International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

open47siDespite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Munster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)type primary therapy (80% +/- 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% +/- 7.2% and 50% +/- 12%, respectively). When ALL-or AML-specific gene fusions were excluded, 5-year EFS of CD19(+) leukemia was 83% +/- 5.3% on ALL-type primary treatment compared with 0% +/- 0% and 28% +/- 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19(+) ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19(-) and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with >= 5% blasts after remission induction. The results provide a basis for a prospective trial.openHrusak, Ondrej; De Haas, Valerie; Stancikova, Jitka; Vakrmanova, Barbora; Janotova, Iveta; Mejstrikova, Ester; Capek, Vaclav; Trka, Jan; Zaliova, Marketa; Luks, Ales; Bleckmann, Kirsten; Möricke, Anja; Irving, Julie; Konatkowska, Benigna; Alexander, Thomas B.; Inaba, Hiroto; Schmiegelow, Kjeld; Stokley, Simone; Zemanova, Zuzana; Moorman, Anthony V.; Rossi, Jorge Gabriel; Felice, Maria Sara; Dalla-Pozza, Luciano; Morales, Jessa; Dworzak, Michael; Buldini, Barbara; Basso, Giuseppe; Campbell, Myriam; Cabrera, Maria Elena; Marinov, Neda; Elitzur, Sarah; Izraeli, Shai; Luria, Drorit; Feuerstein, Tamar; Kolenova, Alexandra; Svec, Peter; Kreminska, Olena; Rabin, Karen R.; Polychronopoulou, Sophia; Da Costa, Elaine; Marquart, Hanne Vibeke; Kattamis, Antonis; Ratei, Richard; Reinhardt, Dirk; Choi, John K.; Schrappe, Martin; Stary, JanHrusak, Ondrej; De Haas, Valerie; Stancikova, Jitka; Vakrmanova, Barbora; Janotova, Iveta; Mejstrikova, Ester; Capek, Vaclav; Trka, Jan; Zaliova, Marketa; Luks, Ales; Bleckmann, Kirsten; Möricke, Anja; Irving, Julie; Konatkowska, Benigna; Alexander, Thomas B.; Inaba, Hiroto; Schmiegelow, Kjeld; Stokley, Simone; Zemanova, Zuzana; Moorman, Anthony V.; Rossi, Jorge Gabriel; Felice, Maria Sara; Dalla-Pozza, Luciano; Morales, Jessa; Dworzak, Michael; Buldini, Barbara; Basso, Giuseppe; Campbell, Myriam; Cabrera, Maria Elena; Marinov, Neda; Elitzur, Sarah; Izraeli, Shai; Luria, Drorit; Feuerstein, Tamar; Kolenova, Alexandra; Svec, Peter; Kreminska, Olena; Rabin, Karen R.; Polychronopoulou, Sophia; Da Costa, Elaine; Marquart, Hanne Vibeke; Kattamis, Antonis; Ratei, Richard; Reinhardt, Dirk; Choi, John K.; Schrappe, Martin; Stary, Ja

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020). Interpretation: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. Funding: American Lebanese Syrian Associated Charities and the National Cancer Institute