Red cell and platelet transfusion burden following myeloablative allogeneic haemopoietic stem cell transplantation.

BACKGROUND: Adult allogeneic haemopoietic stem cell transplant (HSCT) usually requires blood transfusion support of red cells and platelets. There are few studies describing transfusion burden after allogeneic HSCT. AIMS: This study aims to quantify and identify determinants of transfusion burden after allogeneic HSCT to improve planning, inventory management and patient counselling. METHODS: A retrospective audit of blood use (red cells and platelets) of all adult HSCT (n = 169) was performed over an 8-year period extracted from pathology and hospital databases. ABO compatibility, graft type, conditioning regimens and patient factors were analysed for up to 12 months post transplant. RESULTS: Transfusion burden was lower than expected and lower than reported by other groups. The median number of units transfused was four red cells and four platelets by day 30, and six red cells and six platelets by day 365. The median time to transfusion independence was 12 days for red cells and 16 days for platelets. Factors associated with increased red cell use included sex, disease stage, graft type (cord blood) and ABO compatibility. Disease stage and graft type (cord blood) were associated with increased platelet transfusion. CONCLUSIONS: Donor and patient characteristics are associated with transfusion burden after allogeneic HSCT. Determining transfusion burden in HSCT and identifying determinants of increased transfusion use assist in inventory planning and patient information.

Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of Eurocord and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

We performed a retrospective analysis on 421 adult patients who underwent unrelated cord blood transplantation (UCBT) for ALL. Median age was 32 years; 46% were in first CR (CR1), 32% in CR2 and 22% had advanced disease. Double UCBT was performed in 173 patients (41%). Myeloablative conditioning (MAC) was given to 314 patients (75%). Cumulative incidence (CI) of 60-day neutrophil recovery was 78%. CI of acute and chronic GVHD was 33 and 26%, respectively. Non-relapse mortality (NRM) at 2 years was 42%. Age⩾35 years (P<0.0001), advanced disease at UCBT (P<0.0001) and use of MAC (P<0.0001) were associated with increased NRM. Relapse incidence (RI) at 2 years was 28%; use of reduced intensity conditioning (RIC) (P=0.0002) was associated with increased RI. Two-year leukemia-free survival (LFS) was 39% for patients in CR1, 31% for CR2 and 8% for advanced disease. In multivariate analysis, factors associated with decreased LFS rate were: age ⩾35 years (P=0.034), use of MAC (P=0.032) and advanced disease (P<0.0001). These results show that UCBT is a valuable option to treat high-risk adult ALL when in remission. Strategies to decrease toxicity and relapse are needed to improve final outcomes.

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP-EBMT analysis.

To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR)=0.4, P=0.01) and for those transplanted in CR1 and CR2 (HR=0.3, P=0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P=0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR=2, P=0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes.

Cord blood transplantation in Western Australia.

BACKGROUND/AIMS: Thirty-one umbilical cord blood transplants performed in Western Australia were retrospectively examined in order to document local experience and relevant prognostic factors. Three cord units were from human leucocyte antigen-matched siblings and the remainder were unrelated single (n= 22) or double (n= 6) cord blood transplants. METHODS: Twenty patients were transplanted for malignant conditions and 11 for non-malignant conditions. Cord units contained a median of 5.6 × 107 total nucleated cells/kg and 1.4 × 105 CD34+ cells/kg. Cumulative incidence of neutrophil engraftment was 76% at day 60. RESULTS: Of those who did not engraft, two patients remain alive following subsequent allogeneic bone marrow transplant. There were no deaths caused by graft-versus-host disease. Overall survival at median follow up of 28 months was 62%. Two year overall survival was influenced by type of disease (non-malignant = 91 ± 9% vs malignant = 41 ± 13%, P= 0.005), total nucleated cell dose (>3.5 × 107/kg = 87 ± 9% vs <3.5 × 107/kg = 34 ± 15%, P= 0.01) and CD34 dose (>1.7 × 105/kg = 92% vs <1.7 × 105/kg = 46%, P= 0.04). Age and human leucocyte antigen match did not influence survival. Four relapses occurred, all of which were fatal. CONCLUSION: Cord blood transplantation for malignant and non-malignant disease is practised in Western Australia and outcomes are satisfactory. Trends and techniques in cord blood transplantation in this state are comparable with those observed nationally and overseas. Although numbers are small, cell dose appears to be predictive of overall survival

Outcomes, infections, and immune reconstitution after double cord blood transplantation in patients with high-risk hematological diseases.

