scholarly journals The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings

2021 ◽  
Vol 8 ◽  
pp. 204993612110365
Author(s):  
Kundan Mishra ◽  
Suman Kumar ◽  
Sandeep Ninawe ◽  
Rajat Bahl ◽  
Ashok Meshram ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Febrile Neutropenia ◽  
Burkholderia Cepacia ◽  
Myeloid Leukemia ◽  
Tertiary Care ◽  
Care Hospital ◽  
Significant Difference ◽  
The Mean ◽  
Acute Myeloid

Introduction: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30–66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML. Method: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included. Result: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12–71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days ( p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 ( p = 0.063). Thirteen patients (23.63%) died during the study period. Discussion: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections. Conclusion: Infections continues to be a major cause of morbidity and mortality among AML patients.

Relationship Between Cleaved L-Selectin Levels and the Outcome of Acute Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3115-3122 ◽  
Author(s):  
M. Extermann ◽  
M. Bacchi ◽  
N. Monai ◽  
M. Fopp ◽  
M. Fey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Plasma ◽  
Multivariate Statistical ◽  
Free Survival ◽  
The Mean ◽  
American Society ◽  
The Relationship ◽  
Acute Myeloid

Abstract High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels ≥3.12 μg/mL (≥3 SD above the mean of healthy controls: “increased”). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P < .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with “normal” sL-selectin levels had higher probability of achieving complete remission (CR) than with “increased” levels: 81% versus 64%, respectively (P = .06). When adjusting for clinically relevant covariates predictive for CR (sex, age, Auer rods), “normal” sL-selectin levels were significantly associated with CR (odds ratio, 3.08; 95% confidence interval [CI], 1.10 to 8.58;P = .03). Moreover, patients with “increased” sL-selectin levels (≥3.12 μg/mL) had shorter event-free survival (EFS) (median 7.3 v 12 months, P = .008) and overall survival (median 1 v 2.05 years, P = .03) than patients with sL-selectin <3.12 μg/mL. Multivariate statistical analysis (adjusted for age and presence of Auer rods) indicated that sL-selectin was an independent prognostic factor for EFS (hazard ratio [HR], 1.96; 95% CI, 1.21 to 3.17, P = .006) and overall survival (HR, 1.80; 95% CI, 1.09 to 2.98; P = .02). Thus, plasma sL-selectin may be a useful prognostic marker in the evaluation of AML at diagnosis. © 1998 by The American Society of Hematology.

scholarly journals Posaconazole for the prophylaxis of invasive aspergillosis in acute myeloid leukemia: Is it still useful outside the clinical trial setting?

2020 ◽  
Vol 11 ◽  
pp. 204062072096584
Author(s):  
Tsung-Chih Chen ◽  
Ren Ching Wang ◽  
Yu-Hui Lin ◽  
Kuang-Hsi Chang ◽  
Li-Ya Hung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Invasive Aspergillosis ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Antifungal Prophylaxis ◽  
Remission Induction ◽  
Prophylaxis Group ◽  
Significant Difference ◽  
Acute Myeloid

Background: Posaconazole prophylaxis during remission induction chemotherapy not only decreases the incidence of invasive aspergillosis (IA) but also improves the overall survival rate among patients with acute myeloid leukemia (AML). However, it remains debatable whether this result applies to patients in a real-world setting. Methods: We retrospectively assessed 208 adult patients with newly diagnosed AML who underwent remission induction therapy. These 208 patients were stratified into the posaconazole prophylaxis group ( n = 58) and no antifungal prophylaxis group ( n = 150). Results: Multivariate analyses showed that induction failure significantly increased the risk of proven or probable IA during the first induction chemotherapy [hazard ratio (HR), 10.47; 95% confidence interval (CI), 1.73–63.45; p = 0.011] and the entire course of AML treatment (HR, 4.48; 95% CI, 1.71–11.75; p = 0.002). However, posaconazole prophylaxis did not reduce the risk of IA during the first induction chemotherapy (HR, 1.47; 95% CI, 0.14–15.04; p = 0.746) and during the entire course of AML treatment (HR, 1.09; 95% CI, 0.29–4.09; p = 0.896). Furthermore, there was no significant difference in overall survival between these two groups of patients (514 versus 689 days; p = 0.454). Conclusion: Successful induction remains fundamental to reducing the risk of IA among AML patients undergoing remission induction chemotherapy.

