Treatment-Related Mortality (TRM) in Children with Down Syndrome (DS) and B-Lymphoblastic Leukemia (B-ALL): An Interim Report from the Children's Oncology Group Trials AALL0932 and AALL1131

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2502-2502 ◽  
Author(s):  
Karen R. Rabin ◽  
Johann Hitzler ◽  
Vilmarie Rodriguez ◽  
Reuven Schore ◽  
Anne Angiolillo ◽  
...  
Keyword(s):  
Patient Characteristics ◽  
Induction Treatment ◽  
Interim Report ◽  
Oncology Group ◽  
Gram Negative ◽  
Post Induction ◽  
Early Responder ◽  
Standard Risk ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Background: Children with DS and B-ALL have historically experienced excessive TRM, primarily from infection. Here we provide an interim report on TRM in children with DS and newly diagnosed B-ALL enrolled on Children's Oncology Group (COG) trials for NCI standard risk (SR) (AALL0932) and high risk (HR) B-ALL (AALL1131). Methods: As of 06/30/2015, 203 SR DS-ALL patients have completed Induction on AALL0932 with 146 receiving post-Induction treatment on AALL0932. Eighty-eight HR DS patients have completed Induction on AALL1131, with 80 receiving post-Induction treatment on AALL1131. An additional 26 SR DS patients with poor early response received post-Induction therapy on AALL1131. Adverse events were graded according to NCI CTCAE v4.0, with enhanced data collection for targeted toxicities including infectious toxicities, and enhanced supportive care recommendations. Results: Patient characteristics are summarized in Table 1. TRM on AALL0932 occurred during Induction in 2/203 (1.0%) and post-Induction in 3/146 (2.1%), compared to 17/5528 (0.3%) and 12/3119 (0.4%) in non-DS SR patients (Fisher exact p=0.14 for Induction and p=0.03 for post-Induction). TRM on AALL1131 occurred during Induction in 4/88 (4.5%) and post-Induction in 5/106 (4.7%), compared to 34/2116 (1.6%) and 13/1258 (1.0%) in non-DS AALL1131 patients (p=0.06 for Induction and p=0.01 for post-Induction). Timing, cause, and other circumstances surrounding TRM are provided in Table 2. Gram-negative organisms accounted for the majority of fatal bacterial infections in patients with HR DS-ALL. Conclusion: TRM continues to be higher on current COG trials for patients with DS-ALL compared to non-DS patients. Most of the toxic deaths occur during intensive treatment phases due to infection in the context of profound neutropenia. Patients with HR B-ALL have a higher incidence of toxic death, notably in patients over 15 years of age. Based on our findings, hospitalization and antimicrobial prophylaxis during intensive treatment phases should be considered in children with DS-ALL due to their increased risk of infection-related mortality. Table 1. Patient Characteristics AALL1131 AALL0932 DS-ALL Non-DS ALL DS-ALL Non-DS ALL N 117 2689 207 5619 Median Age at Diagnosis (Years) 10.5 10.3 4.8 4.5 Gender  Male 62 1511 117 2981  Female 55 1178 90 2637 Table 2. Treatment-Related Mortality Case Characteristics Case Age Gender Treatment Phase Site of Infection Organism AALL1131 (High Risk) 1 15 F Induction D#29 (RER) Pneumonia, ARDS HMPV (pre-treatment) 2 21 F Induction D#29 (SER) Sepsis 3 17 F Induction D#22 (SER) Sepsis, typhlitis Escherichia coli 4 12 M Induction D#16 (RER) Sepsis, pneumonia (+baseline CHD, AV canal s/p repair 2003) Influenza B 5 19 M Consolidation D#18 Sepsis Citrobacter 6 2 F Delayed Intensification D#101 ARDS/capillary leak (+baseline CHD) Rhinovirus 7 15 F Delayed Intensification D#45 Sepsis, pneumonia Klebsiella, enterovirus, rhinovirus 8 27 M Delayed Intensification D#52 Sepsis Gram negative bacillus 9 14 M Delayed Intensification D#22 Sepsis AALL0932 (Standard Risk) 1 7.3 M Induction Febrile neutropenia, hypotension, cardiorespiratory failure None reported 2 3.0 F Induction Febrile neutropenia, sepsis, liver failure Viridans group Strepococcus coagulase negative staphylococcus HSV, EBV and HHV 3 3.4 M Consolidation Meningitis, brainstem infarction None reported 4 9.7 F Interim Maintenance I Sepsis, Stevens Johnson syndrome/TEN None reported 5 7.2 M Interim Maintenance II Death NOS None reported RER, rapid early responder; SER, slow early responder; CHD, congenital heart disease; AV, atrioventricular; ARDS, acute respiratory distress syndrome; HMPV, human metapneumovirus; TEN, toxic epidermal necrolysis; HSV, herpes simplex virus; EBV, Epstein-Barr virus; HHV, human herpesvirus. Disclosures Hunger: Sigma Tau: Consultancy; Jazz Pharmaceuticals: Consultancy; Merck: Equity Ownership; Spectrum Pharmaceuticals: Consultancy.

Adjuvant docetaxel and cyclophosphamide (DC) with prophylactic growth colony stimulating factor (GCSF) on days 8 and 12 in breast cancer patients: A retrospective analysis.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 202-202
Author(s):  
Rinat Yerushalmi ◽  
Salomon M. Stemmer ◽  
Daniel Hendler ◽  
Victoria Neiman ◽  
Noa Beatrice Ciuraru ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Bone Pain ◽  
Patient Characteristics ◽  
Prophylactic Antibiotics ◽  
Breast Cancer Patients ◽  
Included Patient ◽  
Stimulating Factor ◽  
Treatment Related Mortality ◽  
Related Mortality

202 Background: Four cycles of docetaxel/cyclophosohamide (DC) produced superior survival compared with doxorubicin/cyclophosphamide in the treatment of early breast cancer. The study reported 5% of febrile neutropenia (FN) events using prophylactic antibiotics with no growth factor (GF) support. The worldwide adoption of this protocol yielded several reports on substantially higher rates of FN events (up to 46%), prompting the addition of GCSF by most centers. We explored the use of GF support on days 8 and 12 to the original DC protocol. This report summarizes treatment related morbidity of the DC protocol with GF support given on days 8 and12. Methods: All consecutive patients with stages I-II breast cancer who were treated with the DC protocol in our institute from April 2007 to March 2012 were included. Patient characteristics and toxicity were reported. Results: 131 patients were identified. Median age- 60y (25-81), 65y and older- 25%; 5 patients did not complete the 4 planned cycles (12/524 cycles were missed). Fifteen patients (11.5%) experienced at least one event of FN (4 patients had 2 events), all requiring hospitalization. FN events occurred in 19 out of 512 cycles (3%). Median age of the patients who required hospitalization due to FN was 60y (42-73). Results were comparable in the older group (≥65): 15% developed FN with 6 NF events out of 130 cycles (4.6%), p>0.05. There were additional 14 hospitalizations events due to other causes (diarrhea n=2, chest pain=2, cellulitis n=2, COPD n=1, tonsillitis n=1, fever n=2, bone pain n=1, observation after treatment n=1 and hearing problem n=1, unknown n=1). Six patients had grade 2-3 diarrhea. 2/6 required hospitalization. There was no treatment related mortality. Conclusions: Primary prophylactic growth factor support on days 8 and 12 provides a safe and economic option to deliver the DC protocol. Our results are in line with other retrospective protocols using longer schedules of GF support.

Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study

Blood ◽  
2012 ◽  
Vol 119 (10) ◽  
pp. 2409-2416 ◽  
Author(s):  
Junya Kanda ◽  
Hiroh Saji ◽  
Takahiro Fukuda ◽  
Takeshi Kobayashi ◽  
Koichi Miyamura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Hla Dr ◽  
Increased Risk ◽  
Related Donor ◽  
Risk Of Treatment ◽  
Standard Risk ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract To clarify which is preferable, a related donor with an HLA-1 Ag mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host (GVH) direction (RD/1AG-MM-GVH) or an HLA 8/8-allele (HLA-A, HLA-B, HLA-C, and HLA-DRB1)–matched unrelated donor (8/8-MUD), we evaluated 779 patients with acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome who received a T cell–replete graft from an RD/1AG-MM-GVH or 8/8-MUD. The use of an RD/1AG-MM-GVH donor was significantly associated with a higher overall mortality rate than the use of an 8/8-MUD in a multivariate analysis (hazard ratio, 1.49; P < .001), and this impact was statistically significant only in patients with standard-risk diseases (P = .001). Among patients with standard-risk diseases who received transplantation from an RD/1AG-MM-GVH donor, the presence of an HLA-B Ag mismatch was significantly associated with a lower overall survival rate than an HLA-DR Ag mismatch because of an increased risk of treatment-related mortality. The HLA-C Ag mismatch or multiple allelic mismatches were frequently observed in the HLA-B Ag-mismatched group, and were possibly associated with the poor outcome. In conclusion, an 8/8-MUD should be prioritized over an RD/1AG-MM-GVH donor during donor selection. In particular, an HLA-B Ag mismatch in the GVH direction has an adverse effect on overall survival and treatment-related mortality in patients with standard-risk diseases.

scholarly journals Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000

Blood ◽  
2016 ◽  
Vol 127 (17) ◽  
pp. 2101-2112 ◽  
Author(s):  
Anja Möricke ◽  
Martin Zimmermann ◽  
Maria Grazia Valsecchi ◽  
Martin Stanulla ◽  
Andrea Biondi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Early Treatment ◽  
Survival Benefit ◽  
Induction Treatment ◽  
Early Treatment Response ◽  
Key Points ◽  
Pediatric All ◽  
Overall Survival Benefit ◽  
Treatment Related Mortality ◽  
Related Mortality

Key Points Dexamethasone vs prednisone in induction of pediatric ALL led to significant relapse reduction and increased treatment-related mortality. No overall survival benefit was achieved with dexamethasone except in the subset of patients with T-cell ALL and good early treatment response.

scholarly journals Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children's Oncology Group

2020 ◽  
Vol 26 (12) ◽  
pp. 2891-2897 ◽  
Author(s):  
Christine L. Phillips ◽  
Adam Lane ◽  
Robert B. Gerbing ◽  
Todd A. Alonzo ◽  
Alyss Wilkey ◽  
...  
Keyword(s):  
Oncology Group ◽  
Genomic Variants ◽  
Pediatric Aml ◽  
Treatment Related Mortality ◽  
Related Mortality

scholarly journals Optimum Induction Chemotherapy for Pediatric Acute Myeloid Leukemia: Experience From A Developing Country

2020 ◽  
Vol 25 (4) ◽  
pp. 288-294
Author(s):  
Tariq Ghafoor ◽  
Shakeel Ahmed ◽  
Sumaira Khalil ◽  
Tanzeela Farah
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Disease Free Survival ◽  
Induction Treatment ◽  
Pediatric Aml ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Acute Myeloid

OBJECTIVES Treatment outcome in children with acute myeloid leukemia (AML) has improved in the developed world but remains poor in developing countries. We assessed the role of etoposide in induction chemotherapy in pediatric AML. METHODS This analysis retrospectively compared 2 induction chemotherapy regimens consisting of daunorubicin and cytarabine with etoposide (ADE) and without etoposide (AD). All newly diagnosed cases of AML younger than 18 years from January 1, 2012, onwards who completed their treatment before January 31, 2019, were included. Data of 186 cases, including 117 males (62.9%) and 69 females (37.1%), were analyzed. Demographic, initial presentation blood counts, and AML subtypes were almost identical in both groups. RESULTS Complete remission rates were almost identical for the ADE versus the AD group (78.8% vs 80.0%, p = 0.980). Treatment-related mortality was higher, albeit not significantly, in the ADE (25 of 105; 23.8%) versus the AD (16 of 81; 19.8%) group (p = 0.508). Overall survival was 32 of 105 (30.5%) in the ADE and 43 of 81 (53.1%) in the AD group (p = 0.079), and disease-free survival was 29 of 105 (27.6%) and 39 of 81 (48.1%) in ADE and AD groups (p = 0.056), respectively. CONCLUSIONS Etoposide in induction treatment of pediatric AML is associated with increased episodes of bacterial and fungal infections and high treatment-related mortality. Moreover, it does not offer any survival benefit. In low- and middle-income countries like Pakistan, it should not be used in the induction treatment protocol.

