The Use Of Simple Patient Blood Management Strategies As An Alternative To Platelet and Red Cell Transfusion In Autologous Stem Cell Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2140-2140
Author(s):  
Patricia A. Locantore-Ford ◽  
Shakira Jeanene Grant ◽  
Gina Keck

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.

2020 ◽  
pp. 107815522094158
Author(s):  
Lauren D Curry ◽  
Brandi Anders ◽  
Emily V Dressler ◽  
LeAnne Kennedy

During autologous stem cell transplant, granulocyte colony-stimulating factors (G-CSF) serve the integral role of mobilizing hematopoietic cells into the peripheral blood for subsequent collection by leukapheresis. Filgrastim (Neupogen®) is a G-CSF and affects hematopoietic cells by stimulating growth and differentiation of neutrophils. Filgrastim-sndz (Zarxio®), a biosimilar of filgrastim, received landmark approval as the first biosimilar product approved by the FDA in the United States. As a result of the recent FDA approval, our medical center made the conversion in August 2016 from using filgrastim to filgrastim-sndz to provide patients the same benefits of the filgrastim injection at a reduced cost. This retrospective, observational cohort study evaluated the comparative efficacy of the filgrastim-sndz biosimilar in 147 patients who underwent mobilization prior to stem cell transplant with filgrastim between 1 August 2015 and 31 July 2016 or filgrastim-sndz between 1 September 2016 and 30 November 2017. The mean number of CD34 cells collected during apheresis was 7.38 × 106 in the filgrastim group and 8.86 × 106 in the filgrastim-sndz group. Filgrastim-sndz was significantly non-inferior, as the difference between filgrastim and filgrastim-sndz was −1.48 × 106 with an upper 95% confidence bound equal to −0.24 × 106 that did not include the non-inferiority margin of 1 × 106 ( p = 0.0006). The median number of days of apheresis was 2 in both groups ( p= 0.3273). In conclusion, the biosimilar product was non-inferior for mobilization and the conversion from filgrastim to filgrastim-sndz afforded patients similar efficacy for mobilization in stem cell transplant at a reduced cost.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4917-4917
Author(s):  
A. Keith Stewart ◽  
Young Trieu ◽  
Suzanne Trudel ◽  
Greg Pond ◽  
Joseph Mikhael ◽  
...  

Abstract Alkylating agents remain among the most potent therapies available for treatment of Multiple Myeloma (MM). Their use prior to, or following, autologous stem cell transplant (ASCT) is, however, compromised by concerns about stem cell quality and by myelosuppression limiting effective dose delivered. To address this concern we have studied a combination of cyclophosphamide 500 mg p.o. once weekly and prednisone 100 mg p.o. on alternate days in 66 patients requiring salvage therapy post-ASCT. Dose reductions were allowed for toxicity beginning at cycle 2. On an intent to treat basis, 66 patients received this regimen, however, 7 of these patients were not fully evaluable for response due to non-secretory disease. Of the 59 patients evaluable for response, the median time from transplant to treatment was 26.4 months (range, 6.0 to 66.6). The median time from post-transplant relapse to start of cyclophosphamide and prednisone (C/P) therapy was 1.4 months. The median number of therapies from time of diagnosis to C/P initiation was 2 (range, 1.0 to 5.0). At the date of analysis, treatment with C/P is ongoing in 12 (20.3%) patients, with a median duration of 3.6 months (range, 1.9 to 11.6). The 47 patients who have completed C/P therapy were treated for a median time of 5.5 months (range, 0.5 to 21.7). The reason for discontinuation among these 47 patients included disease progression (42.6% of patients discontinued), plateau disease (21.3%), receiving a second transplant (17.0%), toxicity (10.6%), or switched to another regimen (8.5%). A partial response (&gt;50% protein reduction) was obtained in 37.3% of patients, 18.6% attained minimal response (25–50% protein reduction), 33.8% patients stable disease, while 10.2% patients had progressed on treatment. The estimated median (95% CI) months of progression-free survival after start of C/P treatment is 14.9 (8.7, 21.7). Twenty-three (38.9%) of patients have relapsed after C/P treatment, a median (range) of 8.7 (0.5–65.7) months after start of C/P treatment. At 6 months 74.3% (95% C.I. 61.9% – 89.1%) of patients were progression-free with 28% (95% CI: 16.1–49.2%) progression free at two years. At time of analysis, 44 (74.6%) patients are still alive, with a median follow up of 10.6 months (range, 1.2 to 65.7) since the start of C/P therapy. Fifteen patients have died at a median 13.0 months (range, 1.4 to 61.7) since the time of C/P initiation. The median overall survival (95% C.I.) is estimated to be 35.9 months (24.2, NA). These results demonstrate that the combination of oral cyclophosphamide and prednisone is an effective (56% MR or PR), very well tolerated (10% discontinued due to toxicity) and convenient treatment as salvage MM therapy post-ASCT. The relative lack of myelosuppression allows for re-collection of stem cells and salvage transplant while retaining other active second line agents for later relapse. This regimen thus compares favorably with recent salvage therapeutics introduced in MM and is now being studied in combination with these newer active agents and in induction therapy.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2731-2731 ◽  
Author(s):  
Kyriakos P Papadopoulos ◽  
Scott E. Smith ◽  
Joyce Steinberg ◽  
Renelle Papa ◽  
Javier Lopez-Jimenez ◽  
...  