The FLAG Chemotherapy Regimen Is an Alternative to Anthracycline Based Therapy for the Treatment of Acute Myeloid Leukemia for Patients with Multiple Co-Morbidities or Preexisting Cardiac Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 961-961
Author(s):  
Lalit Saini ◽  
Robert Turner ◽  
Loree Larratt ◽  
Joseph Brandwein ◽  
Marlene Ann Hamilton ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Cardiac Disease ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Advanced Age ◽  
Cell Transplant ◽  
Poor Risk ◽  
Significant Difference ◽  
Acute Myeloid

Abstract BACKGROUND: Anthracycline based treatment for acute myeloid leukemia (AML) can be associated with significant morbidity and mortality amongst older patients or those with significant co-morbidities. Furthermore, for patients with previous anthracycline exposure or preexisting cardiac disease anthracyclines pose an increased risk of cardiotoxicity. For such patients intensive treatment options are limited. The FLAG (fludarabine, cytarabine and filgrastim) regimen is a non-anthracycline based chemotherapy useful for relapsed/refractory AML and as initial therapy for “fit” eligible patients. We present our experience using FLAG as first line therapy in a cohort of newly diagnosed AML patients with advanced age, significant co-morbidities or preexisting cardiac disease. METHODS: A single institution retrospective chart review was undertaken of patients treated with FLAG as frontline therapy from 2004 – 2013 with follow-up until June 2014. All patients were considered ineligible for standard ‘3+7’ treatment by the attending physician. RESULTS: Over the study period 56 patients received FLAG. Due to patient refusal or induction complications bone marrow assessments to ascertain remission status were not performed in 10 patients – to minimize bias these patients were evaluated for toxicity and overall survival (OS) but excluded from complete remission (CR) and relapse free survival (RFS) analysis. Of the 56 patients, 68% were males. The median age was 69 (21 – 80) with 79% aged ≥ 60 and 43% aged ≥ 70. Fifty-five percent (31) of the patients had primary AML and cytogenetics were favorable in 5% (3), intermediate in 66% (37), poor-risk in 21% (12) and failed in 7% (4). Forty-six percent (26) were treated with FLAG due to preexisting cardiac disease and others due to advanced age (20%), poor performance status (16%), co-morbidities (16%) or previous anthracycline exposure (2%). The ages of patients treated with FLAG due to cardiac disease or other reasons was similar (63.5 years vs. 66.9 years, p=0.27). Amongst patients with cardiac disease a pre-chemotherapy cardiac evaluation revealed wall motion abnormalities in 39% and an ejection fraction (EF) ranging from 33% - 81% with a borderline (≤ 50-51%) EF in 46%. Febrile neutropenia was observed in 82% (46) of patients, 27% (15) required intensive care support and the induction mortality was 16% (9). Amongst patients evaluated for a CR (46/56), 48% (22/46) obtained a CR. Although a CR was seen in 100% (3/3), 46% (15/33) and 37% (3/8) of patients with favorable, intermediate and poor-risk cytogenetics respectively there was no statistically significant difference (p=0.22) between groups. A CR was obtained in two additional patients following a second course of FLAG for an overall CR rate of 52% (24/46). Of these 24 patients, 8 (33.3%) received no additional treatment while 16 (66.7%) received consolidative chemotherapy. Of 10 eligible patients, 4 proceeded to an allogeneic stem cell transplant (allo-SCT) including two with preexisting cardiac disease. Of patients not transplanted 50% (10/20) eventually relapsed. There was no difference in relapse rates for those receiving FLAG for age/co-morbidities vs. cardiac disease (60% vs. 40%, p= 0.66) or for patients age <60 vs. ≥ 60 (50% vs. 50%, p=1.0). The median RFS was 441 days with no difference between patients treated with FLAG for cardiac reasons vs. other reasons (p=0.33) or for patient’s age < 60 vs. ≥ 60 (p=0.66). The median OS for the 56 patients was 278 days with 1 and 2 year survivals of 44% and 22% respectively. The median OS for patient’s age < 60 was higher than those age ≥ 60 (1102 days vs. 218 days, p=0.009) but there was no difference in the OS between patients treated with FLAG for cardiac disease and those treated for other reasons (305 days vs. 254 days, p=0.202). The median survival of patients with favorable, intermediate and unfavorable risk cytogenetics was 523 days, 311 days and 87 days respectively but this was not statistically significant (p=0.25) likely due to limited patient numbers. Conclusions: The FLAG regimen is a non-anthracycline based regimen that may serve as an alternative to the standard ‘3+7’ induction for AML in older adults or those with significant co-morbidities including preexisting cardiac disease. It is associated with comparable remission rates and overall survival in older patients. In addition, it may allow some patients with preexisting cardiac disease to proceed to allo-SCT. Disclosures No relevant conflicts of interest to declare.

