title: 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).
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.
authors: Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. knagafuji@med.kurume-u.ac.jp
authors: Koji
authors: K
authors: Nagafuji
authors: Toshihiro
authors: T
authors: Miyamoto
authors: Tetsuya
authors: T
authors: Eto
authors: Tomohiko
authors: T
authors: Kamimura
authors: Shuichi
authors: S
authors: Taniguchi
authors: Takashi
authors: T
authors: Okamura
authors: Eiichi
authors: E
authors: Ohtsuka
authors: Takashi
authors: T
authors: Yoshida
authors: Masakazu
authors: M
authors: Higuchi
authors: Goichi
authors: G
authors: Yoshimoto
authors: Tomoaki
authors: T
authors: Fujisaki
authors: Yasunobu
authors: Y
authors: Abe
authors: Yasushi
authors: Y
authors: Takamatsu
authors: Shouhei
authors: S
authors: Yokota
authors: Koichi
authors: K
authors: Akashi
authors: Mine
authors: M
authors: Harada
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000235:genetics*; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
references: Pediatr Blood Cancer. 2010 Dec 15;55(7):1287-95
references: 20535816
references: J Clin Oncol. 2009 Feb 20;27(6):911-8
references: 19124805
references: Blood. 2008 Jun 15;111(12):5755; author reply 5755
references: 18544698
references: Bone Marrow Transplant. 1998 Aug;22(3):253-7
references: 9720738
references: Leuk Lymphoma. 2002 May;43(5):1001-6
references: 12148878
references: Blood. 2004 Dec 1;104(12):3507-12
references: 15315963
references: Blood. 2006 Feb 1;107(3):1116-23
references: 16195338
references: Int J Hematol. 2010 Oct;92(3):481-9
references: 20830615
references: N Engl J Med. 2006 Jan 12;354(2):166-78
references: 16407512
references: J Clin Oncol. 2007 Mar 1;25(7):813-9
references: 17327603
references: Br J Haematol. 2010 Jan;148(1):80-9
references: 19863538
references: Blood. 2007 Feb 1;109(3):910-5
references: 17023577
references: Blood. 2008 Jun 15;111(12):5755
references: 31653127
references: Cancer. 2004 Dec 15;101(12):2788-801
references: 15481055
references: Nat Rev Clin Oncol. 2011 May 31;8(7):417-24
references: 21629213
references: Biol Blood Marrow Transplant. 2009 Jan;15(1 Suppl):11-6
references: 19147070
references: J Clin Oncol. 2002 Feb 15;20(4):1094-104
references: 11844835
references: Blood. 2007 Feb 1;109(3):944-50
references: 17032921
references: Leukemia. 2002 Aug;16(8):1432-6
references: 12145681
references: Leukemia. 2007 Apr;21(4):706-13
references: 17287857
references: Cancer. 2010 Mar 1;116(5):1165-76
references: 20101737
references: Blood. 2006 Jul 15;108(2):465-72
references: 16556888
references: Blood. 2012 Aug 30;120(9):1868-76
references: 22442346
references: J Clin Oncol. 2008 Apr 10;26(11):1843-9
references: 18398150
references: Eur J Haematol. 2006 Dec;77(6):471-9
references: 16978239
references: Blood. 1988 Jan;71(1):123-31
references: 3422030
references: Leukemia. 2007 Sep;21(9):1907-14
references: 17611565
references: Blood. 2005 Dec 1;106(12):3760-7
references: 16105981
references: Blood. 1996 Jun 15;87(12):5251-6
references: 8652840
references: Haematologica. 2004 Feb;89(2):145-53
references: 15003889
references: Haematologica. 2007 May;92(5):612-8
references: 17488684
references: Blood. 2008 Sep 1;112(5):1646-54
references: 18502832
references: Leuk Lymphoma. 2001 Apr;41(3-4):297-307
references: 11378542
references: Blood. 2009 Apr 30;113(18):4153-62
references: 19141862
references: Blood. 1991 Jan 15;77(2):331-9
references: 1824678
references: Cancer. 2013 Jan 1;119(1):90-8
references: 22744771
references: Blood. 2008 Feb 15;111(4):1827-33
references: 18048644