Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1504-1504
Author(s):  
Dana Marie Walker ◽  
Yimei Li ◽  
Yuan-Shung Huang ◽  
Alix Eden Seif ◽  
Marko Kavcic ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cancer Patients ◽  
Pediatric Cancer ◽  
Myeloid Leukemia ◽  
Administrative Database ◽  
Secondary Aml ◽  
Secondary Acute Myeloid Leukemia ◽  
Increased Risk ◽  
Pediatric Cancer Patients ◽  
Acute Myeloid

1504 Background: Dexrazoxane (DXZ) is an effective cardioprotectant in children with leukemia and solid tumors. However, the potential risk of secondary acute myeloid leukemia (AML) limits DXZ use. We compared the incidence of secondary AML in pediatric cancer patients with and without DXZ exposure to estimate the risk of DXZ-associated secondary AML. Methods: We conducted a retrospective cohort study of anthracycline exposed pediatric cancer patients (excluding de novo AML) hospitalized from January 1999 to March 2011 in 43 freestanding children’s hospitals in the Pediatric Health Information System (PHIS) database. Secondary AML was defined as an ICD9 code for AML that occurred at least 90 days after first anthracycline exposure. Proportions of patients with secondary AML were compared between patients with and without an exposure to DXZ after the initial anthracycline exposure. Results: During the study period of interest, 15,532 pediatric cancer patients were exposed to anthracycline, of which 1404 (9.04%) subsequently received DXZ. Secondary AML was identified in 235 (1.51%) patients. Patients ≥ 10 years of age, black patients, patients in New England and the Midatlantic regions, and those with bone tumors were significantly more likely to have received DXZ. The unadjusted incidence of secondary AML in the DXZ exposed and unexposed patients did not differ significantly (1.21% v. 1.54%, p=0.3308). After adjusting for these variations in demographics, the incidence of secondary AML still did not significantly differ between DXZ exposed and unexposed patients (p=0.6224). Conclusions: Our findings suggest that DXZ exposure does not lead to an increased risk of secondary AML in children. These data are important given the conflicting results from individual clinical trials about the risk of DXZ-associated secondary AML. While subject to well-known limitations of administrative database analyses, these data represent the largest cohort of DXZ exposed patients with available data on the occurrence of secondary AML. Additional multivariate analyses of chemotherapeutic covariates and time to secondary AML are ongoing.

Allogeneic Hematopoietic Stem Cell Transplantation for Secondary Acute Myeloid Leukemia- a Report from the Acute Leukemia Working Party of the EBMT

