Background Monitoring minimal residual (MRD) in paediatric pacients with ALL is the most important way to detect relapse, to individualised the treatment (selection of the intensity and the duration of chemotherapy), to evaluate the early response on chemotherapy, to see the long term prognostic and also to decide the indication/moment of stem cell transplantation
MRD is detect by three methods: flow cytometry- detect the abnormal immunophenotypes and polymerase chain reaction (PCR) detect the amplification of antigen- receptor genes/amplification of fusion transcripts. MRD sensitivity must be : minimal 10-4 to be taken in to account, must be affordable, fast, accurate and applicable. The positivity is defined by the presence of 0.01% or more, the risk of relapse is proportional to the level of MRD, especialy on day 33 and 78. Most studies establish the importance of MRD in children with ALL and also in adults.
aims : The present study evaluated the monitoring MRD in accordance with the ALL- BFM 2002 protocol
Methods paediatric patients with ALL – diagnosed in Fundeni Clinical Institute, during 2014–2016 were included in this prospective study, after performing consent procedure. The diagnosis was based on CBC with peripheral blood smear, bone marrow exam, flow cytometry- to detect the abnormal immunophenotypes, cytogenetics(to detect the number) and molecular biology (to detect the presence of abnormal genes). The MRD have been taken in day15, 33(induction- therapy), day 78 (first day of consolidation ), in the first day of reinduction and in the last one, and in the mentenance therapy also fallow up MRD (at 3,6,9 and 12 month). The most common method used was flow cytometry, but also the molecular for the pacient with abnormal gene(BCR-ABL, TEL-AML1, E2A-PBX)
Results In the 3 –years interval, we diagnosed 114 patients with ALL between 1.01.14 until 1.01.17. Major was ALL- B lineage 98%,ALL- T lineage13,15%, B and T lineage 1,7%, repartition by subtypes: L1 93,9%, L2 4,38%, L3 0,87%. Abnormal genes detection was positive for E2A-PBX 3,5%, BCR-ABL 6,14%, TEL-AML 16,66%, MLL 3,5%, SIL-TAL 0,8%, without abnormal genes 67,54%. Monitoring MRD the results was 11, 4% positive in day 33, and remained positive in day 78 in 2.63% cases- in present they are in remission. The HRG was 13,15% cases, we obtain the molecular remission of all and they remained under our close supervision for the eventuality stem cell transplantation. The survival of HRG therapy was 73,33% cases.
Coclussion Our patients had favourable outcome following ALL-BFM 2002 protocol, at TP1 88,6% obtained molecular remission. The results are remarcable the remission at TP2 was in 97,3% and remained in remission until present. They will be closly monitoring in our clinic until they will became adults
??In this 3 years study we also included one pacient with relapse, at 5 years from the first diagnosis. Was a girl, with ALL, B lineage, L1 subtypes, TEL-AML1 positive. We obtained the second remission but unfortunate she died because of severe infection (Pseudomonas Aeruginosa Sepsis). The rest of the pacient are in molecular remission until present.