Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study
Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71-4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).
Collection of Peripheral Blood Progenitor Cells in One Day is Associated with Decreased Donor Toxicity compared to Two Days in Unrelated Donors
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Peripheral blood stem cells (PBSC) have been increasingly used for allogeneic hematopoietic cell transplantation compared to bone marrow stem cells. Currently, the National Marrow Donor Program (NMDP) policy recommends 5 days of daily filgrastim followed by either 1 or 2 days of apheresis for unrelated donors, depending on collection center choice. To date, there are no studies that compare the differences in donor experience between one and two days of apheresis. We examined 22,348 adult unrelated donor collections in 184 centers from 2006-2016. 20,004 (89.5%) donors had collections on 1 day vs. 2,344 (9.5%) over 2 days. Information on why donors were apheresed in one day vs. two days were not available. Donors who underwent apheresis in 1 day were more likely to be male (67% vs. 46%, p<0.001), younger (age <30 years 48% vs. 36%, p<0.001) and have a higher body weight (83.0 kg vs. 75.9 kg, p<0.001) and BMI (BMI>30: 30% vs. 22%, p<0.001). Successful collection of the requested CD34(+) cell count was achieved on the first day in 82% of one day collections vs 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34(+) cells/L in the product on the second day of apheresis was higher than the first day (23.8x10(6) CD34(+)/L 1(st) day vs. 28.7x10(6) CD34(+)/L 2(nd) day, p<0.001). Donors collected in one day were less likely to experience citrate toxicity (36% vs 52%, p<0.001), hospitalizations (1% vs 6%, p<0.001), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% vs. 26%, p<0.001). Female sex, older age, collection via central lines, and greater BMI were factors associated with greater likelihood for development of toxicity whereas less toxicity was noted in those with higher CD34(+) counts and more blood processed on the first day of collection. We conclude that although unrelated donors can be successfully collected in one or two days, one day apheresis procedures were associated with less overall toxicity and we therefore recommend single day collections, especially if the requested number of cells have been collected in one day.
Adult unrelated donor collections in 184 centers from 2006-2016, (n=22,348)
Peripheral blood stem cell collection over 1 day (n=20,004)
Peripheral blood stem cell collection over 2 days (n=2,344)
Successful collection of the requested CD34(+) cell count was achieved on the first day in 82% of one day collections vs 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34(+) cells/L in the product on the second day of apheresis was higher than the first day (23.8x10(6) CD34(+)/L 1(st) day vs. 28.7x10(6) CD34(+)/L 2(nd) day). Donors collected in one day were less likely to experience citrate toxicity (36% vs 52%,), hospitalizations (1% vs 6%), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% vs. 26%). Female sex, older age, collection via central lines, and greater BMI were factors associated with greater likelihood for development of toxicity whereas less toxicity was noted in those with higher CD34(+) counts and more blood processed on the first day of collection.
Peripheral Blood Stem Cell Harvest HPC Count Is an Effective Surrogate Marker for CD34+ Cell Count in Allogeneic Stem Cell Transplant Setting
Translational oncology. 2020;13(7):100788
OBJECTIVE We assessed the predictive potential of XN-HPC for CD34+ cell count as obtained through Sysmex automated hematology analyzers (XN-1000). METHODS This study was conducted at the National Institute of Blood Diseases and Bone Marrow Transplantation in 84 donors between December 2012 and December 2017 in the first phase and later validated in 112 donors between December 2017 and December 2018. Sysmex XN-1000 and BD FACS Calibur estimated XN-HPC and CD34+cells of peripheral blood apheresis product, respectively. Spearman's correlation was assessed between XN-HPC and CD34+ cell count followed by receiver operating characteristic curve calculation to determine the XN-HPC cutoff for a CD34+ count of ≥2 million cells/kg of recipient's body weight RESULTS There is a moderately positive correlation (P value = .003) between XN-HPC and CD34+ count. Receiver operating characteristic curve analyses demonstrated that a cutoff value for XN-HPC of ≥1.845x10(6)cells/kg of recipient's body weight has a specificity and sensitivity of 100% and 78.2%, respectively, for predicting the CD34+ count of ≥2 million cells/kg of recipient's body weight. This cutoff value of XN-HPC was prospectively validated in 112 donors. The positive predictive value was found to be 100%, while negative predictive value was 17%. CONCLUSION XN-HPC has a highly promising potential to serve as a cost-effective and time-saving surrogate for CD34+ cell count.
