Count Recovery in AML Patients Achieving a Complete Response.

Abstract Abstract 2062 Poster Board II-39 AML is typically defined as “de novo” or “secondary”, the latter referring to patients diagnosed only after persistent blood count abnormalities (AHD) or after prior “chemotherapy” (PCT) for other illnesses. Patients with secondary AML may have a different bone marrow microenvironment leading to prolonged neutrophil and platelet recovery times following induction chemotherapy. Accordingly, we compared time from start of chemotherapy to neutrophil recovery (>1,000/μl) and platelet recovery (>100,000/μl) in 424 patients who achieved a complete response (CR) following treatment with ara-C-containing induction therapy at MD Anderson Hospital from 1995 to 2008. We divided the 424 patients as follows: (1) no AHD, no PCT (236 patients); (2) AHD, no PCT (131 patients); (3) PCT, no AHD (28 patients); and (4) AHD and PCT (29 patients). Because time to recovery may also be influenced by cytogenetics and age we subdivided patients in each of the four groups according to age (< vs. ≥ 60) and cytogenetics (normal vs. complex or -5/-7). Despite very differing CR rates, time to neutrophil recovery in patients achieving CR while statistically longer in PCT patients (p=0.05) was from a medical standpoint essentially uninfluenced by AHD and PCT status (table, median delays 2 days with PCT). Platelet recovery was affected by such status (p<0.001) being delayed by a median of 6-8 days in patients who had received PCT. Age had no effect on time to neutrophil (p=0.42) or platelet (p=0.23) recovery, while complex or -5/-7 cytogenetics had a statistically significant (p=0.002 neutrophils, 0.009 platelets) but medically insignificant (median delays of 2 days) effect on recovery time. There was no interaction between age or cytogenetics and AHD or PCT status. A similar analysis in patients who do not achieve CR would be of interest, but might be confounded by the difficulty in distinguishing between the effects of chemotherapy and those of residual AML on count recovery. Our data suggest that older patients, patients with complex or -5/-7 cytogenetics, and patients with secondary AML should not be excluded from clinical trials because of concern about prolonged time to count recovery. Group CRs CR Rate Median Days to > 1000 Neut Median Days to > 100,000 Plt No AHD no PCT 236 68% 27 28 AHD no PCT 131 50% 27 30 PCT no AHD 28 44% 29 34 AHD + PCT 29 35% 30 36 Age < 60 255 64% 28 29 Age ≥ 60 169 48% 26 30 Normal cyto 281 69% 27 29 Complex cyto or -5/-7 143 41% 29 31 Disclosures: No relevant conflicts of interest to declare.

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5-Azacytidine (AZA) Compared to Intensive Chemotherapy in Elderly Acute Myeloid Leukemia (AML) Patients: Results of a Retrospective Single Centre Matched Analysis,

Blood ◽

10.1182/blood.v118.21.3620.3620 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3620-3620 ◽

Cited By ~ 1

Author(s):

Elsa Lestang ◽

Sameh Ayari ◽

Patrice Chevallier ◽

Thierry Guillaume ◽

Fanny Rialland ◽

...

Keyword(s):

