Minimal Residual Disease

Bone Marrow Transplantation (2004) 33, 535–542. doi:10.1038/sj.bmt.1704386 Published online 12 January 2004

Preemptive treatment of minimal residual disease post transplant in CML using real-time quantitative RT-PCR: a prospective, randomized trial

Y-J Kim1, D-W Kim1, S Lee1, N-G Chung1, J-Y Hwang1, Y-L Kim1, C-K Min1 and C-C Kim1

1Catholic Hematopoietic Stem Cell Transplantation Center, The Catholic University of Korea, Seoul, South Korea

Correspondence: Dr D-W Kim, Department of Internal Medicine, St Mary's Hospital, #62, Youido-dong, Youngdeungpo-gu, Seoul 150-713, South Korea. E-mail: dwkim@catholic.ac.kr

Received 8 December 2002; Accepted 18 September 2003; Published online 12 January 2004.

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Abstract

Immunotherapy in the form of donor lymphocyte infusions in early-phase relapse might be advantageous as it induces a higher response, but this may be offset by increased toxicity, especially during the early period after transplantation. Among 45 consecutive patients receiving an allograft for CML, 13 patients were diagnosed to have molecular relapse (MRel), as defined by real-time quantitative reverse transcriptase-polymerase chain reaction, and another four patients were diagnosed to have cytogenetic relapse (CRel) within 6 months. Patients with MRel were randomly assigned to either a 'no therapy' group (group A, n=6), in which immunotherapy was reserved until CRel, or an 'immunotherapy' group (group B, n=7). In group A, all MRel progressed to CRel, and molecular remission (MR) was achieved in four (67%) after immunotherapy. The remaining two patients died of extensive GVHD and fungal pneumonia. In group B, only two MRel progressed to CRel and the remaining five (71%) achieved MR. Two patients died in the absence or loss of response. In patients relapsing directly into CRel (n=4), immunotherapy induced MR in two patients (50%). Earlier intervention played a role in preventing disease progression but this effect was not translated into better survival, which could have been overcome by imatinib mesylate, which induced MR and cytogenetic remission in nonresponders without toxicity.

Keywords:

chronic myelogenous leukemia, hematopoietic stem cell transplantation, minimal residual disease, relapse, real-time quantitative PCR, immunotherapy

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