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Transfusion Support in Hematology-Oncology Patients

Transfusion Support in Hematology-Oncology Patients. Darrell J. Triulzi, M.D. Professor of Pathology University of Pittsburgh Medical Director The Institute for Transfusion Medicine Pittsburgh, PA. Transfusion Support in Hematology/Oncology Patients. Platelet therapy Leukoreduction

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Transfusion Support in Hematology-Oncology Patients

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  1. Transfusion Support in Hematology-Oncology Patients Darrell J. Triulzi, M.D. Professor of Pathology University of Pittsburgh Medical Director The Institute for Transfusion Medicine Pittsburgh, PA

  2. Transfusion Support in Hematology/Oncology Patients • Platelet therapy • Leukoreduction • Transfusion transmitted CMV • Irradiated Blood Components: Prevention of Transfusion associated Graft vs Host disease

  3. Blood Products Whole Blood Packed RBCs Platelet-rich Plasma Plasma Platelets Cryoppt-reduced Plasma Cryoprecipitate Plasma Derivatives Albumin IVIg

  4. Whole Blood Platelets • 60 ml each (approx.) • >5.5 x 1010 platelets/bag • Storage: 5 days at room temp, constant agitation • Dose: 1 unit/10 kg up to 40 kg Adults (>40 kg) - Pool of 4 (= 1 unit of apheresis plts) •  plt ct  20 – 35K

  5. Whole blood platelet concentrate

  6. Apheresis Platelet Donation • 1.5 -2.0 hr donation • -Returns red cells and plasma • - Collects 1-3 full adult doses of plts

  7. Apheresis Platelets • 200-400 ml • >3.0 x 1011 plts/bag (equiv to 5-6 WBPCs) • Storage: 5 days @ room temp, constant agitation • Dose: 1 apheresis plt product per transfusion • plt ct  20 – 40K

  8. Apheresis Platelets • 200-400 ml • >3.0 x 1011 plts/bag (equiv to 5 WBPCs) • Storage: 5 days @ room temp, constant agitation • Dose: 1 apheresis plt product per transfusion

  9. Single Donor Platelets

  10. Clinical Indications for Platelets • Significant bleeding in a patient with thrombocytopenia • Planned invasive procedure in a patient with thrombocytopenia • Risk of spontaneous bleeding (eg CNS, lung) due to severe thrombocytopenia • Bleeding or invasive procedure and platelet dysfunction

  11. Achieving hemostasis in bleeding thrombocytopenic patients Cessation of overt bleeding in 51/57 episodes when plt increment exceeded 40K Cessation of overt bleeding in 17/18 pts when plt increment exceeded 30-40K Transfusion for Bleeding Investigator Observation Freireich, Ann Int Med 1963;59:277 Djerassi, NEJM 1963;268:221 Recommendation: Transfuse to > 50K

  12. Invasive Procedures No increase in bleeding complications w/ plt ct 50-100K vs. > 100K No excess surgical bleeding when plt ct > 50K Transfusion for Surgery Investigator Observation Toy, 1990, 1991 Minor procedures: thoracentesis, line placement, etc. Bishop, Am J Hematol 1987;26:147 - Major intra-abdominal/ intra-thoracic surgeries Recommendation: Transfuse if < 50K

  13. Stool blood loss in 28 aplastic, thrombocytopenic patients Ann. Review of Med, Vol. 31, 1980 Bleeding risk vs. plt ct The Lancet, Vol. 338, 1991 Prophylactic Transfusion 100 300 Bleeding Episodes/1000 days Minor Bleeding Stool Blood Loss (ml/day) n=280 75 Major Bleeding n=805 50 150 n=642 n=3588 n=687 25 75 25 0 0 0 5 10 15 20 25 0 - 5 6-10 11-15 16-20 >20 Platelet Count/μL x 103 Risk Category by Plt Ct/μL x 103

  14. Threshold for Prophylactic Plt Transfusion in Adult AML 225 new AML pts (not m3) Random, prospective A: (135) Tx @ < 10K B: (120) Tx @ < 20K 21.5% fewer plt Txs in 10K grp No signif difference in RBC Txs Major bleeding: 21.5% (10K) vs 20% (20K),p=0.41) Risk similar 10 vs. 20K threshold Rebulla et al. NEJM, 337:26:1872-5, 1997. Safety & Cost-Effectiveness of 10K vs. 20K Platelet Trigger 105 new AML pts (not M3) Prospective, 17 centers A: (110) 10K vs. B: (106) 20K Less plt Txs (~60%) in 10K grp No signif difference in RBC Txs Bleeding (WHO grade 2-4): 18% vs. 17% (p=0.8) One-third lower cost w/ 10K vs. 20K trigger w/ no associated increase in bleeding risk Wandt H et al. Blood, 91:10:3601-6, 1998. Prophylactic Transfusion

