Fanconi Syndrome
Conditions
Brief summary
This observational protocol will allow for an independent, prospective evaluation of the improvement in survival of patients with Fanconi disease in hematological deadlock due to the absence of an HLA-identical donor and having received a haploidentical transplant.
Detailed description
Fanconi's disease is characterised by a constitutional defect in DNA repair which results in the occurrence of bone marrow failure and haematological malignancies, mainly myeloid: at the age of 40, the cumulative incidence of these two types of pathology reaches almost 100%. The only curative treatment for haemtalogocial diseases is allogenic hematopoietic stem cell transplant. Transplantation modalities must be adapted to the particular susceptibility of these patients to DNA bridging agents and radiotherapy. HSC transplantation is indicated with an unaffected matched related or matched unrelated donor when the patient has severe bone marrow failure or a poor prognostic clonal evolution (cytogenetic evolution or proven haemopathy). Alternative transplants (9/10 pheno-identical, haplo-identical and placental blood donors) were no longer proposed in most cases due to the frequency of severe complications (graft-versus-host disease, viral infections) and the catastrophic medium-term survival of around 40% (Dufort, Bone Marrow Transplant 2012, Gluckman Biol Blood Marrow Transplant. 2007). The development over the last decade of new haploidentical or phenoidentical 9/10 transplant protocols with unmodified grafts and GVH prophylaxis with post-transplant cyclosphosphamide or ex vivo T-depletion adapted to the particular susceptibility of patients with Fanconi disease has reduced the incidence of these severe complications. This observational protocol will allow for an independent, prospective evaluation of the improvement in survival of patients with Fanconi disease in hematological deadlock due to the absence of an HLA-identical donor and having received a haploidentical transplant
Interventions
OTHERBlood sampling
Additional blood samples at J100, M6, M12, M24
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Months to 60 Years
Inclusion criteria
* Diagnosis of Fanconi disease confirmed by chromosome breakage test and/or genetic analysis * aged between 6 months and 60 years * with severe pancytopenia (2 of the following criteria: reticulocytes \< 60 G/L, PNN \< 0.5 G/L and/or platelets \< 20 G/L or patients with more than 6 transfusions in the last 12 months) * with clonal progression (poor prognostic cytogenetics, myelodysplastic syndrome or acute leukaemia) * with an unaffected haploidentical donor * having signed the consent after having read the information note, consent of both parents for minors, of the guardian for patients under guardianship * having a social security scheme (beneficiary or entitled person)
Exclusion criteria
* with an unaffected matched related or HLA 10/10 matched unrelated donnor * under guardianship
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival Rate | 2 years after transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Engraftment | At day 100 | Engraftment at least 3 consecutive days with neutrophils \> 0.5 G/L and 7 consecutive days with platelets \> 20 G/L, with predominantly whole blood donor chimerism |
| Absolute neutrophils count | At 1 month | — |
| Absolute number of platelets | At 1 month | — |
| Incidence of grade 2 to 4 Acute Graft versus Host Disease | At 3 months | — |
| Incidence of Acute cortico-resistant Graft versus Host Disease | At 3 months | — |
| Incidence of Chronic Graft versus Host Disease | At 24 months | — |
| Incidence of relapse | At 12 months | — |
| Progression free survival | At 12 months | — |
| Incidence of reactivation of cytomegalovirus infection | At 12 months | — |
| Incidence of reactivation of Epstein Barr virus infection | At 12 months | — |
| Graft-versus-host disease-free, relapse-free survival (GRFS) | At 24 months | — |
| Incidence of cardiac toxities | At 12 months | — |
| Overall survival | At 12 months | — |
| Quality of Life questionnaire for adults | At inclusion | Quality of life will be assessed for adult using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ) EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. |
| Quality of life questionnaire for minors | At inclusion | Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning. |
| Rate of chimerism | At 1 month | — |
| Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood | 3 months after transplant | — |
| Ferritine levels | At 3 months | — |
| Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE) | At 3 months | — |
Contacts
Primary ContactFlore Sicre de Fontbrune, Dr
Backup ContactMatthieu RESCHE-RIGON, Pr
Outcome results
None listed