Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Anemia

Postoperative Complications

Hematologic Diseases

Cécile AUBRON, PU PH

Cécile AUBRON, PU-PH

Oncologic patients experience anemia and anemia is associated with poor prognosis. Transfusion is associated with adverse events, and equipoise remains on the optimal transfusion strategy in oncologic patients in surgical setting. The primary objective of this study is to determine the impact of anemia and red blood cells (RBC) transfusion on post-operative complications and mortality.

Between 36 and 75% of oncologic patients experience anemia and anemia is associated with poor prognosis. Up to 40% of surgical oncologic patients receive red blood cells (RBC). However, transfusion is associated with adverse events, and equipoise remains on the optimal transfusion strategy in oncologic patients in surgical setting. The primary objective of this study is to determine the impact of anemia and red blood cells (RBC) transfusion on post-operative complications and mortality. This is a retrospective, single center study. All adults admitted to the intensive care unit (ICU) after oncologic surgery within the study period are eligible.

Anemia and Red Blood Cells Transfusion in Oncological Surgery

Impact of Perioperative Anemia and Red Blood Cells Transfusion on Post-operative Complications After Oncological Surgery

mortality or any respiratory, cardiac, renal, thromboembolic, infectious and/or hemorrhagic post operative complications

University Hospital, Brest

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Chrysarobin

Hemoglobin concentrations will be maintained in the range of 7.5 to 9.0 g per deciliter, with a transfusion given when the hemoglobin concentration is below 7.5 g per deciliter.

Hemoglobin concentrations will be maintained in the range of 10.0 to 12.0 g per deciliter, with a transfusion given when the hemoglobin concentration is below 10.0 g per deciliter.

This transfusion policy holds to any time from the start of surgery until discharge. The physicians caring for the patient will be instructed to administer transfusion, one unit at a time, and to measure the patient's hemoglobin concentration after each unit is transfused. In both groups, no further units will be given if the goal hemoglobin was obtained (7.5 g per deciliter for the restrictive arm and 10.0 g per deciliter for the liberal one). All other management decisions are left to the discretion of the patients' physicians. Attending physicians can administer RBC transfusions outside the rules of the protocol (i.e more than 1 unit at a time, without determining pre-transfusion hemoglobin) if severe acute bleeding occurs or other forms of circulatory shock.

Red blood cells transfusion

Idit Matot, Prof

The rationale for perioperative red blood cell (RBC) transfusion is based on the observation that anemia is an independent risk factor for morbidity and mortality after cardiac operations. However, transfusions have been associated with high rates of morbidity and mortality in critically ill patients, and some recent studies have shown worse outcomes, including increased occurrence of renal failure and infection, as well as respiratory, cardiac, and neurological complications, in transfused compared with non transfused patients after cardiac surgery. On the basis of past clinical observations, some authors have suggested that hematocrit should be maintained at around 30% and hemoglobin concentration at 10 g/dL. Recently, however, this hemoglobin threshold has been reconsidered because of recognized risks associated with transfusion and greater appreciation of the importance of individual physiological responses to anemia. In a comparative trial of 428 patients undergoing elective coronary artery bypass graft(CABG) surgery, Bracey et al reported that reducing the hemoglobin trigger to 8 g/dL did not adversely affect patient outcomes and resulted in lower costs. An important multicenter Canadian Study by Hebert et al that included a large number of critically ill patients revealed that A restrictive strategy of red-cell transfusion (hemoglobin concentration maintained between 7.0and 9.0g/dL) is at least as effective as and possibly superior to a liberal transfusion (hemoglobin concentration between 10 and 12 g/dL) strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina, in terms of reducing organ dysfunction and mortality.

The investigators would like to determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produce equivalent results in orthopedic-oncology patients undergoing surgery.

Restrictive Versus Liberal Red Cell Transfusion Strategy in Orthopedic-Oncology Patients Undergoing Surgery - a Randomized Controlled Study

Functional outcome during hospital stay and at 6 weeks as defined by the Modified Rivermead Mobility Index attached below (a functional index that measures different functionalities of the patient. This index is daily measured by the physiotherapist's group

A composite end point that includes all cause mortality and morbidity occurring till 6 weeks post surgery.

The investigators will also evaluate the incidence of RBC transfusions and the number of units transfused.

