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. 2013 Feb 6:6:14.
doi: 10.1186/1756-8722-6-14.

Monitoring of minimal residual disease (MRD) is useful to predict prognosis of adult patients with Ph-negative ALL: results of a prospective study (ALL MRD2002 Study)

Koji Nagafuji  1 , Toshihiro Miyamoto, Tetsuya Eto, Tomohiko Kamimura, Shuichi Taniguchi, Takashi Okamura, Eiichi Ohtsuka, Takashi Yoshida, Masakazu Higuchi, Goichi Yoshimoto, Tomoaki Fujisaki, Yasunobu Abe, Yasushi Takamatsu, Shouhei Yokota, Koichi Akashi, Mine Harada
Affiliations

Monitoring of minimal residual disease (MRD) is useful to predict prognosis of adult patients with Ph-negative ALL: results of a prospective study (ALL MRD2002 Study)

Koji Nagafuji et al. J Hematol Oncol. .

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) for patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is much more intensive than multi-agent combined chemotherapy, although allogeneic HSCT is associated with increased morbidity and mortality when compared with such chemotherapy. Minimal residual disease (MRD) status has been proven to be a strong prognostic factor for adult patients with Ph-negative ALL.

Methods: We investigated whether MRD status in adult patients with ALL is useful to decide clinical indications for allogeneic HSCT. We prospectively monitored MRD after induction and consolidation therapy in adult patients with Ph-negative ALL.

Results: Of 110 adult ALL patients enrolled between July 2002 and August 2008, 101 were eligible, including 59 Ph-negative patients. MRD status was assessed in 43 patients by the detection of major rearrangements in TCR and Ig and the presence of chimeric mRNA. Thirty-nine patients achieved CR1, and their probabilities of 3-year overall survival and disease-free survival (DFS) were 74% and 56%, respectively. Patients who were MRD-negative after induction therapy (n = 26) had a significantly better 3-year DFS compared with those who were MRD-positive (n = 13; 69% vs. 31%, p = 0.004). All of 3 patients who were MRD-positive following consolidation chemotherapy and did not undergo allogeneic HSCT, relapsed and died within 3 years after CR.

Conclusions: These results indicate that MRD monitoring is useful for determining the clinical indications for allogeneic HSCT in the treatment of ALL in CR1.

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Figures

Figure 1
Figure 1
Impact of post-induction minimal residual disease (MRD) status on overall survival (OS) and disease-free survival (DFS). Patients who were MRD negative after induction therapy (first course A) (n = 26) had a significantly better 3-year DFS compared with those who were MRD positive (n = 13) (69% vs. 31%, p = 0.004).
Figure 2
Figure 2
Effect of time taken to become minimal residual disease (MRD)-negative on disease-free survival (DFS). Patients who were MRD positive after induction and became MRD negative after consolidation chemotherapy C in the first course (n = 7) had a significantly worse DFS compared with patients who were MRD negative after induction chemotherapy A in the first course (n = 26) (69% vs. 29%, p = 0.004).
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