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Different molecular levels of post-induction minimal residual disease may predict hematopoietic stem cell transplantation outcome in adult Philadelphia-negative acute lymphoblastic leukemia.

Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Peruta B, Borlenghi E, Pogliani EM, Di Bona E, Cassibba V, Scattolin AM, Romani C, Ciceri F, Cortelezzi A, Gianfaldoni G, Mattei D, Audisio E, Rambaldi A - Blood Cancer J (2014)

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Affiliation: 1] UOC Ematologia, Ospedale dell'Angelo, Mestre-Venezia, Italy [2] USC Ematologia, Ospedale Papa Giovanni XXIII, Bergamo, Italy.

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the risk-oriented application of allogeneic stem cell transplantation (allo-SCT) in patients who remain MRD-positive (MRD+) following induction and consolidation study by the strong statistical correlation between MRD TP1 and TP2/3 results... P=0.03), respectively... RI was 43% compared with 69% (n=11) (P=0.08 and 0.05), and a RI of 23% compared with 64% (P=0.09) (Figures MRD+ patients were rescued by an allo-SCT correlated with post-induction the last consolidation course... The study conclusions are that in terms of RI the outcome (MR2) did very badly even after an allo-SCT, although this was of transplantation failure, obtainable well ahead of SCT by studying post-induction MRD, and therefore most useful for an effective SCT planning, net of several confounding a MR2 profile, further intensification of chemotherapy is not expected to be

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Outcomes by quantitative MRD ranges. Shown are long-term survival, DFS and RIrates according to MRD quantitative ranges and SCT therapy (6-year probability isgiven for each group). (a–c) All patients with MRD study(n=136): CMR (n=64) 0.73, 0.63, 0.36; MR(n=21) 0.57, 0.52, 0.33; MR1 (n=17)0.53, 0.47, 0.50; MR2 (n=34), 0.24, 0.15, 0.76.(d–f), MRD+ patients receiving allo/auto-SCT(n=43): MR/MR1 (n=24) 0.50,0.46, 0.43; MR2 (n=19) 0.26, 0.16, 0.69.(g–i) MRD+ patients receiving allo-SCT(n=26): MR/MR1 (n=15) 0.60, 0.60,0.23; MR2 (n=11), 0.27, 0.18, 0.64.
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fig1: Outcomes by quantitative MRD ranges. Shown are long-term survival, DFS and RIrates according to MRD quantitative ranges and SCT therapy (6-year probability isgiven for each group). (a–c) All patients with MRD study(n=136): CMR (n=64) 0.73, 0.63, 0.36; MR(n=21) 0.57, 0.52, 0.33; MR1 (n=17)0.53, 0.47, 0.50; MR2 (n=34), 0.24, 0.15, 0.76.(d–f), MRD+ patients receiving allo/auto-SCT(n=43): MR/MR1 (n=24) 0.50,0.46, 0.43; MR2 (n=19) 0.26, 0.16, 0.69.(g–i) MRD+ patients receiving allo-SCT(n=26): MR/MR1 (n=15) 0.60, 0.60,0.23; MR2 (n=11), 0.27, 0.18, 0.64.