P-Glycoprotein Inhibitor Valspodar (PSC 833) Increases the Intracellular Concentrations of Daunorubicin In Vivo in Patients With P-Glycoprotein–Positive Acute Myeloid Leukemia

2000 ◽  
Vol 18 (9) ◽  
pp. 1837-1844 ◽  
Author(s):  
U. Tidefelt ◽  
J. Liliemark ◽  
A. Gruber ◽  
E. Liliemark ◽  
B. Sundman-Engberg ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Area Under The Curve ◽  
Leukemic Cells ◽  
Psc 833 ◽  
P Glycoprotein ◽  
Significant Difference ◽  
The Mean ◽  
Acute Myeloid

PURPOSE: The aim of the present study was to evaluate the effect of the cyclosporine derivative valspodar (PSC 833; Amdray, Novartis Pharma, Basel, Switzerland) on the concentration of daunorubicin (dnr) in leukemic blast cells in vivo during treatment.PATIENTS AND METHODS: Ten patients with acute myeloid leukemia (AML) were included. Leukemic cells from seven of the patients were P-glycoprotein (Pgp)–positive. dnr 100 mg/m2was given as a continuous infusion over 72 hours. After 24 hours, a loading dose of valspodar was given, followed by a 36-hour infusion of 10 mg/kg per 24 hours. Blood samples were drawn at regular intervals, and concentrations of dnr and its main metabolite, daunorubicinol, in plasma and isolated leukemic cells were determined by high-pressure liquid chromatography.RESULTS: The mean dnr concentrations in leukemic cells 24 hours after the start of infusion (before valspodar) were 18.8 μmol/L in Pgp-negative samples and 13.5 μmol/L in Pgp-positive samples. After 8 hours of valspodar infusion, these values were 25.8 and 24.0 μmol/L, respectively. The effect of valspodar was evaluated from the ratio of the area under the curve (AUC) for dnr concentration versus time in leukemic cells to the AUC for dnr concentration against time in the plasma. For the seven patients with Pgp-positive leukemia, the mean ratio increased by 52%, from 545 on day 1 to 830 on day 2 (P < .05) when valspodar was given. In the three patients with Pgp-negative leukemia, no significant difference was observed.CONCLUSION: These results strongly suggest that valspodar, by interacting with Pgp, can increase the cellular uptake of dnr in leukemic blasts in vivo.

scholarly journals Outcome analysis of acute myeloid leukemia patients treated with high dose daunorubicin

2019 ◽  
Vol 6 (9) ◽  
pp. 3347-3351
Author(s):  
Roya Dolatkhah ◽  
Effat Irani Jam ◽  
Alireza Nikanfar ◽  
Ali Esfahani ◽  
Sayed Hadi Chavooshi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Outcome Analysis ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference ◽  
Disease Free ◽  
Acute Myeloid