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 63-63
Author(s):  
Bipin N. Savani ◽  
Myriam Labopin ◽  
Ariane Boumendil ◽  
Gerhard Ehninger ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Working Party ◽  
Registry Study ◽  
Hematopoietic Stem ◽  
Secondary Aml ◽  
Relapse Risk ◽  
Secondary Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Secondary acute myeloid leukemia (sAML) is a very heterogeneous group of disease derived from myelodysplasia, chronic myeloproliferative disorders or after exposure to chemotherapy and or radiation therapy (therapy related AML) or due to exposure to environmental carcinogens. sAML has traditionally been considered a devastating disease with inferior outcomes compared to de novo AML, affecting a vulnerable population of heavily pretreated, especially older patients. Allogeneic hematopoietic stem cell transplantation (HCT) is the only potential curative therapy and usually considered in patients with low comorbidities and transplant related risk score. However, relapse is the most frequent cause of failure after HCT, occurring in more than 50% of the patients. No systematic large analysis of HCT for sAML is available to study the risk factors and outcome. Therefore, the EBMT Acute Leukemia Working Party has performed a retrospective registry study on patients with sAML (n=4256) undergoing HCT. Patients who underwent HLA-identical sibling (n=2290) or unrelated donor (n=1966) peripheral blood (n=3781) or bone marrow transplantation (n=475) from 2000 to 2013 are included in the study. All unrelated donors were Human Leucocyte Antigens (HLA)-matched (10/10) (n=1532) or one locus mismatched (9/10) (n=434). 1901 (45%) patients received ablative (MAC) and 2355 (55%) reduced-intensity conditioning (RIC) regimen. Median age at transplant was 56 years, IQR 48-63 (MAC 51, IQR 42-58; RIC 60, IQR 54-64). Median time from diagnosis of sAML to HCT was 6.2 months, IQR 4.1-12.0 (MAC 5.6, IQR 3.8-9.7; RIC 7.0, IQR 4.4-14.12; p<0.0001). At time of transplant, 2313 (54%) patients were in CR1, 278 (7%) in ≥CR2 and active diseases in 1665 (39%) patients. 158 (4%) patients had prior autologous HCT (MAC 58 [3%], RIC 100 [4%], p=0.049). Median follow-up of surviving patients was 26 months (IQR 7 -56). Two year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) were 33% (95% CI, 32-35%) and 25% (95% CI, 24-27%), respectively. The Kaplan-Meier estimate of overall survival (OS) and leukemia-free survival (LFS) at 2 years were 46% (95% CI, 44-48%) and 41% (95% CI, 39-43%), respectively. Acute GVHD (grade II-IV) occurred in 1043 (26%) patients. The 2-year cumulative incidence of chronic GVHD was 54% (95% CI, 51-56). Two year OS, LFS, RI and NRM of MAC and RIC groups were 48% (95% CI, 46-50) vs. 44% (95% CI, 42-47), p=0.06, 44% (95% CI, 41-46) vs. 39% (95% CI, 37-41), p=0.003, 30% (95% CI, 28-32) vs. 36% (95% CI, 34-38), p<0.0001, 26% (95% CI, 24-28) vs. 25% (95% CI, 24-27), p=0.273, respectively. Two year OS of patients in CR1, ≥CR2 and active disease before HCT was 54% (95% CI, 52-56), 45% (95% CI, 39-52) and 35% (95% CI, 33-38), respectively (p<0.0001). In multivariate analysis adjusted for variable with different distribution between groups, the type of conditioning (RIC vs. MAC) had no impact on OS and LFS, however RIC group had higher RI (HR, 1.3, 95% CI 1.12-1.44, p=0.0001) and lower NRM (HR 0.8, 95% CI 0.72-0.96, p=0.01). Older age at HCT was an independent adverse prognostic factor for OS, LFS and NRM. Time from diagnosis to HCT had no impact on transplant outcome. Patients receiving PB grafts had superior OS (HR 0.84, 95% CI 0.73-0.97, p=0.01), LFS (HR 0.85, 95% CI 0.74-0.97, p=0.02) and lower RI (HR 0.83, 95% CI 0.70-0.99, p=0.049) compared with BM. Patients in remission and receiving HCT from HLA-identical siblings were independently associated better outcome. In summary, our registry study in the largest cohort of patients studied so far receiving HCT for secondary AML, demonstrated that about 45% of patients with secondary AML can attain long term survival after HCT. Patients receiving ablative regimens were associated with lower relapse risk and patients in remission had superior survival. Patients receiving PB grafts were associated potent graft-versus leukemia effects with decreased relapse risk and improved survival. Post- transplant pre-emptive therapy to decrease relapse risk might improve outcome further in these high risk populations. Disclosures Niederwieser: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Glass:Roche, MSD, Takeda, Riemser, Ctilifesciences: Honoraria, Research Funding. Esteve:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Schmid:Janssen Cilag: Other: Travel grand; Neovii: Consultancy.

Mitoxantrone and Cytarabine Induction, High-Dose Cytarabine, and Etoposide Intensification for Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia: Children’s Cancer Group Study 2951

2003 ◽  
Vol 21 (15) ◽  
pp. 2940-2947 ◽  
Author(s):  
Robert J. Wells ◽  
Mary T. Adams ◽  
Todd A. Alonzo ◽  
Robert J. Arceci ◽  
Jonathan Buckley ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Remission Rate ◽  
Good Prognosis ◽  
High Dose ◽  
Secondary Aml ◽  
Secondary Acute Myeloid Leukemia ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Purpose: To evaluate the response rate, survival, and toxicity of mitoxantrone and cytarabine induction, high-dose cytarabine and etoposide intensification, and further consolidation/maintenance therapies, including bone marrow transplantation, in children with relapsed, refractory, or secondary acute myeloid leukemia (AML). To evaluate response to 2-chlorodeoxyadenosine (2-CDA) and etoposide (VP-16) in patients who did not respond to mitoxantrone and cytarabine. Patients and Methods: Patients with relapsed/refractory AML (n = 101) and secondary AML (n = 13) were entered. Results: Mitoxantrone and cytarabine induction achieved a remission rate of 76% for relapsed/refractory patients and 77% for patients with secondary AML, with a 3% induction mortality rate. Cytarabine and etoposide intensification exceeded the acceptable toxic death rate of 10%. The response rate of 2-CDA/VP-16 was 8%. Two-year overall survival was estimated at 24% and was better than historical control data. Patients with secondary AML had similar outcomes to relapsed or refractory patients. Initial remission longer than 1 year was the most important prognostic factor for patients with primary AML (2-year survival rate, 75%), whereas for patients with primary AML, with less than 12 months of initial remission, survival was 13% and was similar to that of refractory patients (6%). Conclusion: Mitoxantrone and cytarabine induction is effective with reasonable toxicity in patients with relapsed/refractory or secondary AML. The cytarabine and etoposide intensification regimen should be abandoned because of toxicity. Patients with relapsed AML with initial remissions longer than 1 year have a relatively good prognosis.

