Paediatric Immunohaematology

Ospedale San Raffaele



  • Paediatric Immunology
  • Paediatric Haematology
  • Neuropediatric Metabolic Diseases


  • 15-20 gene therapy/transplantations

The Paediatric Immunohematology Unit is a centre of excellence for the treatment of genetic blood disorders by gene and cell therapy. The Unit deals with the diagnosis and treatment of children affected by haematological, immunological and metabolic diseases with neurological involvement, with particular regard to genetic diseases. The centre is composed of a highly specialized team with a long experience in the diagnosis, research and treatment of patients suffering from genetic diseases. The Unit is the Reference Centre for the diagnosis of Primary Immunodeficiency Disease (PID) and other paediatric haematological diseases.

The Unit actively collaborates with the San Raffaele’s Telethon Institute for Gene Therapy (SR-Tiget) for the clinical application of the experimental protocols of gene and cell therapy and is part of the Stem Cells Programme for the transplantation of hematopoietic stem cells. Clinical and research activity is documented by a large number of publications in national and international scientific journals.

The Unit’s activity is divided into the following specialized branches:

  • Paediatric immunology
    • Primitive immunodeficiency
    • Autoimmune diseases
  • Paediatric haematology
    • platelet diseases
    • Anaemias
    • Neutropenia
  • Neuropediatric metabolic diseases



Inherited Genetic Disorders

In the recent years, hematopoietic stem cell (HSC) gene therapy (GT) has become an attractive therapeutic strategy for inherited genetic disorders, offering several potential advantages over allogeneic hematopoietic stem cell transplantation.

Adenosine deaminase - severe combined immunodeficiency (ADA-SCID)

Since 2000, more than 80 patients affected by adenosine deaminase - severe combined immunodeficiency (ADA-SCID), Wiskott-Aldrich Syndrome (WAS), Metachromatic Leukodystrophy (MLD), and Beta-thalassemia (BTHAL) have been treated with ex-vivo hematopoietic stem cell gene therapy at the Unit. Outcome of the first 18 ADA-SCID patients treated with hematopoietic stem cell gene therapy showed 100% survival with improved metabolic functions and immune recovery, leading to reduction in infections, in the absence of leukemic transformation.1  GT for adenosine deaminase - severe combined immunodeficiency (Strimvelis) is the first ex vivo hematopoietic stem cell gene therapy approved worldwide, that is being administered to ADA-SCID patients only at Ospedale San Raffaele. In 2016 marketing authorization for ADA-SCID GT was granted to GlaxoSmithKline Healthcare (GSK) by the European Medicine Agency; current license holder is Orchard Therapeutics.

Metachromatic Leukodystrophy (MLD)

Data on this ongoing experimental treatment is also very encouraging. A recent ad-hoc analyses of early-onset Metachromatic leukodystrophy (MLD) patients who received treatment in the pre-symptomatic or very early-symptomatic stage showed evidence of safety and therapeutic benefit in terms of motor and cognitive functions.2

Wiskott-Aldrich Syndrome

Wiskott-Aldrich Syndrome patients treated with GT showed improvement in immune functions and platelet counts, with reduction in severe infections and severe-moderate bleeding episodes and improvement of eczema (Ferrua, Cicalese, et al., ESID 2016).


Preliminary data on the clinical trial for beta thalassemia suggests that GT is well tolerated and leads to significantly reduced transfusion requirement (Marktel et al., ASH 2017).

Mucopolysaccharidosis type I–Hurler syndrome (MPS-IH)

A new clinical trial is ongoing for Mucopolysaccharidosis type I–Hurler syndrome (MPS-IH), a lysosomal storage disease caused by a deficiency of the lysosomal enzyme α-L-iduronidase (IDUA). Without treatment, the disease is characterized by progressive multisystem morbidity and current therapeutic strategies provide little or partial benefit. Patients will receive infusion of autologous hematopoietic stem cells transduced with a lentiviral vector driving the expression of supra-normal levels of IDUA enzyme. This approach has been shown to be safe and efficacious in the MPS-I mouse preclinical model (Visigalli et al., 2010).

Additional Information & Research Activity

Other studies ongoing to improve the knowledge of genetic diseases include the natural history study for Metachromatic leukodystrophy (MLD), advanced diagnosis and natural history of primary immunodeficiency and immune dysregulation disorder, and immune reconstitution after hematopoietic stem cell transplantation for genetic disorders.

The Paediatric Immunohematology Unit has dedicated spaces and personnel, including physician-scientists, haematologists, paediatricians, resident fellows in Paediatrics, physiotherapists, psychologists, and research nurses. The Unit acts in strict cooperation with the San Raffaele Stem Cell Programme (Head Prof. Fabio Ciceri) and the San Raffaele Telethon Institute for Gene Therapy. The Unit has received JACIE accreditation, is UNI‐ENO ISO 9001 certified as part of the San Raffaele Stem Cell Program, accredited by the Italian Paediatric Haematology‐Oncology Association (AIEOP) and is a Referral Centre for the diagnosis of primary immunodeficiency and other paediatric haematological disorders. It has adopted the diagnostic and therapeutic protocols of AIEOP, the Italian Network for Primary Immunodeficiency (IPINET) and the European Blood and Marrow Transplant Group (EBMT).

Moreover, the Unit has all the expertise for carrying in-house advanced therapies-based clinical trials in paediatric patients according to Good Clinical Practice (GCP). The Unit has access to 3 paediatric inpatient rooms (with filtered air and isolation) in the BMT Unit, as well as 4 Day Hospital beds and an outpatient clinic in a dedicated building within the Paediatric Department. Children who do not need special isolation are hospitalized in the Paediatrics Unit, which hosts 50 beds, 40 for children and 10 for new-borns. The outpatient activities are carried out in three different clinics: one for immunological, one for haematological, and one for rare neurological disorders.



The Unit’s diagnostic and research laboratories equipment allows the most precise diagnosis of immunological and haematological defects, i.e. genetic investigations (next generation sequencing, in collaboration with the laboratory of molecular clinical biology), flow cytofluorimetry, functional tests.

The SR-Tiget Clinical Lab is a certified laboratory, in which tests required for clinical trial endpoints are performed following GCLP requirements. The SR-Tiget Clinical Lab can perform tests for all phases Clinical Trials, including phase I trials.



1(Cicalese, Ferrua et al., Blood, 2016)
2(Sessa, Lorioli et al., Lancet 2016)