Abstract Abstract 2731 Background: Survivin is responsible for preservation of cell viability and regulation of mitosis in tumor cells. Survivin is overexpressed in the majority of aggressive B-cell lymphomas and thus is an attractive target in subjects with relapsed lymphoma. YM155 is a survivin suppressant that in vitro, when combined with rituximab, synergistically enhances the induction of apoptosis in lymphoma cells. In human DLBCL xenograft models, this combination significantly inhibits tumor growth and prolongs survival. Based on these preclinical combination data and single agent clinical data, a Phase 2 study utilizing YM155 rituximab was initiated. Methods: The study employs a two-stage group sequential method, designed to enroll a total of 40 subjects with an interim futility assessment (Stage I). Eligible patients have histologically confirmed relapsed CD20-positive primary or transformed diffuse large B cell lymphoma (DLBCL) or grade 3 follicular lymphoma (FL) and are either not candidates or previously had an autologous stem cell transplant (ASCT). Subjects had received ≥ 1 prior anthracycline containing regimen with a documented response to the last regimen prior to study entry. Induction, ASCT and maintenance therapy were considered as one regimen. The dosing regimen was YM155 5 mg/m2/day as a 168 hour (7-day) continuous infusion in a 14 day cycle and rituximab 375 mg/m22 Days 1 and 8 cycles 1 – 4 and then repeated every 10 cycles. The primary endpoint of the study is objective response rate (ORR) per modified IWG 2007. Imaging studies are performed every 8 weeks (4 cycles) after initiation of therapy. In order to continue enrolling in the study, an overall response rate of 4/16 (25%) must be achieved. Results from the completed Stage I are reported here. Results: Sixteen subjects, the majority of whom were male 13/16 (81%), were enrolled in Stage I. The median age was 62.9 (range: 32 – 78) with a majority of subjects 15/16 (93.8%) with DLBCL. IPI/FLIPI scores were intermediate in 10 subjects (62.5%) and high in 3 subjects (18.8%). The median number of prior therapies was 2 (range: 1 – 5), 16/16 (100%) of patients received rituximab in 1st or subsequent lines of therapy. Seven patients (43.7%) had prior ASCT. The median number of cycles of YM155 administered was 11 (1–37). The overall response rate was 9/16 (56.3%) with 2/16 (12.5%) CR, 7/16 (43.8%) PR and 4/16 (25%) SD. The median time to response was 53 days (range: 52 – 109). Median duration of response and median PFS has not been achieved. Clinical benefit rate was 13/16 (81.3%). The most common adverse events reported, regardless of relationship, were pyrexia 8/16 (50%), cough 7/16 (43.8%), asthenia 5/16 (31%) and fatigue, back pain, vomiting, neutropenia and thrombocytopenia each 4/16 (25%). Five subjects (31.3%) experience Grade 4 adverse events and 2 (12.5%) had Grade 5 adverse events (disease progression and respiratory failure), neither of which was considered related to therapy. The most common Grade 4 event was neutropenia 4/16 (25%), with all other Grade 4 events occurring in only 1 subject (febrile neutropenia, thrombocytopenia, general physical health deterioration, infusion site extravasation, central line infection, infective thrombosis, mediastinitis, dyspnoea, pleural effusion). Conclusion: In subjects with relapsed aggressive NHL receiving combination YM155 and rituximab, the ORR for Stage I was 56.3%, which exceeds the requirement to continue to Stage II. Overall the combination regimen was well tolerated with limited hematologic toxicities. Stage II enrollment is ongoing. Disclosures: Papadopoulos: Astellas: Consultancy, Research Funding. Steinberg:Astellas Pharma: Employment. Papa:Astellas Pharma: Employment. Keating:Astellas Pharma: Employment.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5505-5505
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Shaun DeJarnette ◽  
Clint Divine ◽  
Tara L Lin ◽  
Leyla Shune ◽  
...  

