Tracking Silent Hypersensitivity Reactions to Asparaginase during Leukemia Therapy Using Single-Chip Indirect Plasmonic and Fluorescence Immunosensing

Microbial asparaginase is an essential component of chemotherapy for the treatment of childhood acute lymphoblastic leukemia (cALL). Silent hypersensitivity reactions to this microbial enzyme need to be monitored accurately during treatment to avoid adverse effects of the drug and its silent inactivation. Here, we present a dual-response anti-asparaginase sensor that combines indirect SPR and fluorescence on a single chip to perform ELISA-type immunosensing, and correlate measurements with classical ELISA. Analysis of serum samples from children undergoing cALL therapy revealed a clear correlation between single-chip indirect SPR/fluorescence immunosensing and ELISA used in clinical settings (<i>R</i>² > 0.9). We also report that the portable SPR/fluorescence system had a better sensitivity than classical ELISA to detect antibodies in clinical samples with low antigenicity. This work demonstrates the reliability of dual sensing for monitoring clinically relevant antibody titers in clinical serum samples

Previous and new treatment strategies for standard risk relapse (SRR) and High risk relapse or refractoriness (HRRR), before and after 2007.

<p>HSCT, haematopoietic stem cell transplantation; AraC, Cytarabine; COG, Children Oncology Group; DFCI, Dana-Farber Cancer Institute.</p

Characteristics of relapsed or refractory patients at diagnosis of relapse or refractory disease.

<p>Characteristics of relapsed or refractory patients at diagnosis of relapse or refractory disease.</p

Characteristics at first presentation of ALL patients who subsequently relapsed or were refractory to first-line induction.

<p>Characteristics at first presentation of ALL patients who subsequently relapsed or were refractory to first-line induction.</p

EFS by strategy.

<p>Before 2007, all relapsed patients were offered an hematopoietic stem cell transplantation (HSCT) after a single cycle of chemotherapy. After 2007, HSCT was offered to patients with high risk relapse, after at least 3 cycle of chemotherapy (A) 5-year EFS of all relapses or refractoriness: 41% vs 60%, (B) 5-years EFS of standard risk relapses (SRR): 57% vs 67%, and (C) 5-years EFS of high risk relapses or refractory (HRRR): 11% vs 56%.</p

Survival of all relapsed and refractory ALL patients.

<p>(A) 5- years EFS for all patients: 44% (B) 5 years EFS for standard risk relapse (SRR): 59% versus high risk relapse or refractory (HRRR): 31%.</p