Peripheral Blood Allogeneic Stem Cell Mobilization: Can We Predict a Suboptimal Mobilization?

Allogeneic peripheral blood stem cells mobilization is now the basis of most stem cell transplants. In a very limited number of cases, mobilization is suboptimal leading to further collection procedures, to suboptimal cell doses infusion with delayed engraftment time, increased risks of transplant procedure and of related costs. To date we have no recognized and shared criteria for early estimating the probability of poor mobilization in healthy donors. We then analyzed allogeneic peripheral blood stem cell donations performed at the Fondazione Policlinico Universitario A.Gemelli IRCCS Hospital from January 2013 to December 2021 in order to identify premobilization factors associated with successful mobilization. The following data were collected: age, gender, weight, complete blood cell count at baseline, G-CSF dose, number of collection procedures, CD34+ cell count in peripheral blood on the first day of collection, CD34+ cell dose per kg body weight of recipient. Mobilization efficacy was defined according to the number of CD34+ cells in peripheral blood on day +5 of G-CSF administration. We classified donors as sub-optimal mobilizers or good mobilizers according to the achievement of the 50 CD34+ cell/µL threshold. We observed 30 suboptimal mobilizations in 158 allogeneic peripheral blood stem cell donations. Age and baseline white blood cell count were factors significantly associated with negative or positive impact on mobilization, respectively. We did not find significant differences in mobilization based on gender or G-CSF dose. Using cut-off values of 43 years and 5.5×109/L WBC count, we built a suboptimal mobilization score: donors who reach 2, 1 or 0 points have a 46%, 16% or 4% probability of suboptimal mobilization, respectively. Our model explains 26% of the variability of mobilization confirming that most of the mobilization magnitude depends on genetically determined factors; however, suboptimal mobilization score is a simple tool providing an early assessment of mobilization efficacy before G-CSF administration begins in order to support allogeneic stem cells selection, mobilization and collection. Through a systematic review, we looked for confirmation of our findings. According to the published articles, all the variables we included in our model are confirmed to be strongly related to the success of mobilization. We believe that score system approach could be applied in clinical practice to assess the risk of mobilization failure at baseline allowing for a priori intervention.

Inline and offline extracorporeal photopheresis: Device performance, cell yields and clinical response.

BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment for graft-vs-host-disease (GvHD). Photopheresis can be performed in offline or inline method. The first uses a conventional cell separator for collection of mononuclear-cells that are photoactivated by a separate device and manually reinfused; the second one involves a dedicated device performing the entire procedure (collection, photoactivation and reinfusion). STUDY DESIGN AND METHODS: The objective was to compare the two methods and cell product features to highlight key process, devices performance, and to evaluate ECP clinical response. Patients developing steroid-resistant GvHD underwent ECP as second-line treatment using either inline (Therakos CellEx) or offline system (Terumo BCT Spectra or Optia and UVA PIT system). Data about patients' features, pre-apheresis blood-count, cell product characteristics and clinical response were collected for analysis. RESULTS: We evaluated 494 procedures performed on 28 patients from April 2018 to March 2019. The offline procedure allows to achieve greater cell yield, it is characterized by larger processed blood volume, longer runtime, and higher ACD consumption. The inline procedure shows shorter runtime, high mononuclear-cells percentage and low percentage of granulocytes in cell product. We observed a significant difference in cell yields between inline and offline system; furthermore we did not find a significant relationship between cell dose and clinical response. CONCLUSION: Inline ECP is fast, highly automated and productive, making it particularly suitable for ECP treatments. Offline ECP collects high cell yields implying longer procedure and greater operator intervention. Our study did not find a significant relationship between cell dose and GVHD response.

Days Alive Outside Hospital and Readmissions in Patients Undergoing Allogeneic Transplants from Identical Siblings or Alternative Donors.

