Transfusion Strategy in Hematological Intensive Care Unit

Study Overview
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Brief Summary
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Patients with acute hematological disease (acute leukemia, aplastic anemia, hematopoietic stem cells autologous or allogeneic ...) and hospitalized in an intensive care unit hematology require compensation of anemia and thrombocytopenia by blood transfusions of red blood packed cells (RBP) or platelet concentrates (PC).The AFSSAPS (Agence Française de Sécurité Sanitaire des Produits de Santé) recommendations (2002) specify the need to transfuse 2 RBP in case of symptomatic anemia usually for a hemoglobin between 6 and 10 g / dL. These recommendations allow to transfuse a single RBP for very elderly patients or in cases of associated heart disease (heart failure). A recent development (2012) on post-transfusion pulmonary edema overload recommends transfusion unit by unit for high risk patients. More recently, a Swiss team has historically compared transfusion policies in 2 139 patients with hematological malignancies. The first group received 2 RBP transfusion in case of symptomatic anemia or hemoglobin level <6 g / dL. The other group only received 1 RBP at each transfusion. In total 2212 units in 1548 transfusions were performed and the 1 RBP transfusion policy has resulted in a 25% decrease in the number of RBP used without any complication. In a prospective single-center pilot study, we showed that transfusing a single RBP was possible without increasing the side effects of anemia, without complications and allow an overall reduction in consumption of red blood cell units. Several meta-analyzes reported in intensive care or bleeding situations that a restrictive use of transfusions significantly reduces cardiac events, bleeding, bacterial infections and mortality. The number of patient to be treated to prevent one death is 33. The main objective is to demonstrate in a randomized trial that the restrictive strategy (transfusion of a single unit at each transfusion) is not inferior to the liberal strategy (transfusion of 2 unit at each transfusion) in terms of severe complication. Transfusion are performed in case of hemoglobin level <8g/dL. Key secondary objectives are to reduce the number of RBP used and the cost of hospitalization with a comparison of complications/mortality in the 2 groups.

Official Title
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Randomized Multicenter Trial of Two Transfusion Strategies for Patient Receiving Chemotherapy for Acute Leukemia or Hematopoietic Stem Cells With Medico-economic Evaluation of Cost Minimization.

Conditions
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Transfusion Related Complication

Intervention / Treatment
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* Drug: Single red blood packed cells Transfusion
* Drug: Two packed red blood cells Transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inpatients with either acute leukemia patient receiving intensive chemotherapy or autologous transplantation for lymphoma, allogeneic stem cell transplantation Exclusion Criteria: ischemic heart failure acute promyelocytic leukemia ALKERAN autologous conditioning (myeloma patient) disseminated intravascular coagulation hemorrhagic syndrome stroke any vital distress at diagnosis creatinine clearance <50 ml/min liver disease with ALT (alanine aminotransferase)/AST(aspartate aminotransferase) ≥2.5 ULN (upper limit of normal) (except if related to tumor) pregnant female autoimmune hemolytic anemia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARM A<br>Two packed red blood cells will be transfused in patient with anemia defined as a hemoglobin level below 8 g / dL. Clinical and biological monitoring will be carried out later each day. If the hemoglobin is <8 g / dL, two new packed red blood cells are transfused and so on. | Drug: Two packed red blood cells Transfusion<br> <br> |
| Experimental: ARM B<br>Single red blood packed cells Transfusion will be administered in patient with anemia defined as a hemoglobin level below 8 g/dL. Clinical and biological monitoring will be carried out later each day. If the hemoglobin is <8 g / dL, a single unit is transfused and so on. | Drug: Single red blood packed cells Transfusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of severe complications (grade 3 or more) | complications are defined as: stroke, transient ischemic attack, acute coronary syndrome, heart failure, arrhythmias or conduction cardiac disease, deep vein thrombosis, pulmonary embolism, elevated troponin, transfer to intensive care unit, death from any cause, new or progressive radiographic infiltrates, infections related to transfusion. | up to 1 month after the last day of hospitalization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of RBP transfused |  | up to 1 month after the last day of hospitalization | 
| Incidence of bleeding | number of patient with bleeding grade 3 or more | up to 1 month after the last day of hospitalization | 
| Transfusion related events | Number of transfusion related events defined as any complication that the physician declared to be related to the transfusion (fever, infection, pulmonary edema..) | up to 1 month after the last day of hospitalization | 
| Time to erythroid recovery | Time from randomization to last transfusion | up to 1 month after the last day of hospitalization | 
| Quality of life | Functional Assessment of Cancer Therapy and QLC30 | up to 1 month after the last day of hospitalization | 
| time of aplasia | from 1st day with neutrophils<500 to first day with neutrophils>500/mm3 | up to 1 month after the last day of hospitalization | 
| Transfusion performance | difference between hemoglobin level before and 24 hours after transfusion | up to 24 hours | 
| transfusion in out patient | number of RBP transfused after leaving the unit | up to 1 month after the last day of hospitalization | 
| Failure to respect the randomisation arm | number of patient in arm B that received 2 RBP instead of single RBP | up to 1 month after the last day of hospitalization |