High risk of invasive fungal infections in adult acute lymphoblastic leukemia patients receiving induction and salvage chemotherapy

2016 ◽  
Vol 58 (8) ◽  
pp. 2017-2018 ◽  
Author(s):  
Ming-Hsun Bryan Keng ◽  
Hui-Lin Clara Keng ◽  
Ban-Hock Tan ◽  
Gee-Chuan Wong
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Salvage Chemotherapy ◽  
Invasive Fungal Infections ◽  
Adult Acute Lymphoblastic Leukemia

scholarly journals Incidence of Invasive Fungal Infections (IFI) in Pediatric Acute Lymphoblastic Leukemia (ALL) and the Impact of Antifungal Prophylaxis in an Endemic Area

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1215-1215
Author(s):  
Simone M Chang ◽  
Mason Holt ◽  
Lauren Hernandez ◽  
Natalie Slone ◽  
Jun Zhao ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Cumulative Incidence ◽  
Endemic Area ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
European Organization ◽  
The Impact

Abstract Background In pediatric hematologic malignancy, the incidence of invasive fungal infections (IFI) is ~ 5-10% and leads to significant morbidity and mortality. Acute lymphoblastic leukemia (ALL) accounts for the largest group at risk and has the largest absolute number of IFI. Antifungal prophylaxis has the potential to mitigate risk of invasive infections in ALL but is not currently standard of care due to the paucity of data in ALL subgroups. A recent systematic review showed a significant reduction in proven/probable IFI and fungal infection-related mortality in pediatric patients when using a mold active agent compared with fluconazole, therefore an echinocandin was selected for systemic antifungal prophylaxis in our institution. In this study we investigate the incidence of IFI in patients with ALL in a highly endemic area (Ohio River Valley) and describe the impact of echinocandin prophylaxis in this population. Methods We conducted a retrospective cohort study of consecutive patients <25 years with ALL from 2015 to 2021 at Norton Children's Hospital, Louisville, KY. IFI was classified as possible, probable, or proven as defined by the 2020 European Organization for Research and Treatment of Cancer/ Mycoses Study Group Consensus Group. Patients were then analyzed in 2 subgroups based on prophylaxis with caspofungin. Inpatient administration of caspofungin was given to patients with high-risk B-ALL (HR B-ALL) and T-ALL as outlined in Table 1. Patient and IFI characteristics were collected, and cumulative incidence analyses used for subgroup comparisons. Results Demographics and patient characteristics are summarized in Table 2. Between 2015 to 2020 we identified 100 patients with ALL. Mean age at diagnosis was 7.2 years and 43% were female. We identified 14 unique cases of IFI in 13 patients with ALL who did not receive prophylaxis with caspofungin during 2015 to 2020 (14%). Prior to the implementation of prophylaxis, IFI occurred in 0% (0/43) of the SR B-ALL group, 18.2% (6/33) in HR B-ALL group and 35% (8/23) in T-ALL group. IFI incidence was highest in induction and consolidation phases (71.4%) and implicated species during these phases included Aspergillus, Candida, Fusarium, and Papulasopora. From April 2020 to July 2021, there were 22 newly diagnosed patients with ALL, 11 (50%) of whom received inpatient prophylaxis with caspofungin. There was 1 case (4.5%) of reported IFI during delayed intensification (no prophylaxis at the time of infection). As seen in Figure 1, patients with HR B-ALL and T-ALL who were hospitalized and received caspofungin during induction saw a notable decrease in the cumulative incidence of IFI, from 18.3% to 0% at 6 months into treatment before reaching similar levels in the patients who did not receive prophylaxis. Conclusion In our pediatric population, patients with T-ALL and HR B-ALL were more likely to develop IFI than those with SR B-ALL. Prophylaxis with caspofungin and inpatient hospitalization during induction were effective strategies for reducing the incidence of IFI in induction and consolidation for our high-risk leukemia population. This approach should be validated in larger studies with special consideration being given to patients in fungal endemic areas. Figure 1 Figure 1. Disclosures Raj: Terumo Medical Corporation: Honoraria, Speakers Bureau; Forma therapeutics: Consultancy; Global biotherapeutics: Speakers Bureau.