Mentions: The study enrolled 304 patients with Ph− ALL (Table1). Two-hundred fifty-eight entered CR (85%). Sensitive molecularprobe(s) were available for 200 CR patients (77.5%). Of these, 141 completedconsolidation (70.5%) and 59 did not because of early SCT (n=13),relapse (n=41) and treatment toxicity (n=5). One-hundredthirty-six of 141 evaluable patients completed the MRD study: 76 were classifiedMRD− (56%) and 60 MRD+ (44%) (Supplementary Figure S2). Forty-three of the 60 MRD+ patients(71.6%) underwent SCT as per protocol design (26 allo-SCT, 17‘hypercycles' with auto-SCT) after a median of 2.2 months from the lastconsolidation cycle (range 0.5–15.4 months). Allo-SCT was from unrelated andsibling donors in 14 and 12 patients; and the stem cell source was bone marrow in 11,peripheral blood in 13 and cord blood in 2 patients, respectively. Long-term studyresults are available in Supplementary Figure S3,including outcomes according to clinical risk class. According to the current analysis,there were 64 CMR patients (47%), 21 MR patients (15.5%), 17MR1patients (12.5%) and 34 MR2 patients (25%). Notably, these wereall distinct subjects, summing up to the total of 136 MRD-evaluable cases, with nooverlapping across different MRD subgroups. Therefore, all CMR-negative patients wereMRD− at all evaluable TPs, and as such were excluded from allo-SCT by design(Table 1). Apart from that, a proportion of the remainingpatients could express lower MRD levels at some TP, a finding that was progressivelyless frequent from MR1 to MR2 patients (<10% CMR and20% MR at another TP) and affected mainly different individuals, suggestingconsistency of the MRD risk reclassification, as already indicated in this clinicalstudy by the strong statistical correlation between MRD TP1 and TP2/3results.2 After a minimum observation of4 years and a maximum close to 13.5 years, estimated 6-year survival and DFS ratesranged from 73% and 64% in CMR patients to 24% and 15% inMR2 patients, respectively, mostly in relation with an increasing RI(Figures 1a–c, all Ps <0.0001), exceptfor CMR and MR groups. Although 6-year DFS was improved following allo-SCT in MRD+patients (42% versus 18% with auto-SCT, P=0.035; Supplementary Figure S4), posttransplantation outcome wassensibly affected by post-induction MRD level (Figures1d–f). Notably, SCT results were superimposable in MR andMR1 groups (not shown), with a cumulative survival and DFS rate of46% and 50% (n=24) compared with 16% and 26%in MR2 patients (n=19) (P=0.02 andP=0.03), respectively. RI was 43% compared with 69%(P=0.16). The best overall results were observed after allo-SCT inMR/MR1 patients, with cumulative survival and DFS rates of 60%(n=15) compared with 27 and 18% in MR2 subset(n=11) (P=0.08 and 0.05), and a RI of 23%compared with 64% (P=0.09) (Figures1g–i).


Different molecular levels of post-induction minimal residual disease may predict hematopoietic stem cell transplantation outcome in adult Philadelphia-negative acute lymphoblastic leukemia.

Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Peruta B, Borlenghi E, Pogliani EM, Di Bona E, Cassibba V, Scattolin AM, Romani C, Ciceri F, Cortelezzi A, Gianfaldoni G, Mattei D, Audisio E, Rambaldi A - Blood Cancer J (2014)