Double unrelated cord blood transplant (dUCBT) has been used to circumvent cell dose limitation of single UCBT; however, few data are available describing outcomes, infectious disease, and immune recovery. We analyzed 35 consecutive dUCBT recipients with high-risk malignant disorders (n=21) and bone marrow failure syndromes (n=14). Median follow-up was 32 months. Conditioning regimen was myeloablative in 14 and reduced intensity in 21 patients. Median infused nucleated cell dose was 4 × 10(7) /kg. Median time to absolute neutrophil count >0.5 × 10(9) /L was 25 days. Cumulative incidence (CI) of acute grade II-IV graft-versus-host disease was 47%. Estimated overall survival at 2 years was 48%. CI of first viral infections at 1 year was 92%. We observed 49 viral infections in 30 patients, 34 bacterial infections in 19 patients, and 16 fungal or parasitic infections in 12 patients. Lymphocyte subset analyses were performed at 3, 6, 9, and >12 months after dUCBT. Decreased T-cell and B-cell counts with expansion of natural killer cells were observed until 9 months post transplantation. Recovery of thymopoiesis measured by T-cell receptor excision circles was impaired until 9 months after dUCBT, when the appearance of new thymic precursors was observed. Delayed immune recovery and high incidence of infectious complications were observed after dUCBT in patients with high-risk hematological diseases.

Unrelated cord blood transplantation in adults with myelodysplasia or secondary acute myeloblastic leukemia: a survey on behalf of Eurocord and CLWP of EBMT.

The aim of our study was to evaluate, through the Eurocord and European Group for Blood and Marrow Transplantation (EBMT) registries, outcomes and risk factors for outcomes in adult patients who underwent single or double unrelated cord blood transplantation (UCBT) for myelodysplastic syndrome (MDS) or secondary acute myeloblastic leukemia (sAML). A total of 180 adults with MDS (n=39) or sAML (n=69) were analyzed. Risk factors for outcomes were analyzed using the Fine and Gray method and the Cox model. Median age was 43 (18-72) years. In all, 77 patients (71%) received a single UCBT. Myeloablative conditioning regimen (MAC) was given to 57 (53%) patients. Median numbers of nucleated and CD34(+) cells at freezing were 3.6 × 10(7) and 1.1 × 10(5) kg. At 60 days, cumulative incidence of neutrophil recovery was 78±4% and was independently associated with the number of CD34(+) cells per kg (>1.1 × 10(5); P=0.005) and advanced disease status (blasts <5% at time of UCBT, P=0.016). A 2-year non-relapse mortality (NRM) was significantly higher after MAC (62 vs 34%; P=0.009). A 2-year disease-free-survival (DFS) and overall survival (OS) were 30 and 34%, respectively. In multivariate analysis, patients with high-risk disease (blasts >5% and International Prognostic scoring system (IPSS) intermediate-2 or high in MDS) had significant poorer DFS (hazard ratio (HR): 1.76; P=0.047). In spite of high NRM, these data indicate that UCBT is an acceptable alternative option to treat adults with high-risk MDS or sAML, without a suitable human leukocyte antigen (HLA)-matched donor.

Pediatric related and unrelated cord blood transplantation for malignant diseases.

The use of umbilical or placental donor cord blood transplantation (CBT) in children with malignant and non-malignant diseases has witnessed important progress, mainly because of better cord blood donor choice and patient selection translating into better patient outcome. Approximately 2000 children with malignant diseases (about 75 % with acute leukemias) have been transplanted with a related (n=199) or unrelated CBT (UCBT, n=1663) and reported to Eurocord registry from 1990-2008. Disease-specific studies have been carried out after UCBT for acute lymphoblastic and myeloid leukemia and myelodysplastic syndromes in others to identify the risk factors that may improve outcomes. Outcomes after CBT have been compared with other alternative allogeneic hematopoietic SCT (HSCT) donors. Briefly, after CBT, myeloid engraftment is delayed, acute and chronic GVHD decreased and disease-free survival was not statistically different when compared with HLA identical and other alternative HSCT donor. Therefore, any physician has to carefully evaluate, for each single pediatric patient in need of an allograft, all the possible alternatives in order to choose the best hematopoietic stem cell donor, taking into account type of disease, urgency of transplantation, donor characteristics and center experience. This review will analyze the current results of CBT for pediatric patients with malignant diseases and the advantages and limitations of using this stem cell source.