Elderly Patients ◽

De Novo ◽

Conflicts Of Interest ◽

Intensive Therapy ◽

Subcutaneous Administration ◽

Intensive Chemotherapy ◽

Single Centre ◽

Secondary Aml ◽

Elderly Aml ◽

Significant Difference

Abstract Abstract 3620 AML in elderly patients is characterized by a poor prognosis, especially in those patients aged >70, and/or in frail patients with comorbidities or poor performance status (PS). Moreover, several studies already suggested that elderly AML patients with unfavorable karyotype may not benefit from intensive chemotherapy. With this background, and using a matched analysis, this report aimed to assess the outcome of a single centre series of elderly AML patients who received either non intensive therapy by hypomethylating agents, or standard induction with intensive therapy. All patients were aged over 60 and had de novo or secondary AML. For the purpose of this comparison, the cohort was divided in two distinct groups. Group A included 36 cases treated by intensive chemotherapy between 1995 and 2005 according to the GOELAMS AML-SA2002 or SA3&4 protocols (5+7 induction with idarabicine 5 mg/m2/d and cytarabine 100 mg/m2/d). In this group, patients who could achieve CR received either 3 or 6 consolidation courses delivered over 1 or 2 years (according the protocol AML-SA2002 versus SA3&4). Group B included another 36 patients who were treated between 2006 and 2010 with AZA according to the recommendations of the “compassionate use program” authorized by the French Health Agency (one cycle of AZA = 7 days of subcutaneous administration 75mg/m2 every 28 days until progression).In this group, response was assessed after 3 cycles and qualified using IWG criteria. These two groups were matched based on cytogenetic features and age. The median age for the total cohort was 72 years (range, 60–86). Groups were comparable for WBC, % marrow blasts infiltration, WHO subtypes, and cytogenetic features at diagnosis. A higher rate of secondary AML was observed in the AZA arm. CR and CR with incomplete hematological recovery (CRi) rates were significantly higher in the intensive vs. AZA arm (63% vs. 28%, p<0.0001). However, there was a trend for a higher rate of partial remission (PR) in the AZA Arm (25% vs. 5%, p=0.02). With a median follow-up of 13.3 months (range, 5–80) from diagnosis, median overall survival (OS) was comparable between the two arms: 10.4 vs. 10.3 months, p=0.3) In multivariate analysis for OS including treatment strategy, the strongest prognostic factors were an unfavorable karyotype (HR=2.05, 95%CI, 1.09–3.85; p=0.03), PS status (0 vs. 1–2; HR=2.04 95%CI, 1.16–3.58; p=0.01) and platelets number at diagnosis (analyzed as a continuous variable) (HR=1, 95%CI, 0.99–1.00; p=0.04). Of note, the treatment arm was not found to be a significant determinant for OS: (AZA vs intensive chemotherapy.; HR=1.86, 95%CI, 0.86–3.16; p=0.13). This analysis suggests that the use of AZA as an alternative to intensive chemotherapy in elderly patients with de novo or secondary AML may lead to similar OS, despite a significant difference in terms of CR and CRi rate. The different mechanism of action of AZA in comparison to conventional chemotherapy, and the higher rate of PR that can be achieved after AZA therapy might contribute to improved OS through relatively long lasting disease control. These results set the frame for a prospective controlled trial to test AZA as an ambulatory alternative to standard intensive chemotherapy in elderly AML patients, especially those patients with unfavorable karyotype or poor PS and comorbidities. Disclosures: No relevant conflicts of interest to declare.

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Twice Daily Fludarabine and Cytarabine Combination (BID-FA) Is Effective in Pts with De Novo Acute Myeloid Leukemia (AML), Relapsed/Refractory (R/R) AML, High-Risk Myelodysplastic Syndromes (MDS), and Blast Phase Chronic Myeloid Leukemia (CML-BP)

Blood ◽

10.1182/blood.v120.21.4939.4939 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4939-4939

Author(s):

Hady Ghanem ◽

Hagop M. Kantarjian ◽

Farhad Ravandi ◽

Jorge E. Cortes ◽

Naveen Pemmaraju ◽

...

Keyword(s):

