Poster Display Malignancy and PID

LONG-TERM ENZYME REPLACEMENT THERAPY (ERT) IN ADA-SCID PATIENTS: THE SHADOW OF MALIGNANCIES

Lecture Time
10:27 - 10:28
Presenter
  • Fulvio Porta, Italy
Room
Poster Area
Date
20.09.2019, Friday
Session Time
10:00 - 17:00
Board Number
78
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

ADA-SCID is a rare disease(10-15% of SCID) due to the mutations of the ADA-gene resulting in the accumulation of high systemic levels of ADA toxic metabolites.There are 3 treatment options:HSCT from matched sibling donor(the best therapeutic options), Enzyme Replacement Therapy(ERT) with PEG-ADA to manage disease in short term, autologous Gene Therapy(GT) or allogeneic HSCT from MUD/parents.Long term ERT is a therapeutic options although with time long-term immune reconstitution may be sub-optimal in some patients.

Methods

In our center 29 ADA patients were diagnosed,of which three were treated with ERT from diagnosis.

Results

The patients were diagnosed early:1 prenatal diagnosis, at 2 months and 3 months of age.They started immediately ERT.Median time of ERT follow up is 20 years.They are well detoxified(median value of %dAXP is 0.65%), but have very low level of lymphocytes.An approach to correct the immunological situation by GT with peripheral stem cells, considering the bone marrow stem cell exhaustion in these patients, was hypothesized but was inapplicable.At diagnosis, approximately 20 years ago, gene therapy wasn’t a consolidates therapy and ERT seemed the more solid therapeutic option.In the process of programming HSCT, unfortunately, one of these patients has developed plasmablastic lymphoma after 21 years of ERT.Last follow up shows 12/mm3 CD3+, 10/mm3 CD19+ and %dAXP 1.7%.

Conclusions

Our experience shows that ERT gives a good therapeutic option as bridge therapy for HSCT.For patients in long-term ERT, would be beneficial the use of the newly approved recombinant PEG-ADA.Nevertheless strict monitoring would be necessary to check the results of this new therapeutical approach.

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