Influence of alternative donor type on early survival after hematopoietic stem cell transplantation for acute myeloid leukemia lacking a sibling donor.

Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for acute myeloid leukemia. In the absence of an HLA-matched related or unrelated donor (MRD or MUD), the best alternative donor source remains controversial. Umbilical cord blood and haploidentical donors offer a shorter delay from indication to transplantation. This retrospective multicentre study of a French registry compares overall survival in the 18 months following registration in the absence of a MRD between four types of donors. Between 2012 and 2016, 1302 patients were transplanted using MUD (control, n = 803), mismatched MUD (n = 219), umbilical cord blood (n = 153) and haploidentical (n = 127) donors. Multivariate analyses were conducted for overall survival after registration, after transplant, and transplant-related mortality. After adjustment for variables, the type of donor did not influence any of the three end points. Our results confirmed the significant negative impact of longer time between registration and transplant: HR = 1.04 [1.02-1.06] (p < 0.0001). This indicates a positive correlation between better survival and shorter registration-to-transplantation wait time. In the absence of a sibling donor, the alternative stem cell source does not impact early survival in acute myeloid leukemia patients. The minimization of registration-to-transplantation time should be considered when weighing the alternative donor options.

Audits of collection and apheresis centers: guidelines by the World Marrow Donor Association Working Group Quality and Regulation.

According to the Standards of the World Marrow Donor Association (WMDA), unrelated stem cell donor registries and donor centers are responsible for compliance of their collection and apheresis centers with these Standards. To ensure high stem cell product quality and high standards for safety and satisfaction of voluntary unrelated stem cell donors, we here present guidelines for audits of collection and apheresis centers that can be used by new and established donor registries, as well as by collection centers in preparation of audits. We define the general requirements and recommendations for collaboration with the collection and apheresis centers and define critical procedures for the collection of the stem cell product, such as information session, medical assessment, product collection, quality controls, product handover for transportation, and donor follow-up. The specific guidelines are accompanied by detailed checklists and forms that can be found in Supplementary Information and may be used during an initial or follow-up on-site or paper-based audit.

[Non eligibility criteria for hematopoietic stem cell donors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Critères de non-qualification des donneurs des cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

The evolution of HLA typing and transplantation techniques makes it easier to identify a donor for hematopoietic stem cell (HSC) transplantation. This activity, strongly regulated by regulatory or normative texts, implies in addition biological, medical, para-medical and sometimes psychological evaluations. The benefit/risk discussion is complicated because it must take into account the benefit/risk ratio for the recipient, and the donor risk. No Evidence-Based Medicine data is available and serious events are very rare situations. Biovigilance declarations and their analysis are of fundamental importance. Certain obvious and definite contraindications could be detected very early in the process. It is important to assess whether a risk factor or pathology contributes to increasing the risk associated with collection. In case of recipient risk, the situation should be discussed with the patient team. These recommendations focus on adult peripheral blood HSC donors. They refer to donor information, confidentiality of exchanges, the impact of moral or material pressures, declarations of biovigilance, collegiality and traceability of difficult decisions, desirable experience and training for doctors in charge, use of expert advice informed by an explicit exchange on the possible risks, parsimony of therapeutic interventions and minimization of risks for the donor. We also recommend creation, availability and use by the community of tools and documents (registries, questionnaires, synthetic recommendations, feedback, and collegial qualification meetings) useful for practice.

Management of psychiatric complications in unrelated donor before unrelated peripheral hematopoietic stem cell collections.

Allogeneic hematopoietic stem cell transplantation can efficiently treat patients with severe hematological diseases. A human leukocyte antigen-compatible donor is required for performing transplantation. The occurrence of unexpected acute severe diseases in a donor can compromise the feasibility of allogeneic hematopoietic stem cell transplantation. However, when a severe health problem occurs in a donor while the recipient has already received a conditioning regimen, hematologists have to find the best solutions for the recipient, while the team in charge of the donor has to find the best medical solutions for the donor. We describe here the occurrence of psychiatric acute complications in an unrelated donor while the myeloablative conditioning regimen had already been given to the recipient. We report the successive decisions that were made in an emergency based upon the expertise of physicians specialized in hematology, apheresis, cell therapy, and psychiatry to preserve the donor's health and recipient's life.

Evaluation of an algorithm based on peripheral blood hematopoietic progenitor cell and CD34+ cell concentrations to optimize peripheral blood progenitor cell collection by apheresis.

