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 Invasive Fungal Infections in Patients with High-Risk MDS and AML Treated with Azacitidine

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5251-5251
Author(s):  
Helena Pomares ◽  
Montserrat Arnan ◽  
Isabel Sánchez-Ortega ◽  
Anna Sureda ◽  
Rafael F. Duarte
Keyword(s):  
High Risk ◽  
Treatment Cycle ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Low Risk ◽  
Severe Neutropenia ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
European Organization

Abstract Introduction: The incidence of invasive fungal infections (IFI) and need for antifungal prophylaxis in patients with high-risk myelodysplastic syndromes and acute myeloid leukemia (MDS/AML) treated with hypomethylating agents is currently unknown. Methods: We retrospectively analyzed the incidence of IFI in all MDS/AML patients receiving azacitidine (75 mg/m2/day 7 days every 28-day cycle) in our center between June 2007 and June 2015. IFI diagnosis follows the European Organization for Research and Treatment of Cancer and Mycosis Study Group (EORTC/MSG) 2008 Criteria. Patients did not receive antifungal prophylaxis. Results: One hundred and twenty one consecutive unselected patients (86 MDS and 35 AML; Table 1) received a total of 948 cycles of azacitidine in this series (median 5, range 1-43). One hundred and ten (91%) received azacitidine frontline and 11 (9%) following refractoriness or relapse after previous intensive chemotherapy. Seventy one patients received ≥4 azacitidine cycles. Forty two (35 %) patients had complete medullar and cytogenetic responses. Two hundred and seventy four azacitidine cycles (28%) in 49 patients (40%) were administered during and/or led to prolonged grade IV neutropenia (<0.5x109/L ³10 days), and caused febrile neutropenia episodes in 121 cycles (12% of total, 44% of neutropenic cycles) in 45 patients (37%), range 1-6 per patient. Four IFI occurred in these patients: one possible, two probable and one proven (Table 2). The incidence of IFI was 0.42% per treatment cycle and 3.3% per patient treated for the overall series, and 0.72% per treatment cycle and 4.1% per patient treated among those with prolonged severe neutropenia. Of note, all cases of IFI occurred in either the first or the second azacitidine courses. Two patients died from IFI, leading to an IFI-related mortality rate of 1.65% per patient treated and 0.21% per treatment cycle. The numbers needed to treat with primary prophylaxis, even for an ideal agent that could potentially prevent all IFI, are well in excess of 100 courses of azacitidine and well over 20 patients throughout their treatment course, to prevent one single IFI in these patients, even among those with neutropenia. Conclusion: Our data show that patients with MDS/AML treated with azacitidine have a very low risk of IFI, including those with concurrent severe prolonged neutropenia. Primary antifungal prophylaxis should not be recommended for this subset of patients. This very low risk of IFI is a potential additional benefit from treatment of MDS/AML with hypomethylating agents, compared to conventional intensive chemotherapy. Prospective studies are needed to better address this issue. Disclosures Sureda: Takeda: Consultancy, Speakers Bureau.

scholarly journals Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jaime Sanz ◽  
Jacques-Emmanuel Galimard ◽  
Myriam Labopin ◽  
Boris Afanasyev ◽  
Moiseev Ivan Sergeevich ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Donor Type ◽  
Matched Sibling ◽  
The Impact

Abstract Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

scholarly journals Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children’s Oncology Group

2017 ◽  
Vol 35 (23) ◽  
pp. 2700-2707 ◽  
Author(s):  
Kristina K. Hardy ◽  
Leanne Embry ◽  
John A. Kairalla ◽  
Shanjun Helian ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
Corticosteroid Treatment ◽  
Neurocognitive Functioning ◽  
Neurocognitive Outcomes ◽  
Leucovorin Rescue ◽  
B Lineage ◽  
The Impact

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue. Patients were also randomly assigned to corticosteroid therapy that included either dexamethasone or prednisone. A neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed (PS) was conducted 8 to 24 months after treatment completion (n = 192). Results The method of MTX delivery and corticosteroid assignment were unrelated to differences in neurocognitive outcomes after controlling for ethnicity, race, age, gender, insurance status, and time off treatment; however, survivors who were age < 10 years at diagnosis (n = 89) had significantly lower estimated IQ ( P < .001) and PS scores ( P = .02) compared with participants age ≥ 10 years. In addition, participants who were covered by US public health insurance had estimated IQs that were significantly lower ( P < .001) than those with US private or military insurance. Conclusion Children with high-risk B-lineage ALL who were age < 10 years at diagnosis are at risk for deficits in IQ and PS in the absence of cranial radiation, regardless of MTX delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.