Abstract: Acute Myeloid Leukemia (AML) is a malignant hematopoietic disease caused by the presence of a malignant clone in the bone marrow. The classic AML treatment includes a combination of an Anthracycline and Cytarabine. This study aimed to evaluate the effect of high doses of Daunorubicin on patients' outcome. Methods: During the study period, 16 AML patients received induction therapy with Cytarabine (100 mg/m2/d) for 7 days and Daunorubicin (90 mg/m2/d) for 3 days. Outcome analysis was performed to evaluate the overall survival (OS) and disease-free survival (DFS) during 2 years of study. Results: The mean age of patients was 38+/-12.38 years, with the age range between 16 and 54 years old. Seven patients (43.8%) were females, and 9 cases (56.3%) were males. OS was 81.3%, with a mean of 396.88 days. (95% CI: 306.99-486.77). DFS was 83.3%, with a mean of 383.57 days (95% CI: 299.88-467.26). The log-rank test showed a significant difference in DFS of AML sub-types, as M1 subtypes had lower DFS (P log-rank= 0.013). Although M1 subtypes had a lower OS, there was no significant difference in OS between subgroups (P log-rank= 0.067). Conclusion: Although disease-free survival was improved by increasing the dose of daunorubicin, there was no difference in the overall survival between the AML subgroups and sexes.  

scholarly journals The Use of Cyclosporine in Association with Chemotherapy As Induction Treatment in Patients with Acute Myeloid Leukemia (AML) and High Rhodamine Efflux at Diagnosis Results in Higher Complete Hematological Remission Rates, but Does Not Prolong Overall Survival

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4896-4896 ◽  
Author(s):  
Luisa C A Koury ◽  
Lorena Lobo Figueiredo-Pontes ◽  
Belinda Pinto Simoes ◽  
Luciana C O Oliveira ◽  
Leandro F F Dalmazzo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Induction Treatment ◽  
Term Survival ◽  
The Mean ◽  
Hematological Remission ◽  
Acute Myeloid

Abstract The overexpression of P-glycoprotein (Pgp) in leukemic blasts of Acute Myeloid Leukemia (AML) is associated with lower complete remission (CR) rates and shorter disease-free (DFS) and overall survival (OS). Cyclosporine A (CSA) is a competitive inhibitor of Pgp capable of reduce the P-gp mediated drug efflux. List et al. reported that CSA addition to treatment with cytarabine and daunorubicine reduced the resistance to induction treatment (IT) and prolonged DFS and OS. The effect was greater in AML patients with higher Pgp expression (Blood 2001; vol 98, n 12: 3212-20). Based on this study, we tested the effect of the association of CSA to IT in cases with high Pgp expression, which was established using the Rhodamine effux test as previously described (Pétriz, J. and García-López, J. Leukemia 1997; vol 11: 1124-30). The cut off value of the mean fluorescence intensity adopted to define high P-gp expression was ≥ 1.10. A total of 21 high P-gp AML patients were randomized in two groups: 1. Daunorubicin (DNR) 60mg/m² in continuous infusion -CI- 3x+Cytarabine 100 mg/m² CI 7x + CSA 16mg/m² CI 3x; (CSA group) and 2. DNR 60mg/m² CI 3x + Cytarabine 100 mg/m² CI 7x (Conventional IT group). Patients who did not achieve Complete Hematological Remission (CHR) in the first cycle of chemotherapy received a second course. The 2 groups did not differ regarding age (mean ± S.D.: 44.5 ± 11.9 vs. 48.5 ± 15.2 years in CSA and conventional IT group, respectively), leukocyte counts at diagnosis (44,200 ± 56,100 vs. 21,540 ± 20,200/µl), frequency of de Novo AML (81.8 vs. 80%) and of Core Binding Factor Leukemia cases (18.2 vs. 10%). The median follow up among survivors was of 6.2 years. The mean serum levels of CSA at 24 hours after infusion was of 1,157 ng/mL (range: 4 - 1,600ng/mL), which was similar to that reported by List et al. The CHR rate after the first cycle of induction was higher in the group using CSA (63.6% vs. 30%; p = 0.09) but the DFS (2.05 years vs. not reached; p= 0.27) and OS (4.08 vs. 21.12 months; p = 0.19) were higher in conventional IT group. These results may reflect the effect of the second course of induction in patients who failed to achieve CHR (CHR after second IT: 0% vs. 33.3%, p=0.34, in CSA and conventional IT group, respectively) and higher relapse rate in CSA group (42.8% vs. 33.3%, p=0.78). Furthermore, there was a lower frequency of induction deaths (18.2% vs. 9%; p = 0.59) and of hyperbilirubinemia (bilirubin > 1,5x the upper limit of normality) in the Conventional IT group (6 vs. 0 patients; p = 0.02). There were no cases of acute cardiac toxicity. The study was interrupted due to the cost of CSA and the lack of significant improvement in the outcomes. In conclusion, despite the higher rate of CR after one cycle of chemotherapy, there was not improvement in long term survival of AML patients with high Pgp expression treated with CSA in combination with anthracyclines and cytarabine. Disclosures No relevant conflicts of interest to declare.

