Comparative Health Status and Quality of Life of Patients With Sickle Cell Disease (SCD) Who Underwent Matched-sibling Hematopoietic Stem Cell Transplantation Versus Non Transplanted SCD Case-control Patients (TRANSPLANTORN2)

The long term burden of morbidity and mortality in the natural history of sickle cell disease has not been compared up to date to the risks and mortality of a curative option like bone marrow transplantation in severe sickle-cell disease patients. Given this lack of data, primary-care Sickle Cell Disease (SCD) physicians and transplant physicians are prevented from a factual debate over the benefit/risk ratio for each patient and refining indications of transplant in patients. Therefore, the present study seeks to describe and compare the very long-term outcomes after either Human Leukocyte Antigen (HLA) -matched sibling transplantation (study arm) and "non-transplant care" for severe sickle cell disease SCA patients in order to yield robust comparative data regarding both arms.

The main objective is to assess the benefit of Hematopoietic stem cell transplantation (HSCT) regarding quality of life compared to standard care after 10 years, in patients with severe Sickle Cell Disease (SCD).

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Other: Spermogram; Other: Hospital Anxiety and Depression Scale (HADS); Other: SF36 Quality of life questionnaire; Other: Psychologist interview; Other: Optional sera banking; Other: Optional DNA banking

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, Pr; Phone Number: +33142499742; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Jean-Hugues Dalle, Pr; Phone Number: +33140033692; Email: jean-hugues.dalle@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Study population (exposed-patients), all criteria should be fulfilled:

1. Patients alive with Sickle Cell Anemia (SCA, meaning SS and Sbeta0 sickle cell anemia genotype)
2. Patients transplanted from allogeneic HLA-compatible sibling donor or from sibling cord blood unit from the 1st of January 2000 and the 31st of December 2012, whatever the age at transplant
3. Patients having received conditioning regimen containing busulfan 1mg/kg/dose (or equivalent adjusted body-weight dosage according to recommendation) x 16 doses + cyclophosphamide 200mg/kg total dose + anti-thymoglobuline
4. For patient under 18 years at time of enrolment, signed informed consent from both parental representatives
5. For patient aged 18 years old : signed informed consent
6. Having an affiliation to a social security regime

Control-population (Non-exposed patients) :

For each allografted patient, one non-exposed patient will be matched, based on the following criteria:

• Gender
• Age at the date of transplantation of the exposed patient (+/- 1 year)
• Foetal hemoglobin (HbF) level (+/- 3%) before treatment intensification (defined as the initiation of either hydroxyurea or a transfusion program)

• Hb level (+/- 0,9 g/dl) before treatment intensification

  1. For patient under 18 years at time of enrolment, signed informed consent from both parental representatives
  2. For patient above 18 years of age: signed informed consent
  3. Having an affiliation of to a social security regime

Exclusion Criteria:

Study population:

• Transplantation from donor other than sibling or related cord-blood
• Conditioning regimen other than busulfan 16mg/kg total dose + cyclophosphamide 200mg/kg total dose + anti-thymoglobuline

For both population:

• Absence of signed informed consent
• Having any debilitating medical or psychiatric illness, which preclude understanding of the inform consent as well as optimal treatment and follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients transplanted from allogeneic HLA-compatible sibling donor or from sibling cord blood unit	Other: Spermogram; Spermogram will be proposed to men; Other: Hospital Anxiety and Depression Scale (HADS); Anxiety and depression will be evaluated 10 years after HSCT; Other: SF36 Quality of life questionnaire; Quality of life will be evaluated 10 years after HSCT; Other: Psychologist interview; During a follow-up visit; Other: Optional sera banking; One in the study; Other: Optional DNA banking; Once in the study
Other: Controlled patients - not transplanted	Other: Spermogram; Spermogram will be proposed to men; Other: Hospital Anxiety and Depression Scale (HADS); Anxiety and depression will be evaluated 10 years after HSCT; Other: SF36 Quality of life questionnaire; Quality of life will be evaluated 10 years after HSCT; Other: Psychologist interview; During a follow-up visit; Other: Optional sera banking; One in the study; Other: Optional DNA banking; Once in the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of quality of life assessed by SF36	It will be assessed by the Short-form 36 (SF36) scale. The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability. Ware JE, Sherbourne CD. The Medical Outcomes Study 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992;30:473-83.	10 years after HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of quality of life	Questionnaire including data about employment, education level, social financial support.	10 years after HSCT
Proportion of patients with anxiety and depression	Anxiety and depression levels will be assessed using the Hamilton Anxiety Depression scale : The HAD scale is a self-assessment scale for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. HADS is a self-administered scale of 14 items which assessed levels of depression and anxiety, divided into 2 subscales of 7 items (Anxiety or HADS-A, Depression or HADS-D). Each item is scored on a scale of 0 to 3. A score is generated for each of the two sub-scales (sum of the 7 items, ranging from 0 to 21). Limit scores, for each of the scores, distinguish: non-cases or asymptomatic ones (score ≤ 7); probable or borderline cases (score 8-10); clearly or clinically symptomatic cases (score ≥ 11)	10 years after HSCT
Evaluation of gonadal function	Spermogram in men (proposed not requested), Luteinising Hormone (LH), Follicle-Stimulating Hormone (FSH), estrogen, Anti-Müllerian Hormone (AMH) in women, testosterone in men, Amenorrhea in women.	10 years after HSCT

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Hematopoietic stem cell transplantation
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: APHP200008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No