Fludarabine and Targeted Busulfan Is Safe and Effective Conditioning Before Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in First Remission

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 891-891
Author(s):  
Ghada M Kunter ◽  
Janelle Perkins ◽  
Lia Perez ◽  
Joseph Pidala ◽  
Teresa Field ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Unrelated Donor ◽  
Risk Of Relapse

Abstract Abstract 891 Background: Chemotherapy for adult patients with acute lymphoblastic leukemia (ALL) is associated with high risk of relapse and an overall 2-year survival of 40 to 50%. Allogenic hematopoietic cell transplantation (HCT) in first complete remission (CR1) decreases the risk of relapse and improves outcome over chemotherapy for adult ALL pts, but non-relapse mortality (NRM) is a drawback especially in older patients. In the MRC UKALL XII/ECOG E2993 trial, the 2 year NRM of patient with an allogenic donor was 19% in standard risk patients and 36% in patients over 35 years or those with high risk leukemia. We tested safety and efficacy of a non-irradiation regimen consisting of fludarabine (FLU) and pharmacokinetically-targeted busulfan (BU) for adults with ALL in CR1. Methods: We report the outcomes of 42 consecutive patients with ALL in CR1, 21 positive for the Philadelphia chromosome (Ph+). All patients were in complete morphologic remission before HCT. The median age was 33 (range: 19–62) years, 19 were females and 23 males. Median time from diagnosis to HCT was 6 (range: 3–45) months. Thirty patients were treated to achieve an average daily BU area under the curve (AUC) of 5300 microM-min for 4 days, and 12 patients were treated on a clinical trial to achieve an average daily BU AUC of 6000 to 7500 microM-min for 4 days. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus in all patients, in combination with either methotrexate (88%) or sirolimus (12%). Twenty (48%) patients received grafts from matched related donor, 16 (38%) from matched unrelated donor and 6 (14%) from a mismatched unrelated donor. The median follow-up of surviving patients is 2 (median 1.2–4.3) years. Results: Overall survival at 2 years was 66% (95% CI 52%–81%) for all patients, 70% (95% CI 51%–88%) for Ph- and 63% (95% CI 41%–85%) for Ph+ patients (p=0.59). Overall survival did not differ by age, above or below 35 years (p=0.39). Disease-free survival at 2 years was 59% (95% CI 44%–74%) for all patients, 65% (95% CI 45%–84%) for Ph- and 52% (95% CI 28%–74%) for Ph+ pts (p=0.49). The cumulative incidence of relapse at 2-year was 27% (95% CI 16%–45%). The cumulative incidence of acute GVHD grades II–IV was 64% (95% CI 51%–81%) and grades III–IV GVHD was 25% (95% CI 13%–47%). The cumulative incidence of non-relapse mortality (NRM) was 5% (95% CI 1%–18%) at 100 days and 14% (95% CI 7%–30%) at 2 years. Conclusions: These data show that FLU with myeloablative doses of PK targeted BU is an effective alternative to total body irradiation and etoposide or cyclophosphamide for conditioning patients with ALL without an increased risk of relapse after HCT. The low NRM allows to safely delivering myeloablative chemotherapy and allogenic HCT to older patients. This HCT regimen should be prospectively compared to chemotherapy for adult patients with ALL. Disclosures: No relevant conflicts of interest to declare.

Unrelated Cord Blood Does Not Increase An Overall Risk Of Invasive Fungal Infections Compared To Unrelated Bone Marrow: A Single Center Retrospective Analysis For 749 Recipients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4541-4541 ◽  
Author(s):  
Yuki Asano-Mori ◽  
Hideki Araoka ◽  
Muneyoshi Kimura ◽  
Daisuke Kaji ◽  
Hikari Ota ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Systemic Corticosteroids ◽  
Grade Ii ◽  
Unrelated Cord Blood