Tel-Aviv Sourasky Medical Center

Neoplasms

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Chromosome 5q Deletion

Antineoplastic Agents

Lenalidomide

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Experimental treatment branch with Lenalidomide 5 mg/day (oral use)

Treatment with Revlimid (lenalidomide), oral use, 5 mg daily during study treatment (104 weeks).

Placebo, oral use, daily during study treatment (104 weeks)

Placebo

Consuelo del Cañizo, MD

María Díez Campelo, MD

Trial Design:

This clinical trial is a phase III multicenter, randomized, double blind and controlled with placebo trial and with two arms designed to assess the efficiency and toxicity of the scheme Lenalidomide versus observation in a series of 60 patients with low risk myelodysplastic syndrome associated to 5q deletion with anemia (Hb≤12g/dL) but without the need of transfusion. Patients are randomized in the study in a 2:1 ratio. They will receive treatment for 104 weeks until progression of the disease, which implies that the patient suffering from anemia due to myelodysplastic syndrome requires transfusion of at least 2 UCH/56 days (2 months) with a minimum follow up of 112 days (4 months), or unacceptable toxicity.

Disease:

Low risk myelodysplastic syndrome associated to the loss of 5q without transfusion requirements.

Total number of patients:

In total 60 patients will be included, 40 assigned to the treatment branch and 20 to the placebo branch.

Calendar:

First patient first visit: February 2010, and Last patient last visit expected in February 2016. (Recruitment was initially expected to take place over a period of 24 months and was expected to be finished in February 2012, but due to low rate of recruitment it was extended until the population sample is included in the trial).

General summary of myelodysplastic syndrome with alteration in 5q. Myelodysplastic syndromes (MDS) are a very heterogenic group of diseases characterized by the presence of morphologic features of dyshemopoiesis in bone marrow (BM) and in peripheral blood (PB), which is translated into an inefficient hematopoiesis. This will lead to the concomitant development of peripheral cytopenias which will be the cause of complications in these patients and, in most cases, the cause of death. In addition, these patients have an increased risk of developing acute leukemia, and this risk increases with the progression of the disease.MDS represents an incurable disease with standard treatments with a quite variable survival mean ranging from 3 months to 15 years depending on the number of blasts, the number of cytopenias and the type of cytogenetic disorders2. The sole curative treatment of the MDS is the allogenic transplant of hematopoietic progenitors but this option is only available for a 5% of the patients with MDS.

Lenalidomide, initially known as CC-5013, is an analogue of the immunomodulator Drug Thalidomide (Thalidomid®; Pharmion Corp., Boulder, CO, USA), which was the first drug with anti-angiogenic and immunomodulator properties investigated in MDS. Lenalidomide has, as well as thalidomide, a broad array of potential activities against dysplastic cells, not fully known, among which we find immunomodulator and non-immunomodulator properties (anti-angiogenic effect, anti-proliferative and pro-apoptotic). The greater advantage of Lenalidomide in comparison with thalidomide is that the former is between 50 and 2000 times stronger tan thalidomide in what respects to its immunomodulator effects. And moreover, the toxic profile of Lenalidomide seems lower than that of its analogue; Thalidomide.

There is no treatment indication on the present times for patients with low risk MDS associated to the loss of 5q without transfusion dependent anemia. The results with Lenalidomide are highly promising for patients with low risk MDS associated to the loss of 5q when (it has so been tested) there is red blood cells transfusion dependent anemia. In this sense, the proposal consists on being able to state that treatment with Lenalidomide can be efficient from diagnose preventing CH transfusions with an acceptable toxicity.

In this sense, the present study has the intention to treat early patients with low-risk MDS associated to the loss of 5q with a view to prevent CH transfusion. Therefore, we could extend in these patients the time until CH transfusion and even assess the possibility of eradicating the disease at a cytogenetic/morphologic level. In the present trial and given the characteristics of the patients, we have chosen the option of supplying Lenalidomide at a dose of 5mg/day. The option of considering a lower dose to the one currently considered as "standard" (10mg/day) is to reduce toxicity, mainly hematologic, in patients who do not receive treatment normally. A dose with lower toxicity has been chosen which has revealed itself efficient.