  15. PERCENT OF DAYS WITH ≥ GRADE 2 BLEEDING VERSUS EACH DAY’S MORNING PLATELET COUNT* 30 25 20 DAYS WITH ≥ GRADE 2 BLEEDING (%) 15 10 5 0 1-5 >100 11-15 21-25 31-35 41-45 51-55 61-65 71-75 81-85 91-95 PLATELET COUNT (x 103/L) *Data from 1,272 patients with morning platelet counts on 24,309 days. Data reported as percentage with 95% confidence intervals.

  16. Prophylaxis vs No Prophylaxis • 600 patients randomized to Prophylaxis at 10k/ul vs no prophylaxis • Both groups given plt tx for bleeding or procedures • >15 yo with hematologic malignancy or stem cell transplant • Assessed daily for bleeding • Primary endpoint rate of WHO ≥grade 2 bleeding Stanworth et al NEJM 2013;368:1771-80

  17. Baseline Characteristics Stanworth et al NEJM 2013;368:1771-80

  18. Prophylaxis vs No Prophylaxis No deaths from bleeding Stanworth et al NEJM 2013;368:1771-80

  19. To control or prevent bleeding due to deficiencies of platelet number or function Plt ct <10K/μL – prophylaxis, stable pt Plt ct <20K/μL – prophylaxis in patient with clinical factors such as sepsis, DIC, high fevers, splenomegaly Plt ct <50K/μL – bleeding or undergoing invasive procedure Indications for Platelet Transfusions in Heme-Onc Patients

  20. Platelet Transfusions for Platelet Dysfunction

  21. Platelet Refractoriness 40K Usual Response 30K Disease-related platelet consumption: Bleeding, Sepsis, DIC, Splenomegaly, VOD, Amphotericin B, etc. Platelet Count 20K Antibody Mediated:Plt crossmatching, HLA-matched 10K 0 3 6 12 24 Hours

  22. Indications for Apheresis Platelets • To control or prevent bleeding in patients refractory to WBPCs (HLA-matched or cross-match compatible platelets) • To reduce donor exposures in patients receiving a limited number of transfusions • Otherwise, same as for WBPCs

  23. Plt ct >100K/μL w/o platelet dysfunction ITP or TTP unless bleeding is life-threatening Prophylactic use with massive blood transfusion Prophylactic use following cardiac bypass Contraindications to Platelet Transfusion

  24. Recent advances in Platelet Transfusion Practice Does the dose of platelets transfused affect hemostasis in thrombocytopenic patients? How important are the characteristics of the platelet component such as the source, ABO matching, or storage duration in prevention of bleeding?

  25. Platelet Recovery and Survival 50K Usual Response Platelet Count 25K Recovery CCI >7500 Survival CCI>4500 10K 0 3 6 12 24 Hours Post transfusion

  26. “DETERMINATION OF THE OPTIMAL PROPHYLACTIC PLATELET DOSE STRATEGY TO PREVENT BLEEDING IN THROMBOCYTOPENIC PATIENTS” (PLADO Trial) Slichter SJ, Kaufman RM, Assman SF, McCullough J, Triulzi DJ, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. New Eng J Med 2010;362:600-13. Study was conducted at 26 participating hospitals within the Transfusion Medicine/Hemostasis Clinical Trials Network supported by the National Heart, Lung and Blood Institute of the National Institutes of Health

  27. STUDY DESIGN Three-Arm Prospective Randomized Trial) Platelets/m2(BSA)** Medium Dose (MD)* 2.2 x 1011 Lower Dose (LD) 1.1 x 1011 (½ MD) Higher Dose (HD) 4.4 x 1011 (2x MD) *Medium dose corresponds most closely to the current standard transfusion dose of 6 pooled platelet concentrates or 1 apheresis platelet collection. ** An acceptable dose was within 25% either above or below the target dose. The transfusion service was given each patient’s study dose but not the patient’s randomization arm.