Intensification of Chemotherapy Does Not Improve Prognosis of Standard Risk Patients Undergoing Therapy for Acute Myelogenous Leukemia: Results of the Pediatric Clinical Trial AML-BFM 98.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1793-1793
Author(s):  
Ursula Creutzig ◽  
Dirk Reinhardt ◽  
Joerg Ritter ◽  
Guenter Henze ◽  
Johannes Hermann ◽  
...  
Keyword(s):  
Clinical Trial ◽  
De Novo ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
Standard Risk ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract In order to further improve survival of children undergoing therapy for acute myeloid leukemia (AML), the multicenter clinical trial AML-BFM 98 intensified chemotherapy for standard risk (SR) patients (pts.). In addition, this randomized trial prospectively evaluated whether 2 short cycles of chemotherapy resulted in better prognosis than a 6-week consolidation. Patients and Methods: Between July 1998 and June 2003, 461 pts. < 18 years with de novo AML were enrolled in the trial AML-BFM 98. The SR group consisted of 170 (37%) pts. (FABM1/M2 with Auer rods or M4eo with ≤ 5 % blasts in the day 15 bone marrow; all pts. with FAB M3). All other pts. (n=291) were considered as high-risk (HR) pts.. In contrast to trial AML-BFM 93, a 2nd induction (HAM) was included in the treatment strategy for SR pts. (excluding FAB M3) which consisted of high-dose cytarabine (3g/m/12h x3 days) and mitoxantrone (10mg/m/d x2 days). Both SR and HR pts. were then randomly assigned to receive a 6-week consolidation or two short cycles of therapy. Compared to the 6-week consolidation, the short cycles contained higher doses of cytarabine, but the same cumulative dose of anthracylines. All other therapy elements [first induction (AIE; cytarabine, idarubicin and etoposide), intensification (HAE; high dose cytarabine, etoposide), and maintenance therapy] were identical in studies 93 and 98. Results: Overall, 407 out of 461 (88%) pts. achieved remission (CR). Five-year survival, event-free survival (EFS) and disease-free survival (DFS) were 59%±3%, 49%±3% and 55%±3%, respectively. Estimated survival and pEFS were similar to those of study 93 (58%±2% and 50%±2%, p logrank .09 and .80). Analysis of SR pts. (FAB M3 excluded) showed that the additional application of HAM did not improve the prognosis of SR pts. compared to AML-BFM 93 [CR rate 92% vs. 91%, p(chi)=.78; 5-year pEFS 58%±5% vs. 66%±4%; p logrank =.24]. However, when comparing HAM in study 98 and the 2nd chemotherapy cycle in study 93, significantly more severe infections (grade 3/4) occurred with HAM. Overall treatment related mortality in CR was 4% in both HR and SR pts., which was similar to trial AML-BFM 93. In addition, the outcome of pts. randomized for the 6-week consolidation was similar to that of the short cycles (p logrank .81). However, morbidity was lower in the short cycle arm (6 vs. 11 deaths in CCR, 2 vs. 4 in SR pts.). Conclusion: Our results indicate that in SR pts. with AML, a more intensive chemotherapy consisting of HAM does not result in improved survival. Therefore, new treatment options should be considered in this patient group. At the same time, optimizing treatment using the less toxic therapy with short cycles and improvement of supportive care strategies might help to reduce treatment related mortality and improve outcome in children with AML.