Outcomes by quantitative MRD ranges. Shown are long-term survival, DFS and RIrates according to MRD quantitative ranges and SCT therapy (6-year probability isgiven for each group). (a–c) All patients with MRD study(n=136): CMR (n=64) 0.73, 0.63, 0.36; MR(n=21) 0.57, 0.52, 0.33; MR1 (n=17)0.53, 0.47, 0.50; MR2 (n=34), 0.24, 0.15, 0.76.(d–f), MRD+ patients receiving allo/auto-SCT(n=43): MR/MR1 (n=24) 0.50,0.46, 0.43; MR2 (n=19) 0.26, 0.16, 0.69.(g–i) MRD+ patients receiving allo-SCT(n=26): MR/MR1 (n=15) 0.60, 0.60,0.23; MR2 (n=11), 0.27, 0.18, 0.64.
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fig1: Outcomes by quantitative MRD ranges. Shown are long-term survival, DFS and RIrates according to MRD quantitative ranges and SCT therapy (6-year probability isgiven for each group). (a–c) All patients with MRD study(n=136): CMR (n=64) 0.73, 0.63, 0.36; MR(n=21) 0.57, 0.52, 0.33; MR1 (n=17)0.53, 0.47, 0.50; MR2 (n=34), 0.24, 0.15, 0.76.(d–f), MRD+ patients receiving allo/auto-SCT(n=43): MR/MR1 (n=24) 0.50,0.46, 0.43; MR2 (n=19) 0.26, 0.16, 0.69.(g–i) MRD+ patients receiving allo-SCT(n=26): MR/MR1 (n=15) 0.60, 0.60,0.23; MR2 (n=11), 0.27, 0.18, 0.64.
Mentions: The study enrolled 304 patients with Ph− ALL (Table1). Two-hundred fifty-eight entered CR (85%). Sensitive molecularprobe(s) were available for 200 CR patients (77.5%). Of these, 141 completedconsolidation (70.5%) and 59 did not because of early SCT (n=13),relapse (n=41) and treatment toxicity (n=5). One-hundredthirty-six of 141 evaluable patients completed the MRD study: 76 were classifiedMRD− (56%) and 60 MRD+ (44%) (Supplementary Figure S2). Forty-three of the 60 MRD+ patients(71.6%) underwent SCT as per protocol design (26 allo-SCT, 17‘hypercycles' with auto-SCT) after a median of 2.2 months from the lastconsolidation cycle (range 0.5–15.4 months). Allo-SCT was from unrelated andsibling donors in 14 and 12 patients; and the stem cell source was bone marrow in 11,peripheral blood in 13 and cord blood in 2 patients, respectively. Long-term studyresults are available in Supplementary Figure S3,including outcomes according to clinical risk class. According to the current analysis,there were 64 CMR patients (47%), 21 MR patients (15.5%), 17MR1patients (12.5%) and 34 MR2 patients (25%). Notably, these wereall distinct subjects, summing up to the total of 136 MRD-evaluable cases, with nooverlapping across different MRD subgroups. Therefore, all CMR-negative patients wereMRD− at all evaluable TPs, and as such were excluded from allo-SCT by design(Table 1). Apart from that, a proportion of the remainingpatients could express lower MRD levels at some TP, a finding that was progressivelyless frequent from MR1 to MR2 patients (<10% CMR and20% MR at another TP) and affected mainly different individuals, suggestingconsistency of the MRD risk reclassification, as already indicated in this clinicalstudy by the strong statistical correlation between MRD TP1 and TP2/3results.2 After a minimum observation of4 years and a maximum close to 13.5 years, estimated 6-year survival and DFS ratesranged from 73% and 64% in CMR patients to 24% and 15% inMR2 patients, respectively, mostly in relation with an increasing RI(Figures 1a–c, all Ps <0.0001), exceptfor CMR and MR groups. Although 6-year DFS was improved following allo-SCT in MRD+patients (42% versus 18% with auto-SCT, P=0.035; Supplementary Figure S4), posttransplantation outcome wassensibly affected by post-induction MRD level (Figures1d–f). Notably, SCT results were superimposable in MR andMR1 groups (not shown), with a cumulative survival and DFS rate of46% and 50% (n=24) compared with 16% and 26%in MR2 patients (n=19) (P=0.02 andP=0.03), respectively. RI was 43% compared with 69%(P=0.16). The best overall results were observed after allo-SCT inMR/MR1 patients, with cumulative survival and DFS rates of 60%(n=15) compared with 27 and 18% in MR2 subset(n=11) (P=0.08 and 0.05), and a RI of 23%compared with 64% (P=0.09) (Figures1g–i).

View Article: PubMed Central - PubMed

Affiliation: 1] UOC Ematologia, Ospedale dell'Angelo, Mestre-Venezia, Italy [2] USC Ematologia, Ospedale Papa Giovanni XXIII, Bergamo, Italy.

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the risk-oriented application of allogeneic stem cell transplantation (allo-SCT) in patients who remain MRD-positive (MRD+) following induction and consolidation study by the strong statistical correlation between MRD TP1 and TP2/3 results... P=0.03), respectively... RI was 43% compared with 69% (n=11) (P=0.08 and 0.05), and a RI of 23% compared with 64% (P=0.09) (Figures MRD+ patients were rescued by an allo-SCT correlated with post-induction the last consolidation course... The study conclusions are that in terms of RI the outcome (MR2) did very badly even after an allo-SCT, although this was of transplantation failure, obtainable well ahead of SCT by studying post-induction MRD, and therefore most useful for an effective SCT planning, net of several confounding a MR2 profile, further intensification of chemotherapy is not expected to be

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