scholarly journals De Novo and Secondary Acute Myeloid Leukemia, Real World Data on Outcomes from the French Nord-Pas-De-Calais Picardie Acute Myeloid Leukemia Observatory

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4013-4013 ◽  
Author(s):  
Loïc Renaud ◽  
Olivier Nibourel ◽  
Celine Berthon ◽  
Christophe Roumier ◽  
Céline Rodriguez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Supportive Care ◽  
Real World ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Secondary Aml ◽  
Secondary Acute Myeloid Leukemia ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Background. Population-based registries may provide data complementary to that from clinical intervention studies. Registries with high coverage of the target population reduce the impact of selection on outcome and the subsequent problem with extrapolating data to nonstudied populations like secondary Acute Myeloid Leukemia (AML). Actually, secondary AML are frequently excluded from clinical trials so the registries constitute the only way to fine data for establishing recommendations for the management of these patients in the real world. Method. The French Nord-pas-de-calais Picardie AML observatory containing 1 582 AML patients diagnosed between 2000 and 2015. We compared 974 primary AML to 514 Secondary AML include AML arising from a pre-existing myelodysplastic (n=211), myeloproliferative (n=88) or myelodysplastic/myeloproliferative (n=57) disease and therapy related AML (t-AML) (n=158). Results. Median survival and 5 years overall survival were respectively 420 days [95%IC: 349-491] and 32% for patients with de novo AML; 157 days [95%IC: 118-196] and 7% for patients with secondary AML. 1101 patients were classified according to the MRC as favorable, intermediate and unfavorable, respectively 18(5.2%), 178(51.9%) and 147(42.9%) patients with secondary AML including 100(29.2%) complexes karyotypes and 117(15.4%), 468(61.7%) and 173(22.8%) patients with de novo AML including 121 (15.9%) complexes karyotypes. 987 patients were classified according to the ELN as favorable, intermediate-1, intermediate-2 and unfavorable for respectively 35(11.7%), 53(17.7%), 67(22.%) and 144(48.2%) patients with secondary AML and 219(31.8%), 167(24.%), 136(19.8%) and 166(24.1%) patients with de novo AML. The age at diagnosis was significantly different (p < 10-3) with a median of 72.6 years for secondary AML and 63.2 for de novo AML. 206 (40.4%) patients with secondary AML received demethylating agents versus 184 (19%) for de novo AML and 152(29%) received high dose chemotherapy (HDC) versus 619 (63.9%) patients with de novo AML. Best supportive care was the only treatment for 170 (17.5%) de novo AML and 164 (31.9%) secondary AML patients. For patients over than 60 years old, median survival and 5 years overall survival were respectively 182 days [95%IC: 136.5-127.4] and 12.9% for 559 patients with de novo AML; 128 days [95%IC: 95.0-161.0] and <4% for 413 patients with secondary AML. Conclusion. The poor prognosis of secondary and t- AML is confirmed by this registry study. Possible explanations for this worse outcome could be older age at diagnosis and increased frequency of complex karyotypes which lead to less intensive therapy or supportive care only. In this specific population, the choice of demethylating agent therapy was frequently made because of the weak efficacy of HDC and increased frequency of side effects in this vulnerable group. Disclosures No relevant conflicts of interest to declare.

scholarly journals Therapy-related acute myeloid leukemia in a patient with neuroblastoma: case report

2020 ◽  
Vol 19 (3) ◽  
pp. 105-113
Author(s):  
D. T. Utalieva ◽  
I. I. Kalinina ◽  
D. Yu. Kachanov ◽  
D. A. Evseev ◽  
A. P. Shcherbakov ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Topoisomerase Ii ◽  
Alkylating Agents ◽  
Platinum Compounds ◽  
First Line ◽  
Secondary Acute Myeloid Leukemia ◽  
Increased Risk ◽  
Acute Myeloid ◽  
Rule Out

Modern, risk-adapted treatment approaches for intermediate and high-risk neuroblastoma (NB) have led to an increasing numbers of survivors. However, intensive multimodal treatment strategy is associated with a significantly increased risk of secondary malignancies. It is currently known that alkylating agents, topoisomerase II inhibitors, and platinum compounds induce treatment-related leukemia. This article presents a literature review and description of a clinical case of secondary acute myeloid leukemia (s-AML) developed 57 months after the initial diagnosis in a patient with intermediate-risk NB who received intensive first-line and post-relapse chemotherapy. The debut of s-AML required a differential diagnosis to rule out a relapse of NB. Parents gave their consent to use information about the child, including fotos, in the article.

Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide.