High Risk ◽

Complete Remission ◽

Myeloid Leukemia ◽

De Novo ◽

Chromosomal Abnormalities ◽

Conflicts Of Interest ◽

High Dose ◽

Platelet Recovery ◽

De Novo Aml ◽

To Receive

Abstract Abstract 4939 Background: High dose cytarabine containing regimens are still considered standard options for pts (pts) with AML relapsing after a first complete remission (CR1) lasting more than 12 months. No standard options exist for pts relapsing after shorter remission duration or with primary refractory disease. We conducted a phase II study assessing the efficacy and safety of twice daily fludarabine and cytarabine (BID FA) in pts with R/R AML, high-risk MDS and CML-BP. Pts and Methods: 147 pts with de Novo AML, R/R AML, intermediate-2 and high-risk MDS, and CML-BP, with a performance status of 3 or less, as well as normal organ functions were eligible. Pts were scheduled to receive fludarabine 15 mg/m2 intravenously (IV) q12 hrs on days 1 to 5 as well as cytarabine at the dose of 0. 5 g/m2IV over 2 hrs q12 hrs on days 1 to 5. GO was administered at the dose of 3 mg/m2 IV on day 1 for the first 70 pts enrolled. Courses were repeated every 4 to 6 weeks for a maximum of 7 courses. Pts with CML-BP were allowed to receive concomitant tyrosine kinase inhibitors. Four pts with AML who had FLT3 mutation were allowed to receive BID FA and sorafenib. Results: A total of 147 pts were treated. The median age was 63 years (range, 20 to 85 years). 131 (89%) had AML, 7 (5%) had high-risk MDS, and 9 (6%) had CML-BP. Of the 131 AML pts, 17 (12%) were de novo AML, 50 (38%) were in first salvage: first CR duration (CRD1) of less than 12 months in 39 pts (29%), and more than 12 months in 11 (9%) pts. Cytogenetic studies showed diploid karyotype in 52 pts (35%) and unfavorable chromosomal abnormalities involving chromosomes 5 and 7 in 30 pts (20%). 128 pts (87%) had a PS ≥1. Sixty-four pts (44%) had failed previous intensive chemotherapy, while 21 (14%) had failed targeted and hypomethylating agents. Forty-three (29%) pts had failed both. Overall, 34 pts (23%) achieved a complete remission (CR) and 8 (6%) achieved a CR without platelet recovery (CRp), for an overall response rate (ORR) of 29%. 6 pts received reinduction therapy, of which 3 achieved a CR. The CR rates for AML pts with frontline therapy, with relapsed AML with CRD1 ≥12 months, relapsed AML with CRD1< 12 months, and R/R AML beyond first salvage were 47%, 64%, 21%, and 14%, respectively. In CML-BP, 2 (22%) of 9 pts had objective responses (1 CR, 1 CRp). 1 of the 7 pts with MDS responded (Table 1). The treatment was well tolerated with only 7 of the pts experiencing grade 3 and 4 toxicities including mainly skin rash and increased liver enzymes. The overall 4-week mortality rate was 13%. With a median follow-up of 24 months (range, 10 to 33), 20 patients (14%) remained alive. The overall 6-month survival rate was 44%. The median overall survival (OS) and event free survival (EFS) were 5 months (range, 0. 1 to 33) and 1 month (range, 0. 1 to 33), respectively. The median CR/CRp duration was 12 months. Median OS for pts with de novo AML, a CRD1≥12 months, pts with CRD1<12 months and pts receiving second salvage and beyond were 8, 12, 5, and 4 months respectively. Median EFS for pts with de novo AML, a CRD1≥12 months, pts with CRD1<12 months and pts receiving second salvage and beyond were 3, 7, 1 and 1 month respectively. Conclusion: BID FA appears to be active with an ORR of 29% in a heavily pre-treated population. This combination is safe with a low rate of 4-week-mortality of 13%. Disclosures: No relevant conflicts of interest to declare.

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Helicobacter pylori eradication affects platelet count recovery in immune thrombocytopenia

Scientific Reports ◽

10.1038/s41598-020-66460-5 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Ayoung Lee ◽

Junshik Hong ◽

Hyunsoo Chung ◽

Youngil Koh ◽

Soo-Jeong Cho ◽

...

Keyword(s):

Helicobacter Pylori ◽

Platelet Count ◽

Immune Thrombocytopenia ◽

Complete Response ◽

Long Term Effects ◽

Infection Group ◽

Platelet Recovery ◽

First Line Therapy ◽

H Pylori ◽

Count Recovery

Abstract Helicobacter pylori (H. pylori) infection is on the rise as a cause of immune thrombocytopenia (ITP). It has been suggested that platelet recovery can be achieved following successful microbial eradication, although, the exact pathophysiology has yet to be fully elucidated. This study evaluated the long-term effects of H. pylori eradication monotherapy on platelet count recovery in patients with ITP. H. pylori eradication was analysed in 61 ITP patients. Patients who maintained a complete response (CR) for more than six months were classified as sustained responders (SR). The prevalence of H. pylori infection was 54.3% (75/138), and the success rate of eradication with first-line therapy was 71.4% (35/49). Patients who had achieved a CR at 2 months maintained a higher platelet count thereafter. At 1 year following eradication, platelet counts had increased 2.78 times in the eradicated group, 1.36 times in the sustained infection group, and 1.33 times in the no infection group compared with the baseline (P = 0.016).

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Cytogenetics and De Novo/Secondary AML but Not Age Are the Main Determinants for CR Rate and Hematological Recovery in Acute Myeloid Leukemia (AML) Using Intermediate Doses of Cytarabine (AraC) Delivered at the Presumptive Saturating Infusion Rate.

Blood ◽

10.1182/blood.v106.11.1851.1851 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1851-1851

Author(s):

Cornelia Becker ◽

Haifa Al Ali ◽

Rainer Krahl ◽

Wolfram Poenisch ◽

Dirk Hasenclever ◽

...

Keyword(s):