Abstract INTRODUCTION: Autologous stem cell transplant (ASCT) is a potentially curative option for lymphoma, yet there remains a bias against offering this therapy to the elderly. Patients above age 65 are nearly always excluded from clinical trials with ASCT, limiting our understanding of the efficacy and toxicities of ASCT in this population. This lack of data and bias against ASCT in the elderly may delay referral for patients who may benefit from a transplant. Here, we report our single institution outcomes from all patients aged 65 and greater who underwent autologous stem cell transplant for lymphoma at our institution. DESIGN AND METHODS : We identified 93 consecutive patients ³ 65 years of age (median age 68.6 years) with lymphoma who underwent autologous stem cell transplantation at University of Kansas Medical Center from 2000 to 2015. After IRB approval, data was extracted using the institutional database. These patients had frequently received at least two treatments, were often beyond first complete remission at the time of transplantation and received their transplants later after diagnosis. Table 1 below summarizes the pre-transplant characteristics of our patients. RESULTS: All patients received G-CSF mobilized peripheral blood stem cells. Engraftment data is available for 87 out of 93 patients. Median number of days to neutrophil recovery (Absolute neutrophil count >500) was 11 (range 9-14). Median number of RBC and platelet transfusion in this group was 2 (range 0-10) and 3 (range 0-39), respectively. Non-relapse mortality at 100 days for the entire group was 2.15%. Overall survival at 100-days was 96.8%. Three patients (3.2 %) developed grade IV pulmonary toxicity and one patient developed grade IV veno-occlusive disease. With a median follow up of 744 days (41-2431), a disease free survival of 373 days was noted. In 63 patients who underwent transplant prior to 2013, 1-year and 2-year overall survival was found to be 84.2% and 72.1 respectively. Of the deaths in first year, 6 (55%) were related to relapse/progression, two (18%) due to pulmonary toxicity, 2 (18%) due to cardiac toxicity and 1 (9%) due to infection. In 17 patients (18.2%), transplant was performed completely/partially as an outpatient procedure. CONCLUSIONS: Although retrospective in nature, these results suggest that transplant related mortality in elderly patients with lymphoma is similar to historic younger cohorts. Chronological age should not be used alone in evaluating lymphoma patients for autologous stem cell transplantation. Instead, a comprehensive evaluation using Hematopoietic cell transplant comorbidity index and geriatric assessment should be used to guide decision-making. As the elderly population grows, an individualized approach to each patient considering all available treatment options is needed to make a potentially curative ASCT for high risk or relapsed lymphoma available to more patients. Table 1. No of patients (%) GenderMale Female 60 (65) 33 (35) Age at ASCT, median (range) 68.6 ( range 65-80) Hodgkin Disease Non Hodgkin Disease 5 (5) 88 (95) NHL subtypes Diffuse Large B- Cell Lymphoma Mantle Follicular Other 35 (40) 18 (20) 16 (18) 19 (22) Disease Status at ASCTCR1 CR 2 or more CRU PR Relapse1 Relapse 2 or more Primary Refractory 29 (31.2) 29 (31.2) 6 (6.5) 19 (20.4) 5 (5.4) 2 (2.2) 3 (3.2) Response to most recent chemoComplete remission Partial remission Progressive disease 64 (68.9) 19 (20.4) 10 (10.8) HCT-CI (% from those with obtained data) 0 1-2 3 or more N/A 15(19.0) 23(29.1) 41(51.9) 14 Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4905-4905
Author(s):  
Hannah McNally ◽  
Luke Mountjoy ◽  
Alison Collings

