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Meta-analysis of the impact of MRD in adult B-ALL
Characteristics of studies and patients in the meta-analysis
Disease stage and treatment
Key characteristics of the studies included in the meta- analysis (Table 1) were considered in order to provide con-
Table 1. Characteristics of studies included in the meta-analysis.
text when analyzing clinical outcomes according to MRD status.20,31–36,41–56 Most studies assessing MRD status in adults with B-ALL were published from 2011 onwards, with the exception of a prospective study in Germany35 and a Polish study.47 Studies were mainly conducted in
First author Year Total Ph number status
of patients (with MRD data)
Included in primary analysis
MRD MRD method level
PCR 10−5
PCR 10−4
PCR NA
Flow 10−4
(6 color)
PCR 10−5
Flow 10−4
(6 color)
PCR 10−4
PCR 10−4 PCR 10−4
Flow 10−3
(3 color)
PCR 10−4 PCR 10−4
PCR 10−4
PCR NA
Mix 10−3
Mix Mix
PCR NA
Flow 10−4
(6 color)
PCR 10−5 PCR NA PCR 10−4 PCR 10−5 PCR 10−4
Flow 10−4
PCR 10−4
Flow 10−3 (3 color)
PCR 10−4
MRD test location
NA
Central NA Local
Local
Local
NA
Central Central
Central
NA
NA
Central
Local Local Local Central Local
Central Central Central Central NA
Local
Central
Central
NA
ALL phenotype
B-cell
B-cell B-cell B-cell
B-cell
B-cell
Mix (79% B-cell)
B-cell
Mix (66% B-cell)
Mix
(75% B-cell)
B-cell
Mix (76% B-cell)
B-cell
B-cell B-cell B-cell B-cell B-cell
B-cell B-cell B-cell B-cell B-cell
B-cell
Mix
(66% B-cell)
Mix (75% B-cell)
B-cell
MRD timing
Disease Pre-MRD Post-MRD Risk
stage at MRD
tx
Targeted
Targeted Targeted Targeted
Targeted
Targeted
Chemo
Chemo Chemo
Chemo
Chemo
Chemo
Targeted
Targeted Chemo Targeted HSCT Chemo
Targeted Targeted Targeted Targeted Targeted
Targeted
Chemo
Chemo
Chemo
tx
group
Lussana56
Gökbuget41 Chiaretti42 Jabbour43
Nishiwaki34
Ravandi44
Bassan49
Beldjord46 Gökbuget20
Holowiecki47
Patel48
Bassan45
Gökbuget36
Bachanova31 Giebel32 Tucunduva33 Wassmann35 Weng50
Yanada51
Wetzler52
Yoon53 Lim54
Short55
2016 106 (73) Pos
2015 116 (112) Neg 2015 63 (60) Pos 2017 78 (78) NA
2016 432 (432) Pos
2016 340 (260) Mix
2014 159 (106) Neg
2014 860 (423) Neg 2012 1648 (580) Neg
2008 131 (116) Neg
2010 161 (161) Neg
2014 304 (141, Neg [98 included
in the analysis])
2014 189 (73) Neg
2014 197 (185) Pos 2010 123 (123) Neg 2014 98 (98) Pos 2005 27 (27) Pos 2013 125 (106) Mix
2008 100 (85) Pos 2014 34 (13) Pos 2016 173 (169) Pos 2016 82 (78) Pos 2016 202 (122) Pos
Pre-HSCT CR1
HSCT NA
Mix NA Mix NA Mix NA
HSCT NA
Mix NA
Mix Mix
Mix Mix Mix Mix
Mix Mix
Mix Mix
Mix Mix
Mix Mix
HSCT NA HSCT High HSCT NA
Targeted NA
Mix NA
Mix NA NA NA HSCT NA Mix NA Targeted NA
Mix NA
Mix Standard/
high Mix Mix
HSCT/ Standard/
Chemo high
≤ 3 months from induction CR1a
≤ 3 months from induction CR1
≤ 3 months from induction CR2 or later
Pre-HSCT CR1
≤ 3 months from induction CR1 ≥ 3 months from induction CR1
≤ 3 months from induction CR1 ≤ 3 months from induction CR1
≤ 3 months from induction CR1 ≤ 3 months from induction CR1
> 3 months from induction CR1
≤ 3 months from induction CR2 or later
Pre-HSCT CR1 Pre-HSCT CR1 Pre-HSCT CR1b Post-HSCT CR1c
≤ 3 months from induction CR1 ≤ 3 months from induction CR1
Included in subgroup analysis
Post-HSCT CR1 Pre-HSCT CR1 ≤ 3 months from induction CR1 ≤ 3 months from induction CR1
> 3 months from induction CR1
> 3 months from inductione CR1
> 3 months from induction CR1
> 3 months from induction/ CR1
pre-HSCTe
Ravandi44,d 2016
Gökbuget20,d 2012
Holowiecki47,d 2008
Patel48,d 2010
340 (260) Mix
1648 (580) Neg
131 (116) Neg
161 (161) Neg
aCR1 65%, CR2 34%, CR3 2%; bCR1 81%, CR2 19%; cCR1 78%, CR2 22%; dStudy included in primary analysis with additional subgroups available for inclusion in subgroup analyses. eMinimal residual disease was assessed at multiple time points, both ≤3 months and >3 months after induction. ALL: acute lymphoblastic leukemia; Central: central laboratory; CR1: first complete remission; CR2: second complete remission; CR3: third complete remission; Chemo: chemotherapy; Flow: flow cytometry; HSCT: hematopoietic stem-cell transplantation; Local: local laboratory; Mix: mixed; MRD: minimum residual disease; NA: not available; Neg: negative; PCR: polymerase chain reaction; Ph: Philadelphia chromosome; Pos: positive; R/R: relapsed and/or refractory; Targeted: targeted agent (e.g., tyrosine kinase inhibitor, blinatumomab, inotuzumab); tx: treatment.
haematologica | 2019; 104(10)
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