Background Invasive fungal infections (IFIs) are of great concern after allogeneic hematopoietic stem cell transplantation (HSCT), the risk of which is considered to be particularly prominent among cord blood transplantation (CBT) recipients. Patients and Methods We retrospectively analysed the records of 749 adult patients who underwent CBT or unrelated bone marrow transplantation (uBMT) for the first time at the Toranomon Hospital between 2002 and 2012, and who had neither prior history nor suspicious findings of IFIs. As prophylaxis for IFIs, fluconazole (FLCZ) or itraconazole (ITCZ) capsules were conventionally used until around 2006, which were then changed to newer mold-active agents including ITCZ oral solution, voriconazole or micafungin after their approval in Japan, the choice of which was subjected to physician's discretion. Results Engraftment achieved in 418 CBT patients and 198 uBMT patients with a significantly longer neutropenic period in CBT patients (median 20 days vs 18 days, P<0.001), whereas 37 patients underwent re-transplantation and 96 died before engraftment. The incidences of grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were significantly less frequent after CBT compared to uBMT (40% vs 54% and 17% vs 46%, both P<0.001). Systemic corticosteroids at ≥0.5mg/kg/day was given in fewer CBT patients compared to uBMT patients (59% vs 66%, P=0.07). The median durations of immunosuppressants and antifungal prophylaxis were significantly shorter in CBT patients compared to uBMT patients (118 days vs 302 days and 315 days vs 491 days, both P<0.001). As prophylaxis for IFIs, 194 CBT patients and 91 uBMT patients received FLCZ/ITCZ capsules, while 341 CBT patients and 123 uBMT patients received newer mold-active agents. Seventy-nine patients (57 in CBT and 22 in uBMT) developed IFIs with a cumulative incidence of 12.2%, at a median of 27 (1-1646) days after HSCT. About 60% of the patients developed IFIs by day 50 and the percentage reached more than 90% until 1 year. The median onset was significantly earlier in CBT patients compared to uBMT patients (day 19 vs day 61, P=0.007). The cumulative incidence of IFIs was significantly higher in CBT patients compared to uBMT patients during 50 days after HSCT (7.9% vs 3.8%, P=0.04), but became significantly lower thereafter until 1 year (2.7% vs 6.9%, P=0.02), and an overall incidence was almost similar between the 2 groups (12.6% vs 11.6%, P=0.58) (Figure 1). Four patients had 2 infectious episodes caused by different fungal species, and a total of 83 infectious episodes were documented. Eighty-one cases were breakthrough infection during antifungal prophylaxis (FLCZ/ITCZ capsules in 28, and newer mold-active agents in 53). Invasive aspergillosis (IA) was the most common, accounting for 67.9% (proven in 11, probable in 46), followed by invasive candidiasis (IC), (19.3%; candidemia in 15, encephalitis in 1). Although the incidences of IA and IC were comparable between CBT and uBMT patients, relatively rare type of IFIs caused by Trichosporon (4 cases), Mucor (2 cases) and Rodotorula (1 case) exclusively occurred in CBT patients, except one case of Fusarium infection in a patient who relapsed after uBMT. Grade II-IV acute GVHD, extensive chronic GVHD and systemic corticosteroids at ≥0.5mg/kg/day were identified as significant risk factors of IFIs for both groups (HR 1.89, P=0.01, HR 4.16, P=0.006, and HR 1.83, P=0.02). However, the impact of all these were not apparent in CBT patients (HR 1.59, P=0.16, HR 2.18, P=0.29 and HR 1.48, P=0.22), in contrast with the powerful impact in uBMT patients (HR 2.51, P=0.049, HR 10.23, P=0.03 and HR 2.87, P=0.03). Although the cessation of antifungal prophylaxis significantly increased the risk of IFIs in uBMT patients (HR 5.95, P=0.01), it showed no impact in CBT patients (HR 0.87, P=0.89). IFIs were main causes of death in 21 patients, which significantly affected non-relapse mortality in both CBT and uBMT patients (HR 3.93 and HR 6.08, both P<0.001). Conclusion Unrelated cord blood did not increase an overall incidence of IFIs, because higher risk in the early post-transplant period was counterbalanced by the dramatically decreased risk due to lower frequencies of GVHD and its treatment in the later period. Particular attention might be required to the early-onset IFIs due to fungi other than Aspergillus or Candida species, in order to further decrease the risk of IFIs after CBT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Influence of antifungal prophylaxis on the occurrence of fungal infections in patients undergoing allogeneic transplantation

