RBC Transfusion

Transcription

1 RBC Transfusion 2014년혈액종양내과춘계연수강좌 Won SikLee, M.D., Ph.D. Division of Hemato-Oncology, Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital

2 Background Red Cell Transfusions are common medical intervention 1 - to augment oxygen delivery to tissues In 1997, 11 million units for transfused in the US % of use in the surgical setting Patients undergoing hematopoietic stem cell transplant ar e traditionally high volume users units/patient (autologous HSCT) units/patient (allogeneic HSCT) 1 Goodnough. Transfusion Medicine. NEJM Wallace et al. Transfusion Kekre et al. Transfusion 2011

3 Q1) What is your Hb threshold for RBC tra nsfuison in HSCT setting regardless of sympt om? 1. 6 mg/dl 2. 7 mg/dl 3. 8 mg/dl 4. 9 mg/dl mg/dl

4 There is no universal accepted threshold for red cell transfusion Historically, thresholds of 100 g/l - Early guidelines in the 1990s suggest levels between 60 and 100 g/l depending on situation and co-morbidities of the patient A threshold of 70 g/l is appropriate and leaves some mar gin of safety over the critical level of g/l. In patients with indications of cardiac disease, it may be safer to mai ntain the hemoglobin above 90 g/l. Transfusion at hemoglobin above 100 g/l is unlikely to be appropriat e unless there are specific indications. Audet et al. Annals of Int Med 1992; Calder et al. CMAJ; 1997 Royal College of Physicians of Edinburgh. Transfusion Medicine 1994 Stehling et al. Anesthesiology 1996 BC Transfusion Advisory Group 2002

5 A Clinical Practice Guideline From the AABB Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dl) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dl or less (Grade: weak recommendation; moderate-quality evidence). Carson JL et al. Transfusion 2012

6 A Clinical Practice Guideline From the AABB Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence). Carson JL et al. Transfusion 2012

7 Transfusion Requirements in Critical C are : TRICC study Hebert et al. NEJM 1999 To determine whether a restrictive strategy (7-10g/L) of red-cell transfusion and a liberal strategy (10-12g/L) 30 mortality Designed as an equivalence trial Enrolled 838 patients 418 (restrictive strategy) 420 (Liberal strategy) influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; lowquality evidence).

8 TRICC Study: Results 1. Overall, 30-day mortality was similar in the two groups (18.7 percent vs percent, P= 0.11). 2. However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill those with an Acute Physiology and Chronic Health Evaluation II score of 20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group, P=0.02) Hebert et al. NEJM 1999

9 TRICC Study: Results 8.7% vs 16.1% 5.7% vs 13.0% Hebert et al. NEJM 1999

10 2012 ASH guideline: RBC Transfuison

11 Are red cell transfusions harmful? Proposed mechanisms linking transfusion of red cells and adverse clinical consequences 1.Red cell storage leads to impaired ability of red cells to carry oxygen and stimulate the inflammatory cascade. 2.Red cell transfusion may trigger and even prime the host for subsequentinflammatory injury 3.The altered immune responses following red cell transfusions may predispose transfusion recipients to SIRS, sepsis syndrome, nosocomialinfections and multiple organ dysfunction Lacroix J et al. NEJM 2007 Kirpalani H et al. J Pediatr, 2006

12 Red Cell Transfusions: Cohort Studies Risk of Death Infectious complications Acute Respiratory distress Marik et al. Critical Care Medicine 2008

13 Could transfusions be beneficial? 1. A more liberal transfusion strategy was superior 1,2 Cardiac Disease 2. Pre-HSCT Hemoglobin is associated with inferior transplant outcomes and increased toxicity 3 It remains unclear whether improvements in hemoglobin levels prior and/or during transplant would abrogate these negative outcomes. 1 Wu et al. NEJM Herbert et al. NEJM Xenocostas et al. Transfusion 2003

14 Red cell Transfusions in HSCT at PMH 519 allogeneic HSCT 1.Average of 6.8 ± 6.4 units of red cells between 0 60 days after HSCT. 2.Increased numbers of red cell transfusions were associated with the before-hsct hemoglobin level. 3.The before HSCT hemoglobin level was also associated with increased mortality within 6 months of HSCT. Xenoscostas et al. Transfusion 2003