Abstract Olanzapine has been shown to significantly decrease nausea and emetic episodes associated with chemotherapy in patients undergoing hematopoietic stem cell transplant (Monson, Greer, Kreikemeier, & Liewer, 2020). Additionally, Olanzapine has been shown to improve clinical outcomes in autologous stem cell transplant patients when added to triplet anti-emetic therapy of ondansetron, fosaprepitant and dexamethasone without any negative effects on time to engraftment (Clemmons, et al., 2018). Although this study did not show any delay in time to engraftment, there is only a small amount of data looking at this question, including Clemmons et al. (2016) and Trifilio et al. (2017). Other studies (Navari et al., 2016) demonstrated a decrease in chemotherapy related nausea and vomiting in patients receiving Olanzapine, but did not provide data on engraftment times as this was in standard chemotherapy recipients. At Colorado Blood Cancer Institute (CBCI), Olanzapine was used for a period of time for anti-emetic prophylaxis both pre and post autologous stem cell transplant. There was concern regarding whether or not Olanzapine was causing delays in time to engraftment or even potentially graft failure and use of the drug in transplant anti-emetic regimens was discontinued. We hypothesized that Olanzapine does not cause higher incidence of graft failure, as compared to patients who do not receive Olanzapine as part of their anti-emetic regimen during the pre and post autologous stem cell transplant period. A retrospective analysis (n = 272) was conducted on patients who underwent autologous stem cell transplant between 2019 and 2020. 134 of these patients received Olanzapine during conditioning and up until time of engraftment, and 138 patients had no Olanzapine exposure throughout their conditioning and transplant. Conditioning regimens were equal between the two groups (Table 1). The average number of days on Olanzapine was 10.7, and the average dose was 7.5mg daily. For the purposes of this study engraftment was defined as the first day post stem cell infusion that the patient had an absolute neutrophil count (ANC) of greater than or equal to 500. Findings showed that the mean day of engraftment in the patients with Olanzapine exposure was 14.69; in the non-Olanzapine group, the mean day of engraftment was 12.64 (Table 2). Using the two-sample t-test, this difference (2.05 days, 95% CI (1.60-2.51)) is significant (p&lt;.0001). Based on our findings, there is evidence to support Olanzapine causing a slightly delayed time to engraftment in autologous stem cell transplant patients, but not a higher incidence of graft failure, although a randomized controlled trial would be needed to fully investigate. There is clear data showing increased ability to manage chemo therapy induced nausea and vomiting. While a randomized controlled trial would be needed to fully investigate, given there is not a proven increase in graft failure, Olanzapine should be considered as a desirable option to treat and prevent chemotherapy induced nausea and vomiting in autologous stem cell transplant patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Olanzapine (Zyprexa) - Used off-label for the treatment and prevention of chemotherapy induced nausea and vomiting


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