Infusion Rate ◽

De Novo ◽

Remission Rate ◽

Univariate Analysis ◽

Disease Classification ◽

High Dose ◽

Platelet Recovery ◽

Secondary Aml ◽

Hematopoietic Reconstitution ◽

Fab Classification

Abstract Outcome of elderly patients with AML is usually poor. Increased incidence of high risk AML and intolerance against dose escalation are the main causes for treatment failure. Pharmacokinetic measurements indicated that intracellular Ara-CTP formation is saturated at much lower infusion rates than used in high dose AraC schedules, probably causing AraC accumulation in the plasma and increased toxicity. Therefore, the East German Study Group (OSHO) used intermediate doses of AraC delivered at the presumptive saturating infusion rate over a prolonged period of time. The same schedule was applied to younger (≤60 years of age, AML 96) and older (>60 years of age, AML 97) patients with AML. In the present evaluation, determining factors for complete remission rate and hematopoietic reconstitution were identified. Methods: All 690 patients entered in the AML 96 (n=370) and AML 97 (n=320) study of the OSHO and treated with one or two courses of induction therapy (AraC 2 g/m2 iv on day 1,3,5,7 in combination with idarubicine 12 mg/m2 day 1–3 or mitoxantrone 10 mg/m2 iv day 1 to 3) followed by 2 consolidation courses were evaluated. The following baseline variables were studied in univariate analysis for their impact on CR rate: sex (M vs. F), age (≤ 60 years vs. >60 years; continuous variable), cytogenetics at diagnosis (normal, favourable, unfavourable and others), disease classification (de novo or secondary AML), WBC (<2/2–90/>90 x 109/l), FAB-classification (M0/M1/M2/M3/M4/M5/M6/M7), LDH (≤ 2 x ULN vs. > 2 ULN) and the use of G-CSF (yes or no). Factors significant in this analysis were included in a multivariate model (logistic regression). Hematopoietic reconstitution was defined as the first of two consecutive days with leucocytes >1000/μL and platelets >50000/μL. Results: As shown in the multivariate analysis, the most important and highly significant parameter for CR rate was cytogenetics at diagnosis (p=10−11) followed by disease classification (de novo or secondary AML; p=0,001), WBC (p=0,003) and sex (p=0,018). In contrast, we could not demonstrate any significant influence of age (p=0,64), G-CSF (p=0,16) and FAB classification (p=0,38) on CR rate. Significant factors for the recovery of leukocytes were the use of G-CSF (p= 10−12), cytogenetics (p=10−4) and disease classification (de novo or secondary AML; p=0,04). AML classification (de novo or secondary AML; p=0,00002) and cytogenetics (p=0,001) but not age (p=0,17) were determinants for platelet recovery. Conclusion: Cytogenetics at diagnosis and disease type (de novo vs. secondary) were the most important determinants for CR rate using intermediate dose AraC. We could not demonstrate any influence of age on CR rate and hematological recovery.

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The Value of Post-Remission Therapy in Older Adults with Acute Myeloid Leukemia (AML).

Blood ◽

10.1182/blood.v114.22.1043.1043 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1043-1043

Author(s):

Mikkael A. Sekeres ◽

Alex Z Fu ◽

Marc Earl ◽

Matt Kalaycio ◽

Anjali Advani ◽

...

Keyword(s):

Complete Remission ◽

Propensity Score ◽

De Novo ◽

Conflicts Of Interest ◽

Intensive Therapy ◽

Disease Free Survival ◽

Risk Groups ◽

Individual Characteristics ◽

Propensity Score Method ◽

Secondary Aml

Abstract Abstract 1043 Poster Board I-65 Background: In older (age 3 60) AML patients (pts) who are induced into complete remission, it is unclear whether post-remission therapy provides additional benefit. Methods: We examined all older AML pts treated with cytarabine-based induction chemotherapy at a single institution between 1997 and 2008. Data on known prognostic factors (age, white blood cell count (WBC) at diagnosis, cytogenetic risk groups (as defined by CALGB 8461) and AML etiology (de novo vs. secondary AML)) were collected. Of 240 pts identified, 25 had unknown post-remission status, leaving 215 pts for analyses: 81 receiving cytarabine-based post-remission therapy (PRT) for 1-2 cycles; 134 received no PRT. A cohort study using a propensity score method was conducted in which pts receiving PRT and those not receiving PRT were matched in a 1:1 ratio to address potential sample selection bias and to better balance patient characteristics. A logistic regression was used to predict the propensities of receiving PRT using individual characteristics: age, gender, race, WBC at presentation, AML cytogenetics, secondary AML, re-induction, FAB classification, and complete remission (CR). Overall survival (OS) was measured from the time of diagnosis; disease-free survival (DFS) from the time of CR. Individual characteristics and survival between groups were assessed by the routines of linear, categorical, and survival analyses. Results: Median age was 68 years (range, 60-81). Patients receiving PRT were more likely to be younger (67 vs 69 years, P=.003), male (67% vs. 52%, p=.04), have de novo AML (75% vs. 50%, p=.0012), favorable- or intermediate-risk cytogenetics (65% vs. 36%, p<.0001), to have M3 AML (5% vs. 0%), and to have achieved a CR (100% vs. 48%, p<.0001). There were no differences between groups in race, WBC at admission, reinduction rates, or comorbid conditions including renal dysfunction, hepatic dysfunction, and cardiac comorbidity. Median DFS and OS for those receiving PRT vs. no PRT were.45 and.34 years, and 1.13 and.69 years (p=.026 and p<.001, respectively, Figure 1). Only 3 patients underwent a bone marrow transplant after relapse, and there was no correlation between the total amount of chemotherapy received during induction for PRT, or OS. After 1:1 propensity score matching (n=88), there were no differences in baseline characteristics, re-induction, or CR rates, yet DFS and OSl remained significantly greater for pts receiving PRT vs. those who did not (Hazard Ratios.48 and.30, p=.05 and p<.0001, respectively). Conclusions: Even after adjusting for patient disease and treatment factors that could influence PRT administration, older AML pts receiving at least one cycle of PRT lived significantly longer than those who did not. PRT should be considered as a standard part of intensive therapy for older AML pts. Disclosures: No relevant conflicts of interest to declare.

