Eighty-two children and adolescents who underwent allogeneic transplantation for acute lymphoblastic leukaemia in remission (period 2001-2011, median follow-up 4·9 years) had been assessed for minimal residual disease (MRD) by real-time quantitative polymerase chain reaction before and at 1, 3, 6, 9 and 12 months after transplantation. Five-year event-free survival (EFS) and cumulative incidence of relapse were 77·7% [standard error (SE) 5·7] and 11·4% (SE 4·4), respectively, for patients with pre-transplant MRD <1 × 10(-4) (68%), versus 30·8% (SE 9·1; P < 0·001) and 61·5% (SE 9·5; P < 0·001), respectively, for those with MRD ≥1 × 10(-4) (32%). Pre-transplant MRD ≥1 × 10(-4) was associated with a 9·2-fold risk of relapse [95% confidence interval (CI) 3·54-23·88; P < 0·001] compared with patients with MRD <1 × 10(-4). Patients who received additional chemotherapy pre-transplant to reduce MRD had a fivefold reduction of risk of failure (hazard ratio 0·19, CI 0·05-0·70, P = 0·01). Patients who experienced MRD positivity post-transplant did not necessarily relapse (5-year EFS 40·3%, SE 9·3), but had a 2·5-fold risk of failure (CI 1·05-5·75; P = 0·04) if any MRD was detected in the first 100 d, which increased to 7·8-fold (CI 2·2-27·78; P = 0·002) if detected after 6 months. Anticipated immunosuppression-tapering according to MRD may have improved outcome, nevertheless all patients with post-transplant MRD ≥1 × 10(-3) ultimately relapsed, regardless of immunosuppression discontinuation or donor-lymphocyte-infusion. In conclusion, MRD before transplantation had the strongest impact on relapse and MRD positivity after transplantation, mostly if detected early and at low levels, did not necessarily imply relapse. Additional intensified chemotherapy and modulation of immunosuppression may reduce relapse risk and improve ultimate outcome.

Balduzzi, A., Di Maio, L., Silvestri, D., Songia, S., Bonanomi, S., Rovelli, A., et al. (2014). Minimal residual disease before and after transplantation for childhood acute lymphoblastic leukaemia: is there any room for intervention?. BRITISH JOURNAL OF HAEMATOLOGY, 164(3), 396-408 [10.1111/bjh.12639].

Minimal residual disease before and after transplantation for childhood acute lymphoblastic leukaemia: is there any room for intervention?

BALDUZZI, ADRIANA CRISTINA
Primo
;
DI MAIO, LUCIA;BONANOMI, SONIA;CONTER, VALENTINO;Biondi, A;CAZZANIGA, GIOVANNI ITALO;Valsecchi, M
2014

Abstract

Eighty-two children and adolescents who underwent allogeneic transplantation for acute lymphoblastic leukaemia in remission (period 2001-2011, median follow-up 4·9 years) had been assessed for minimal residual disease (MRD) by real-time quantitative polymerase chain reaction before and at 1, 3, 6, 9 and 12 months after transplantation. Five-year event-free survival (EFS) and cumulative incidence of relapse were 77·7% [standard error (SE) 5·7] and 11·4% (SE 4·4), respectively, for patients with pre-transplant MRD <1 × 10(-4) (68%), versus 30·8% (SE 9·1; P < 0·001) and 61·5% (SE 9·5; P < 0·001), respectively, for those with MRD ≥1 × 10(-4) (32%). Pre-transplant MRD ≥1 × 10(-4) was associated with a 9·2-fold risk of relapse [95% confidence interval (CI) 3·54-23·88; P < 0·001] compared with patients with MRD <1 × 10(-4). Patients who received additional chemotherapy pre-transplant to reduce MRD had a fivefold reduction of risk of failure (hazard ratio 0·19, CI 0·05-0·70, P = 0·01). Patients who experienced MRD positivity post-transplant did not necessarily relapse (5-year EFS 40·3%, SE 9·3), but had a 2·5-fold risk of failure (CI 1·05-5·75; P = 0·04) if any MRD was detected in the first 100 d, which increased to 7·8-fold (CI 2·2-27·78; P = 0·002) if detected after 6 months. Anticipated immunosuppression-tapering according to MRD may have improved outcome, nevertheless all patients with post-transplant MRD ≥1 × 10(-3) ultimately relapsed, regardless of immunosuppression discontinuation or donor-lymphocyte-infusion. In conclusion, MRD before transplantation had the strongest impact on relapse and MRD positivity after transplantation, mostly if detected early and at low levels, did not necessarily imply relapse. Additional intensified chemotherapy and modulation of immunosuppression may reduce relapse risk and improve ultimate outcome.
No
Articolo in rivista - Articolo scientifico
Scientifica
Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Combined Modality Therapy; Humans; Prognosis; Child; acute lymphoblastic leukaemia; Child, Preschool; Infant; minimal residual disease; relapse; Treatment Outcome; Hematopoietic Stem Cell Transplantation; Neoplasm Recurrence, Local; childhood; allogeneic transplantation; Adolescent; Male; Female
English
396
408
13
Balduzzi, A., Di Maio, L., Silvestri, D., Songia, S., Bonanomi, S., Rovelli, A., et al. (2014). Minimal residual disease before and after transplantation for childhood acute lymphoblastic leukaemia: is there any room for intervention?. BRITISH JOURNAL OF HAEMATOLOGY, 164(3), 396-408 [10.1111/bjh.12639].
Balduzzi, A; DI MAIO, L; Silvestri, D; Songia, S; Bonanomi, S; Rovelli, A; Conter, V; Biondi, A; Cazzaniga, G; Valsecchi, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/53563
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