Clinical Implications of Acute Myeloid Leukemia Presenting as Granulocytic Sarcoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2155-2155
Author(s):  
Batia Ronit Avni ◽  
Deborah Rund ◽  
Moshe Levin ◽  
Sigal Grisaro ◽  
Dina Ben-Yehuda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Medical Center ◽  
Granulocytic Sarcoma ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Risk Of Death ◽  
Significant Difference ◽  
Acute Myeloid

Abstract Abstract 2155 Introduction: Granulocytic sarcoma (GS), also known as chloroma, is described as an extramedullary tumor composed of immature myeloid cells. It has been reported to develop in 2–8% of patients with acute myeloid leukemia (AML) and can occur prior to, concomitantly with, or following the diagnosis of AML. Rarely patients present with GS as an isolated mass without evidence of AML (Byrd JC, J Clin Oncol. 1997). Due to the rarity of this disorder, large series of patients are seldom reported and the prognosis and optimal treatment of patients presenting with GS are not clear. Objectives: In this retrospective study we analyzed the presenting characteristics, treatments and overall survival of all patients presenting with isolated granulocytic sarcoma (GS) or GS with concomitant acute myeloid leukemia (AML) at presentation and compared them to all AML patients, treated at our institution during the same period. Methods: We identified cases who were diagnosed as having GS (with or without bone marrow involvement by AML) and cases of AML (without evidence GS at diagnosis) using ICD-9 codes in the hospitalization data base of the Hadassah Medical Center between 1990 and 2005. We excluded patients with GS at the time of relapse. All GS cases were biopsy-proven. Results: The study population consisted of 19 GS and 235 AML non-GS patients. The median age of these patients was 41 and 48 years, respectively. There was no statistically significant difference between the groups regarding gender, age, cytogenetic risk groups, rate of complete remission (CR), number of cycles of chemotherapy needed to achieve CR and rate of first relapse. Hematopoietic stem cell transplant (HSCT) (either autologous or allogeneic) was performed in 10 of 19 patients (52.6%) in the GS group and in 66 of 235 (28.1%) in the AML group (p=0.025). The overall survival in the GS group (median 16 months) was not significantly different (p= 0.60) from the AML group. The median time to death in subjects who had radiotherapy (6/19) was identical (median 21 months, p=0.79) to that of subjects who did not receive radiotherapy. Transplantation was associated with prolonged survival in both GS and AML groups (p=0.018 and p<0.0001 respectively). At the end of the follow up, 4 patients in the GS group who underwent HSCT were alive, compared to none in the group who did not undergo HSCT. Karyotype was found to be a prognostic factor in both the GS and AML groups (p=0.0034 and p<0.0001 respectively). In a multivariate analysis there was no statistically significant difference in the risk of death between subjects in the AML and the GS group; hazard ratio (HR) = 0.83, 95% CI (0.456-1.516), p=0.55, after controlling for age, karyotype and transplantation. As expected, in the model, age less than 47.5 years (HR=0.646 (p=0.0022)) and favorable and intermediate karyotype (HR=0.13 (p<0.0001) and HR=0.44 (p<0.0001) respectively, compared to unfavorable) were associated with a lower risk of death. Subjects who did not undergo transplantation had an increased risk of death compared with subjects who underwent the procedure (HR=1.88, p=0.0023) (Fig. 1). Conclusions: To the best of our knowledge this is the first retrospective series of GS patients with concomitant AML at diagnosis compared to all other AML patients in one medical center. The addition of radiotherapy as a treatment modality for GS patients did not appear to change survival. Patients with GS at diagnosis might benefit from upfront aggressive treatment with HSCT. Due to the rarity of this disorder and the remaining open questions, a prospective multi-center study is necessary to address these issues. Disclosures: No relevant conflicts of interest to declare.

