Plasma methotrexate levels and toxicities in children with acute lymphoblastic leukemia treated with two different doses of methotrexate.

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Conference: 
2012/2013. tanév
Session: 
Pediatrics, infectology, pulmonology
Presenting author
Name (format for foreign students: Last Name, First Name): 
Pandita, Ankur

Abstract data

Előadás címe: 
Plasma methotrexate levels and toxicities in children with acute lymphoblastic leukemia treated with two different doses of methotrexate.
Abstract: 

Background
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Methotrexate, a structural analogue of folic acid, is a key component in all modern ALL treatment protocols. It is mostly given as high-dose (HD) Mtx (>1gr/m2) but a consensus of optimal dose is still to be decided.
The aim of the study was to retrospectively analyze the Mtx levels, leucovorin rescue and toxicity profile in patients given 2gr/m2/24h (mM block) vs. 5gr/m2/24h (M block) of Mtx consolidation therapy according to the BFM-ALL IC 2009 protocol currently used in 14 countries worldwide, including Hungary.
Method
13 patients (mean age 6.9 yrs) were diagnosed with ALL at the Dep. of Pediatric Hematology-Oncology of the University of Debrecen, MHSC, between June, 2011 and October, 2012. Of these, 12 achieved complete remission and were randomized to receive either 2gr/m2/24h or 5gr/m2/24h Mtx consolidation therapy. Mtx infusions were given every 14th day, at 4 different occasions. Plasma Mtx measurements were made at 24h, 42h, 48h or until levels were ≤0,25 μmol/L. Acute toxicities, Mtx levels and leucovorin length and cumulative dose were gathered from patient charts and summarized.
Results
One patient was excluded because of age (<1 yr) and one died during induction therapy. Of the remaining 11 patients, 9 were diagnosed with B-ALL and 2 with T-ALL. Both mM and M blocks were well tolerated and there were no fatalities. One patient was switched from M to mM blocks due to extremely high plasma Mtx levels associated with severe acute toxicity. Plasma Mtx levels were higher in patients receiving 5gr/m2/24h. This explains why higher cumulative doses and longer rescue schedules of leucovorin were employed and correlates with the higher frequency of drug-induced toxicities observed.
Conclusion
HD Mtx treatment is a feasible component of anti-ALL therapy regardless of the dose applied. As expected, the higher doses were associated with a more intensive exposure of the drug, thus requiring a longer rescue period. It remains to be seen if the greater expressed toxicities and treatment cost associated with the M vs. mM blocks would result in lower rates of relapse in children with ALL.

First tutor
Name: 
Dr. Kiss Csongor
Department: 
Gyermekgyógyászati Intézet, Gyermek Hematolgóiai-Onkológiai Tanszék
Prize: 
különdíj

Támogatók: Támogatók: Az NTP-TDK-14-0007 számú, A Debreceni Egyetem ÁOK TDK tevékenység népszerűsítése helyi konferencia keretében, az NTP-TDK-14-0006 számú, A Debreceni Egyetem Népegészségügyi Karán folyó Tudományos Diákköri kutatások támogatása, NTP-HHTDK-15-0011-es A Debreceni Egyetem ÁOK TDK tevékenység népszerűsítése 2016. évi helyi konferencia keretében, valamint a NTP-HHTDK-15-0057-es számú, A Debreceni Egyetem Népegészségügyi Karán folyó Tudományos Diákköri kutatások támogatása című pályázatokhoz kapcsolódóan az Emberi Erőforrás Támogatáskezelő, az Emberi Erőforrások Minisztériuma, az Oktatáskutató és Fejlesztő Intézet és a Nemzeti Tehetség Program