We have studied the number of days alive outside the Hospital (DAOH) and the number of readmissions within the first 100 days after transplant in 185 patients who received an allogeneic hemopoietic stem cell transplant (HSCT). The donors were matched siblings (SIB; n=61), or alternative donors (ALT; n=124). The median number of DAOH for SIB transplants (78 days, range 21-84) was significantly greater than DAOH for ALT donor grafts (73 days, range 2-87) (p=0.0003). Other positive predictors of DAOH were the use of reduced-intensity regimens (p=0.01), grade 0-I acute graft versus host disease (GvHD) (p=0.0006), and a comorbidity index equal or less than two (p=0.04). Fifty-one patients required readmission (22%), which was predicted by grade II-IV acute GvHD (p=0.009), higher comorbidity index (p=0.06), and ALT donors as compared to SIBS (p=0.08). The CI of readmission was 18% (95%CI 10-31) for SIB and 30% (95%CI 23-39) for ALT donor grafts. The non relapse mortality (NRM) for patients re-admitted was 25% (95%CI 15-43%), compared to 5% (95%CI 2-12%) for patients not readmitted (p=0.0001). In a multivariate analysis, readmission was the strongest predictor of non-relapse mortality (NRM) (HR 2.0) (p=0.0006) and survival (HR 3.4) (p<0.0001). IN CONCLUSION: ALT donor transplants have lower numbers of DAOH, as compared to SIB grafts, which implies longer stay in hospital and higher costs. Readmission to hospital within 100 days, is predicted by acute GvHD, comorbidity index, donor type, and has a significant strong impact on non-relapse mortality and survival.

Inline extracorporeal photopheresis: evaluation of cell collection efficiency.

BACKGROUND: Extracorporeal photopheresis (ECP) therapy has proved to be an effective and safe treatment for graft-versus-host-disease (GvHD), an important complication after hematopoietic stem cell transplantation. In 2016, we acquired Therakos CellEx, a dedicated inline ECP device to accomplish a significant increase in ECP activity. In literature, we found few data reporting CellEx performance evaluated in terms of collection efficiency to qualify the device. Hence, we decided to collect and analyze our data in order to build a reference in terms of expected results of the procedure. Here we report our data of ECP performed using CellEx in a 12-month period focusing on collection efficiency assessment, as well as procedural and apheretic product characteristics. STUDY DESIGN AND METHODS: We collected data of patients undergoing ECP from April 2018 to March 2019 using CellEx in order to evaluate collection efficiency. RESULTS: Between April 2018 and March 2019 we treated 28 adult patients affected by GvHD performing 319 ECP using CellEx. CellEx mononuclear cell product was characterized by high mononuclear cell percentage and low percentage of granulocytes, resulting particularly suitable for ECP treatments. Median collection efficiency for total nucleated cells and for mononuclear cells was 31.2% and 62.3%, respectively. CONCLUSION: Collection efficiency of CellEx was comparable to that usually obtained by cell separators designed for cell collection and was comparable to that of offline systems. Our results provide a detailed performance evaluation for inline ECP system users.

Hyperleukocytosis and leukostasis: management of a medical emergency.

INTRODUCTION: Hyperleukocytosis is defined as a white blood cell count greater than 100,000/mL in patients affected by acute leukemia and often it is associated with increased morbidity and mortality, that can be up to 40% if unrecognized. Areas covered: Risk factors include younger age, myelomonocytic or monocytic/monoblastic morphology, microgranular variant of acute promyelocitic leukemia and T-cell ALL, and some cytogenetic abnormalities. Poor prognosis due to high early death rate secondary to leukostasis. The mechanisms at the origin of leukostasis are still poorly understood. The management of acute hyperleukocytosis and leukostasis involves supportive measures and reducing the number of circulating leukemic blast cells, with careful monitoring of fluid balance, control of uric acid production and control of urine pH to prevent tumour lysis syndrome. Expert commentary: Several studies have been performed to ameliorate the outcome of this setting of patients. The high number of leukocytes may cause 3 main complications: disseminated intravascular coagulation (DIC), tumor lysis syndrome (TLS), and leukostasis. Although hyperleukocytosis and tumour lysis syndrome are still a challenge for clinicians, a better prognosis for these conditions is emerging in the last years.