Autologous Stem Cell Transplants in Jehovah's Witness: Series of ...

Autologous Stem CellTransplants inJehovah’s Witness:Series of 100 PatientsPatricia A. Ford, MDGina Keck, RNNicole Brown, MDPennsylvania HospitalPhiladelphia, PA

Center for Bloodless Medicine & Surgery‣ Established in 1998 atPennsylvania Hospital‣ 203 total transplants (As of09/15/11)‣ 102 JW‣ 18 Breast‣ 7 Ovarian‣ 1 Neuroblastoma‣ 45 Hodgkin’s Lymphoma‣ 44 NHL‣ 83 MM‣ 2 POEMS‣ 2 Amyloid‣ 1 APL8007006005004003002001000Patients Treated by CBMS726660633602604FY07 FY08 FY09 FY10 FY11

Challenges‣ Standard treatment for high-risk or relapsed lymphomaand multiple myeloma: HDC and ASCT‣ Most transplants require RBC and platelet support dueto anemia and profound thrombocytopenia‣ Jehovah’s Witnesses do not accept major blood productsfor religious reasons (Genesis 9:4, Leviticus 17:10, Acts15:29).‣ Report the result of a series of 100 JW who have beentreated with HDC and ASCT without use of blood productsvon Tresckow B, Engert A. Curr Hematol Malig Rep. 2011; 6(3): 172-9.Nademanee A et al. Biol Blood Marrow Transplant. 2011; 17(10): 1481-9.Wandt H et al. Bone Marrow Transplant. 2006; 37(4): 387-92.Kekre N et al. Transfusion. 2011; Ahead of print.

Eligibility‣ All JW undergoing HDC and ASCT at Pennsylvania Hospital05/1996-01/2011‣ Ejection fraction > 50%‣ Diffusion capacity of CO > 50%‣ CrCl > 60mL/min‣ ECOG ≥ 2

Pre-Transplant and Tx•Use IV Fe & erythropoietinto target Hgb = 11 g/dL•Peripheral blood stemcells mobilized using G-CSFand plerixafor to obtainminimal collections of 4.0X 10 6 CD34+ cells/kgProcess•Peripheral blood stemcells processed in 5%albumin in place of freshfrozen plasma•Transplant delayed untilpatient reaches minimumprotocol requirements:•Hgb = 11g/dL•Platelets = 100,000/µLHDC•Patients receive standardHDC for primarymalignancyPrimeDelay

Post-Transplant SchemaBrown NM, Kim SY, and Ford PA. Bone MarrowTransplant. 2009; 44: 391-2.

Patient CharacteristicsTotal Patients (n) 100Age Mean 51 (21-70)Diagnosis (n)LymphomaMMBreastAmyloidosis514522CD34+ Cells Re-infusedPost HDC (10 6 )6.1 (1.0-24.6)

EngraftmentANC > 500µL for 3 days 9.6 days (5-18)Hgb (g/dL)OnsetDecrease in HgbNadirDays Hgb < 812.0 (7.0-15.3)5.3 (2.2-10.2)6.6 (2.0-11.6)7.8 (0-28)Platelet (10 3 /µL)OnsetDays Plt < 10NadirDays until Plt ≥ 20170 (65-502)3.9 (0-14)8.1 (1-50)10.5 (0-20)

Mortality‣ 6% mortality rate‣ Anemia (1%)‣ Presumed sepsis (1%)‣ Multi-organ failure due topancytopenia (1%)‣ Cardiac events (3%)‣ National mortality rate 1-3.5%for lymphoma and MM

Mortality‣ 6% mortality rate‣ Anemia (1%)‣ Presumed sepsis (1%)‣ Multi-organ failure due topancytopenia (1%)‣ Cardiac events (3%)‣ National mortality rate 1-3.5%for lymphoma and MMMorbidity‣ Bleeding events‣ 13% Grade 1‣ Subconjuctival hemorrhage(5), epistaxis (5), minorvaginal bleeding (2),hematuria (1), minor oralbleeding (1), thigh hematoma(1)‣ 1% Grade 3 (GI)‣ 1% Grade 4 (temporal infarct)‣ All managed without transfusions‣ Cardiac complications‣ 26%‣ New onset arrhythmias (12),profound HTN (10), CHF (10),acute MI (1)‣ No correlation betweencomplications and Hgb nadir

Cardiac Complications‣ Unexpected 26% cardiac complications‣ Cardiac toxicity could result from patients with pre-existing cardiac problemswhose conditions may have been be exacerbated by:‣ Cardiotoxic HDC regimen‣ cyclophosphamide, melphalan‣ Older age (p=0.005)‣ Pt developing cardiac complication: 54 ± 10 y/o‣ Pt who did not develop cardiac complication: 46 ± 13 y/o‣ Co-morbidities‣ Present in 58% of patients who developed cardiotoxicity‣ HTN, hyperlipidemia, CAD, DVT, sickle-cell anemia, alpha-thalassemia‣ Renal-impairment‣ Present in 35% of patients who developed cardiotoxicityBrockstein BE et al. Bone Marrow Transplant. 2000; 25: 885-894Guglin M et al. Europace. 2009; 11: 1579-1586.Feliz V et al. Clinical Cardiology. 2011; 34(6): 359-9Mileshkin LR et al. Leukemia Lymphoma. 2005; 46(11): 1575-9

Conclusions‣ Using our blood management techniques, HDC with ASCT canbe safely performed without the use of blood products‣ Our reported 26% risk of cardiac complications were managedwith telemetry monitoring, antiarrhymics and volumeresuscitation‣ More extensive cardiac screening warranted for select patientswho are older or have cardiovascular risks prior to HDC andASCT‣ Many of the blood management strategies utilized in bloodlessASCT may be appropriate in all patients undergoing HDC andASCT and help minimize risk for transfusion transmitteddiseases, immunosuppression, and immunologic reactions

JW; NHL, 3 months post-transplant