Safety and Feasibility of Hematopoietic Progenitor Stem Cell Collection by Mobilization with Plerixafor Followed by Apheresis vs Bone Marrow Harvest in Patients with Sickle Cell Disease in the Multi-center HGB-206 Trial
American journal of hematology. 2020
A new protocol for improving efficiency of autologous peripheral blood stem cell collection in patients with high white blood cell counts
Journal of clinical apheresis. 2020
BACKGROUND Collection efficiency (CE) of peripheral blood stem cell (PBSC) collections is negatively affected by increasing white blood cell (WBC) counts of the patient. This study compared a new optimized mononuclear cell (MNC) collection protocol (OPP) to the standard MNC collection protocol recommended by the manufacturer (STP) for PBSC collection in patients with WBC counts >35 000/muL. STUDY DESIGN AND METHODS Single-center, retrospective, and observational study of 81 autologous PBSC collections on Fenwal Amicus cell separators in 70 adult patients. RESULTS Median peripheral WBC count (x10(3) /muL; 44.2 in OPP group vs 46.5 in STP group) and median CD34(+) count (105/muL in OPP group vs 40/muL in STP group) at the beginning of PBSC collection did not differ significantly. Median CE2 (45% vs 31%; P < .001) as well as CD34(+) yield of the apheresis product both with regards to median absolute CD34(+) content (x10(6) ; 793 vs 188; P = .001) as well as median CD34(+) content (x10(6) )/kg body weight (8.93 vs 2.51; P = .002) were significantly higher for the OPP. Overall, 18/21 (86%) patients with the OPP obtained their target CD34(+) amount with a single apheresis session, compared to 25/50 (50%) with the STP (P = .005). PBSC collections using OPP lasted significantly longer (median 377 minutes vs 260 minutes; P < .001) than with the STP. CONCLUSIONS The OPP significantly improves CE2 for PBSC collections on Fenwal Amicus cell separators in patients with pre-apheresis WBC counts >35 000/muL and significantly reduces the necessity for multiple apheresis sessions. The OPP is therefore suited to reduce both patient burden and cost in autologous PBSC collection.
Autologous stem-cell collection following VTD or VRD induction therapy in multiple myeloma: a single-center experience
Bone marrow transplantation. 2020
Triplet-drug regimen bortezomib-thalidomide-dexamethasone (VTD) and bortezomib-lenalidomide-dexamethasone (VRD) are considered as standard of care induction prior autologous stem-cell transplantation (ASCT) in myeloma. In addition to improve response rate, induction therapy should preserve an adequate stem-cell collection. In the present retrospective study, we analyzed stem-cell collection in 325 newly diagnosed myeloma patients who received either VTD or VRD induction before ASCT. Stem-cell mobilization consisted of intravenous cyclophosphamide plus G-CSF. Plerixafor was administered preemptively to rescue mobilization. In comparison with VTD, VRD induction was associated with a more frequent use of plerixafor (19.3% versus 5.4%, p?=?0.004) and with an increased number of apheresis to reach adequate collection (>2 apheresis required in 42.3% versus 30.2%, p?=?0.05). Moreover, more patients experienced collection failure in the VRD group (6% versus 1.8%, p?=?0.004). The median number of CD34-positive cells (×10(6)/kg) was lower in the VRD group: 8.5 versus 9.3 (p?=?0.05) in the VTD group. The vast majority of patients underwent ASCT (93% versus 98%, in VRD and VTD group, respectively). These data highlight the need of optimal stem-cell collection strategy, especially in the context of tandem transplantation and incorporation of anti-CD38 monoclonal antibody into induction.
Retrospective comparison between COBE SPECTRA and SPECTRA OPTIA apheresis systems for hematopoietic progenitor cells collection for autologous and allogeneic transplantation in a single center
Journal of clinical apheresis. 2020
INTRODUCTION COBE SPECTRA [COBE] (Terumo, BCT Lakewood CO) apheresis system has been the most used device for hematopoietic progenitor cells (HPC) collection. Recently, it has been replaced by the SPECTRA OPTIA [OPTIA] (Terumo, BCT Lakewood CO) apheresis system. The aim of our study is to compare both methods for HPC collection. MATERIAL AND METHODS We retrospectively compared 302 HPC collection apheresis procedures (115 allogeneic donors and 187 autologous). The study cohort was divided according to the apheresis system used to analyze the differences between COBE and OPTIA, specifically efficacy of apheresis procedure and product characteristics. RESULTS OPTIA collections result in a higher CD34(+) collection efficiency in both groups (autologous 45.3% vs 41%, P?.006; allogeneic 54.9% vs 45%, P?.0001). The total of CD34(+) cells ×10(6) /kg recipient collected in the product were comparable in both groups (autologous 2.9 in OPTIA group vs 2.8 in COBE group, P = .344; allogeneic 6.2 in OPTIA group vs 5.8 in COBE group, P = .186). The percentage of platelet loss in autologous donors was significantly lower (35.7% vs 40.8%, P?.01). Regarding quality of the product, we observed a significantly lower hematocrit in products collected with OPTIA in both groups (1.8% vs 4%, P?.0001) as well as significantly lower amount of leukocytes (median 153.4 vs 237.2?×?10(9) /L in autologous, P?.0001; 239.5 vs 340.2?×?10(9) /L in allogeneic P?.0001). CONCLUSION Both apheresis systems are comparable in collection of hematopoietic progenitor cells, with significantly higher collection efficiency with the OPTIA system. Collection products obtained with OPTIA contain significantly lower hematocrit and leukocytes.