Outcomes for B-Precursor Patients in Legacy Children’s Cancer Group (CCG) and Pediatric Oncology Group (POG) Studies in Childhood Acute Lymphoblastic Leukemia (ALL): A Children’s Oncology Group (COG) Report.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 847-847
Author(s):  
Paul S. Gaynon ◽  
Bruce C. Camitta ◽  
Yousif Matloub ◽  
Paul L. Martin ◽  
Naomi Winick ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Oncology Group ◽  
Cancer Group ◽  
Early Responder ◽  
Pediatric Oncology Group ◽  
Double Trisomy ◽  
Standard Risk ◽  
Very High

Abstract Background: Improved post induction intensification (PII) has led to improved outcome for children with ALL over past decades. The merger of POG and CCG provided an opportunity to compare strategies, specifically, POG: intermediate dose methotrexate (Mtx, 1–2 g/m2) with leucovorin (lv) rescue; CCG: Berlin Frankfurt Münster (BFM) Protocol Ib and Protocol II (delayed intensification, DI), “augmented” with additional vincristine (Vcr), escalating-dose parenteral Mtx with no lv rescue, and l-asparaginase (Asp). Methods: Between 1996 and 2005, POG 9904/5/6 trials and CCG 1991/1961 trials accrued 6774 B-precursor patients, age > 1 year. NCI standard risk (SR) patients received induction with Vcr, Asp, dexamethasone; NCI higher risk (HR) patients received induction with Vcr, Asp, daunorubicin, and prednisone. POG allocated PII based on age, gender, presenting WBC and the presence or absence of double trisomy 4+10 or t(12;21). CCG allocated PII based on age, presenting WBC, and the Induction Day 7/14 marrow response. POG SR patients without trisomies 4+10 were randomized +/− DI. CCG SR patients received at least one DI. CCG SR slow early response (SER) patients received daunomycin in induction and augmented intensification. ALL CCG HR patients received at least one DI and many received “augmented” intensification; some POG HR patients received no DI. A subset of POG HR patients, defined by age, gender, and WBC, with very high risk of relapse were designated “Pragmatic Very High Risk” (VHR) and assigned to a modification of CCG Augmented BFM (Aug BFM, NEJM1998; 338:1663, see Table). Results: The 5-year EFS was 84±2% (n=1831) and 88±2% (n=2539) for POG and CCG SR patients (p<0.003). POG and CCG SR patients with double trisomies 4+10 had 5-year EFS of 91±3% (n=387) with no DI and 95±3% (n=317) with one or two DI’s, respectively. The 5-year EFS was 60±4% (n=992) and 71±2% (n=1412) for POG and CCG HR patients (p< 0.001). Results are similar when adjusted for ethnicity. Both SR and HR patients on CCG trials had a statistically significant 25% reduction in risk of an adverse event. Conclusions: This is a non-randomized cross-study comparison. Differences in patient population, treatment assignment, and clinical practice may affect results and interpretation. However, our data suggest the overall superiority of the CCG modified BFM strategy and support the COG decision to build current trials, e.g., AALL0331 and AALL0232, on this platform. Studies Included POG 9904 POG 9904 POG 9905 POG 9906 CCG 1991 CCG 1991 CCG 1961 CCG 1961 RER: rapid early responder; SER slow early responder; Aug BFM: augmented BFM (NEJM1998; 338:1663); Doxo: doxorubicin; Cpm: cyclophosphamide; Ida: idarubicin ; lv :leucovorin NCI SR NCI SR NCI SR + HR NCI HR NCI SR NCI SR NCI HR NCI HR Double Trisomy 4 + 10 t(12;21) Pragmatic VHR Day 14 RER Day 14 SER Day 7 RER Day 7 SER Mtx 1 g versus 2 g/m2 + lv Mtx 1 g versus 2 g/m2 + lv Mtx 1 g versus 2 g/m2 + lv POG Modified Augmented "BFM" ± Vcr + IV Mtx Daunomycin rescue ± stronger intensification Augmented "BFM’ ±DI ±DI Augmented "BFM" 10 vs 6 months intensification Doxo versus Ida/Cpm