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Efficacy and Safety of 5-Azacytidine Based Regimens in Old AML patients: a Retrospective Study of 29 Patients.

Blood ◽

10.1182/blood.v114.22.4148.4148 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4148-4148

Author(s):

France Roszkiewicz ◽

Berengere Gruson ◽

Ioana Vaida ◽

Gandhi Damaj ◽

Bruno Royer ◽

...

Keyword(s):

Overall Survival ◽

Retrospective Study ◽

De Novo ◽

Conflicts Of Interest ◽

Complete Response ◽

Newly Diagnosed ◽

Overall Response ◽

Co Morbidity ◽

Significant Difference ◽

Wbc Count

Abstract Abstract 4148 Background 5-azacytidine (AZA) is an hypomethylating drug. The international multicenter AZA-001 trial established that AZA significantly improves overall survival (OS) in patients with high risk myelodysplastic syndromes (MDS) compared with conventional care regimens (Fenaux, Lancet Oncol 2009). Some recent reports have raised the question of a possible efficacy of AZA in selected patients with acute myeloid leukaemia (AML). In this study we retrospectively analysed the safety and efficacy of a 7 days-schedule of AZA alone or in combination with an HDAC inhibitor, Valproic acid (VA) and with All-trans retinoic acid (ATRA) in patients with newly-diagnosed and refractory/relapsed AML not eligible for intensive chemotherapy. Patients and Methods A monocentric retrospective study from October, 2006 until March, 2009 analysed 29 patients with AML. Among these patients. There were 11 males and 18 females, median age 70,8 years (range 51,2-84,1), AML de novo in 15 patients (3 relapse) and secondary in 14 patients (2 post MPD and 12 post MDS). Median WBC count was 2,5 (range 0,7-140).109/L, 4 patients had WBC more than 10.109/L. The median rate of bone marrow blasts is 30%. 12/27 (44%) patients and 15/26 (56%) have respectively an intermediate and poor risk caryotype. Fifteen (54%) were newly-diagnosed patients, 14 (46%) were refractory/relapsed patients. Median co morbidity index (Sorror, J Clin Oncol 2007) of patients is 2 (0-7). Patients received daily AZA 75mg/m2 J1-J7, ± VA 35 to 50 mg/kg J1-J7 and ATRA 45mg/m2 J8-J28 every 4 weeks. Results 5 azacytidine was used alone for 6/29 (21%) patients and in combination with VA and ATRA for 23/29 (79%) patients. Compliance to the planned therapy was good. Average number of AZA administration was 6 days. To date a total 150 treatment-cycles with a median of 5 cycles/patient were applied (1-14). Treatment was well tolerated. Neutropenia grade3III and thrombopenia grade3III occurred respectively in 26/150 cycles (17%) and in 31/150 (20%). Infections grade3III were observed in 14/150 cycles (9,3 %). Overall response was 62% (17/29): 9 complete response (CR=31%), 3 partial response (PR=10%), 5 haematological improvement (HI=21%), There were 2 stable diseases (SD=7%). 28% of responses were obtained after 1 cycle, 56% after 3 and 89% after 4. Median overall survival (OS) was 13,2 months (0.3-26). We did not observe any significant difference on OS regarding: age, cytogenetics, de novo vs secondary AML, newly diagnosed vs refractory/relapsed patients. OS for patients with SD was similar to patients with CR, PR or HI. WBC >10.109/L before treatment was not correlated with a shorter survival (7.73 months vs 13.2 months p=0,6). Correlation was found between OS and clearance of the creatinine (p=0.005). In conclusion, AZA based regimens seems well tolerated and an effective treatment in AML, with an overall response of 62% and an OS of 13,2 months. A minimum of 4 cycles of treatment is necessary to evaluate the efficacy. OS of patients achieving CR, PR or HI is not significantly different of those with SD. Treatment should be continued until progression of the disease. Disclosures: No relevant conflicts of interest to declare.

