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Invasive fungal infections uncommon among children with acute lymphoblastic leukemia

ATLANTA — A small percentage of children, adolescents and young adults with acute lymphoblastic leukemia treated with the UKALL2011 protocol developed invasive fungal infections, according to a retrospective study presented at the ASH Annual Meeting and Exposition.

“The incidence of invasive fungal infections among patients with ALL treated with the UKALL2011 protocol is low,” Maeve A. O’Reilly, MB, specialist in pediatric hematology at London Hospital, said during her presentation. “In addition, the mortality associated with these infections also is low. There is certainly the potential to compromise the timely delivery of chemotherapy because 18 of our 22 patients had a delay and/or omission of therapy, but it did not appear to have an impact on outcome.”

Invasive fungal infections are a major cause of morbidity and mortality in adult hematological malignancies. However, epidemiological data in pediatric ALL is scarce because of differing chemotherapy protocols, patient populations, diagnostic strategies and definitions of invasive fungal infections, as well as variations in the use of prophylactic and empiric systemic antifungals.

Retrospective studies showed incidence rates for invasive fungal infections as low as 0.01% in Canada, but as high as 10% in the United States and 13% in Poland. A 2010 case-controlled study in Australia reported a 22% incidence rate.

To determine the incidence and outcome of invasive fungal infections among children, adolescents and young adults treated with the UKALL2011 protocol, O’Reilly and colleagues assessed data from 296 patients (median age, 5 years; range, 10 months to 24 years; 43% male) with ALL (B lineage, n = 249; T lineage, n = 43; unknown n = 4) treated at two large London hospitals from 2013 through December 2016.

Researchers categorized patients’ cytogenetic risk profile for B-ALL as classified as good (n = 133), intermediate (n = 86), poor (n = 20) or not available (n = 10).

Researchers classified invasive fungal infections — collected at induction, consolidation, interim maintenance and delayed intensification of the UKALL2011 protocol — as proven, probable and possible according to revised EORTC criteria.

Sixteen young adult patients aged 20 to 24 years received antifungal prophylaxis with oral itraconazole — or liposomal amphotericin B when vinca alkaloids were scheduled — during induction and consolidation when their neutrophil count fell below 1.5 × 109/L.

The other patients did not receive routine antifungal prophylaxis.

Median follow-up was 17 months.

Over a 4-year period, researchers observed eight cases (2%) of proven invasive fungal infections, four (1.5%) probable infections and 11 (4%) possible infections.

Seven patients had positive mycological results, including five with Candida spp., one with Aspergillus spp. and one with Scedosporium spp.

Four cases of disseminated disease occurred during induction, including two central nervous system diseases.

Invasive fungal infections led to a median delay of 3 weeks (range, 1-15) for chemotherapy treatments among 16 cases. Omission of chemotherapy occurred for two cases, and significant dose reductions occurred for four cases.

At 17 months (range, 4-39), follow-up data were available for 22 of the 23 patients diagnosed with a proven, probable or possible infection; the other patient was lost to follow-up.

Twenty patients were alive and in ongoing remission. Three patients proceeded to hematopoietic stem cell transplant — two died of transplant complications, including one for whom invasive fungal infection recurrence was a contributing factor.

“Our data do not support the routine administration of prophylactic antifungal therapy in children and young people undergoing chemotherapy for ALL due to its poor positive-predictive value,” O’Reilly said. “It is also not standard practice in the U.K. to perform invasive diagnostic procedures in this setting. Therefore, it is very difficult to accurately classify these infections.” – by Chuck Gormley

Reference:

O’Reilly MA, et al. Abstract 102. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.

Disclosures: O’Reilly and other study authors report no relevant financial disclosures.

ATLANTA — A small percentage of children, adolescents and young adults with acute lymphoblastic leukemia treated with the UKALL2011 protocol developed invasive fungal infections, according to a retrospective study presented at the ASH Annual Meeting and Exposition.

“The incidence of invasive fungal infections among patients with ALL treated with the UKALL2011 protocol is low,” Maeve A. O’Reilly, MB, specialist in pediatric hematology at London Hospital, said during her presentation. “In addition, the mortality associated with these infections also is low. There is certainly the potential to compromise the timely delivery of chemotherapy because 18 of our 22 patients had a delay and/or omission of therapy, but it did not appear to have an impact on outcome.”

Invasive fungal infections are a major cause of morbidity and mortality in adult hematological malignancies. However, epidemiological data in pediatric ALL is scarce because of differing chemotherapy protocols, patient populations, diagnostic strategies and definitions of invasive fungal infections, as well as variations in the use of prophylactic and empiric systemic antifungals.

Retrospective studies showed incidence rates for invasive fungal infections as low as 0.01% in Canada, but as high as 10% in the United States and 13% in Poland. A 2010 case-controlled study in Australia reported a 22% incidence rate.

To determine the incidence and outcome of invasive fungal infections among children, adolescents and young adults treated with the UKALL2011 protocol, O’Reilly and colleagues assessed data from 296 patients (median age, 5 years; range, 10 months to 24 years; 43% male) with ALL (B lineage, n = 249; T lineage, n = 43; unknown n = 4) treated at two large London hospitals from 2013 through December 2016.

Researchers categorized patients’ cytogenetic risk profile for B-ALL as classified as good (n = 133), intermediate (n = 86), poor (n = 20) or not available (n = 10).

Researchers classified invasive fungal infections — collected at induction, consolidation, interim maintenance and delayed intensification of the UKALL2011 protocol — as proven, probable and possible according to revised EORTC criteria.

Sixteen young adult patients aged 20 to 24 years received antifungal prophylaxis with oral itraconazole — or liposomal amphotericin B when vinca alkaloids were scheduled — during induction and consolidation when their neutrophil count fell below 1.5 × 109/L.

The other patients did not receive routine antifungal prophylaxis.

Median follow-up was 17 months.

Over a 4-year period, researchers observed eight cases (2%) of proven invasive fungal infections, four (1.5%) probable infections and 11 (4%) possible infections.

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Seven patients had positive mycological results, including five with Candida spp., one with Aspergillus spp. and one with Scedosporium spp.

Four cases of disseminated disease occurred during induction, including two central nervous system diseases.

Invasive fungal infections led to a median delay of 3 weeks (range, 1-15) for chemotherapy treatments among 16 cases. Omission of chemotherapy occurred for two cases, and significant dose reductions occurred for four cases.

At 17 months (range, 4-39), follow-up data were available for 22 of the 23 patients diagnosed with a proven, probable or possible infection; the other patient was lost to follow-up.

Twenty patients were alive and in ongoing remission. Three patients proceeded to hematopoietic stem cell transplant — two died of transplant complications, including one for whom invasive fungal infection recurrence was a contributing factor.

“Our data do not support the routine administration of prophylactic antifungal therapy in children and young people undergoing chemotherapy for ALL due to its poor positive-predictive value,” O’Reilly said. “It is also not standard practice in the U.K. to perform invasive diagnostic procedures in this setting. Therefore, it is very difficult to accurately classify these infections.” – by Chuck Gormley

Reference:

O’Reilly MA, et al. Abstract 102. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.

Disclosures: O’Reilly and other study authors report no relevant financial disclosures.

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