Impact of Alemtuzumab exposure on immune reconstitution, autoimmunity, risk of infection, chimerism and Graft-versus-Host Disease in children with non-malignant diseases undergoing allogeneic stem cell transplantation. ARTIC International Multicenter Observational Study.

Impact of Alemtuzumab exposure on immune reconstitution, autoimmunity, risk of infection, chimerism and Graft-versus-Host Disease in children with non-malignant diseases undergoing allogeneic stem cell transplantation. ARTIC International Multicenter Observational Study. - ARTIC study

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON55607

Enrollment

Registered

2019-11-22

Start date

2020-03-01

Completion date

Unknown

Last updated

2025-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Group of inherited blood diseases that affect red blood cells (e.g. sickle cell disease thalassemia) and/or white blood cells (e.g. severe combined immunodeficiency characterized by a profound reduction or absence of T lymphocyte function) requiring an allogeneic stem cell transplantation.

Interventions

None listed

Eligibility

Age

2 Years to 17 Years

Inclusion criteria

Inclusion criteria: • diagnosis of severe congenital immune deficiency or of congenital hematological disorder with an indication for HSCT, e.g. (severe) combined immunodeficiency ((S)CID), hemophagocytic lymphohistiocytosis (HLH), chronic granulomatous disease (CGD), thalassemia major, sickle cell disease (SCD); • age at diagnosis and at the time of HSCT =14 years old (>=12 years old in the Netherlands); • in case of multiple alloHSCT per patient, further transplantations will only be considered if a minimal serotherapy-free interval of 3 months is preceding the second transplant

Exclusion criteria

Exclusion criteria: • patients who do not fulfill the inclusion criteria; • patients with known hypersensitivity to Alemtuzumab; • patients treated with other serotherapy drugs (e.g. anti-thymocyte globulin - ATG) within the same conditioning regimen prior to HSCT; • patients who received any other serotherapy in the last 3 months before starting this observational study; • known HIV-positivity; • severe uncontrolled infections before alloHSCT; • active malignancies; • pregnancy/lactation.

Design outcomes

Primary

Measure	Time frame
Campath® (Alemtuzumab) levels measured 15-30 minutes before (please note: no sample will be taken before the first Alemtuzumab dose) and after each Campath® (Alemtuzumab) administration as well as at day 0 (= day HSCT), +1, +7, +14, +21 and at week +4 and +6 after alloHSCT.	—

Secondary

Measure	Time frame
Explorative secondary Endpoints (outcome parameters) • Immune reconstitution: -- Lymphocytes / neutrophils / monocytes / T cells (total, CD4+ and CD8+ subsets, CD4+/CD8+ ratio) / NK cells / B cells count are measured at week +2 (if peripheral leucocytes are measurable yet), +3, +4, +6, +8, +10 and +12 after alloHSCT; -- Neutrophil (CD15+ cells) engraftment -- Recovery of CD4+ T cells -- Recovery of CD8+ T cells - Chimerism analysis of total peripheral blood mononuclear cells (PBMC) at week +4, +8, +12 and at +6, +9 and +12 months after alloHSCT; • Incidence of acute and chronic graft-versus-host-disease (GvHD) and grading according to classic Glucksberg-Seattle scale and NIH criteria respectively; • Overall survival (OS); • Event free survival (defined as without death or retransplantation); • Cumulative incidence of treatment-related mortality (TRM); • Cumulative incidence of graft failure (defined as non-engraftment or rejection); • Incidence of viral primary infections or reactivations (e.g. cytomegalovirus, Epstein-Barr-virus, human herpesvirus 6, adenovirus) within the first 100 days; • Incidence of Donor Lymphocyte Infusion (DLI) within the first 100 days; • Incidence of bacterial, parasitic and fungal primary infections within the first 100 days; • Incidence of autoimmune reactions (e.g. autoimmune cytopenia, autoimmune haemolytic anemia) within 10 years after alloHSCT (serum samples will be taken if indicated); • Incidence of secondary immune-mediated endocrine disorders (e.g. gonadal dysfunction, hypothyreosis).	—

Measure

Time frame

Explorative secondary Endpoints (outcome parameters) • Immune reconstitution: -- Lymphocytes / neutrophils / monocytes / T cells (total, CD4+ and CD8+ subsets, CD4+/CD8+ ratio) / NK cells / B cells count are measured at week +2 (if peripheral leucocytes are measurable yet), +3, +4, +6, +8, +10 and +12 after alloHSCT; -- Neutrophil (CD15+ cells) engraftment -- Recovery of CD4+ T cells -- Recovery of CD8+ T cells - Chimerism analysis of total peripheral blood mononuclear cells (PBMC) at week +4, +8, +12 and at +6, +9 and +12 months after alloHSCT; • Incidence of acute and chronic graft-versus-host-disease (GvHD) and grading according to classic Glucksberg-Seattle scale and NIH criteria respectively; • Overall survival (OS); • Event free survival (defined as without death or retransplantation); • Cumulative incidence of treatment-related mortality (TRM); • Cumulative incidence of graft failure (defined as non-engraftment or rejection); • Incidence of viral primary infections or reactivations (e.g. cytomegalovirus, Epstein-Barr-virus, human herpesvirus 6, adenovirus) within the first 100 days; • Incidence of Donor Lymphocyte Infusion (DLI) within the first 100 days; • Incidence of bacterial, parasitic and fungal primary infections within the first 100 days; • Incidence of autoimmune reactions (e.g. autoimmune cytopenia, autoimmune haemolytic anemia) within 10 years after alloHSCT (serum samples will be taken if indicated); • Incidence of secondary immune-mediated endocrine disorders (e.g. gonadal dysfunction, hypothyreosis).

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Countries

Netherlands

Outcome results