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Prognostic Implications of CD14 Positivity in Acute Myeloid Leukemia Arising From Myleodysplastic Syndrome,

Blood ◽

10.1182/blood.v118.21.3523.3523 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3523-3523

Author(s):

Yunsuk Choi ◽

Sungdoo Kim ◽

Young-Hun Park ◽

Jae Seok Lee ◽

Dae-Young Kim ◽

...

Keyword(s):

Induction Chemotherapy ◽

Hematopoietic Cell Transplantation ◽

De Novo ◽

Conflicts Of Interest ◽

Risk Group ◽

Free Survival ◽

Secondary Aml ◽

Hla Dr ◽

Prognostic Implications ◽

De Novo Aml

Abstract Abstract 3523 Introduction: Secondary AML that has evolved from MDS shows different clinical features and outcomes compared to de novo AML. Prognostic implications of immunophenotypes have been studied in de novo AML, whereas those have not well been defined in secondary AML from MDS. Methods: This retrospective study involved analysis of data from 65 adult patients, 37 males and 28 females, who were diagnosed with AML arising from MDS at a single institute. Data for baseline clinico-pathological features, treatments, and outcomes were collected from medical records of each patient. Immunophenotyping was performed for the markers including TdT, CD34, CD13, CD33, CD117, CD14, CD56, HLA-DR, CD3, CD7, CD10, and CD19 using flow cytometry. Results: At the time of MDS diagnosis, the WHO subtype was RA/RARS in 5, RCMD in 10, RAEB-1 in 17, RAEB-2 in 29, and unknown in 4. For the treatment of MDS, hypomethylating agents were given to 17 patients and 2 patients underwent allogeneic hematopoietic cell transplantation (HCT). Median duration of MDS prior to diagnosis of AML was 4.9 months (range, 0.3–91.1). At the time of AML evolution, median age was 50.7 years (range, 18–80), and cytogenetic risk group was good-risk in 1, intermediate-risk in 45, and poor-risk in 18. Proportion of positivity of each immunophenotype marker was as follows: TdT (5%), CD34 (65%), CD13 (98%), CD33 (97%), CD117 (90%), CD14 (22%), CD56 (10%), HLA-DR (93%), CD3 (2%), CD7 (35%), CD10 (8%), and CD19 (2%). After the evolution to AML, 52 patients received induction chemotherapy consisted of cytarabine plus idarubicin or daunorubicin and 8 patients underwent allogeneic HCT as initial treatment of AML. Complete remission (CR) was induced in 27 patients after treatment. At a median follow-up time of 29.2 months (range, 2.6–116.2) among surviving patients, 49 patients died, 13 relapsed, and 53 died or relapsed. Median overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were 7.6, 26.1, and 5.4 months, respectively. Of immunophenotype markers, CD14 positivity only showed prognostic implications at the univariate analyses: lower CR rate after induction chemotherapy (P=0.034) and shorter survivals (OS, P<0.001; RFS, P=0.078, and EFS, P<0.001). Differences in OS and EFS remained significant after adjustment for other variables (OS, HR, 4.49, 95% CI, 2.16–9.87, P<0.001; EFS, HR, 4.06, 95% CI, 2.03–8.13, P<0.001). Other prognostic variables included age of 60 years or older (shorter OS [P=0.003] and EFS [P=0.020]), WBC over 60,000/mcl (shorter OS [P<0.001] and EFS [P=0.001]), and poor cytogenetic risk group (shorter OS [P=0.005]). Conclusions: Surface expression of CD14 on leukemic blasts was an independent prognostic factor for survivals in the patients with AML arising from MDS. Disclosures: No relevant conflicts of interest to declare.

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Poor Outcome in Secondary Acute Myeloid Leukemia (AML): A First Report From the Population-Based Swedish Acute Leukemia Registry

Blood ◽

10.1182/blood.v120.21.130.130 ◽

2012 ◽

Vol 120 (21) ◽

pp. 130-130 ◽

Cited By ~ 1

Author(s):

Soren Lehmann ◽

Vladimir Lazarevic ◽

Ann-Sofi Hörstedt ◽

Erik Hulegårdh ◽

Christer Nilsson ◽

...