15 Could transfusions be beneficial? 3.Younger duration of storage of blood was associated superior cardiovascular outcomes 1 4.Quality of Life A higher transfusion trigger may better facilitate a outpatient transplant based program Correlations with better quality of life with a higher hemoglobin Cancer Heart Disease Chronic Kidney Disease Menorrhagia Patient knowledge of Hb 1 Koch et al. NEJM 2008

16 Red Cell Transfusion Trigger Studies: Randomized Controlled Trials

17 Red Cell Transfusion Trigger Studies: Randomized Controlled Trials Carson et al. Cochrane Database 2012 Issue 5

18 What should the red cell transfusion trigger be in Hematopoietic Stem Cell Transplant? The critical care population may be the closest to the HSCT population Perhaps 70g/L should be the standard in patients undergoing HSCT.

19 Transfusion practice and HSCT: Survey of red cell transfusion triggers Canadian Bone Marrow Transplant Group (CBMTG) (n=15)- Programme Directors 14 centres used a red cell transfusion trigger of 80g/L 1 centre used a red cell transfusion trigger of 70g/L Preferences of individual transplant physicians not available. No clear rationale for stated red cell transfusion trigger.

20 Are there any transfusion trigger studi es in HSCT? 69 patients (from 3 Canadian Centres) 16 patients undergoing HSCT Groups were randomized to standard thresholds for red cell transfusion (<80 g/l) compared with an augmented red cell transfusion scheme to maintain Hb > 120 g/l. The primary outcome was bleeding. Webert et al. Transfusion Jan;48(1):81-91

21 Are there any transfusion trigger studi es in HSCT? They noted that patients randomized to the more liberal transfusion arm received greater number of red cell transfusions vs RBC transfusions/pt-day, p=0.003 No differences in bleeding events or requirement for platelet transfusions. Did not report on toxicity, morbidity or mortality outcomes of HSCT. Webert et al. Transfusion Jan;48(1):81-91

22 Are there any transfusion trigger studi es in HSCT? Multicentre randomized Pediatric HSCT study Transfusion trigger of either 70g/L or 120g/L Primary Endpoint: Engraftment Enrolled 6 patients All 3 patients on the 120g/L arm developed VOD 2 requiring intensive care Study halted by DSMB Robitaille et al. BBMT 2013

23 Transfusion of Red cells In Hematopoi etic Stem cell Transplantation (TRIST) Multicentre Canadian RCT (n=3) 1,2 Completed a pilot RCT of 100 patients receiving HSCT 70g/L vs. 90g/L Now embarking on a Phase III study Non-inferiority study Aiming to recruit another 200 patients Primary endpoint of Quality of Life (FACT-BMT scale) Secondary endpoints include: TRM, LOS hospital stay, ICU admissions, GVHD, Incidence of Infections, Transfusion requirements Incidence and grade of bleeding, Incidence of adverse transfusion reactions, Bearman Toxicity Score, Sinusoidal Obstruction Syndrome and Cost effectiveness/utility 1 Tay et al. Trials Clinicaltrials.gov NCT

24 Summary Red cell Transfusion Thresholds 1.Red cell transfusions are integral part of the overall care of patients receiving HSCT. 2.A red cell transfusion threshold as low as 70g/L in recipients of HSCT is likely safe. Quality of life/vitality remains unclear Hyper-transfusion using threshold of 120g/L in children is detrimental 3.The ongoing TRIST study will inform practice.

25 Q2) What kind of blood type of RBC do you transfuse for patient with postbmt D3 Hb 6. 0 mg/dl (Donor: type B, Recipient: type A)? 1. A 2. B 3. AB 4. O 5. Any blood type is OK!

26 ABO incompatible HSCT ABO and Rh compatibility are not required for the successful outcome of BMT Red cell-incompatible donors: 30 50% Immediate and delayed hemolytic transfusion reactions ar e expected complications Immunohematological consequences of red cell-incompati ble transplantation include delayed red blood cell recovery, pure red cell aplasia and delayed hemolysis from viable ly mphocytes carried in the graft ( passenger lymphocytes ). No deleterious effects on transplant outcomes, such as granulocyte and platelet engraftments, the incidences of acute or chronic GvHD, relapse risk or OS, have been consistently demonstrated. Rowley et al. BMT 2011

27 ABO and SCT Any allogeneic SCT will be one of: ABO-Identical Major ABO Incompatible Minor ABO Incompatible Bidirectional (Major/ Minor ) 40-50% of MUD-recipient pairs are ABO incompatible (ABOi SCT) 25% sibling donor-recipient pairs are ABOi Peri-transplant transfusion management of ABOi transplant is not standardized. Worel et al Vox Sang 2010 Raimondi et al BMT (GITMO) 2004