1993 ◽  
Vol 11 (2) ◽  
pp. 209-217 ◽  
Author(s):  
N J Winick ◽  
R W McKenna ◽  
J J Shuster ◽  
N R Schneider ◽  
M J Borowitz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood All ◽  
Secondary Aml ◽  
Secondary Acute Myeloid Leukemia ◽  
Drug Induction ◽  
B Lineage ◽  
Acute Myeloid

PURPOSE To describe the occurrence of secondary acute myeloid leukemia (AML) in children with acute lymphoblastic leukemia (ALL) treated with etoposide (VP-16). PATIENTS AND METHODS Two hundred five consecutive children with early B-lineage ALL were treated according to the Dallas/Fort Worth (DFW) protocol between January 1986 and July 1, 1991. Therapy included a four-drug induction followed by consolidation and continuation phases of nightly oral mercaptopurine (6-MP) and repetitive courses of divided-dose oral methotrexate (dMTX) and asparaginase (L-asp). Three doses of VP-16 and cytarabine (Ara-C) were given during consolidation and later, during continuation, two doses were given 3 to 4 days apart, every 9 weeks. Intrathecal (IT) chemotherapy was given throughout the treatment period. RESULTS Two hundred three of the 205 patients entered remission. Only eight of these 203 children have had a bone marrow relapse (ALL). However, 10 other children have developed secondary AML 23 to 68 months following the diagnosis of ALL. Overall event-free survival (EFS) at 4 years is 79.3% +/- 5.1%, with a risk of secondary AML at 4 years of 5.9% +/- 3.2%. CONCLUSION This experience provides strong evidence for a link between epipodophyllotoxin therapy and secondary AML since none of these children received alkylating agent therapy or irradiation. This serious complication raises concern as to the appropriate use of epipodophyllotoxins in the treatment of childhood ALL.

scholarly journals Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial

2021 ◽  
Author(s):  
Michael Heuser ◽  
B. Douglas Smith ◽  
Walter Fiedler ◽  
Mikkael A. Sekeres ◽  
Pau Montesinos ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
De Novo ◽  
Secondary Acute Myeloid Leukemia ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

AbstractThis analysis from the phase II BRIGHT AML 1003 trial reports the long-term efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized (2:1) patients to receive glasdegib + LDAC (de novo, n = 38; secondary acute myeloid leukemia, n = 40) or LDAC alone (de novo, n = 18; secondary acute myeloid leukemia, n = 20). At the time of analysis, 90% of patients had died, with the longest follow-up since randomization 36 months. The combination of glasdegib and LDAC conferred superior overall survival (OS) versus LDAC alone; hazard ratio (HR) 0.495; (95% confidence interval [CI] 0.325–0.752); p = 0.0004; median OS was 8.3 versus 4.3 months. Improvement in OS was consistent across cytogenetic risk groups. In a post-hoc subgroup analysis, a survival trend with glasdegib + LDAC was observed in patients with de novo acute myeloid leukemia (HR 0.720; 95% CI 0.395–1.312; p = 0.14; median OS 6.6 vs 4.3 months) and secondary acute myeloid leukemia (HR 0.287; 95% CI 0.151–0.548; p < 0.0001; median OS 9.1 vs 4.1 months). The incidence of adverse events in the glasdegib + LDAC arm decreased after 90 days’ therapy: 83.7% versus 98.7% during the first 90 days. Glasdegib + LDAC versus LDAC alone continued to demonstrate superior OS in patients with acute myeloid leukemia; the clinical benefit with glasdegib + LDAC was particularly prominent in patients with secondary acute myeloid leukemia. ClinicalTrials.gov identifier: NCT01546038.

scholarly journals Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34+ Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Marcus Bauer ◽  
Christoforos Vaxevanis ◽  
Haifa Kathrin Al-Ali ◽  
Nadja Jaekel ◽  
Christin Le Hoa Naumann ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Multispectral Imaging ◽  
Immune Cell ◽  
Genetic Alterations ◽  
Spatial Proximity ◽  
Secondary Acute Myeloid Leukemia ◽  
Acute Myeloid

Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34+ hematopoietic cells was determined by multispectral imaging (MSI) in 147 BM biopsies (BMB) from patients with MDS, secondary acute myeloid leukemia (sAML), and controls. Results: In MDS and sAML samples, a high inter-tumoral immune cell heterogeneity in spatial proximity to CD34+ blasts was found that was independent of genetic alterations, but correlated to blast counts. In controls, no CD8+ and FOXP3+ T cells and only single MUM1p+ B/plasma cells were detected in an area of ≤10 μm to CD34+ HSPC. Conclusions: CD8+ and FOXP3+ T cells are regularly seen in the 10 μm area around CD34+ blasts in MDS/sAML regardless of the course of the disease but lack in the surrounding of CD34+ HSPC in control samples. In addition, the frequencies of immune cell subsets in MDS and sAML BMB differ when compared to control BMB providing novel insights in immune deregulation.

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