Presence of promyelocytes in peripheral blood as a novel predictor of the optimal timing for single-step peripheral blood stem cell collection
Journal of Nippon Medical School = Nippon Ika Daigaku zasshi. 2020
BACKGROUND Peripheral blood stem cell (PBSC) collection places a burden on the patient and ideally should be completed in a single procedure. Consequently, a convenient predictive factor is needed for clinical use. METHODS This retrospective study included 72 patients who underwent autologous PBSC collection. A median volume of 3.9x10(6) CD34-positive cells/kg (range: 0.3-47.4x10(6) cells/kg) was collected on the first day. We defined failure as an inability to collect 2.0x10(6) cells/kg on the first day. Patients were classified into failure (n = 25, 34.7%) and success groups (n = 47, 65.3%), and their clinical backgrounds were analyzed. RESULTS The success group included a significantly larger number of cases in which a differential white blood cell count of the peripheral blood on the day of PBSC collection detected promyelocytes (n = 34, 72.3% vs. failure group: n = 11, 44.0%; P0.008). Sixty-two patients underwent autologous PBSC transplantation with a median of 5.6x10(6) transplanted cells/muL (range: 1.60-47.4x10(6) cells/muL). Among transplanted patients, no significant differences were observed between the success and failure groups in terms of the intervals until neutrophil, platelet, and red blood cell engraftment. CONCLUSION The presence of promyelocytes in peripheral blood may be a useful indicator of the optimal timing for single-step PBSC collection.
Apheresis machines variably overestimate mononuclear cell collection volume
Journal of clinical apheresis. 2020
INTRODUCTION Calculation of the actual number of CD34+ cells in the collection product is based on the volume of the collected product and its concentration of CD34+ cells measured in the lab. The number of CD34+ cells infused correlates closely with the pace of hematopoietic reconstitution following autologous or allogeneic stem cell transplantation. METHODS We studied peripheral blood stem cell collections in a single apheresis center with two Spectra Optia devices, using mononuclear cell collection or continuous mononuclear cell collection procedures. The collection volume displayed by the apheresis device was compared with the volume determined by a weight-based method. RESULTS Fifty-two consecutive CD34 collections in 35 different donors (range 1-4 daily procedures per donor) were analyzed. The machines reported larger collection volumes (P < .001). The mean collection volume reported by the machine was 274.37 mL (range 162-396). The mean manually measured collection volume was 261.82 mL (range 155-371.40). Mean overestimation by machine was 12.53 mL (range -0.95 to 31.24; 95% confidence interval 10.94-14.11) or 4.88% (range -0.26 to 10.28). Median overestimation of the absolute number of CD34 was 10.29 x 10(6) (range -2.83 to 141.84 x 10(6) ). CONCLUSION Both Spectra Optia machines overestimated the collection volume after peripheral blood stem cell collection. Although the mean variation falls within the expected range, in some cases, this overestimation may be clinically relevant if no other method of measurement is used.
Vascular access for optimal hematopoietic stem cell collection
Journal of clinical apheresis. 2020
BACKGROUND Autologous and allogeneic hematopoietic stem cell transplantation of cytokine-mobilized peripheral blood stem cells (PBSCs) is increasingly used to treat patients with hematologic disorders. Different types of vascular access have been exploited for the apheresis procedure, including peripheral veins (PV) and central venous catheter (CVC). In some cases, PV access is unavailable. There are few published data on the efficiency and quality of harvesting with different types of vascular access. This study brings out complications and morbidity of this procedure linked to these different access. METHODS We performed a comparative, retrospective, single-center study of hematopoietic stem cell collection using these two types of vascular access. We compared the efficiency and complication rate for 617 adults apheresis sessions in 401 patients and healthy donors, for PBSC collection via PV or CVC between 2010 and 2016. The quality of the HSC product was evaluated in terms of the total CD34?+?count and neutrophil contamination. RESULTS The PV and CVC groups did not differ significantly in terms of the quality of the apheresis product, mean?±?SD CD34?+?cells collected in PV group was 383.1?±?402.7?×?10e6 and 298.8?±?372.7?×?10e6 and the level of neutrophil contamination was 21.0?±?17.8% in the PV group and 20.6?±?18.4% in the CVC group. The complication rate did not differ between the two groups. CONCLUSION The type of vascular access for apheresis hematopoietic stem cell harvesting must be determined by trained staff. Successful harvesting can be performed via PV then CVC is not needed or not available.