Clinical features and outcome of children with first marrow relapse of acute lymphoblastic leukemia expressing BCR-ABL fusion transcripts. BFM Relapse Study Group

Abstract

Although the Philadelphia chromosome (Ph1) has been identified as an adverse prognostic factor in acute lymphoblastic leukemia (ALL), little is known about the incidence and clinical course of relapsed Ph1- positive ALL in children. The incidence was determined by screening of 170 consecutive children with first bone marrow relapse of ALL using the reverse transcriptase-polymerase chain reaction (RT-PCR) and comparison, with cytogenetic analysis. Among these 170 children, 20 (12%) were found to be BCR-ABL-positive, representing a rate that is about three times higher than that reported for newly diagnosed ALL. Ten of the cases were identified by RT-PCR only. In none of the 21 patients with T-cell immunophenotypes could an expression of the BCR- ABL mRNA be detected. BCR-ABL positivity was associated with a significantly shorter duration of first remission (P = .0086) and higher white blood cell (P = .0157) and blast cell counts (P = .0304) at relapse diagnosis. All patients were treated according to the ALL- REZ BFM 87 and 90 relapse trials of the BFM Relapse Study Group. The intensive multiagent chemotherapy induced a second complete remission in only 60% of children with BCR-ABL-positive ALL compared with in 91% of those without BCR-ABL expression (P = .0023). The prognosis of BCR- ABL-positive ALL in children is poor, with a probability of event-free survival at 2 years of 8% versus 50% in those without BCR-ABL mRNA or cytogenetic analysis should become part of the routine diagnostic panel for children with newly diagnosed ALL and is fundamental for children presenting with an early bone marrow relapse.

Allogeneic bone marrow transplantation in first remission rescues children with Philadelphia chromosome‐positive acute lymphoblastic leukemia: Tokyo Children's Cancer Study Group (TCCSG) studies L89‐12 and L92‐13*

“…More than half of the relapsed patients did not respond to another course of induction chemotherapy. This was consistent with a previous observation [19]. Most patients who achieved a second remission relapsed before the transplantation.…”

Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X

“…The 12 patients with Phþve ALL included two with longterm survival, one of whom had received a bone marrow transplant. This abnormality has been detected in a high proportion of relapsed patients (Beyermann et al, 1996) and Phþve ALL does appear to be an indication for bone marrow transplantation in first remission. It may be significant that the two long-surviving children were the only two in the group who also had high hyperdiploidy; it has recently been suggested that patients with this finding have superior survival to others with Phþve ALL (Rieder et al, 1996).…”

Clinical features, early treatment responses, and outcomes of pediatric acute lymphoblastic leukemia in china with or without specific fusion transcripts: A single institutional study of 1,004 patients

“…The prognosis of patients with BCR‐ABL fusion was the worst in childhood ALL [34, 35]. Therefore, in protocols BCH‐2003 and CCLG‐2008, these patients were directly stratified into the high‐risk group.…”