This study uses National Inpatient Sample survey data to characterize trends in red blood cell, plasma, and platelet transfusions in the United States between 1993 and 2014, a period of time during which trials were demonstrating the safety of restrictive red blood cell transfusion strategies.
Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood (UCB) graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic graft-versus-host disease (GVHD). But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very-high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% versus 11% p<0.0001) and decrease in one year progression-free (20% versus 55%, p=0.004) and overall survival (30% versus 62%, p=0.02). Less than 100% UCB chimerism in the CD3 lineage was associated with increase rate of disease recurrence (46% versus 12%, p=0.007). Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% versus 15%, p=0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful graft-versus-leukemia (GVL) effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high.
Background. ROTEM® test results can be affected by the citrate to blood ratio in the tested sample. Overfilling or underfilling specimen tubes can change this ratio. Objectives. The aim of this study was to determine the impact of under- and overfilling citrate test tubes on ROTEM® EXTEM measurements. Results. Overall repeated measures ANOVA demonstrated significant differences of CT (p = 0.004), CFT (p = 0.005), A5 (p = 0.001), A10 (p <0.001), and MCF (p < 0.001). Pairwise comparison revealed that underfilling significantly altered the results of those parameters reflecting functional clot firmness (A5, A10, and MCF), while overfilling led to a prolongation of the CT results only. No differences were observed for alpha angle and maximum lysis. Conclusion. Both underfilling and overfilling specimen tubes have significant influence on the results of the ROTEM® EXTEM test, although the small observed bias is likely of limited clinical relevance. However, it seems prudent to limit the maximum allowed difference in filling to less than ± 10%. All ROTEM® operators should be aware of this pre-analytical variable.
Cryopreserved umbilical cord blood transplants are increasingly used as a source of hematopoietic stem cells, however quality of cords vary significantly. Post-thaw testing at cord banks is not yet routinely available or standardized, and cord blood bank (CBB) viability and potency assessments may differ from that of receiving centers. We attempt to correlate post-thaw testing at CBBs with that of our transplant center.
Abstract PURPOSE: Delayed engraftment and cord graft failure (CGF) are serious and often fatal complications after unrelated cord blood (UCB) hematopoietic cell transplantation (HCT), precluding use of low cell dose UCB. The haplo-cord HCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34+ selected haploidentical graft. Although haplo-cord HCT aims to achieve durable UCB hematopoiesis, the haplo graft provides early temporary engraftment. We describe the frequency, complications and risk factors of CGF after haplo-cord HCT after reduced-intensity conditioning (RIC). PATIENTS AND METHODS: Adult hematologic malignancy patients from the University of Chicago or the Weil Cornell medical centers who underwent haplo-cord HCT between 2007 and 2013 were included. Conditioning consisted of fludarabine, melphalan, and rATG (and TBI 400 cGY if high CNS relapse risk), followed by infusion of a CD34+ selected G-CSF mobilized haploidentical graft and the best HLA matched single UCB unit of at least 0.5 or 1.0 x 10^7 total nucleated cells (TNC)/kg, depending on the protocol. CGF was defined as <5% cord blood chimerism by Day 60 in the unfractionated or CD3 compartments irrespective of neutrophil or platelet counts. Death before Day 60 excluded patients from the primary outcome of CGF at Day 60. Univariate analyses were performed to identify potential risk factors for CGF: Fisher's Exact test for dichotomous and logistic regression for continuous predictor variables. RESULTS: 107 patients were evaluated. Chimerism data were not available on two, and 11 (10.3%) died before Day 60, leaving 94 evaluable patients for CGF. Diseases indications were: AML (51%), ALL, (12%), MDS (11%), and other (25%). Median age of patients was 50 years (range 18-73) and many had active disease at HCT (47%). The mean UCB collected dose was 2.1x10^7 TNC/kg (range 0.77-8.3x10^7 TNC/kg) and HLA cord match was 4/6 in 24% and 5/6 or 6/6 in 73%. Few patients had UCB doses below 1x10^7 TNC/kg (N=5). CGF occurred in 14 of 94 (15%) evaluable patients. Of these, 7 died within 1 year of transplant date. The causes of deaths were: poor graft function (N=2), infection (N=2), relapse or progressive disease (N=2) and unknown (N=1). The other 7 remain alive (range: 7 months to 5.5 years) with haplo-derived or mixed haplo-recipient hematopoiesis. Four are in remission and three have relapsed disease. Median survival for the CGF group was 12.7 months. In univariate analyses, no UCB factor, including cell doses, major ABO mismatch, donor specific antibodies, CMV status, and HLA-match, was associated with CGF. (Table) However, higher haploidentical TNC and CD34+ doses were associated with greater risk of CGF. CONCLUSION: Approximately 15% of patients experienced CGF after haplo-cord HCT. Most have died or relapsed, but some have had relatively long-term survival due to sustained haploidentical hematopoiesis. Avoidance of high haploidentical cell doses may reduce risk of CGF. We were unable to identify other determinants of CGF. In ongoing studies, we have limited the haplo graft to <5 x10^6 CD34+/kg and are testing the use of lower UCB cell doses when large units can not be identified. Additional follow-up is needed to determine if sustained or greater cord chimerism improves long-term outcomes compared to haplo chimerism after RIC haplo-cord SCT. Table: Graft Composition and Association with Cord Graft Failure (CGF) at Day 60 No CGF CGF p-value Evaluable Patients, N=94 N=80 N=14 Cord Blood Unit: Mean/Value (+/-SD or %) Mean/Value (+/-SD or %) Cord Bank Reported (post-processing): TNC/kg x 10^7 2.1 (+/-1.1) 1.9 (+/-0.63) 0.61 TNC/kg<1.5x10^7, N=92 27 (35%) 3 (21%) 0.54 CD34+/kg x 10^5 0.88 (+/- 0.71) 0.98 (+/- 0.80) 0.65 Viability (%) 95.6 (+/-4.7) 96.9 (+/-4.6) 0.38 Viability <85%, N=82 1 (1.5%) 1 (7%) 0.31 Post Wash: TNC/kg x 10^7 1.5 (+/-0.72) 1.4 (+/-0.43) 0.72 TNC/Kg<1.5x10^7, N=92 47 (60%) 8 (57%) 1.0 Viability (%) 91.8 (+/-5.3) 91.9 (+/-5.3) 0.96 Viability <85%, N=92 6 (8%) 2 (14%) 0.3 Haploidentical Graft: TNC/kg x 10^6 3.8 (+/-1.6) 5.0 (+/-2.2) 0.03 CD34+/kg x 10^6 3.8 (+/-1.6) 4.8 (+/-2.2) 0.055 CD34+/kg <3.0 x 10^6, N=92 30 (38%) 2 (14%) 0.13 CD3/kg x 10^4 1.2 (+/-3) 0.53 (+/-0.6) 0.29 Disclosures Larson: Novartis: Consultancy, Research Funding. Stock:Sigma-Tau: Membership on an entity's Board of Directors or advisory committees, Research Funding. Artz:Miltenyi: Research Funding.