Prognostic value of minimal residual disease measured by fusion‐gene transcript in infants with KMT2A‐rearranged acute lymphoblastic leukaemia treated according to the MLL‐Baby protocol

Abstract

Summary The prognostic value of minimal residual disease (MRD) measured by fusion‐gene transcript (FGT) detection was investigated in 76 infants (aged ≤1 year) with acute lymphoblastic leukaemia (ALL) with lysine methyltransferase 2A (KMT2A) rearrangements. Either at the end of induction or at later time‐points, FGT‐MRD‐positivity was associated with poor outcome. FGT‐MRD‐positivity after first consolidation or first high‐risk block detected 46·5% of infants with extremely poor outcome [disease‐free survival (SE) 0·06 (0·06), cumulative incidence of relapse (SE) 0·91 (0·05)], which was also confirmed in multivariable analysis. Thus, FGT‐MRD measurement at a single time‐point clearly identifies infants with ALL who are curable with conventional chemotherapy and those who would benefit only from other treatment approaches.

Incidence and prognostic value of central nervous system involvement in infants with B‐cell precursor acute lymphoblastic leukemia treated according to the MLL‐Baby protocol

“…Bone marrow samples for MRD monitoring were shipped to the reference laboratories of the MLL‐Baby protocol in Ekaterinburg and Minsk. Fusion gene transcript (FGT)‐MRD detection was performed by both reverse transcriptase‐nested PCR and reverse transcriptase quantitative real‐time PCR (RQ‐PCR) as described previously 15,17 . Patients were considered FGT‐MRD‐negative if KMT2A FGT was not detected with either technique.…”

“…4,5,11 Moreover, there are currently solid data on the role of minimal residual disease (MRD) as the strongest prognostic parameter in infant ALL. 5,[12][13][14][15][16][17][18] Nevertheless, none of these criteria or their combinations allow identification of the relatively large subgroup of patients with a low risk (LR) of relapse, especially among those with KMT2A-r.…”

“…The presence of KMT2A ‐r, age below 6 months, very high initial WBC count (≥300 × 10 9 /L), CNS leukemia, and poor prednisone response (≥1000 blast cells per microliter in peripheral blood [PB] at Day 8 of treatment) are widely used for stratification purposes in various trials 4,5,11 . Moreover, there are currently solid data on the role of minimal residual disease (MRD) as the strongest prognostic parameter in infant ALL 5,12–18 . Nevertheless, none of these criteria or their combinations allow identification of the relatively large subgroup of patients with a low risk (LR) of relapse, especially among those with KMT2A ‐r.…”

Prognostic significance of various 11q23/KMT2A rearrangements in infants with acute lymphoblastic leuekemia

“…Еще одним обязательным условием успеха будущего протокола является использование результатов определения минимальной остаточной болезни. Наши ранее опубликованные данные по оценке минимальной остаточной болезни в рамках протокола MLL-Baby позволили однозначно разделить пациентов на тех, кто может быть излечен с помощью стандартной химиотерапии, и тех, кому необходимы альтернативные способы лечения [41,42].…”

Blinatumomab following haematopoietic stem cell transplantation – a novel approach for the treatment of acute lymphoblastic leukaemia in infants

“…PCR‐based fusion‐gene transcript (FGT) detection was applied as an additional MRD technique. FGT‐MRD detection was performed by both reverse‐transcriptase nested PCR and reverse‐transcriptase quantitative real‐time PCR (RQ‐PCR) 6 . Slow FGT‐MRD response was stated if any FGT‐MRD‐positivity at day 85 or after first high‐risk (HR) block was found 6 .…”