Tolerance of Anemia: Autologous Stem Cell Transplantation Among Bloodless Medicine Patients Can be Safely Conducted at Lower Hemoglobin Thresholds
Authors: Patel Evani , Wootton Parisa , Connolly Clare , Locantore-Ford Patricia A. , Cerecino Fumei , Pesce-Noga Rebecca , Henry David H. 
Published: December 2024

Introduction:
Autologous Stem Cell Transplantation (ASCT) offers high curative rates for patients with Multiple Myeloma (MM), Hodgkin's Lymphoma (HL), and non-Hodgkin's Lymphoma (NHL). Optimization of blood counts prior to ASCT is important to avoid prolonged pancytopenia following conditioning chemotherapy, and to minimize post-transplant complications and mortality. Pennsylvania Hospital's Centre for Transfusion-Free Medicine (CTFM) performed the world's first bloodless ASCT more than 20 years ago utilizing cell adjuncts such as erythropoietin (EPO), intravenous iron, aminocaproic acid, and granulocyte colony-stimulating factor (G-CSF). While there exist no clear guidelines as to a specific hemoglobin level to maintain prior to transplantation, practices often vary with a pre-transplant hemoglobin of 11-12g/dL being recommended from prior literature. We conducted a review of all bloodless medicine patients' hemoglobin levels enrolled at the CTFM with MM, HL, and NHL undergoing autologous stem cell transplantation.
Methods:
This retrospective single-center study included all bloodless medicine patients ≥ 18 years old with HL(n=4), NHL (n=11) and MM (n=44) who received ASCT between January 2016 - December 2023 at Pennsylvania Hospital's CTFM. All patients included were inpatient hospitalization encounters for complete blood count (CBC) monitoring following outpatient stem cell collection, conditioning chemotherapy, and stem cell reinfusion. Patients not admitted post-stem-cell infusion were excluded. Data points were manually extracted through chart review and included hemoglobin values in g/dL on admission, discharge and lowest value recorded during admission; length of stay in days; and 30-day post-reinfusion mortality status. Our primary endpoint was to determine mortality rates stratified by hemoglobin ranges per 1.0g/dL prior to admission. A secondary objective was to determine patients' average length of stay (LOS) stratified based on hemoglobin values prior to admission.
Results:
59 patients with either MM, HL, or NHL were included, no patients were excluded from our CTFM database. The average age of patients was 58.5 years. The average hemoglobin on admission for all patients was 12.3g/dL, while the average hemoglobin on discharge was 9.3g/dL, constituted as grade 1 anemia per Common Terminology Criteria for Adverse Events (CTCAE). The average nadir hemoglobin among all patients was 8.2g/dL. Hemoglobin decreased an average of 4.2g/dL from admission to nadir, and 42% of patients experienced grade 3 anemia during nadir (25/59). Of these 25 patients, 14 patients (56%) had improvement in hemoglobin levels above 8.0g/dL on discharge. A single 30-day post-reinfusion death secondary to treatment-related mortality from profound anemia occurred in a patient with a hemoglobin of 2.8g/dL (grade-4 anemia) in the intensive care unit, who had an admission hemoglobin of 11.2g/dL. The average LOS for all patients was 19.2 days. Sub-group analysis of all patients showed that 5% of patients had hemoglobin values between 9-10g/dL, 10% between 10-11g/dL, 27% between 11-12g/dL, and 57% above 12g/dL on admission. Of these patients, 30-day mortality rates within all sub-groups were 0%, as determined by living status at 30-days post-reinfusion, except for a 6.25% mortality rate (1/16) within the 11-12g/dL group. Among patient subgroups stratified by hemoglobin on admission, there was no statistical difference in length of stay (ANOVA p=0.8), nor 30-day post-reinfusion mortality rates (ANOVA p=0.7).
Discussion:
ASCT for bloodless medicine patients has been increasingly accessible over the past decade due to improvement in strategies for pharmacologic support pre-transplantation, effective cytokine mobilization, reducing bleeding events, and close cardiac monitoring. Our single-center data analysis suggests that bloodless medicine patients may, in-fact, have a higher tolerance of anemia ahead of conditioning chemotherapy for ASCT compared to previous evidence. Given a lack of significant difference in mortality rates between patients with admission hemoglobin levels as low as 9.7g/dL and higher levels, we believe ASCT can be safely performed in select patients with hemoglobin values below 11g/dL with close inpatient CBC monitoring and treatment with cell adjuncts.