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Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial.

Safety and efficacy data on pegylated asparaginase (PEG-ASP) in adult acute lymphoblastic leukaemia (ALL) induction regimens are limited. The UK National Cancer Research Institute UKALL14 trial NCT01085617 prospectively evaluated the tolerability of 1000 IU/m2 PEG-ASP administered on days 4 and 18 as part of a five-drug induction regimen in adults aged 25–65 years with de novo ALL. Median age was 46.5 years. Sixteen of the 90 patients (median age 56 years) suffered treatment-related mortality during initial induction therapy. Eight of the 16 died of sepsis in combination with hepatotoxicity. Age and Philadelphia (Ph) status were independent variables predicting induction death >40 versus ⩽40 years, odds ratio (OR) 18.5 (2.02–169.0), P=0.01; Ph− versus Ph+ disease, OR 13.60 (3.52–52.36), P<0.001. Of the 74 patients who did not die, 37 (50.0%) experienced at least one grade 3/4 PEG-ASP-related adverse event, most commonly hepatotoxicity (36.5%, n=27). A single dose of PEG-ASP achieved trough therapeutic enzyme levels in 42/49 (86%) of the patients tested. Although PEG-ASP delivered prolonged asparaginase activity in adults, it was difficult to administer safely as part of the UKALL14 intensive multiagent regimen to those aged >40 years. It proved extremely toxic in patients with Ph+ ALL, possibly owing to interaction with imatinib.

Haemophagocytic lymphohistiocytosis following fludarabine/cyclophosphamide chemotherapy for chronic lymphocytic leukaemia

Antonella Anastasia* Carmelo Carlo-Stella* Paolo Corradini Flavia Salvi Chiara Rusconi Alessandro Pulsoni Stefan Hohaus Patrizia Pregno Simonetta Viviani Ercole Brusamolino Stefano Luminari Laura Giordano Armando Santoro Department of Oncology and Haematology, Humanitas Cancer Centre, Humanitas Clinical and Research Centre, Rozzano (MI), Department of Medical Biotechnology and Translational Medicine, University of Milano, Department of Haematology and Bone Marrow Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Chair of Haematology, University of Milano, Milano, Division of Haematology, AO SS Antonio e Biagio e C. Arrigo, Alessandria, Division of Haematology, Niguarda Ca’ Granda Hospital, Milano, Department of Cellular Biotechnologies and Haematology, “Sapienza” University, Institute of Haematology, Universit a Cattolica S. Cuore, Roma, Haematology, A.O. Citt a della Salute e della Scienza, Torino, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Division of Haematology, Policlinico S Matteo, Pavia, and Department of Diagnostic Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy. E-mail: carmelo.carlostella@cancercenter.humanitas.it