The Modified Pre-Transplant EBMT Risk Score Is Superior To The HCT-CI Score In Predicting Overall Survival and Non-Relapse Mortality After Allogeneic Hematopoietic Cell Transplantation In Patients With Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2153-2153 ◽  
Author(s):  
Fotios V. Michelis ◽  
Hans A. Messner ◽  
Jieun Uhm ◽  
Anna Lambie ◽  
Laura McGillis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Significant Difference ◽  
Acute Myeloid

Abstract A variety of factors have been investigated for their influence on outcomes post-allogeneic hematopoietic cell transplantation (HCT). Pre-HCT risk scores have been developed such as the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) and the modified EBMT score (mEBMT) for acute leukemias (involving age, CR status, donor type and gender mismatch). The purpose of this single-center study was to investigate the influence of these scores on outcome post-HCT in 350 patients transplanted between 1999 and 2012 for acute myeloid leukemia (AML) and to compare the predictive value of these scores. Median age of all patients at transplant was 49 years (range 18-71 years), 174 patients (50%) were female. HCT was performed in first complete remission (CR1) for 245 patients (70%) and in second complete remission (CR2) for 105 patients (30%). Cytogenetics at diagnosis were available in 289 patients (83%). Donors were matched related (n=213, 61%) or matched unrelated (n=137, 39%). Cytomegalovirus (CMV) serostatus was negative for both donor and recipient in 113 patients (32%). Peripheral blood stem cells were used as a graft source in 272 patients (78%). Myeloablative conditioning was administered to 239 (68%) patients, 111 (32%) received reduced-intensity conditioning (RIC) regimens. The HCT-CI scores were grouped as 0, 1-2 and ≥3 (94, 137 and 119 patients respectively). The mEBMT scores were grouped as 0-1, 2, 3 and 4-5 (32, 134, 120 and 64 patients respectively). Median follow-up duration among survivors was 62 months (range 12-156 months). Univariate analysis demonstrated a significant difference of overall survival (OS) according to the HCT-CI score (p=0.03), 3-year OS 52%, 53% and 39% in HCT-CI score 0, 1-2 and ≥3 (Figure 1). The mEBMT score also demonstrated a significant difference of OS among the patients with scores 0-1, 2, 3 and 4-5 (p=0.002), 3-year OS 75%, 53%, 40% and 39% respectively (Figure 2). The HCT-CI and mEBMT scores could not stratify the patients according to the cumulative incidence of relapse (CIR) with p-value of 0.99 and 0.50 respectively. For cumulative incidence of non-relapse mortality (NRM), the HCT-CI showed a trend of statistical significance (p=0.07), while the mEBMT score could stratify the patients according to the risk of NRM (p=0.01). Multivariable analysis was performed including the HCT-CI and mEBMT scores as previously defined. Covariates already incorporated in the mEBMT score (age, CR status, related donors) were not included in the multivariable analysis. For OS, the HCT-CI score was removed from the final model due to statistical insignificance (p=0.17). However, the mEBMT score was confirmed as an independent prognostic variable for OS (p=0.00002, HR=1.5, 95%CI=1.2-1.8). For NRM, HCT-CI did not maintain significance (p=0.11) while mEBMT again was confirmed as an independent prognostic factor (p=0.0003, HR=1.5, 95%CI=1.2-1.9). The current study showed that the mEBMT score was confirmed as an independent prognostic factor for OS and NRM in patients with AML undergoing HCT, while the HCT-CI score was not confirmed. In conclusion, the mEBMT risk score is superior to the HCT-CI score in predicting OS and NRM following allogeneic HCT in AML patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals NPM1+/FLT3- Patients with Acute Myeloid Leukemia (AML) Have Excellent Clinical Outcome Independent of Age When Treated with Cytotoxic Chemotherapy: Mayo Clinic Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5331-5331
Author(s):  
Mehrdad Hefazi Torghabeh ◽  
Mustaqeem A Siddiqui ◽  
Mrinal M. Patnaik ◽  
Alexandra Wolanskyj ◽  
Darci Zblewski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Cytotoxic Chemotherapy ◽  
Adult Patients ◽  
Prognostic Impact ◽  
Mutational Status ◽  
Significant Difference ◽  
Acute Myeloid