2021 ◽  
Vol 2 (2) ◽  
pp. 92-98
Author(s):  
Jelena Cakić ◽  
Irena Đunić
Keyword(s):  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Oral Candidiasis ◽  
Invasive Pulmonary Aspergillosis ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Antifungal Prophylaxis ◽  
Candida Spp ◽  
Medical Histories ◽  
The Impact

Introduction: Patients with hematologic malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia (AML/ALL), myelodysplastic syndrome (MDS), and those undergoing allergenic stem cell transplantation (alloSCT) are at the highest risk of invasive fungal infections (IFI). The most common causative agents are Candida spp. and Aspergillus spp. Among the strategies for preventing IFIs is the adequate implementation of antifungal prophylaxis recommended by the NCCN (National Comprehensive Cancer Network). Aim: The aim of the study was to analyze the occurrence of IFIs in these patients, as well as to analyze the impact and importance of timely antifungal prophylaxis with regards to the development of these infections. Materials and methods: The retrospective study included 42 patients, of the average age of 35 years, who underwent the allo-SCT program, between 2017 to 2019, and received antifungal prophylaxis at the Clinic for Hematology of the Clinical Center of Serbia (CCS). Based on information obtained from medical histories, databases were formed. Statistical analysis included descriptive statistical methods that were performed in the SPSS program. Results: Nineteen (45.2%) patients presented with the clinical manifestation of oral candidiasis. Invasive pulmonary aspergillosis developed in only 3 (7.1%) patients. There was a statistically significant association between clinically manifest aspergillosis (7.1%) and the presence of antigens (Galactomannan) in these patients (p <0.001). There was also a statistically significant association between clinically manifest aspergillosis and graft weakness: 2 (66.6%) vs. 1 (33.3%), (p = 0.016). Conclusion: The use of adequate antifungal prophylaxis significantly reduces the incidence of IFIs in patients undergoing the allo-SCT program, and this contributes to the reduction of morbidity and mortality.

scholarly journals 986. Incidence of Invasive Fungal Infections in Previously Untreated Patients with Acute Myeloid Leukemia Receiving Venetoclax and Azacitadine

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S584-S584
Author(s):  
Tanit Phupitakphol ◽  
Tanner M Johnson ◽  
Diana Abbott ◽  
Jonathan Gutman ◽  
Daniel Pollyea ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Standard Of Care ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Significant Difference ◽  
The Impact ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) is associated with poor prognosis, particularly in elderly patients with co-morbidities. Low-intensity therapies like azacitidine (aza) were the standard of care and were associated with low response rates and limited survival. Combining venetoclax (ven) with aza demonstrated significant improvements in responses and survival compared to aza alone, and represents the new standard of care for this population. However, as a myelosuppressive regimen, infectious complications, especially invasive fungal infections (IFI), are a potential concern. The incidence of IFI and the role for antifungal prophylaxis have not been well defined for newly-diagnosed AML patients receiving ven/aza. Methods We conducted a retrospective cohort review of AML patients treated with ven/aza at the University of Colorado Hospital from January 2014 to August 2020. Duration of therapy was defined as the time from initiation of treatment through one of the following endpoints (1) patient discontinuation, (2) progression of disease, (3) bone marrow transplantation, or (4) death. Four patients with a history of prior IFI were excluded. We assessed the impact of patient age, sex, duration of neutropenia, antifungal prophylaxis, and AML specific risk factors on the incidence of IFI as defined by the European Mycoses Study Group. Results One hundred forty-four AML patients were included in the study. Ten patients received antifungal prophylaxis and none developed IFI (p=0.21). Twenty-five (17%) patients developed IFI: 2 (8%) had proven IFI, 6 (24%) probable IFI, and 17 (68%) possible IFI. Invasive pulmonary aspergillosis represented all 25 cases of proven, probable, and possible IFI. There was a statistically significant association between prolonged neutropenia ( &gt;60 days) and IFI (p=0.007), whereas age, sex, and SWOG classification were not significantly associated with IFI. Conclusion The incidence of IFI in our AML cohorts treated with ven/aza was 17%, lower than that reported at other institutions. Neutropenia &gt; 60 days was significantly associated with IFI in our AML cohort treated with ven/aza. Although we were not powered to determine whether antifungal prophylaxis impacted IFI, there was no significant difference in IFI for patients who received prophylaxis. Disclosures All Authors: No reported disclosures

