Essential requirements for setting up a stem cell processing laboratory.

The Graft Processing subcommittee of the Worldwide Network for Blood and Marrow Transplantation wrote this guideline to assist physicians and laboratory technologists with the setting up of a cell processing laboratory (CPL) to support a hematopoietic stem cell transplant program, thereby facilitating the start-up of a transplant program in a new location and improving patient access to transplantation worldwide. This guideline describes the minimal essential features of designing such a laboratory and provides a list of equipment and supply needs and staffing recommendations. It describes the typical scope of services that a CPL is expected to perform, including product testing services, and discusses the basic principles behind the most frequent procedures. Quality management (QM) principles specific to a CPL are also discussed. References to additional guidance documents that are available worldwide to assist with QM and regulatory compliance are also provided.

Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation.

This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.

Characterization of hemopoietic engraftment kinetics and development of secondary cytopenia in AML post auto-SCT and its correlation with survival outcome.

We performed a single center retrospective analysis of 84 autologous hemopoietic stem cell transplants done for AML to characterize the pattern of hemopoietic engraftment, post-transplant cytopenia and their impact on survival outcome. Following autologous transplant and engraftment, 30 patients (35.7%) had a transient secondary decline in their plt counts, which was not associated with graft rejection, relapse or infection. The median time to onset of thrombocytopenia was 59 days post transplant, with spontaneous recovery after a median period of 41 days. A secondary decline in ANC also occurred in eight patients. Patients with secondary plt decline had a significantly earlier primary plt engraftment (median 15 days) and a trend towards earlier neutrophil engraftment compared with patients who maintained steady plt counts (median 21 days). There was a trend towards a lower incidence of secondary plt decline in patients who received BM stem cells compared with those who received PBSC. No cause was evident for the occurrence of a secondary cytopenia, and it did not adversely affect survival. We conclude that secondary cytopenia is a common and harmless occurrence after autologous transplant especially from PBSC graft.

Blood transfusion requirements and independent predictors of increased transfusion requirements among adult patients on extracorporeal membrane oxygenation -- a single centre experience.

BACKGROUND/OBJECTIVES: More adults undergo extracorporeal membrane oxygenation (ECMO) now. They have high transfusion requirements. This study described transfusion requirements of adults during ECMO in a single institution, and determined factors associated with high transfusion requirements. MATERIALS/METHODS: Retrospective analysis was done on the amount of blood products received by adults during ECMO. Predictors of increased average daily transfusion requirements during ECMO and increased ECMO duration (which correlated positively with total transfusion requirements) were determined. RESULTS: Forty-one patients (median age 50 years) underwent 42 ECMO sessions for respiratory failure (16.7%), cardiogenic shock (76.2%) or massive pulmonary embolism (7.1%). They received 569 red blood cells, 852 platelets, 126 fresh-frozen plasma (FFP) and 220 cryoprecipitate in total during median ECMO duration of 5 (1-15) days. On multivariate analysis, average daily red blood cell transfusion increased with nadir haemoglobin (Hb) during ECMO (Hb(nadir)) of < 7.5 g/dl (P < 0.001). Average daily platelet transfusion increased with recent antiplatelet agents (P = 0.015) and maximum Hb decline of > 5.5 g/dl during ECMO (P = 0.011). Average daily platelet transfusion > 3 units was also associated with increased ECMO duration (P = 0.024). Average daily FFP transfusion was increased in patients with hypertension (P = 0.007) and Hb(nadir) < 7.5 g/dl (P = 0.050). Patients with sepsis (P = 0.009) or without surgery (P = 0.009) had increased ECMO duration, which correlated positively with total transfusion requirements during the entire ECMO session. ECMO improved mortality of patients with fulminant myocarditis, respiratory failure and massive pulmonary embolism. CONCLUSION: Adult ECMO patients with lower Hb(nadir) require more daily red blood cell and FFP. Hypertension increases daily FFP requirements. Recent antiplatelet agents, larger Hb decline and longer ECMO duration increase daily platelet requirements. Patients with sepsis or on ECMO for medical reasons have longer ECMO duration, which is associated with total transfusion requirements. Some of these factors may be identified early to optimize blood product support.

The management of perioperative bleeding.

Excess perioperative bleeding remains a major complication following surgery, resulting in increased morbidity and mortality. The principal causes of non-surgical haemostatic perioperative bleeding are a pre-existing undetected bleeding disorder, related to the nature of the operation itself or from coagulation abnormalities arising from massive blood loss. Very often, it is a combination and coexistence of various pathologies. Identifying patients at risk remains a major component of preventing excessive blood loss. Understanding the haemostatic changes occurring in the perioperative period, especially in complex procedures like cardiopulmonary bypass and orthotopic liver transplantation is crucial in developing new strategies for the management of perioperative bleeding. Pharmacological interventions, especially aprotinin, tranexamic acid, desmopressin and increasingly, recombinant VIIa are being used both in prophylaxis and therapeutically to stop bleeding. The use of near patient testing like thromboelastography and platelet function analyser has allowed for more detailed assessment of the various steps of haemostasis. One of the main goals is to reduce the usage of allogeneic blood transfusion and its attendant risks.