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L-asparaginase is an integral component of therapy for acute lymphoblastic leukemia. However, asparaginase-related complications, including the development of hypersensitivity reactions, can limit its use in individual patients. Of considerable concern in the setting of clinical allergy is the development of neutralizing antibodies and associated asparaginase inactivity. Also problematic in the use of asparaginase is the potential for the development of silent inactivation, with the formation of neutralizing antibodies and reduced asparaginase activity in the absence of a clinically evident allergic reaction. Here we present guidelines for the identification and management of clinical hypersensitivity and silent inactivation with Escherichia coli- and Erwinia chrysanthemi- derived asparaginase preparations. These guidelines were developed by a consensus panel of experts following a review of the available published data. We provide a consensus of expert opinions on the role of serum asparaginase level assessment, indications for switching asparaginase preparation, and monitoring after change in asparaginase preparation., (Copyright© Ferrata Storti Foundation.)

We report the incidence and outcome of venous thrombosis (VT) in the UK acute lymphoblastic leukaemia (ALL) 2003 trial. VT occurred in 59/1824 (3.2%) patients recruited over 5 years with 90% occurring during a period of Asparagine depletion. Pegylated Escherichia Coli Asparaginase (Peg-ASP) 1000 units/m(2) was used throughout. Thirty-four children received further Peg-ASP, most with concurrent heparin prophylaxis. There were no episodes of bleeding or recurrent thrombosis. Optimal Asparagine depletion is central to success of modern regimes for treatment of ALL. This report confirms a significant risk of thrombosis with such therapy, but demonstrates that re-exposure to Asparaginase is feasible and safe.

CAMPATH-1H (C-1H) is widely used in vivo and / or in vitro for T cell depletion in hematopoietic SCT. This humanised monoclonal antibody is specific for CD52, a marker coexpressed on the majority of human lymphocytes with CD48 and other glycosylphosphatidyl-inositol (GPI) anchored proteins. We detected CD52 / CD48 dual expression on >99% of CD3(+) lymphocytes from normal individuals and all 15 post-SCT patients whose transplants did not utilise C-1H. By contrast, 23 / 26 patients with transplants involving C-1H (in vivo, in vitro or both) exhibited populations lacking CD52 expression that accounted for 49.7% (4.2-86.2%) of the CD3+ lymphocytes (median and range) in samples evaluated at a median of 2 months post-SCT. Most CD52- cells also lacked CD48 expression. These GPI- T cells were of either donor or mixed donor / recipient origin. They were predominant in the early months after SCT at times of profound lymphopenia and inversely correlated with the recovery of the absolute lymphocyte count (r= - 0.663, P<0.0001). The presence of CD52- cells has been correlated previously with clinical outcome after CAMPATH therapy for both malignant and nonmalignant diseases.

Detection of residual disease after completion of therapy or following bone marrow transplantation (BMT) in patients with acute promyelocytic leukaemia (APL) predicts relapse and is associated with a poor prognosis. Here we describe the successful treatment of residual disease post-transplant in APL using prolonged all-trans retinoic acid (ATRA) therapy in two children in whom autologous BMT (ABMT) had been performed in second complete remission (CR). ATRA treatment was well tolerated and found to be beneficial despite its prior use as a component of the initial induction protocol. ATRA therapy post-transplant led to molecular remission as determined by fluorescence in situ hybridization (FISH) as well as reverse transcriptase-polymerase chain reaction (RT-PCR) analyses and remission now exceeds 3.5 years in both patients. Overall, this study not only demonstrates that ATRA may successfully salvage APL patients with residual disease post-transplant, but also suggests a potential role for retinoids post-consolidation as a means of eliminating residual disease which could be beneficial even in patients previously exposed to ATRA as a component of the induction protocol.

This article discusses research on the clinical spectrum of intrathecal methotrexate (IT MTX)-related stroke-like syndrome (SLS) in patients with acute lymphoblastic leukaemia (ALL) who were treated during the Medical Research Council UKALL 2003 trial in Great Britain. Researchers reviewed 203 investigator-generated reports of neurological serious adverse effects associated with IT MTX administration and learned that 31 cases are consistent with an SLS-type presentation.