Clinical trial NCT00937053: Maintaining a Higher Level of Haemoglobin: Effect on the White Cells After Bone Marrow Transplantation in Children.
Official title: The Effect of Maintaining a Higher Haemoglobin Level on Neutropenia Duration After Bone Marrow Transplantation in Children.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neutropenia
Keywords: Neutropenia
Transfusions
Hemoglobin
Bone marrow transplant
Hematopoietic stem cell transplant
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: Nancy Robitaille, MD
First posted: 2009-07-10
Enrollment: 6
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if maintaining a high hemoglobin level in children that underwent bone marrow transplant will accelerate the neutrophil recovery.

Detailed description: The investigators know that children requiring bone marrow transplant need to first go through a myeloablative regimen, which induces a neutropenia. The length of the neutropenia has an incidence on the risk of contracting bacterial and fungal infections that could be lethal. It is then important to find ways to accelerate the neutrophil recovery, so patient survival can be improved.

Studies conducted in the '70s and '80s suggested that if the hemoglobin level could be kept at a higher level, then the neutrophil recovery would be accelerated. Other studies also support the hypothesis that if the stem cells do not need to produce red cells because these are being supplied through transfusions, then the stem cells would differentiate into non-erythroid cell lines.

As of now, for patients undergoing a bone marrow transplant, it is standard practice to transfuse with red cells based on the condition of the patient or if the hemoglobin level falls below 70 g/L. Hematopoietic growth factors have been used to increase the speed of the neutrophil recovery, but studies conducted so far do not demonstrate that mortality and length of hospitalization have been reduced by the specific use of G-CSF. In more recent studies, these agents have been shown to also have negative effects, such as delayed platelet recovery and impaired immune recovery. In addition, the prophylactic use of G-CSF was also associated with graft-versus-host disease, treatment-related mortality and death.

In conclusion, this study will determine if maintaining a higher hemoglobin level has an effect on the neutrophil recovery after allogenic bone marrow transplantation in children.

Eligibility criteria: Inclusion Criteria:

1. Patients between 1 year of age and 18 years of age at the time of transplantation (18 years is the upper limit of childhood in CIBMTR definitions)
2. Patients planned to undergo a related or unrelated allogeneic bone marrow transplant for a malignant or benign disease (except for sickle cell disease)
3. Conditioning regimen must be myeloablative, i.e. include busulfan greater or equal to 12 mg/kg or Total Body Irradiation greater or equal to 10 Gy, except for patients with acquired severe aplastic anemia
4. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before enrolment in the trial
5. Patient must agree to receive blood transfusion
6. Patient (or their legal guardians) must sign an Informed consent Form

Exclusion Criteria:

1. Patients receiving autologous bone marrow transplant, cord blood transplant or peripheral stem cell transplant
2. Sickle cell disease (since higher hemoglobin level increases blood viscosity and puts these patients at risk for stroke)
3. Hematopoietic growth factor (G-CSF, GM-CSF, stem cell factor, erythropoietin) planned before transplantation (post-transplant decision of hematopoietic growth factors administration as required by the patient's condition will be accepted)
4. Presence of an allo-antibody directed against red blood cells

Primary outcomes:
measure: Time to neutrophil engraftment (defined as the time from transplantation to the first of three consecutive days with a neutrophil count > 0,5 x 109/L, as used in the International Bone Marrow Transplant Registry (IBMTR) criteria).
timeFrame: First 100 days post HSCT
Secondary outcomes:
measure: Time to platelet engraftment (defined as the time from transplantation to the first of three consecutive days with a platelet count > 20 x 109/L, without platelet transfusion 7 days prior (IBMTR criteria)).
timeFrame: First 100 days post HSCT
measure: Transfusions given (red cells and platelets)
timeFrame: First 100 days post HSCT
measure: Hospitalization length
timeFrame: 2 years
measure: Immune reconstitution (lymphoid subsets)
timeFrame: First 100 days post HSCT
measure: Overall survival
timeFrame: 5 years
measure: Graft vs host disease (GVHD)
timeFrame: 2 years
measure: Treatment-related mortality (death without relapse)
timeFrame: 2 years
measure: Relapse
timeFrame: 2 years
measure: Chimerism
timeFrame: 2 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Souther Alberta Children's Cancer Care Program, Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Pediatric Bone Marrow Transplant Unit, British Columbia Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Section of Blood and Marrow Transplant, The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Hematopoietic Stem Cell Transplantation Program, Sainte-Justine Hospital
state: Quebec
city: Montreal
country: Canada
facility: Department of Hematology, The Montreal Children's Hospital
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Michel Duval, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Justine's Hospital
name: Nancy Robitaille, MD
role: PRINCIPAL_INVESTIGATOR
References: