The Use Of Simple Patient Blood Management Strategies As An Alternative To Platelet and Red Cell Transfusion In Autologous Stem Cell Transplant
Authors: Locantore-Ford Patricia A. , Grant Shakira Jeanene , Keck Gina 
Published: October 2019

Abstract

Introduction
High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is considered the standard of care for patients with high-risk or relapsed lymphoma and multiple myeloma (MM). With most patients requiring both red cell transfusion ,and platelet support until marrow engraftment. Jehovah’s Witnesses (JW), based on religious convictions, refuse blood products, and therefore are frequently denied transplants in most centers, due to the presumed fear of death from bleeding and anemia.
We present a series of 119 JW diagnosed with lymphoma (n= 54), (MM) (n= 63) and amyloidosis (n=2) who received treatment with HDC and ASCT without transfusion support.

Methods
All JW undergoing HDC and ASCT at Pennsylvania Hospital between May 1996 and March 2013 were included. Patients were primed pre-transplant with IV iron and erythropoietin to a target Hemoglobin (Hb) > 11g/dl.Cryopreservation of collected cells, was performed using normal saline and albumin instead of fresh frozen plasma. Post apheresis, HDC was delayed to allow Hb levels to rise to ≥ 11 g/dl and platelets ≥100,000. Post-transplant, patients received granulocyte colony-stimulating factor, erythropoietin and initially interleukin-11 which was later discontinued, as there was no benefit observed in the length of time to platelet engraftment. Thrombocytopenia was managed with antifibrinolytic agents (Amicar) and vitamin K, the avoidance of anticoagulation and aspirin, and rarely cryoprecipitate, desmopressin, and nasal vasoconstrictors.

Results

Engraftment
The median number of days to neutrophil engraftment, with absolute neutrophil count ≥1,000/μL, was 10.0 days. The median Hb at the onset of chemotherapy was 11.8 g/dL, (range 7-15.3 g/dL), and the average decrease in Hb was 5.0 g/dL, with an average nadir of 6.8 g/dL. The median number of days with Hb under 8 g/dL was 5.5 days. The median platelet count at onset of chemotherapy was 148 x 103/μL (range of 65 to 502 x 103/μL). The median number of days with a platelet count under 10 x 103/μL was 3.0 days (range 0 to 14 days) with a median platelet nadir of 4.0 x 103/μL (range 1-50 x 103/μL). Patients with lymphoma experienced a lower drop in Hb post cytotoxic regimen than myeloma patients (ΔHb = 4.5g/dl for MM, 6.0g/dl for lymphoma, p < 0.05).The average length of stay (LOS) was 19.0 days.

Bleeding Complications
Bleeding complications were classified using the WHO criteria. Patients with platelet counts greater than 5 x 103/μl experienced no bleeding complications or death due to hemorrhage. There was one grade 4 hemorrhage, a temporal infarct leading to temporary vision loss and confusion, one grade 3 hemorrhage, a major gastrointestinal bleed, and one grade 2 hemorrhage which was hematuria. Sixteen patients experienced grade 1 bleeding episodes consisting of subconjunctival hemorrhage (n=5), epistaxis (n=6), minor vaginal bleeding (n=2), minor oral bleeding (n=1) a thigh hematoma (n=1), and a minor retinal bleed (n=1).

Cardiac Complications
Forty two of the one hundred and nineteen patients who underwent HDC and ASCT, experienced cardiac complications.These included new onset arrhythmias (n=19), profound hypotension (n=15), congestive heart failure (n=10) and acute myocardial infarction (n=1). The mean Hb nadir for patients who experienced a cardiac complication was 6.6 g/dL .Additionally the median age was 56 years (range 21-71years) and the average change in hemoglobin was 5.0g/dl.

Mortality
The 100 day transplant related mortality was 5%.The six deaths recorded were due to sepsis, multi-organ failure due to pancytopenia and cardiac events.

Conclusion
Based on our study we conclude that HDC followed by ASCT, can safely be performed without the need for transfusion support, with low mortality rates and low incidences of major bleeding complications .Anticipated anemia may be managed by ensuring priming of Hb with the use of IV iron and erythropoietin to Hb ≥11 g/dl, and simple patient blood management techniques.
Thrombocytopenia may be managed similarly, by allowing platelet recovery post apheresis to ≥ 100, 000. We also believe that Amicar and Vitamin K offer as good and effective, an alternative to prophylactic platelet transfusion in the management of thrombocytopenia. Additionally these agents may be used to achieve homeostasis in patients who develop platelet refractoriness, and similarly the use in all transplant patients may be appropriate.

Disclosures:
No relevant conflicts of interest to declare.