scholarly journals Inotuzumab ozogamicin for the treatment of acute lymphoblastic leukemia

2018 ◽  
Vol 9 (12) ◽  
pp. 347-356
Author(s):  
J. Michael Savoy ◽  
Mary Alma Welch ◽  
Patrice E. Nasnas ◽  
Hagop Kantarjian ◽  
Elias Jabbour
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Salvage Chemotherapy ◽  
Cell Precursor ◽  
Antibody Drug Conjugate ◽  
Cell Surface Antigens ◽  
Inotuzumab Ozogamicin ◽  
Improved Outcomes ◽  
Adult Acute Lymphoblastic Leukemia

Therapy for adult acute lymphoblastic leukemia (ALL) with multiagent cytotoxic chemotherapy has not been as successful as that for pediatric patients. The advent of targeted monoclonal antibodies against common cell surface antigens (i.e. CD19, CD20, and CD22) has resulted in improved outcomes without additional toxicities. Inotuzumab ozogamicin is an anti-CD22 antibody–drug conjugate approved for the treatment of relapsed or refractory B-cell precursor ALL. It improved outcomes compared with standard salvage chemotherapy. Its combination with low-intensity chemotherapy in the relapse setting and in frontline elderly patients is promising.

Comment on: Invasive fungal infections in children with acute lymphoblastic leukemia

2019 ◽  
Vol 67 (1) ◽  
Author(s):  
Elio Castagnola ◽  
Elena Palmisani ◽  
Alessio Mesini ◽  
Carolina Saffioti ◽  
Concetta Micalizzi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Invasive Fungal Infections

scholarly journals Amsacrine, Etoposide and Methylprednisolone As Part of the Therapy Intensification in Children with Acute Lymphoblastic Leukemia: A Retrospective Analysis in the Trial Coall 08-09

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5168-5168 ◽  
Author(s):  
Gabriele Escherich ◽  
Katharina Wos ◽  
Franziska Schramm ◽  
Martin A. Horstmann
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Treatment Intensification ◽  
Childhood All ◽  
Median Treatment ◽  
Treatment Interval ◽  
Late Responder

Abstract Background The combination of amsacrine, etoposide and methylprednisolone (AEP) is regarded as a salvage treatment option in pediatric acute lymphoblastic leukemia (ALL). A recent study already showed a significant response after the treatment with AEP in children with recurrent/refractory ALL without AEP-related mortality, an acceptable morbidity and moderate myelotoxicity. [1] The CoALL study group, that investigates the treatment of childhood ALL, has implemented this block as a part of a therapy intensification in the current CoALL 08-09 protocol, for patients with a high MRD load ( B-Precursor > 10-³ at the end of induction (EOI), T-ALL >10-³ after the first consolidation block) stratified to the High Risk intensified arm or for patients without remission at the EOI defined as late responder. We examined the toxicity profile and the efficacy of this block in patients that have been treated within the current study. Patients and Methods So far 67 of 624 patients enrolled into the CoALL 08-09 trial, received the combination of amsacrine, etoposide and methylprednisolone as they have been treated according to the High Risk intensified arm (36 c-ALL, 8 pre-B-ALL, 3 pro-B-ALL, 8 T-ALL) or as they were specified as late responder (3 c-ALL, 1 pre-B-ALL, 1 pro-B-ALL, 7 T-ALL). The patients were characterized by a median age of 11 years and a median MRD value of 7x10-3 (B-ALL)/ 1x10-2 (T-ALL). All patients had received one cycle amsacrine 100mg/m²/day i.v. for 2 days, etoposide 500mg/m²/day i.v. for 2 days and methylprednisolone 1000mg/m²/day p.i. for 4 days at the end of the consolidation phase. Results Beside a profound myelosuppression 29 of the 67 enrolled patients exhibited toxicities after receiving AEP, mostly reflected by fever in neutropenia. In two cases septicemia was reported as a serious adverse event. Only three fungal infections, two occurrences of mucositis, four cases of a diabetic metabolic state and two cases of cardiac arrhythmia were reported. There was no osteonecrosis and no steroid-related psychosis reported within this patient cohort. No treatment related death occurred. The median treatment interval was 28 days, 8 days longer than the so far reported median treatment interval. A Kaplan-Meier analysis for event free (EFS) and the overall survival (OS), showed a trend in favor of the current cohort compared to patients of the predecessor trial and a comparable MRD load EOI (pOS: 87.7 SE 4.9 vs 76.3 SE 4.4; pEFS:78.8 SE 6.2 vs 61.1 SE 5.1 p= 0.1) . These patients were treated within the High Risk standard arm without the AEP treatment element. Conclusion Treatment intensification with AEP was well tolerated, without an excess of infectious complications in these heavily pretreated patients. AEP treatment intensification shows a trend towards an improved event-free survival. [1] Horstmann, M. A., Hassenflug, W.-A., zur Stadt, U., Escherich, G., Janka, G., & Kabisch, H. (January 2006). Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in children. Haematologica, S. 1701-3. Disclosures No relevant conflicts of interest to declare.

