Monitoring of Measles-specific Immune Status in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients

Monitoring of Measles-specific Immune Status in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients: a Prospective Cohort Study

Measles, a highly contagious disease, is potentially serious in adult allogenic hematopoietic stem cell transplant (allo-HSCT) recipients. Because of the loss of immunity to vaccine preventable diseases after allo-HSCT, French Health Authorities (Haut Conseil de Santé Publique, HCSP) recommend (re)vaccination of all allo-HSCT recipients against measles-mumps-rubella (MMR) from 24 months post-transplant onwards, in the absence of graft-versus-host disease (GVHD) and at least 3 months after cessation of all immunosuppressive treatments, irrespective of measles serostatus. Nevertheless, some French experts argue that systematic assessment of measles antibody titre is justified after allo-HSCT, prior to revaccination, in order to avoid "unnecessary" revaccination of allo-HSCT recipients who are still seropositive. At the international level, recommendations also vary: the ECIL group and IDSA advocate revaccination of measles seronegative patients only, while some American Hematology experts recommend not to base the decision of revaccination on the serological status, given the inevitable loss of antibodies and specific long-term immune memory in the absence of revaccination.

Several obstacles to the application of the recommendations can therefore be identified: (i) the risk of vaccine-transmitted disease due to the live-attenuated nature of MMR, (ii) the lack of robust data on the immunogenicity and tolerability of the MMR vaccine in this particular population, and (iii) conflicting recommendations to guide the decision of revaccination.

This study aims at answering the question of whether some allo-HSCT recipients may retain a measles-specific cellular immune memory at distance from their allo-HSCT.

Inclusion Criteria:

Study population:

• Aged ≥ 18 years and ≤ 75 years,
• Have received an allo-HSCT ≥ 24 months ago,
• In complete remission of initial hematologic disease and with successful engraftment (recipient chimerism <0.3% on whole blood),
• Without extensive chronic GVHD,
• Having given their written consent,
• Affiliated to a social security plan,
• Able to attend all scheduled visits and to comply with all study procedures.

Healthy volunteers:

• Aged ≥ 18 years and ≤ 75 years,
• Having a history of measles (=convalescent) or have been vaccinated in the past with two doses of MMR (=vaccinated),
• Having given their written consent,
• Affiliated to a social security plan.

Exclusion Criteria:

Study population:

• History of autoimmune disease or acquired immunodeficiency (other than the hematological disease),
• Patients undergoing pharmacological immunosuppression or biotherapy or extracorporeal photopheresis at the time of inclusion, or whose immunosuppressive treatment (corticosteroids and anti-rejection agents) has been stopped less than 3 months ago, or whose biotherapy (anti-cytokines, anti-JAK, anti-CD20 etc.) has been stopped less than 3 months ago (12 months for anti-CD20 including rituximab), or whose extracorporeal photopheresis has been stopped less than 3 months ago,
• Patients having received ≥ 1 infusion of IVIG in the 8 months prior to inclusion,
• Patients whose last HSCT was an autograft,
• Patients with known chronic active infection with human immunodeficiency virus (HIV) and/or hepatitis B or C virus(es),
• Patients deprived of liberty by judicial or administrative decision,
• Patients under legal protection or unable to consent to the study,
• Patients participating in another interventional research study with an exclusion period still in progress at pre-inclusion,
• Pregnant, parturient or breast-feeding women.

Healthy volunteers:

• History of autoimmune disease or acquired immunodeficiency,
• History of pharmacological immunosuppression or biotherapy discontinued less than 3 months ago (12 months for anti-CD20 including rituximab),
• History of IVIG infusion in the 8 months prior to inclusion,
• Persons deprived of liberty by judicial or administrative decision.