BACKGROUND: Quantification of peripheral blood (PB) CD34+ cells is commonly used to plan peripheral blood progenitor cell (PBPC) collection but is time-consuming. Sysmex has developed a hematology analyzer that can quickly identify a population of immature hematopoietic cells (HPCs) according to cell size, cell density, and differential lysis resistance, which may indicate the presence of PBPCs in PB. This prospective study has evaluated the potential of such method to predict the PBPC mobilization. STUDY DESIGN AND METHODS: A total of 141 patients underwent PBPC mobilization. PB HPCs and PB CD34+ cells were simultaneously quantified with a hematology analyzer (SE2100, Sysmex) and flow cytometry, respectively. The number of blood volumes processed was then based on PB CD34+ cell concentration. RESULTS: The optimal PB HPC level able to predict a minimal level of 10 x 10(6) PB CD34+ cells per L was 5 x 10(6) per L with positive and negative predictive values of 0.93 and 0.36 percent, respectively. For this cutoff point, sensitivity and specificity were 0.81 and 0.65, respectively. The median number of blood volumes processed according to the PB CD34+ cell count allowed us to perform only one apheresis procedure for a majority of patients. CONCLUSION: PB HPC quantification is very useful to quickly determine the initiation of PBPC apheresis especially for patients with higher concentrations. For patients exhibiting a lower HPC count (<5 x 10(6)/L), other parameters such as a CD34 test may be needed. Such a policy associated with a length of apheresis adapted to the richness in the PB CD34+ cells allows for optimizing the organization of centers with an improvement in patient comfort and economical savings.

Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients.

Plasmacytoid dendritic cells (pDCs) are the professional type I interferon (IFN)-producing cells, and upon activation they traffic to lymph organs, where they bridge innate and adaptive immunity. Using multianalyte profiling (MAP), we have mapped the key chemokines and cytokines produced in response to pDC activation, taking into consideration the role of autocrine IFN, as well as paracrine effects on other innate cells (e.g., monocytes and conventional DCs). Interestingly, we identify four distinct cytokine/chemokine loops initiated by Toll-like receptor engagement. Finally, we applied this analytic approach to the study of pDC activity in chronic hepatitis C patients. Based on the activation state of pDCs in fresh blood, the lack of agonistic activity of infectious virions, the production of a broad array of cytokines/chemokines once stimulated, and the direct effects of pDCs on other PBMCs, we conclude that the pDCs from hepatitis C virus (HCV)-infected individuals are fully functional and are, indeed, a viable drug target. In sum, this study provides insight into the use of MAP technology for characterizing cytokine networks, and highlights how a rare cell type integrates the activation of other inflammatory cells. Furthermore, this work will help evaluate the therapeutic application of pDC agonists in diseases such as chronic HCV infection.

Use of hematopoietic progenitor cell count on the Sysmex XE-2100 for peripheral blood stem cell harvest monitoring.

Successful peripheral blood stem cell (PBSC) collection depends on the timing of apheresis based on CD34+ cell enumeration. Because this analysis is expensive and induces organization difficulties, we evaluated hematopoietic progenitor cell (HPC) quantification on the Sysmex XE-2100 as a surrogate analysis. We tested 157 blood samples for CD34+ cells and HPC counts. We found a good linear correlation between HPC and CD34+ and determined simple rules allowing to use HPC count in daily practice. We set a positive cut-off >30 HPC/mm(3) for allowing PBSC harvest and a negative cut-off at 0 HPC/mm(3) for which collection should be delayed. These two situations accounted for 62% of cases and CD34+ cell count by flow cytometry confirmed HPC result in 95% of cases. Between 0 and 30 HPC/mm3, CD34+ enumeration is required for decision-making. We conclude that HPC count may be a useful surrogate for CD34+ enumeration in PBSC harvest monitoring.

CD34 stem cell top-ups without conditioning after initial haematopoietic stem cell transplantation for correction of incomplete haematopoietic and immunological recovery in severe congenital immunodeficiencies.

Haematopoietic stem cell transplantation can be limited by ineffective haematopoiesis and poor immune recovery. A CD34(+) cell infusion without conditioning has the potential to improve stem cell function with limited toxicity. Eighteen patients with congenital immunodeficiencies received CD34(+) boosts for various defects. When given <1 year after the original graft, six of seven cytopenic patients achieved transfusion independence. A second cohort (n = 11) received boosts >1 year after the original graft; only minimal changes in immune function or chimaerism were noted. Unconditioned stem cell boosts have limited toxicity but should be given early after the original graft to be effective.

A double-blind low dose-finding phase II study of granulocyte colony-stimulating factor combined with chemotherapy for stem cell mobilization in patients with non-Hodgkin's lymphoma.

