Minimal residual disease studies are beneficial in the follow‐up of TEL/AML1 patients with B‐precursor acute lymphoblastic leukaemia

Abstract

Summary. The t(12;21)(p13;q22) translocation has been identified as the most common chromosomal abnormality in childhood acute lymphoblastic leukaemia (ALL). Initially, several investigators reported an excellent prognosis in paediatric leukaemias with this translocation, but other studies showed a 20% incidence in relapsed ALL. We performed an extensive analysis of 90 ALL patients. In 17 (19%) cases a TEL/AML1 fusion was found. However, this group was not representative as it included a high number of relapsed patients compared with the normal incidence in B-precursor ALL [54 in continuous complete remission (CCR) and 36 relapsed patients] and only a slightly better prognosis for TEL/AML1-positive patients was found (not significant) (four relapses in 17 TEL/AML1-postive patients vs. 32 relapses in 73 TEL/AML1-negative patients).Comparison of known prognostic factors (age, sex, ploidy, white blood cell count and immunophenotype) between relapsed TEL/AML1-positive and TEL/AML1-positive patients in CCR did not reveal differences, except that the white blood cell count was significantly higher in the relapsed group (P 0´001). Time between diagnosis and relapse was not different for the relapsed TEL/AML1-positive group vs. the relapsed TEL/AML1-negative group. In 11 TEL/AML1-positive patients, the minimal residual disease (MRD) level at the end of induction therapy was quantified in a limiting dilution assay using IGH or TCRD junctional regions as polymerase chain reaction (PCR) targets. In all four relapsed patients, the level of MRD at the end of induction therapy was high (range 0´24±1´2%), whereas in all seven CCR patients, the MRD level was extremely low (0´02 to , 0´001%). In agreement with previous studies in which MRD levels at the end of induction therapy were found to be the strongest risk factor independent of other risk factors, in the present study we show that the MRD level remains a risk factor independent of the presence of a TEL/ AML1 fusion gene.

Outcome of ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia in the NOPHO‐ALL‐1992 protocol: frequent late relapses but good overall survival

“…Most studies on the prognostic implications of t(12;21) have not reported individual data on gender and time in remission. However, the information that can be retrieved from studies providing pertinent data (Nakao et al , 1996; Harbott et al , 1997; Lanza et al , 1997; Satake et al , 1997; Loh et al , 1998; Rubnitz et al , 1999; Codrington et al , 2000; de Haas et al , 2000; Seeger et al , 2001; Tsang et al , 2001; Alvarez et al , 2005; Al‐Sweedan et al , 2007) does not support that boys generally relapse later than girls; based on all studies referred to above, the median remission duration before relapse was 37 months (range 17–102) for boys and 32 months (range 11–109) for girls. Thus, our finding may well be fortuitous and should be interpreted with caution.…”

Frecuencia de los genes de fusión TEL/AML1 y BCR/ABL en pacientes pediátricos con leucemia linfoblástica aguda

“…La translocación del gen TEL puede ir acompañada por otras aberraciones genéticas secundarias, como deleción del otro alelo TEL, duplicación del gen de fusión o trisomía 21, observadas en 36% de los niños con LLA TEL/ AML1(+), los que tendrían un rol sinérgico con la proteína de fusión en la represión de la transcripción, influyendo en la progresión de la enfermedad [38][39][40][41][42][43] . El porcentaje de recaída medular de 23% observado en el grupo TEL/AML1(+), está en concordancia al publicado por De Haas (23%) en una serie de 17 pacientes TEL/AML1(+) 44 . La SLE estimada a 40 meses, aunque es levemente mayor en el grupo TEL/AML1(+) que en el grupo TEL/ AML1(-) (63% y 54%, respectivamente), no es estadísticamente significativa, hallazgo concordante con algunos estudios que no muestran diferencia significativa en la SLE de pacientes TEL/AML1 positivo y negativo 45 .…”

The TEL‐AML1 real‐time quantitative polymerase chain reaction (PCR) might replace the antigen receptor‐based genomic PCR in clinical minimal residual disease studies in children with acute lymphoblastic leukaemia

“…Several large prospective clinical MRD studies have shown that it is important to determine precisely the level of MRD for discrimination between low‐ and high‐risk patients (Cave et al , 1998; Coustan‐Smith et al , 1998; van Dongen et al , 1998). Quantitative analysis of MRD by real‐time quantitative polymerase chain reaction (RQ‐PCR) has contributed to accurate MRD analysis (Pongers‐Willemse et al , 1998; de Haas et al , 2000a; Verhagen et al , 2000). Two different types of PCR targets can be used: clone‐specific antigen receptor rearrangements and the breakpoint fusion regions of chromosome aberrations.…”