Outcome and Toxicities of Modified Augmented Berlin-Frankfurt-Muenster (ABFM) Therapy Used in the Treatment of Acute Lymphoblastic Leukemia in Adolescent and Young Adult Patients, Single Center Experience From Saudi Arabia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3569-3569
Author(s):  
Suhaib Radi ◽  
Anas Merdad ◽  
Mona Al-Dabbagh ◽  
Ahmed Almohanad Absi ◽  
Ahmad Alsaeed ◽  
...  
Keyword(s):  
Overall Survival ◽  
Saudi Arabia ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Complete Remission ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Inclusion Criteria

Abstract Abstract 3569 Introduction: Acute lymphoblastic leukemia (ALL) is a neoplasm of precursor lymphoid cells known as lymphoblasts. ALL is the most common cancer in children. The prognosis among Adolescents and young adults (AYA) is intermediate between children, who have a very good prognosis with a 5-year survival rate of 80%, and adults, who have a worse prognosis with an overall survival of about 30–50%. We found no studies in Saudi Arabia which assessed the use of a Berlin-Frankfurt-Muenster (BFM) to treat patients in the AYA group. The purpose of this study is to measure the outcome and toxicities of the BFM protocol used in treatment of ALL patients in the AYA population seeking treatment at Princess Noorah Oncology Center (PNOC), at the National Guard Hospital, Jeddah, Saudi Arabia. PNOC is a tertiary referral center for the Western region of the Kingdom of Saudi Arabia. Patients referred between the ages of 14 to 25 were treated according to an augmented modified version of the Berlin-Frankfurt-Muenster (BFM) protocol. Patients' treatments were based on risk factor stratification. High risk category was identified based on the presence of one of following factors: phenotype of the leukemia (i.e. T-cell ALL is considered high risk), lack of response to therapy on day 29 of induction, cytogenetics, presence of extramedullary disease e.g. testicular or CNS disease and whether they have received steroid treatment prior to the first diagnostic marrow. High risk group was treated with doubled blocks of interim maintenance, delayed intensification the first of delayed intensification blocks included a high dose methotrexate at the dose of 5g/m2 which was first started at our center in 2008. Methodology: This study is a retrospective chart review. Patients who met the inclusion criteria within the last five years were included. The inclusion criteria were those with confirmed ALL (excluding mature B cell phenotype) aged between 14 to 25 years, and were treated with the Modified Augmented Berlin-Frankfurt-Muenster (ABFM) therapy protocol. 45 patients were indentified who fulfilled the above criteria 4 were excluded due to the lack of data and loss to follow up. Data were analyzed using SPSS version 19. Results: The mean age of 41 patients treated was 16.4 years (range; 14 – 25 years). Of 41 patients treated, 23 (56%) were males. Only one patient (2%) had CNS involvement at presentation. B cell ALL compromised 61% of the patients while 39% were T cell ALL. All 41 (100%) patients achieved complete remission after induction therapy however two patients (5%) required extended induction to achieve a complete remission status. Five (12.2%) patients relapsed at a median follow up of 30 months. Two (4.9%) patients died while in complete remission from treatment related causes. The probability of Overall Survival (OS) is 95.1% and 87.8% at 2 and 3 years, respectively. The probability of Event-free Survival (EFS) of our 41 patients is 90.2% and 82.9% at 2 and 3 years respectively. Thirty three (81%) patients developed febrile neutropenia with a total of 50 documented episodes. Thirty two (64%) of the febrile neutropenia episodes occurred during induction and re-intensification phases those two blocks were associated with a statistically significant increased risk of neutropenia (P < 0.001)compared to other blocks. Five (12%) of patients developed fungal infections there is one patient who developed two separate episodes of fungal infection. Four fungal infection episodes occurred during induction and re-intensification phases which constituted the highest risk phases for the development of fungal infections. In 38% of febrile neutropenic episodes an infectious agent was identified in 8% of episodes the isolate was a fungus. Eight patients (20%) developed Venous Thromboembolism (VTE) with a total of 9 episodes. Discussion & Conclusion: In our study population the OS & EFS were comparable to other reported groups despite the relatively increased numbers of T cell ALL (39%) patients compared to the reported average of 15–25%. The reported incidence of VTE is similar to the incidence reported by other groups while the incidence of fungal infections is relatively more than we would have expected. Complete remissions, survival, relapse and death rates are comparable to international studies. However new measures are required to lower the increased rates of fungal infections & VTE for future patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Febrile Neutropenia in Children with Acute Lymphoblastic Leukemia Treated with BFM Protocols

