12 de Octubre University Hospital

In the context of World AIDS Day, which is celebrated on 1 December, it is essential to reflect on one of the most urgent challenges in the fight against this disease: HIV in the paediatric population. A project led by the Complutense University of Madrid seeks to reduce paediatric mortality by training research leaders in sub-Saharan Africa and applying technology and innovation.

CAR-T cell-based treatments have been successful against some blood tumours, but are much less effective for solid tumours. A phase 1 clinical trial has tested their use in 11 children and young adults with diffuse midline glioma, a tumour of the nervous system that is considered incurable. The results, published in the journal Nature, indicate that the treatment improved functional status in nine of the 11 patients. One of the four who showed a strong response is still healthy four years later.

The regulatory agencies for medicines in the United States and Europe have issued statements informing about a possible risk of developing certain types of tumors following CAR-T cell immunotherapy treatment. What do we know so far? What is the real risk? Does the benefit-risk balance still hold? Has anything changed after these alerts? We answer these questions with expert opinions and the data currently available. 

Cancer immunotherapy, and in particular the so-called checkpoint inhibitors, have improved the prognosis of several types of tumours. However, they are not effective in everyone. Two early-stage clinical trials have tested the addition of a type of immunomodulator to this therapy in patients with lung cancer and Hodgkin's lymphoma, with apparent good results. The results are published in the journal Science.  

CAR-T cell therapies may, in some cases, produce tumours secondary to treatment. A few months ago, the US Food and Drug Administration (FDA) said it was assessing this risk. Now, a study conducted at Stanford University Medical Center (USA) has tracked 724 patients who received this type of treatment since 2016. Of these, 14 developed another blood tumour, but only one was a T-cell lymphoma that could be a direct consequence of the therapy. Further analysis ruled out this link. The results are published in the journal NEJM. 

A study carried out in two hospitals in Denmark has compared the brain health of 120 patients admitted for covid over 18 months with that of other hospitalized patients with similar severity due to pneumonia, heart attack or need for intensive care, as well as with healthy people. The conclusions are that patients with covid worsened with respect to the latter, but did so in a similar way to other hospitalized persons. According to the authors, "although studies are needed to confirm these findings, brain health after covid-19 appears generally comparable to that of other diseases of similar severity."

A meta-analysis, pooling the results of 40 previous studies - involving more than 310,000 children and adolescents in total - concludes that treatment rates for mental disorders in these age groups are "generally low, especially for depression and anxiety". The research, published in JAMA Network Open, shows that the treatment rate for any mental disorder is 38%, ranging from 31% for anxiety, 36% for depression, 49% for conduct disorders and 58% for attention deficit hyperactivity disorder (ADHD).

A phase 2 clinical trial has analysed the safety and efficacy of adding immunotherapy to traditional chemotherapy to treat a subtype of acute lymphoblastic leukaemia in children under one year of age. This subtype of leukaemia, although rare in absolute terms, is the most common in children of this age, and its prognosis in this age group had not improved in recent years. The immunotherapy used, a bispecific antibody that binds to tumour cells on the one hand and T lymphocytes on the other, improved two-year survival from 66% to 93% in treated patients, according to The New England Journal of Medicine (NEJM).

Approved therapies to treat various tumours using CAR-T cells are based on the modification of the patient's own lymphocytes in the laboratory, which delays their administration. A phase 1 clinical trial has used ready-made donor cells to treat patients with multiple myeloma. The results are published in the journal Nature Medicine.

Two preclinical studies published in the journal Science have introduced new bioengineered modifications to CAR-T cells in an attempt to make them more potent and safer in their anti-tumour action. These variations allow their activity to be enhanced only in the vicinity of the tumour or their actions to be regulated on demand.