Minimal Risidual Disease monitoring in Childhood Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Preliminary Results of JPLSG Ph+ALL04.

Abstract 4116

Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) is very rare and poor prognostic condition in children. Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) conducted first nationwide clinical trial for Ph+ALL in children (Ph+ALL04). Ph+ALL04 consists of five therapy phases; Induction phase (five drugs induction), Intensification phase (high-dose CA and BFM Ib), Re-induction phase (four drugs re-induction), Imatinib mono-therapy phase, and hematopoietic stem cell transplantation phase (VP+CY+TBI condioning). Before and after each phase, BCR-ABL minimal residual disease (MRD) was monitored by the real-time PCR method. During the period 2004-08, 44 patients were enrolled in the Ph+ALL04 study. Out of 44 patients, five were resistant to Induction Phase and did not achieve CR. Their levels of BCR-ABL transcript at diagnosis were significantly higher than that of patients achieved CR after Induction phase. After Induction phase, 39 patients achieved CR, and seven of 39 patients also achieved MRD negative. After Intensification phase, two patients relapsed. Thirty-four patients were still in CR, and 10 patients also achieved MRD negative after Intensification phase. One patient relapsed after Re-induction phase and three patients relapsed after Imatinib mono-therapy phase. Thirteen patients were MRD negative before Imatinib mono-therapy phase, and 14 patients were MRD negative after Imatinib mono-therapy phase. Before Hematopoietic stem cell transplantation phase, 14 patients were MRD negative. Twenty-six patients received hematopoietic stem cell transplantation. Out of 26 patients, three relapsed after hematopoietic cell transplantation. Twenty-three patients continued to be in CR and MRD negative for median 2 years after hematopoietic stem cell transplantation. In conclusion, amount of BCR-ABL transcript is a possible predictor for achieving remission after induction therapy in Ph+ALL children. MRD detection during therapy is confirmed the important prognostic indicator in the context of the intensive chemotherapy and hematopoietic stem cell transplantation in Ph+ALL children.