Main efficiency objective:

•To assess if treatment with Revlimid (Lenalidomide) extends the period until the progression to myelodysplastic syndrome del(5q) considered as transfusion independent, documented verification that the patient suffering from anemia due to MDS requires transfusion of at least 2 UCH/56 days (2 months) with a minimum follow up of 112 days (4 months). Revlimid will be compared to the current standard treatment for patients with low risk myelodysplastic syndrome associated with the loss of 5qwithout transfusion dependent anemia, which is the therapeutic abstention and monitoring until its progression.

Secondary efficiency objectives:

* Erythroid response according to the Criteria of the myelodysplastic syndrome International Work Team 2006).
* Duration of the red blood cells transfusion independency (defined as the number of days elapsed between the randomization and the first transfusion after this period free of transfusions).
* Change of hemoglobin concentration (Hb) in relation to baseline levels of patients who show erythroid response.
* Variation in platelets absolute count in relation to baseline levels.
* Variation in neutrophils absolute count in relation to baseline levels.
* Cytogenetic response according to the Criteria of the myelodysplastic syndrome International Work Team.
* Bone marrow response according to the Criteria of the myelodysplastic syndrome International Work Team.
* To assess the safety and tolerance of the Lenalidomide scheme, measured according to the incidence of clinical and laboratory toxicity.
* Global survival, Event Free Survival and Rate of Transformation to Acute Leukemia.
* Time from diagnose to transfusion independence.

Main safety objective:

Safety (type, frequency and severity \[Criteria of normal terminology of adverse reactions of the National Cancer Institute (NCI CTCAE) version 3.0\] of adverse reactions (AR)and list of the AR with Lenalidomide.

Four of the sites of this Clinical Trial are member of the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet) which is partially co-funded by the European Union within the framework of the Third Health Programme. "ERN-2016 - Framework Partnership Agreement 2017-2021." FPA 739541".

Study of REVLIMID (Lenalidomide) Versus Placebo in Patients With Low Risk Myelodysplastic Syndrome

Multicenter, Randomized, Double-blind, Phase III Study of REVLIMID (Lenalidomide) Versus Placebo in Patients With Low Risk Myelodysplastic Syndrome (Low and Intermediate-1 IPSS) With Alteration in 5q- and Anemia Without the Need of Transfusion.

To assess if treatment with Revlimid (Lenalidomide) extends the period until the progression to MDS of(5q) considered as transfusion independent, documented verification that the patient suffering from anemia due to MDS requires transfusion of at least 2 UCH/56 days (2 months) with a minimum follow up of 112 days (4 months). Revlimid will be compared to the current standard treatment for patients with low risk MDS associated with the loss of 5q without transfusion dependent anemia, which is the therapeutic abstention and monitoring until its progression.

Erythroid response according to the Criteria of the MDS International Work Team.

Red blood cells transfusion independency,defined as the number of days elapsed between the randomization and the first transfusion after this period free of transfusions.

Change of the hemoglobin concentration (Hb) in relation to baseline levels of patients who show erythroid response.

Variation in platelets and neutrophils absolute count in relation to baseline levels

Cytogenetic response according to the Criteria of the MDS International Work Team.

Bone marrow response according to the Criteria of the MDS International Work Team.

Global survival, Event Free Survival and Rate of Transformation to Acute Leukemia

Time from diagnose to transfusion independence

Safety (type, frequency and severity \[Criteria of normal terminology of adverse reactions of the National Cancer Institute (NCI CTCAE) version 3.0\] of adverse reactions (AR)and list of the AR with Lenalidomide.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anemia and Red Blood Cells Transfusion in Oncological Surgery	NCT04101240	Anemia Surgery Oncology		18 Years -	University Hospital, Brest
Restrictive Versus Liberal Red Cell Transfusion Strategy in Orthopedic-Oncology Patients Undergoing Surgery - a Randomized Controlled Study	NCT01491308	Red Blood Cells...	Red blood cells...	18 Years -	Tel-Aviv Sourasky Medical Center
Study of REVLIMID (Lenalidomide) Versus Placebo in Patients With Low Risk Myelodysplastic Syndrome	NCT01243476	Myelodysplastic...	Lenalidomide Placebo	18 Years -	Fundación General de la Universidad de Salamanca
Anemia and Red Blood Cells Transfusion in Oncological Surgery	NCT04101240	Anemia Surgery Oncology		18 Years -	University Hospital, Brest
Anemia and Red Blood Cells Transfusion in Oncological Surgery	NCT04101240	Anemia Surgery Oncology		18 Years -	University Hospital, Brest

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