Caspofungin Primary Antifungal Prophylaxis in Acute Leukemia Patients During Induction Therapy: Results of a Prospective Phase II Multicentric Study (ProfilC Study).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1638-1638
Author(s):  
Chiara Cattaneo ◽  
Simona Monte ◽  
Alessandra Algarotti ◽  
Ernesta Audisio ◽  
Erika Borlenghi ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Induction Therapy ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Antifungal Prophylaxis ◽  
Blood Levels ◽  
Predictive Tool ◽  
Who Grade ◽  
Multicentric Study

Abstract Abstract 1638 Poster Board I-664 Background The need for antifungal prophylaxis in acute leukemia (AL) is a very debated topic, considering its potential of inducing resistant strains and of impairing detection of Aspergillus antigen as well as cost-efficacy balance. Targeted prophylaxis, focused on patients (pts) with high risk diseases (e.g. AL during induction therapy), seems to be the most promising strategy. Caspofungin is a well-tolerated echinocandin, with a different mechanism of action with respect to azoles and amphotericin B. Pentraxin 3 (PTX3) belongs to the superfamily of pentraxins acute-phase reactants and may play a protective role against Aspergillus spp (Garlanda et al, Nature 2002). Aims To determine the incidence of invasive fungal infections (IFIs) and invasive aspergillosis (IA), the efficacy and safety of caspofungin as primary antifungal prophylaxis during AL induction and to evaluate PTX3 levels as in vivo predictive tool for IFI development. Patients and Methods From Jan-07 to Jan-09, the incidence of IFIs and IA during induction was evaluated among all pts with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) registered in NILG (Northern Italy Leukemia Group) protocols. Ninety-three pts entered the prospective ProfilC protocol and received Caspofungin prophylaxis (70 mg i.v. d1, then 50 mg i.v./d till leukemia remission). ProfilC epidemiological data were compared with those observed among 82 pts not assigned to ProfilC and treated according to the standard prophylactic (SP) policy adopted by each center (67 itraconazole, 10 fluconazole, 1 posaconazole, 4 no prophylaxis). PTX3 blood levels could be evaluated in 90 pts. Results Considering all 175 pts, M/F ratio was 103/72, median age was 50 (range 18-73); AML/ALL ratio was 138/37. Overall 32 IFIs (18.3%) were observed, 10 probable/proven (5.7%) (8 IA, 1 Candida spp and 1 G. capitatum bacteremias) and 22 possible (12.6%) according to EORTC/MSG criteria. IFIs (probable/proven and possible) were more frequent in AML (6.5% and 14.5%) than ALL (2.7% and 5.4%). Probable/proven IAs were not seen in ALL. The incidence of probable/proven or possible IFIs between ProfilC pts and those treated with SP was 7.5% and 9.7% vs 3.7% and 15.9%, respectively. Specifically, probable/proven or possible IAs were 5.4% and 8.6% in ProfilC group and 3.7% and 14.6% in SP group, respectively. These data show a lower, albeit not statistically significantly, incidence of IFI and IA in ProfilC pts. Fifteen out of the 175 (8.6%) pts died (ProfilC: 9.7%, SP: 7.3%, p=ns) with only one death due to IFI (G. capitatum sepsis). None of the 8 pts with IA died. Five pts experienced WHO grade >2 toxicity (3 hepatic, 1 skin, 1 hepatic and renal), 3 receiving Caspofungin and 2 itraconazole. One of the 5 pts died (itraconazole) of hepato-renal failure. A trend towards an association between lower PTX3 levels and IFI development was shown, since 13.8% of pts with PTX3 levels >10 ng/ml had IFI (probable: 3.4%), compared to 27.8% of those with '10 ng/ml (probable 8.2%). Conclusions Anti-Aspergillus oriented prophylaxis in AL pts was standard policy at most NILG centers. The incidence and letality of probable/proven IFIs and IA were lower than expected and reported by others. Given this epidemiological scenario, the superiority of one drug with respect to others is difficult to demonstrate. Caspofungin was well tolerated during induction and was at least as effective as other prophylactic agents. It may be particularly suited for AL pts with impaired intestinal absorption. High levels of PTX3 (>10 ng/ml) could be protective against IFI/IA, suggesting that PTX3 could be used to identify a very high risk pts population in which an intensified strategy of prophylaxis may be worth testing. Disclosures Off Label Use: Caspofungin as antifungal prophylaxis. Rossi:Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees.

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