Autologous Stem Cell Transplantation without Hematopoietic Support for the Treatment of Hematological Malignancies in 125 Jehovah’s Witnesses

INTRODUCTION High dose chemotherapy (HDC) followed by Autologous stem cell transplant (ASCT) has been shown to provide curative benefit in patients with relapsed lymphoma and multiple myeloma, often times requiring hematopoietic support until marrow engraftment. Due to Jehovah's Witnesses (JW), refusal of blood products treatment challenges arise. This prospective study represents 125 JW with lymphoma (n= 55), multiple myeloma (MM) (n= 68) or amyloidosis (n=2), treated with HDC and ASCT without transfusions. PATIENTS AND METHODS All patients with diagnoses of MM and lymphoma were considered eligible for enrollment, irrespective of prior regimens or complete remissions. Patients were primed pre-transplant with intravenous iron and erythropoietin at a dose of 60,000 units weekly. Cytokine mobilization of stem cells was used preferentially over chemo-mobilization to facilitate apheresis. HDC post apheresis was delayed until hemoglobin (Hb) and platelets approached 11g/dl and 100 x 103/ μL respectively. All patients with multiple myeloma received standard dose Melphalan 200mg/m2, with dose adjustment to 140-150mg/m2 in patients with severe kidney dysfunction. Lymphoma patients received BCNU 300mg/m2 on day 1, Cyclophosphamide 1500mg/m2 day 2-5, and VP16 700mg/m2/day on days 2-4. Post-transplant, blood management techniques included minimization of unnecessary phlebotomy, limitation of potential sources of blood loss, namely from the gastrointestinal tract, by the utilization of proton pump inhibitors and stool softeners and avoidance of antiplatelet agents wherever possible. In menstruating females progestational agents were given to cease menstrual flow. All patients received granulocyte colony stimulating factor (G-CSF) and erythropoietin. Thrombocytopenia was managed with the antifibrinolytic agent aminocaproic acid, phythonadione and rarely cryoprecipitate. RESULTS Ninety percent of patients (n=113) were alive at 100 days post transplantation, and 12 patients had died prior to 100 days. Six patients (4.8%) died prior to day 30 and were considered transplant-related mortalities (TRMs). The etiologies were as follows: profound anemia (n=1), severe sepsis (n=1), multi-organ failure due to pancytopenia (n=1) or cardiac events (n=3). Since March 2010 there have been no additional TRMs. There were 2 life threatening (grade 3 – 4) but non-fatal bleeding complications, 2 grade 2 bleeding complications and minor bleeding (grade 1) in 15 patients. The median decrease in Hb was 5.0 g/dL (range 0-10) for all patients, with a median Hb nadir of 7.0 g/dL. The median total number of days with a platelet count < 10 x 103/μL was 3 days (range 0–14) with a median platelet nadir of 5.0 x 103/μL. Cardiac complications occurred in 40 patients (32%), most commonly arrhythmias (n=23). CONCLUSION ASCT can safely be performed without transfusion support in JWs with acceptable bleeding complications. Though demonstrating a TRM which is higher than that of the national average this appears acceptable for this unique patient population. Furthermore the bloodless approach may be appropriate in a select patient population undergoing HDC followed by ASCT, an approach which would reduce blood transfusion and its associated complications through the utilization of techniques and alternatives such as erythropoietin, aminocaproic acid, phytonadione and iron. Additionally the absence of bleeding complications at platelet counts > 5 x 103/μL, suggest use of a prophylactic platelet transfusion trigger of ≥ 5 x 103/μL, may be appropriate in select patients. | | No. | Median | Range | | ----------------------------------------------------------------------------------------------- | --------------- | ------------ | --------------------- | | Neutrophils | | | | | Days to ANC ≥1,000/mL | 125 | 10 | 4 - 19 | | Hemoglobin | | | | | Hemoglobin at onset of conditioning, g/dL | 125 | 11.8 | 7.0 – 11.8 | | Hemoglobin decrease to nadir, g/dL | 124 | 4.9 | 0.5 – 10.2 | | Hemoglobin nadir, g/dL | 123 | 7.0 | 2.0 – 11.6 | | Duration of grade 3/4 anemia hemoglobin < 8 g/dL | 125 | 9 | 1 - 28 | | Hemoglobin at day +30, g/dL | 98 | 10.9 | 3.5 – 14.9 | | Platelets | | | | | Platelets at onset of conditioning, /mL | 124 | 148 | 65 - 502 | | Platelet nadir, /mL | 123 | 5 | 1 - 50 | | Duration of Grade 4 thrombocytopenia platelets <10x103/μL | 125 | 3 | 0 - 14 | | Duration of Grade 3 thrombocytopenia platelets <20x103/mL Days to platelets > 20,000/µL | 125 125 | 4 11 | 0 – 20 0 - 23 | | Platelet count at day + 30, /mL | 97 | 137 | 17 - 557 | Table 1. Engraftment Parameters Disclosures No relevant conflicts of interest to declare.