Should Troponin Level Be an Exclusion Criterion for Stem Cell Transplantation in Primary Amyloidosis?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3003-3003
Author(s):  
Morie Abraham Gertz ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
Shaji K. Kumar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mortality Rate ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cells ◽  
Patient Characteristics ◽  
Mortality Rates ◽  
Troponin Level ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction: Mortality rates associated with stem cell transplantation are considerably higher than those of autologous stem cell transplantation for other hematologic malignancies. The efficacy of stem cell transplantation in amyloidosis largely is determined by treatment-related mortality rates (range, 11%-25%). Appropriate patient selection is essential to avoid this high mortality rate. Patients & Methods: The primary end point of the study was death from any cause between 4 days before transplantation and d+100 after transplantation. Patient characteristics are shown. Patient characteristics (N=271) Characteristic Median (range) Comment Age, y 58 (33–75) Male 159 (59%) Renal involvement 184 (68%) Cardiac involvement 147 (54%) Peripheral neuropathy 30 (11%) Hepatic involvement 28 (14%) Albumin, g/dL 2.8 (0.8–4.4) Creatinine, mg/dL 1.1 (0.6–12.0) 90% of patients had levels ≤1.7 mg/dL Alkaline phosphatase, U/L 93 (31–1,395) 25% of patients had levels >132 U/L Urinary total protein, g/d 3.35 (0.01–35.4) Percentage of plasma cells in the marrow 7 (0–78) 90% of patients had <17% plasma cells Interventricular septal thickness, mm 13 (7–25) Ejection fraction, % 65 (28–84) Time between diagnosis and stem cell transplantation, mo. 4 (0.8–75) Troponins,μg/L 0.01 (0.01–1.0) 75% of patients had levels ≤0.03 g/L 90% of patients had levels ≤0.08 g/L Results: Among 271 patients undergoing stem cell transplantation, troponin T was a powerful predictor of treatment-related mortality. Patients with troponin levels of 0.06 mg/L or higher had a day 100 all-cause mortality rate of 28%. Day-100 Survival Rate (N=271) Patients Troponin level ≥0.06 μg/L, no. of patients (n=40) Troponin level <0.06 μg/L, no. of patients (n=231) Total no. of patients *P<.001 Died before day 100* 11 16 27 Survived beyond d+100 29 215 244 Patients with troponin levels less than 0.06 mg/L had a day-100 all-cause mortality rate of 7% (P<.001). Figure Figure Despite possibly having multiple causes of death, for 7 of 11 patients with elevated troponin levels, cardiac causality could be inferred. For patients with low levels of troponin, clear cardiac causality was observed in 4 of 16. Among the 40 patients with troponin levels of 0.06 mg/L or higher, the conditioning dosage of melphalan was reduced for 31 patients (78%). Among the patients with troponin levels less than 0.06 mg/L, the dosage of melphalan was reduced for 29% of patients. Conclusion: Troponin levels should be measured in all patients before transplantation. Those with troponin levels exceeding 0.06 mg/L should be considered for less toxic therapies until the clinically optimal use of stem cell transplantation is better defined by randomized clinical trials. The chemotherapy dosage was reduced for 77% of patients in the high troponin group, but acceptable treatment-related mortality rates were not achieved. Clearly, a risk-adapted approach that modified the dosage of conditioning chemotherapy did not compensate for poor patient health or advanced cardiac involvement.

scholarly journals Adolescents and Young Adults (AYA) with Acute Myeloid Leukemia (AML) Have Increased Treatment-Related Mortality with Similar Outcomes -- a Report from the Children's Oncology Group Trials AAML03P1 and AAML0531