The aim of the study was to define the minimal effective dose (MED) of granulocyte colony-stimulating factor (G-CSF) among five daily doses following chemotherapy for peripheral blood stem cell (PBSC) collection. Twenty-five patients were included in this double-blind dose-finding phase II study conducted according to a two-stage Bayesian design. The estimated probabilities of success for PBSC collection for the G-CSF doses of 50, 75, 100, 125 and 150 microg/m2/day were 84%, 87.7%, 91%, 93.9 and 96.4%, respectively. Low G-CSF doses may be used with a similar probability of success as conventional doses and could allow significant savings.

Successful peripheral blood stem cell harvesting with granulocyte colony-stimulating factor alone after previous mobilization failure.

A total of 138 patients whose stem cell mobilization failed following chemotherapy and granulocyte colony--stimulating factor (G-CSF) at a dose of 5 microg/kg/d were given a higher dose of G-CSF (10 microg/kg/d) for 5 days after a 7-day resting period. Stem cell mobilization was successful in 90 patients, who yielded a median of 3.5x10(6) CD34(+) cells/kg, partially successful in 17 patients (1-2.4x10(6) CD34+ cells/kg) and failed in the remaining 31 patients.

Stroke volume monitored by modeling flow from finger arterial pressure waves mirrors blood volume withdrawn by phlebotomy.

Rate-controlled blood withdrawal was used to reduce cardiac preload and consequently stroke volume in patients with normal cardiac function. Twelve patients with asymptomatic hereditary hemochromatosis, undergoing regular phlebotomy therapy, volunteered for the study. An average volume of 375 ml was withdrawn in an average period of 6.4 min. Finger pressure was continuously measured by a Finometer device which includes the Beatscope software for deriving the stroke volume from the blood pressure waveform. Blood withdrawal resulted in reduction of the stroke volume estimates (from 94.0 +/- 5.2 to 80.7 +/- 5.3, P < 0.05) together with a reduced pulse pressure (from 53.0 +/- 3.5 to 47.1 +/- 3.2, P < 0.05). No significant changes in heart rate (75.2 +/- 3.7 versus 78.3 +/- 4.5 beats/min) were observed. Calculated cardiac output was reduced while calculated total peripheral resistance was elevated after blood withdrawal. Beat-to-beat analysis demonstrated a significant linear regression between most of the hemodynamic indices and the volume withdrawn. The highest correlation coefficients were found for the stroke volume (0.88 +/- 0.01, P < 0.001) and the pulse pressure (0.80 +/- 0.04, P < 0.001) corresponding also to the highest slopes for the lines relating these measures to the relative blood volume withdrawn. The non-invasive estimation of finger blood pressure can be used to derive simple on-line indices (pulse pressure, stroke volume using the Modelflow) of cardiac preload, which are of major interest in the monitoring of cardiovascular status.

High-dose CD34+ cells are not clinically relevant in reducing cytopenia and blood component consumption following myeloablative therapy and peripheral blood progenitor cell transplantation as compared with standard dose.

BACKGROUND: No agreement exists about the number of autologous peripheral blood progenitor cells (PBPCs) to transfuse for optimal hematologic recovery after high-dose chemotherapy. STUDY DESIGN AND METHODS: To determine CD34+ cell dosage following high-dose chemotherapy (in terms of hematologic recovery and blood component consumption), the effects of two schedules of CD34+ cell transfusions in a cohort of patients with myeloma or non-Hodgkin's lymphoma were examined. Forty patients (Group 1) received between 2.5 and 5 x 106 CD34+ cells per kg, with a median of 3.4 x 106 per kg following high-dose chemotherapy, and 40 patients (Group 2), selected to match Group 1 for age, diagnosis, prior therapies, and procedure for PBPC mobilization, received a dose of CD34+ cells >5 x 106 per kg, with a median of 8.4 x 106 per kg (5-33). RESULTS: The median number of days to achieve a neutrophil count of >0.5 x 109 per L and unsupported platelets of >20 x 109 per L was identical for the two groups, but the time required to reach 1.5 x 109 neutrophils per L and 50 x 109 platelets per L was greatly delayed in Group 1. No significant difference was observed for the median number of RBC and platelet transfusions, or for the proportion of patients in each group that did not require either platelet or RBC transfusions. CONCLUSION: Our data confirm a dose-response relationship between CD34+ cell dose transfused and time to hematologic recovery after high-dose chemotherapy. However, the minimal Hb and platelet counts for transfusion independence in the two groups are similar when the CD34+ cell dose is greater than 5 x 106 CD34+ cells per kg. Therefore, our data suggest that it is not necessary to go on with apheresis procedures after 5 x 106 CD34+ cells per kg are harvested to sustain one high-dose chemotherapy.