  28. Platelet Dosing Study Low Med High Total Number of patients enrolled 453 449 449 1351 Number of patients with 1 platelet transfusion* 417 423 432 1272 Primary Endpoint: At least one episode of  Grade 2 bleeding 71% 69% 70% 70% (% of patients) Secondary Endpoints: Highest grade of bleeding on study (% of patients): None or Grade 1 30% 32% 30% 31% Grade 2 58% 59% 60% 59% Grade 3 9% 7% 8% 8% Grade 4 3% 2% 2% 2% Hemorrhagic mortality (# of patients) 0 0 1 1 *All data reported will be based on patients who received 1 platelet transfusion. There were no significant differences among the arms for any of these study endpoints. NEJM 2010;362:600-13.

  29. How important are the characteristics of the platelet component such as the source, ABO matching, or storage duration in prevention of bleeding?

  30. 1.0 Apheresis 0.9 WBP 0.8 0.7 0.6 0.5 0.4 Probability of Remaining Event Free 0.3 0.2 0.1 0.0 0 5 10 15 20 25 30 35 Time Since First Platelet Transfusion (Days) No. Patients at Risk Apheresis 552 338 168 68 32 16 4 WBP 220 119 56 30 15 5 PLADO: Platelet Source as a predictor of ≥ Grade 2 bleeding p=0.72

  31. PLADO: ABO matching as a predictor of time to ≥ Grade 2 bleeding p=0.28

  32. PLADO: Duration of platelet storage as a predictor of time to ≥ Grade 2 bleeding p=0.87

  33. PLADO: Analysis of Platelet Characteristics Summary • Although the source of platelets, ABO matching, and duration of storage have a measureable effect on platelet increments, there is no discernable effect of these platelet characteristics on a bleeding outcome when platelet transfusions are used prophylactically in hematology and oncology patients

  34. Transfusion Support in Hematology/Oncology Patients • Platelet therapy • Leukoreduction • Transfusion transmitted CMV • Irradiated Blood Components: Prevention of Transfusion associated Graft vs Host disease

  35. Leukoreduction: Definition • AABB Standards 5.7.4.1 “ Leukocyte reduced blood and components shall be prepared by a method known to reduced the leukocyte number to <5x106 for apheresis platelets and Red Blood Cells…”

  36. Leukoreduction by Filtration

  37. Accepted Indications for Leukoreduction • Reduce the risk of fever chill non-hemolytic reactions • Prevent or delay alloimmunization to HLA antigens • Reduce the risk of CMV transmission

  38. Symptoms & Signs Fever (temp rise at least 1° C or 1.8° F) Chills Dyspnea Tachycardia Flushing Hypertension “Fever-Chill” Reaction Febrile, Non-Hemolytic Transfusion reactions

  39. Febrile, Non-Hemolytic TR • Etiology: • Recipient Ab’s to transfused WBCs • Cytokines in transfused product

  40. Leukoreduction Reduces the Rate of FNHTR *Transfusion Jan 2004 Vol 44.

  41. Accepted Indications for Leukoreduction • Reduce the risk of fever chill non-hemolytic reactions • Prevent or delay alloimmunization to HLA antigens • Reduce the risk of CMV transmission

  42. UVB-PC = Ultraviolet B irrad F-AP = filtered apheresis F-PC = filtered pools Trial to Reduce Alloimmunization to Platelets (TRAP) 530 patients with AML randomized to 4 platelet therapies p<.001 for all 3 study arms Percent Alloimmunized New Eng J Med 1997; 337:1861-9.

  43. UVB-PC = UVB irrad F-AP = filtered apheresis F-PC = filtered pools Trial to Reduce Alloimmunization to Platelets (TRAP): Refractoriness 530 patients with AML randomized to 4 platelet therapies Percent refractory p≤.03 for all 3 study arms New Eng J Med 1997; 337:1861-9.

  44. Accepted Indications for Leukoreduction • Reduce the risk of fever chill non-hemolytic reactions • Prevent or delay alloimmunization to HLA antigens • Reduce the risk of CMV transmission

  45. Transfusion Transmitted Cytomegalovirus

  46. CMV in Blood Donors • 30-80% of blood donors are CMV seropositive . Prevalence increases with age. • CMV is transmitted in a latent non-infectious state in the donor leukocytes. • CMV is transmitted only by cellular blood components eg. red cells, platelets

  47. CMV in Auto or Allo BMT

  48. Concept of CMV “Safe” Blood Components • Leukoreduction can substitute for CMV seronegative components • CMV exclusively WBC associated • >3 log (99.9%) leukoreduction removes virus and greatly reduces infectivity • Conserves seronegative units for patients at highest risk • More readily available

  49. CMV Safe Auto BMT

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