28 Recipient- Donor ABO Compatibility ABO Major Mismatch: Recipient is O-Donor is A - Acute hemolysis at infusion. - Delayed hemolysis from persistent patient antibodies. - Delayed onset of hematopoiesis. ABO Minor Mismatch: Recipient is A- Donor is O - Acute hemolysis at infusion. - Delayed hemolysis from donor antibodies. ABO Major-Minor Mismatch: Recipient is A-Donor is B

29 ABO Compatibility DONOR Blood Group O A B AB RECIPIENT O Compatible Major Major Major A Minor Compatible Major and minor Major B Minor Major and minor Compatibl e Major AB Minor Minor Minor Compatible

30 Does ABO Incompatibility impact SCT outcomes? Contradictory studies ABO incompatibility does not appear to affect graft failure or rejection Further, does not affect survival, although may be related to prolonged RBC aplasia or delayed hemolysis Difficulty in analyzing quality of studies: many many variables impacting patient outcomes with this complex therapy eg, baseline disease/stage/risk, conditioning, comorbidities, SC dose, SC source, GVH prophylaxis, supportive care regimens, transfusion support regimens Worel et al Vox Sang 2010 Raimondi et al BMT (GITMO) 2004

31 Kanda et al Transfusion 2009 Kim et al BMT 2005

32 ABOi SCT impact on Outcome: Nonmyeloablative Transplants Seattle 503 NMA SCT No difference Wang Z et al BJH 2010

33 Stem Cell (HPC) product preparation BM source Major ABO mismatch Red cell depletion Minor ABO mismatch Plasma depletion Bidirectional Both RBC and Plasma depletion PB HPC (Apheresis) Hct kept <2%, typically ~10ml Considered red cell depleted and plasma depleted Cord HPC source Most often RBC and plasma depleted prior to cryostorage Otherwise, washed with dextran/albumin solution to remove lysed RBC ( and donor plasma) post-thaw

34 Marrow Processing Red cell depletion and/or plasma depletion ONLY performed on BM collection. Red cell depletion: Recipient has Ab against Donor red cells. - To avoid hemolysis of donor red blood cells in HPC collection. Plasma depletion: Donor has Ab against Recipient red cell. - To avoid hemolysis of red blood cells in recipient s circulation.

35

36 Rowley et al. BMT 2011

37 MAJOR ABOi SCT: Risks delayed RBC engraftment Recipient lymphocytes continue to produce IHA s (against donor A and B Ag) for up to 3-4 months May delay RBC engraftment, Does not impact Platelet / Neutrophil lines >40d post Major ABO incomp, v 20d RBC chimerism may exist for months Potential for delayed hemolysis PRCA risk varies NMA (8-38%) v MA transplant (16-29%) A antigen incompatibility CSA-only Yazer and Triulzi 2007 Curr Op Hem

38 Product Selection

39 SCT - Minor ABO Incompatible Acute hemolytic transfusion reaction with SC infusion Usually little hemolysis compared to major ABO incompatible transplant Plasma reduce BM-derived SC product Potential severe hemolysis post transplant Passenger Lymphocyte Syndrome

40 Minor ABO Incompatible SCT: Passenger Lymphocyte Syndrome Graft s viable lymphocytes produce IHA against recipient RBC 5-12d post HPC-A; 9-16d post HPC-M DAT positive, intravascular, abrupt onset, possibly severe, usually subsides <2wks Risks: PBSC, unopposed T cell suppression for GVHD prophylaxis, RIC Protect with appropriate RBC support selection and plasma selection Incidence decreasing? : MTX for GVH prophylaxis is protective Rowley et al BMT 2001 Gajewski et al Blood 2008

41 NON-ABO MISMATCHES Major Rh-incomp., patient anti-d antibodies against engrafted donor Rh+ RBCs. Mismatches involving Rh system may cause hemolysis, do not affect survival. Kidd,M,N and S.

42 Product Selection

43 Summary ABO incompatibility in HSCT 1. ABO matching is not required for successful SCT 2. There are potentially significant consequences of ABO mismatched transplant There is controversy about the impact of ABO mismatch on overall survival 3. Transfusion support of ABOi SCT recipients is not standardized