novel strategy. This report is a retrospective, single-center analysis of outcomes in elderly patients with AML managed as outpatients in an ambulatory care day unit. Between April 2009 and March 2011, 14 patients with either relapsed/refractory AML (n=5) or de novo AML (n=9) unsuitable for intensive therapy were treated using prolonged, low-dose cytarabine 20mg/m2/day subcutaneously and thioguanine 80mg/day orally. Treatment was given for 21 days followed by a 14 day break after which the schedule was repeated until remission. After obtaining remission, patients received a maintenance schedule consisting of 14 days on treatment with rest periods increasing from 14 to 28 days according to tolerance and time on therapy, with an intention to continue maintenance for 2 years. All patients received the treatment in an ambulatory care unit with supportive care including filgrastim or pegfilgrastim, blood and platelet transfusion as required, regular clinical review and prophylactic antibiotics and antifungal agents. Patient age ranged from 52 to 89 years (median 75y). All patients had intermediate or poor risk cytogenetics. A morphologic remission according to bone marrow aspirate was obtained in 8 patients (57.1%), with relapse seen in 1 patient at 2.6 months follow-up. Remission was maintained in 7 patients (50%) with follow-up ranging from 4.7 to 26.6 months (median 9.7 months), including 1 patient who was refractory to standard first and second-line induction chemotherapy. Refractoriness to treatment occurred in 5 patients (35.7%). Mortality relating to disease progression occurred in 3 patients (21.4%) and 1 patient died secondary to infection. All patients developed grade 3/4 neutropenia and thrombocytopenia but severe mucositis was not seen. The infection rate was low and hospital admission was uncommon. Nausea was common but manageable and significant liver toxicity was not observed. This study demonstrates that effective management of AML in elderly patients can be achieved in the outpatient setting. The data suggests a surprising efficacy for this strategy, with a remission rate comparable to that reported using standard induction chemotherapy but with a potentially favorable toxicity profile. A prospective study is now underway to further evaluate this protocol. Disclosures: Arthur: AMGEN: Honoraria.

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