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3672-3672 ◽  
Author(s):  
Keith J. August ◽  
Richard Aplenc ◽  
Lillian Sung ◽  
Susana C. Raimondi ◽  
Betsy A. Hirsch ◽  
...  
Keyword(s):  
High Risk ◽  
Study Entry ◽  
P Value ◽  
Age Group ◽  
Oncology Group ◽  
Younger Patients ◽  
High Risk Patients ◽  
Risk Patients ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Background: AYA patients with cancer comprise a unique and understudied population with higher treatment-related toxicity than younger children. Objective: To describe the outcome of AYA patients with AML treated with intensive chemotherapy and GO. Methods: AYA patients (ages 16-21) on Children’s Oncology Group (COG) trials AAML03P1 and AAML0531 were analyzed and compared to younger patients. Both trials included patients with newly diagnosed AML. Differences in disease characteristics, treatment response, treatment-related mortality (TRM) and relapse risk (RR) were compared. Patients received either 5 chemotherapy courses or 3 followed by stem cell transplant (SCT) dependent on donor availability alone in 03P1, and risk stratification and donor availability in 0531. On AAML0531, patients with t(8;21) or inv(16) were considered low risk and did not receive SCT. High risk patients had adverse cytogenetics (-7, -5/5q-), high FLT3-ITD HAR (>0.4) or slow response with >15% marrow disease after induction 1. High risk patients received SCT if any donor was available. All other patients were intermediate risk and received SCT if a matched family donor was available. GO (3 mg/m2/dose) was administered to all patients on AAML03P1 while patients on AAML0531 were randomized to treatment with or without GO. Patients scheduled to receive GO received one dose on induction 1, day 6, and for patients that did not proceed to SCT, a second dose was given on intensification 2, day 7. Results: A total of 1350 patients 21 years old and younger were studied. Significantly different characteristics of AYA compared to younger patients are presented in Table 1, whereas gender, race, ethnicity, t(8;21) and inv(16) were similar between age groups. Table 1: Significant differences by age Age < 16 Years (n=1144) Age 16-21 Years (n=206) p value Normal Cytogenetics 225 (20.5%) 70 (36.5%) <0.001 11q23/MLL rearrangement 256 (23.3%) 22 (11.5%) <0.001 FLT3-ITD high allelic ratio 146 (14.3%) 37 (20%) 0.047 CEBPα mutation 46 (4.8%) 17 (9.4%) 0.012 NPM mutation 58 (6%) 23 (12.8%) 0.001 Death before remission 25 (2.4%) 5 (2.5%) 0.803 CR after Induction I 826 (74.1%) 165 (82.1%) 0.015 MRD negative after Induction I 572 (68.3%) 123 (76.4%) 0.042 5 year EFS and OS from study entry was 44.2% and 60.0% for AYA patients compared to 50.2% and 64.8% for younger patients (p=NS). AYA patients had significantly higher TRM when compared to younger patients: 13.3% vs. 7.3% from study entry (p=0.005) primarily due to death in remission, 12.4% vs. 5.6% (p=0.004). Despite similar 5 yr relapse rates after achieving remission, 38.8% vs, 36.7%, 5 yr DFS (48.8% vs. 57.7%, p=0.058) and OS (63.7% vs. 70.9%, p=0.067) from end of induction 2 trended worse for AYA patients, reflective of the increased treatment-related death in remission. AYA patients that received GO combined with chemotherapy had similar EFS and OS compared to those treated without GO (Figure 1). TRM in AYA patients treated with GO was significantly higher compared to younger patients (15.5% vs. 8.6%, p=0.014). In younger patients, while GO added to chemotherapy did not result in improved OS, a significant improvement in EFS was seen. For these patients, the decrease in the relapse rate was not offset by an increased TRM as was seen in AYA patients (Table 2). Table 2. Differences in outcomes by use of GO GO No GO p value AYA patients (16-21 years) n=137 n=69 5 year OS 60.8% 58.5% 0.682 5 year EFS 44.3% 44.9% 0.754 5 year TRM 15.5% 8.7% 0.21 5 year RR* 36.7% 42.5% 0.262 Younger patients (<16 years) n=706 n=438 5 year OS 65.5% 63.7% 0.580 5 year EFS 52.8% 46.0% 0.018 5 year TRM 8.6% 5.3% 0.045 5 year RR* 32.9% 42.6% <0.001 *In CR patients (AYA GO n=114; no GO n=59; <16y GO n=577, no GO 356) SCT outcomes by age group revealed similar results with increased TRM among AYA SCT recipients (n=37) compared to younger SCT recipients (n=172) (18.9% v 7.8%, p=0.027) and resulted in a lower 5 yr DFS (50.1% v 62.7%, p=0.214) despite similar RR (31% v 29.5%, p=0.854). Conclusion: AYA patients on these studies experienced lower OS and EFS when compared to younger patients. The favorable impacts of GO and SCT were abrogated in AYA patients due to higher TRM negating the improved RR with their use. In the AYA population, further focus upon reducing TRM is needed in order to achieve similar benefits. Figure 1. EFS by age group and GO use Figure 1. EFS by age group and GO use A report from the Children’s Oncology Group Disclosures No relevant conflicts of interest to declare.

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