Summary This study investigated the efficacy of a pre‐emptive strategy based on the combination of Epstein–Barr virus (EBV) viraemia and poor T cell reconstitution in preventing post‐transplant lymphoproliferative disease (PTLD) following T cell depleted stem cell transplant (SCT). EBV viral load and immune reconstitution were prospectively monitored in 70 consecutive children undergoing SCT following reduced intensity conditioning with alemtuzumab. Patients who developed significant EBV viraemia (>40 000 copies/ml blood) were treated pre‐emptively with rituximab if they were within 3 months of SCT or their CD3 count was <0·3 × 109/l. Of 20/70 patients who developed significant EBV viraemia, 13 received pre‐emptive rituximab. The incidence of PTLD was significantly reduced in the pre‐emptive cohort compared to historical controls (1·4% vs. 21·7%, P = 0·003). This difference was more marked among viraemic patients (2·7% vs. 62·5%P < 0·0001). Patients treated with rituximab demonstrated significantly delayed B cell reconstitution at 1 year post‐SCT but this was not associated with an increase in infectious mortality. In 6/6 patients >3 months post‐SCT who had a CD3 count >0·3 × 109/l, reduced immunosuppression only resulted in successful resolution of EBV viraemia without PTLD. This strategy is safe and highly effective in preventing PTLD following T cell depleted SCT, and directs rituximab therapy to patients at highest risk of this complication.

SummaryTreosulfan is an immuno-suppressive and myeloablative alkylating agent that has been introduced as a conditioning agent in stem cell transplantation (SCT). Most studies have been performed in adult patients with malignancy where a low incidence of regimen-related toxicity has been reported. We report the use of treosulfan in 32 consecutive children undergoing SCT for non-malignant disease. Patients received a total treosulfan dose of 36 or 42 g/m 2 /patient given in three daily, divided doses. A range of other conditioning agents and serotherapy was administered to patients who underwent family donor SCT (n = 11), or unrelated donor SCT (n = 21). One patient (3%) died early. Transplant morbidity was limited and mucositis was only mild. Dermatological toxicity was frequent but mild. Twenty-eight patients (87AE5%) established donor cell engraftment. In 25 patients (78%) there was adequate, stable donor engraftment. Four patients have required additional transplant procedures to maintain adequate donor-derived haemopoiesis. Twenty-seven patients (84%) survive with a median follow up of 417 d. There were four late deaths due to progression of the underlying disease, graft-versus-host disease or infection. Treosulfan-based conditioning regimens achieve excellent engraftment with reduced regimen-related toxicity in children with non-malignant disease at high risk for both regimen-related toxicity and graft failure.

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Juvenile myelomonocytic leukemia (JMML) is a rare pediatric malignancy. Hematopoietic stem cell transplantation (SCT) is the only curative approach. However, relapse after SCT remains the major cause of treatment failure. Unlike most other pediatric malignancies, JMML may be susceptible to a graft-versus-leukemia (GVL) effect, although, unlike chronic myeloid leukemia, reports of response to donor lymphocyte infusions (DLIs) remain scanty. This is the first report that describes the successful treatment of relapsed JMML with DLI in the absence of further chemotherapy and provides definite proof of a GVL effect in JMML. (Blood.

The broader application of stem cell transplantation (SCT) for paediatric diseases has been limited by a lack of human leucocyte antigen (HLA)-matched donors. Virtually all children, however have at least one haploidentical parent who could serve as a donor. Such a donor is immediately available and the considerable costs of additional HLA typing, registry and banking expenditures that are necessary to procure an unrelated donor, could be reduced. Recent technological advances appear to have overcome the historical problems of graft rejection and severe graft versus host disease in the haploidentical setting, and in the latest studies the overall survival for children undergoing haploidentical SCT for leukaemia is now comparable with that following unrelated donor bone marrow or cord blood transplantation. Posttransplant infectious complications and leukaemia relapse remain the most important barriers yet to overcome, and new directions in the use of adoptive cellular immunity appear to be promising in this respect. Haploidentical SCT is now a viable option for those children who do not have an HLA compatible sibling or fully matched unrelated donor. The relative merits of a haploidentical family donor versus mismatched unrelated bone marrow or cord blood donation needs to be assessed in prospective, randomized clinical trials.