Partial T Cell-Depleted Peripheral Blood Stem Cell Transplantation from HLA-Identical Sibling Donors for Patients with Severe Aplastic Anemia.

We analyzed the outcomes of 26 consecutive patients with acquired severe aplastic anemia (SAA) undergoing peripheral blood stem cell transplantation (PBSCT) with partial ex vivo T cell depletion with a targeted T cell dose from HLA-identical sibling donors. The median patient age was 37 years (range, 3 to 63 years). Four patients with uncontrolled pneumonia at the time of transplantation died, on days +1, +2, +21, and +26. All evaluable patients engrafted, with a median time to neutrophil recovery of 11 days (range, 10 to 14 days) and a median time to platelet recovery of 19 days (range, 8 to 53 days). Two patients had transient grade I acute graft-versus-host disease (GVHD) with skin involvement, but no patients developed grade II-IV acute GVHD. Two patients had mild skin chronic GVHD, and 1 patient had moderate chronic GVHD with ocular involvement. No relapse was observed after a median follow-up of 114 months (range, 4 to 233 months). The overall cumulative incidence of TRM at 10 years was 19%, whereas it was 5% for those with a Karnofsky Performance Status (KPS) score >60 at the time of transplantation. Disease-free survival, overall survival, and GVHD and relapse-free survival at 10 years were 81%, 81%, and 80%, respectively, for all patients and 95%, 95%, and 90%, respectively, for patients with a KPS score >60 at transplantation. Our data indicate that PBSCT with partial ex vivo T cell-depleted targeted cell dose grafts from an HLA-identical sibling donor is a feasible, safe, and effective approach to reduce GVHD and cure patients with SAA.

A case of megaloblastic anemia simulating a cold autoimmune hemolytic anemia.

CONCLUSIONS: We report a case of pernicious anemia in which the first diagnosis suspicion was cold autoimmune hemolytic anemia (cAIHA) due to the presence of cold autoantibodies. A 47-year-old woman with a medical history of autoimmune thyroid disease came to the hospital with a clinical and serologic presentation of AIHA. However, because of determination of vitamin B12 (VB12) deficiency, she was finally diagnosed with megaloblastic anemia. In the acute period, the patient received short-term corticosteroid therapy and later VB12. The patient's hemoglobin level and general condition showed improvement.

Comparison of transfusion requirements in adult patients undergoing Haploidentical or single-unit umbilical cord blood stem cell transplantation.

OBJECTIVES: Umbilical cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) modalities have been developed to offset the lack of matched donors. In this study, we compare the transfusion requirements of patients undergoing UCBT and haplo-HSCT in a single institution with the aim of providing additional information for clinicians to choose the most adequate alternative graft for HSCT. METHODS: The study reviewed 67 and 46 patients undergoing UCBT and haplo-HSCT, respectively. RESULTS: There were no significant differences for RBC and PLT requirements according to the transplantation modality. Median time to RBC transfusion independence was 35 and 25.5 days in patients who received an UCBT and haplo-HSCT, respectively (P = 0.38), while median time to platelet transfusion independence was 31 days for UCBT patients and 23 for haplo-HSCT patients (P < 0.001). Days until neutrophils > 0.5 × 109 /L were the only variable that significantly influenced RBC and PLT requirements for both transplantation modalities. Cumulative incidence of RBC and PLT transfusion independence at 90 days after transplantation was similar for both UCBT and haplo-HSCT. CONCLUSIONS: Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy.

Factors influencing platelet transfusion refractoriness in patients undergoing allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation has been considered a risk factor for development of platelet transfusion refractoriness. The objective of this study was to assess the platelet transfusion refractoriness rate in patients undergoing allogeneic hematopoietic stem cell transplantation from different sources. We retrospectively reviewed the charts and transfusion records of patients who underwent allogeneic stem cell transplantation at our institution between 2013 and 2015. The evaluation of post-transfusion platelet count was assessed for each transfusion given, from day of progenitor infusion to day 30 after transplantation. Of 167 patients included in this study, 101 received peripheral blood stem cell transplantation (PBSCT) and 66 received umbilical cord blood transplantation (UCBT). Overall, the percentage of platelet transfusions with a 14-h CCI lower than 5000 was 59.3%, being these data significantly higher for UCBT (67.6%) than for PBSCT (31.0%). Seventy-eight percent of patients underwent UCBT become refractory, while 38.6% of patients who received PBSCT were refractory. Factors associated to platelet refractoriness were lower CD34+ cell dose infused, higher number of antibiotics used, presence of anti-HLA I antibodies, and reduced-intensity conditioning regimen. Platelet refractoriness is a frequent and complex adverse event and remains a therapeutic challenge in the management of patients undergoing HSCT. There is a higher rate of platelet refractoriness in patients who received UCBT as compared to patients who received PBSCT.

Anti-D Alloimmunization after RhD-Positive Platelet Transfusion in RhD-Negative Women under 55 Years Diagnosed with Acute Leukemia: Results of a Retrospective Study.

