SummaryEighty-two children and adolescents who underwent allogeneic transplantation for acute lymphoblastic leukaemia in remission (period 2001-2011, median follow-up 4Á9 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 77Á7% [standard error (SE) 5Á7] and 11Á4% (SE 4Á4), respectively, for patients with pre-transplant MRD <1 9 10 À4 (68%), versus 30Á8% (SE 9Á1; P < 0Á001) and 61Á5% (SE 9Á5; P < 0Á001), respectively, for those with MRD ≥1 9 10 À4 (32%). Pretransplant MRD ≥1 9 10 À4 was associated with a 9Á2-fold risk of relapse [95% confidence interval (CI) 3Á54-23Á88; P < 0Á001] compared with patients with MRD <1 9 10 À4. Patients who received additional chemotherapy pre-transplant to reduce MRD had a fivefold reduction of risk of failure (hazard ratio 0Á19, CI 0Á05-0Á70, P = 0Á01). Patients who experienced MRD positivity post-transplant did not necessarily relapse (5-year EFS 40Á3%, SE 9Á3), but had a 2Á5-fold risk of failure (CI 1Á05-5Á75; P = 0Á04) if any MRD was detected in the first 100 d, which increased to 7Á8-fold (CI 2Á2-27Á78; P = 0Á002) if detected after 6 months. Anticipated immunosuppression-tapering according to MRD may have improved outcome, nevertheless all patients with post-transplant MRD ≥1 9 10 À3 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.

Key Points Low or nondetectable MRD pre-HCT leads to similar outcomes, suggesting that MRD negativity is not an absolute prerequisite for HCT. MRD post-HCT is more important than pre-HCT, and monitoring with sensitive techniques can detect very high-risk patients early.

BackgroundHemophagocytic lymphohistiocytosis is a life-threatening disease. Hematopoietic stem cell transplantation still represents the treatment of choice for most patients with this disease.

In conclusion, our study shows that T-regs represent important immune mediators of the clinical benefits of ECP in patients affected by GvHD.

Eligibility criteria for hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia (ALL) vary according to disease characteristics, response to treatment, and type of available donor. As the risk profile of the patient worsens, a wider degree of HLA mismatching is considered acceptable. A total of 138 children and adolescents who underwent HSCT from HLA-identical sibling donors (MSDs) and 210 who underwent HSCT from matched donors (MDs) (median age, 9 years; 68% male) in 10 countries were enrolled in the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in HSCT for pediatric ALL. The 4-year event-free survival (65 § 5% vs 61 § 4%; P = .287), overall survival (72 § 4% versus 68 § 4%; P = .235), cumulative incidence of relapse (24 § 4% versus 25 § 3%; P = .658) and nonrelapse mortality (10 § 3% versus 14 § 3%; P = .212) were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD graft recipients than in MSD graft recipients (hazard ratio [HR], .38; P = .002), and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood stem cell graft recipients than in bone marrow graft recipients (HR, 2.06; P = .026). Compared with the absence of aGVHD, grade I-II aGVHD was associated with a lower risk of graft failure (HR, .63; P = .042) and grade III-IV aGVHD was associated with a higher risk of graft failure (HR, 1.85; P = .020) and nonleukemic death (HR, 8.76; P < .0001), despite a lower risk of relapse (HR, .32; P = .021). Compared with the absence of cGVHD, extensive cGVHD was associated with a higher risk of nonleukemic death (HR, 8.12; P < .0001). Because the outcomes of transplantation from a matched donor were not inferior to those of transplantation from an HLA-identical sibling, eligibility criteria for transplantation might be reviewed in pediatric ALL and possibly in other malignancies as well. Bone marrow should be the preferred stem cell source, and the addition of MTX should be considered in MSD graft recipients.