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5245-5245
Author(s):  
Gul Nihal Ozdemir ◽  
Gulen Tuysuz ◽  
Hilmi Apak ◽  
Alp Ozkan ◽  
Inci Yildiz ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Febrile Neutropenia ◽  
Cause Of Death ◽  
Risk Group ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Newly Diagnosed ◽  
Risk Patients

Abstract Aim: Overall survival from leukemia is less in low and middle-income countries than in high-income countries. The aim of this study is to review febrile neutropenia (FN) episodes in children with acute lymphoblastic leukemia (ALL) treated with BFM (Berlin-Franfurt-Münich) protocols at a single center in Turkey. Methods: Retrospective data were extracted from medical records of children (1-18 years old) with newly diagnosed and relapsed ALL and who were treated between 1995-2010 at Istanbul University, Cerrahpasa Medical Faculty, Pediatric Hematology Oncology Dept. Results: Two hundred -forty-five FN episodes were detected in 96 evaluable children (mean age: 5.9±3.7 years; M/F: 50/46). According to BFM risk groups; 32 were SRG (standard risk group), 56 were MRG (medium risk group) and 8 were HRG (high risk group) patients. Fifteen patients had relapsed on follow-up and 2 of them had a second relapse. The mean number of FN episodes was 2.5 (±1.58; 0-8) per newly diagnosed patient and 3.6 (±1.88; 1-8) per relapsed patient. Febrile neutropenia episodes were more frequent at high risk patients compared to standart risk patients (p≤0.05). Patients diagnosed before year 2000 had less FN episodes compared to patients diagnosed after 2000 (p≤0.05). Fifty-seven of the FN episodes were fever of unknown origin, 16% were clinically documented infection and 27% were microbiologically documented infection. Of the microbiologically documented infections, 44% of them were caused by gram positive bacteria and 43% were by gram negative bacteria. Eight of 96 patients developed invasive fungal infection during initial treatment and 4 out of 15 patients who relapsed. Of 9 patients who expired on follow-up, the cause of death was fungal infections in 4 and FN in 1. Conclusion: The high rate of infectious deaths in leukemia compared to that reported in high-income countries, suggests that improvements in infection care and prevention are necessary to improve survival in patients with leukemia. We showed that over the years FN episodes increased at our center in contrast to better quality of patient care. This increase in infections may be atrributed to more intensive treatment regimens. We also showed that high risk and relapsed patients who are treated more aggresively have increased infection rate. The most common cause of death was fungal infections. Disclosures No relevant conflicts of interest to declare.

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