Abstract Background: Molecular profiling has revolutionized the field of hematology, and in particular myeloid neoplasms. NPM1+/FLT3- mutational status has been shown to have a favorable prognostic impact in patients with acute myeloid leukemia (AML). However, little is known about its interaction with age. Methods: We retrospectively analyzed the overall survival (OS) in newly diagnosed AML patients, whose FLT3 and NPM1 data were available, and were treated with cytotoxic chemotherapy at our institution between 2003 and 2013. Patients 18 to 60 years of age were categorized as adult, and those above 60 years were classified as elderly. Each of the elderly or adult groups were further divided according to the presence or absence of combined NPM1+/FLT3- mutational status. Estimated probabilities of overall survival were calculated using the Kaplan-Meier method, with the log-rank test to compare groups. Demographics and continuous variables were compared using the Wilcoxon rank sum test. Appropriate IRB approval was obtained. Results: Out of 835 patients with AML, 86 patients with both known FLT3/NPM1 mutation status and receiving induction chemotherapy were found. NPM1+/FLT3- mutational status was present in 11 elderly (median age 68 yr, hemoglobin (Hb) 8.7 g/dL, white blood cells (WBC) 9.6 x109/L, platelets (PLT) 100 x109/L, peripheral blood blasts percentage (PB%) 31), and in 11 adult patients (median age 49 years, Hb 9.1 g/dL, WBC 14 x109/L, PLT 67 x109/L, and PB% 21). Twenty-eight elderly patients (median age 66 yr, Hb 9.4 g/dl, WBC 15.7 x109/L, PLT 66 x109/L, and PB% 33), and 36 adult patients (median age 49 years, Hb 9.1 g/dL, WBC 14 x109/L, PLT 67 x109/L, and PB% 21) were carrying genotypes other than NPM1+/FlT3-. There was no statistical significant difference in the median age, Hb, WBC, PLT, and PB% at the time of diagnosis. Out of 86 patients, 79 had intermediate, 6 had adverse, and 1 had favorable cytogenetic risk. All elderly and adult patients with NPM1+/FLT3- genotype had intermediate risk cytogenetics. When treated with cytotoxic chemotherapy, elderly patients with NPM1+/FLT3- genotype demonstrated a significantly better overall survival compared to elderly patients without this genotypes (p=0.015), and interestingly also to adult AML carrying other genotypes (p=0.028). Surprisingly, there was not an improved survival in adults with NPM1+/FLT3- genotype compared to adults carrying other genotypes (p=0.14), but this may have been related to the small numbers in each group. No significant difference in the overall survival was observed between elderly and adult patients who were carrying NPM1+/FLT3- mutational status (p=0.4). The estimated 5-year survival rates for elderly with and without NPM1+/FLT3- status were 71% vs. 14%, and for adults with and without this genotype were 49% vs. 19%, respectively. Conclusion: Age does not have an impact on the OS in AML patients with NPM1+/FLT3- mutational status, arguing strongly for intense chemotherapy in this group. Elderly AML patients with NPM1+/FLT3- genotype have a superior OS compared to both adult and elderly patients carrying other genotypes, when treated with cytotoxic chemotherapy. Further validation in large prospective studies is warranted. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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