Keyword(s):

Acute Leukemia ◽

De Novo ◽

Conflicts Of Interest ◽

Performance Status ◽

Population Based ◽

Induction Treatment ◽

Secondary Aml ◽

Male Predominance ◽

Hematological Disorder ◽

De Novo Aml

Abstract Abstract 130 Secondary AML comprises AML patients with an antecedent hematological disorder (AHD) or previous exposure to chemotherapy and/or radiation (therapy-related AML; tAML). Population-based data on this patient group are scarce. Here, we report for the first time, data on secondary AML from the Swedish Acute Leukemia Registry covering 98% of all AML cases diagnosed in Sweden between 1997 and 2006. In total, 3372 AML patients were registered during this period. Of these, 949 (28%) had secondary AML; 655 (19%) had a history of AHD and 294 (8.7%) had tAML. The proportion of secondary AML increased from 8% in patients below the age of 40 years to 36% in patients between 70–79 years. Of patients with AHD, 423 (65%) had previously been diagnosed with myelodysplastic syndrome (MDS) and 227 (35%) with various types of myeloproliferative disorders (MPN). AML with AHD showed male predominance (57%), whereas tAML showed female predominance (64%). This distribution was significantly different (p<0.001) compared to de novo AML with an equal gender distribution. Median and mean ages for patients with AML with antecedent hematological disorder were 73 and 71 years, which differed significantly from de novo AML with 70 and 66 years, respectively (p<10−11). For tAML, median and mean ages were 71 and 67 years, respectively, not significantly different from de novo AML. Patients with secondary AML had slightly worse WHO/ECOG performance status (WHO PS) with lower incidence of WHO PS 0 (10%: 14%: 18% for AML with AHD:tAML:de novo AML) and a higher incidence of WHO PS 3–4 (27%: 24%: 20%). The proportion of patients with PS 1 and PS2 was similar for secondary AML and de novo AML. Intensive induction treatment was given to 45% of all patients with AHD, to 57% of patients with tAML compared to 68% for patients with de novo AML. In patients below the age of 65, the proportion of intensively treated patients was 76, 85 and 98%, respectively. CR rates for in patients including all ages were 40% for AML with AHD, 54% for tAML and 72 % for de novo AML (p-values<0.0001 for all calculations). CR rates were lower in all cytogenetic risk groups in both AML with AHD and tAML compared to de novo AML (Low risk NA: 70%: 91%; intermediate risk 53%: 56%: 89%; high risk 30%: 43%: 76%). CR rates were lower for both secondary leukemia types within all WHO PS groups, despite similar early death rates in secondary and de novo AML. Median survival for all patients regardless of age or type of treatment was 4 mo, 4 mo and 9 mo respectively for patients with AML with AHD, tAML and de novo AML, respectively. For all patients receiving intensive induction treatment, corresponding figures were 7 mo, 9 mo and 17 mo, and for patients below 65 years of age 7 mo, 9 mo and 38 mo. We conclude that secondary AML is less common in younger patients and that the proportion increases to a third of patients above 70. Patients with AHD and tAML less often receive intensive induction treatment than those with de novo AML and treatment responses are poor regardless of cytogenetic risk group or performance status also in intensively treated patients. Disclosures: No relevant conflicts of interest to declare.

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Pilot Study: Favorable Outcomes with Addition of Topotecan to Busulfan/Melphalan As High-Dose Myeloablative Therapy Followed by Autologous Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood.v120.21.4553.4553 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4553-4553

Author(s):

Joseph Rosenthal ◽

Anna Pawlowska ◽

Jerry Cheng ◽

Steven Kechichian ◽

Debbie Hitt ◽

...

Keyword(s):

