Image of stem cells and a needle to simulate stem cell treatment or transplantation
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Adjusting dosage of the pre-transplant drug anti-thymocyte globulin (ATG) to better take into account factors such as bodyweight, lymphocyte cell counts before the first dose, and the source of the stem cells being used for transplantation can improve outcomes for children undergoing stem cell transplants.

The researchers, based at the Princess Máxima Center for Pediatric Oncology in Utrecht and funded by big pharma Sanofi, found that approximately 80% of the children in their study achieved CD4+ immune reconstitution compared with a rate of around 62% in previous studies that did not apply such a personalized approach.

ATG is given to patients prior to stem cell transplants in order to prevent transplant rejection and graft versus host disease (GVHD), a potentially life-threatening inflammatory reaction to transplantation. However, it has very variable pharmacokinetics and overexposure to ATG can also be damaging and reduce the chance of a graft being successful.

“The better the immune system recovers after a transplant, the better a child’s chances of survival. We suspected that too high a dose and wrong timing of giving a child ATG, one of the drugs that helps prepare for a stem cell transplant, could hinder the recovery of the donor immune cells,” said Caroline Lindemans, a pediatrician specialized in stem cell transplants at the Princess Máxima Center who co-led the study, in a press statement.

To test if personalized dosing of ATG could help improve transplant success, Lindemans and colleagues carried out a study including 58 children undergoing haematopoietic stem-cell transplantation (HSCT) for treatment for cancer or some kind of immune deficiency or disorder.

The children were given a dose of ATG appropriate for their bodyweight and also that took absolute lymphocyte counts before the first dose and the stem cell source into account. Cumulative doses varied between 2–10 mg/kg.

As reported in The Lancet Haematology, a total of 51 children were eligible for inclusion in the final analysis. CD4+ immune reconstitution within 100 days of transplantation in 71% of evaluable participants was the primary endpoint. Overall, 41 of 51 children met this endpoint equating to 80% of the cohort.

“In a previously described cohort of 258 patients, the proportion of patients who reached immune reconstitution within day 100 after HSCT was 62%,” write the authors.

There seemed to be no difference in outcome for patients who received stem cells from different sources. Of the total cohort, two patients died from GVHD. Overall, adverse events were mostly infections or immune disorders. Seven patients died from infections and five from immune disorders.

The researchers were happy with the improvement in outcomes.  “As we had hoped, our results show that an individual dose of ATG leads to better immune recovery. The risk was that the donor stem cells would be rejected in more children, but fortunately that turned out not to be the case. Our research therefore shows this method of dosing medicines makes stem cell transplants safer,” concluded Lindemans.

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