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Conflicts Of Interest ◽

Complete Response ◽

Disease Recurrence ◽

Electrolyte Imbalance ◽

High Dose ◽

Hematopoietic Stem ◽

Platelet Recovery ◽

Post Transplant

Abstract Abstract 4553 High dose (HD) therapy followed by autologous hematopoietic stem cell transplantation (AHCT) has been the mainstay of treatment in patients diagnosed with advanced neuroblastoma (NBL). Busulfan and Melphalan (Bu/Mel) was demonstrated to be superior to other HD regimens and is widely considered as standard treatment. (Ladenstein, Bone Marrow Transplant. 2008 Jun;41 Suppl 2:S118-27), Topotecan (Topo) with or without cyclophosphamide has demonstrated efficacy in treatment of advanced NBL (Kushner, Cancer 116: 3054, 2010). We hypothesize that adding Topo to Bu/Mel as HD therapy followed by AHCT is well tolerated and will result in favorable outcomes. Patients and Methods: Patients with NBL, stage III or IV were eligible and consented to participate in the study. Seven patients were enrolled, the median age was 2.65 yrs (range 2.3 – 4.x yrs), and there were 4 males (57%). All patients were initially treated on COG protocols and in all cases a complete response was documented prior to proceeding with AHCT. Autologous hematopoietic cells were collected, following mobilization with G-CSF, after 2 (n=6) or 3 (n=1) cycles of chemotherapy. All patients were given post transplant radiation therapy to the primary tumor bed and cis-retinoic acid, 3 patients were also given monoclonal antibodies. Data on engraftment, toxicities, event free survival (EFS) and overall survival (OS) were analyzed. Results: The median cell dose was 6.62 × 106 CD34+/kg (5.57×106−7.33 × 107). Engraftment occurred promptly in all patients. Myeloid and platelet recovery occurred at a median of 12 (8–17 days) and 22 (17–41 days), respectively. The treatment was well tolerated with no grade 4 or higher toxicities. Grade 3 toxicities included; mucositis (n=7, 100%), electrolyte imbalance (n=3), diarrhea (n=3), autoimmune hemolysis (n=1) and epistaxis (n=1). Three patients suffered disease recurrence, 156, 821 and 899 days post AHCT. One patient is dead and two continue salvage therapy 55 and 52 months, post transplant, respectively. The 4-year OS and EFS were 87% to 57%, respectively. Conclusion: This novel regimen of Topo/Bu/Mel appears to be well tolerated with low TRM and promising EFS and OS. Further and larger studies are required to establish its role as HD therapy prior to AHCT in patients with advanced NBL. Disclosures: No relevant conflicts of interest to declare.

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Azacitidine in Relapsed and Refractory AML: Efficacy for Patients Relapsing As MDS Post AML

Blood ◽

10.1182/blood.v120.21.4332.4332 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4332-4332

Author(s):

Sarah Ivanoff ◽

Emilie Lemasle ◽

Berengere Gruson ◽

Lavinia Merlusca ◽

Amandine Charbonnier ◽

...

Keyword(s):

Overall Survival ◽

De Novo ◽

Conflicts Of Interest ◽

Regulation Of Gene Expression ◽

Complete Response ◽

Allogeneic Transplantation ◽

Dna Methyltransferases ◽

Duration Of Response ◽

Myeloid Neoplasia ◽

Refractory Aml

Abstract Abstract 4332 Background: Azacitidine (Aza), inhibitor of DNA methyltransferases, plays an important role in epigenetic regulation of gene expression and tumorogenesis, and is active in myeloid neoplasia such as myelodysplasia (MDS) and de novo acute myeloid leukemia (AML). Efficacy of Aza for relapsed and refractory AML has not been so far reported. Methods: We report in 2 french centers (Amiens, Rouen) retrospective study, the results of Aza for relapsed or refractory patients. All patients received Aza (75 mg/m2 per day over 7 days for 4 weeks cycles), until progression, and at least one cycle. Leukocyte blood count was < 10109/l. The primary endpoint was overall response rate (ORR), according to IWG 2006: complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), hematological improvement (HI). Secondary endpoints were duration of response and overall survival (OS). Results: 41 patients (26 males and 15 females) with a median age of 59 years (range 28–78) were studied from August, 2007 and November, 2011 (Table): 15 had refractory and 26 relapsed AML. At relapse 11/26 had MDS, defined by blast count <20% and cytological morphology of MDS in bone marrow aspirate, and 15/26 AML. Patients received in average 6 cycles (1–30): 4 (1–7) for refractory; 7 (1–30) for relapsed (11 (3–30) for MDS post AML; 3 (3–5) for relapsed AML). Overall, the ORR was 34% (7 CR, 5 RP, and 9 HI). For patients with MDS post AML OR was 82% (7 CR, 2 RP, 7 HI), 13% (1 RP, 1 HI) for relapsed AML, and 13% (2 PR and 1HI) for refractory AML. The average duration of response was 4 months (0–39) for the 41 patients: 14 months (0–39) for MDS post AML, 0.3 for relapsed AML, and 0.5 for refractory. Overall survival from diagnosis was 29 months (6.9–87): 38.2 (12–57) for MDS post AML, 30.1 (6.9–87) for relapsed AML and 13.3 (6.9–35.5) for refractory (no significant differences). Overall survival from initiation of Aza was 9.4 months (1.1–39.2): 22.6 (4.8–39.2) for MDS post relapsed and 3.9 (0.3–11.3) for relapsed AML and 6.2 (1.1–13.3) for refractory patients. The differences are not statically significant probably due to small effective of our study. Contrarily to the others 2 groups, 6 patients (55%) with MDS post AML are alive in CR at the latest report; moreover three of them underwent an allogeneic transplantation. Conclusion: Aza seems to efficient for relapsed AML patient, especially for MDS post AML, but inappropriate for refractory patients. Disclosures: No relevant conflicts of interest to declare.

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