BACKGROUND: Anti-D alloimmunization can occur when platelets from RhD-positive donors are transfused to RhD-negative patients, due to red blood cell residues in the platelet concentrates. METHODS: Our objective was to analyze the anti-D alloimmunization rate in a selected group of women under 55 years of age diagnosed with acute leukemia over an 18-year period. We focused the analysis on RhD-negative patients who received RhD-positive platelet transfusions. RESULTS: From January 1998 to October 2016, 382 women under 55 years were diagnosed with acute leukemia. A total of 56 patients were RhD-negative, and 48 (85.7%) received RhD-positive platelets. The median number of platelet concentrates transfused per patient was 23, and 48% of all platelet transfusions were RhD-positive. The 48 RhD-negative patients received a total of 949 RhD-positive platelet concentrates. Two patients developed anti-D: a 36-year-old woman with M3 acute myeloblastic leukemia and a 52-year-old patient with a secondary acute myeloblastic leukemia. CONCLUSION: We conclude that there is a need for agreement in the transfusion guidelines on the recommendation of anti-D alloimmunization prophylaxis. We suggest a possible benefit in favor of anti-D prophylaxis in childbearing women with acute leukemia.

Transfusion management and immunohematologic complications in liver transplantation: experience of a single institution.

OBJECTIVE: Liver transplantation (LT) has traditionally been associated with major blood loss and consequently high blood transfusion requirements. Our objective was to analyze transfusion management and incidence of immunohematologic complications in patients undergoing LT at our institution. METHODS: A retrospective analysis of immunohematologic events and transfusion outcomes was carried out at La Fe University Hospital in Valencia. Data from 654 patients were reviewed: 654 underwent only one LT while 36 underwent second LT. RESULTS: Patients received a median of 3 red blood cell (RBC) concentrates, 2 platelets concentrates (PCs) and 2 fresh frozen plasma units (FFPs). Variables significantly influencing RBC transfusions were: the MELD score, hemoglobin levels, and the platelet counts before LT. 27 patients (4.1%) had a positive antibody screening before transplant. Immunohematologic events occurred in 8% of the patients, mostly in the first month after LT, and involved hemolysis in 13 cases. Mortality was significantly higher in patients developing immunohematologic disorders (42.8 vs. 18.3%; p < 0.001). In the multivariable analysis, only ABO minor incompatibility between donor and recipient significantly increased the appearance of immunohematologic incidences (OR 4.92, 95% CI 2.31-10.50; p < 0.001). CONCLUSION: Transfusion management of patients that underwent LT can be complicated by immunohematologic problems. Blood banks should implement the DAT test in each transfusion to detect them.

T cell-depleted related HLA-mismatched peripheral blood stem cell transplantation as salvage therapy for graft failure after single unit unrelated donor umbilical cord blood transplantation.

Graft failure is a severe treatment complication of unrelated donor umbilical cord blood transplantation (UCBT). Its incidence seems to be higher after UCBT than after transplantation with bone marrow or peripheral blood stem cells (PBSCs). The only curative option is to perform a second transplantation; however, both the ideal stem cell source and the conditioning regimen for this salvage transplantation remain unclear. We report a series of 11 patients who underwent haploidentical PBSC transplantation (PBSCT) as salvage therapy for graft failure after a previous UCBT. The reduced-intensity conditioning regimen consisted of fludarabine 150 mg/m(2) for 3 days and horse antithymocyte globulin 8 mg/kg for 4 days. Ex vivo CD34(+) positive selection was performed in all cases, and no post-transplantation graft-versus-host disease prophylaxis was used. Six of the 9 evaluable patients (67%) eventually engrafted, at a median time of 10 days. The cumulative incidence of engraftment at 28 days was 64% (95% confidence interval [CI], 35% to 92%). Two patients relapsed after PBSCT. The cumulative incidence of TRM was 55% at 2 years (95% CI, 25% to 84%), and the probability of overall survival at 2 years was 36%. Our findings suggest that haploidentical ex vivo T cell-depleted PBSCT is a feasible alternative for treating graft failure after UCBT.

Effect of CD8⁺ cell content on umbilical cord blood transplantation in adults with hematological malignancies.

Total nucleated (TNCs) and CD34(+) cells are considered major determinants of outcome after umbilical cord blood (UCB) transplantation but the effect of other cell subtypes present in the graft is unknown. This single-center cohort study included patients with hematological malignancies who received UCB transplantation after a myeloablative conditioning regimen. UCB units were primarily selected according to cell content, both TNCs and CD34(+) cells, and also according to the degree of HLA matching. Counts of several cell subtypes of the infused UCB unit, together with HLA disparities and other patient- and transplantation-related characteristics, were analyzed by multivariable methodology for their association with myeloid and platelet engraftment, graft-versus-host disease, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Two hundred patients (median age, 32 years) were included in the study. In multivariable analyses, a greater number of CD8(+) cells was significantly associated with better results for myeloid (P = .001) and platelet (P = .008) engraftment, NRM (P = .02), DFS (P = .007), and OS (P = .01). CD34(+) cell content was predictive of myeloid engraftment (P < .001). This study suggests that the outcome after UCB transplantation in adults with hematological malignancies could be better when UCB grafts had a greater CD8(+) cell content.

Results of a preoperative autologous blood donation program for patients undergoing elective major spine surgery.

BACKGROUND AND OBJECTIVES: Spinal surgery has been shown to have a high blood transfusion requirement. Preoperative autologous blood donation (PABD) is a strategy to reduce the allogeneic transfusions in this subset of patients. MATERIAL AND METHODS: We retrospectively reviewed transfusion outcome of patients undergoing elective major spinal surgery from 2005 to 2011, and included in the PABD program. Transfusion outcome was compared with a group of patients that did not enter in the program during the same period. RESULTS: A total of 148 patients were included in the program during the analyzed period. Patients in the PABD program benefited from reduced exposure to allogeneic blood (Odds Ratio: 0.077, 95% confidence interval 0.043-0.140). However, 12.16% (n=18) of these patients received also allogeneic blood (total 40 red blood cell units). Univariate analysis showed the following parameters as significantly predictors of transfusion: inclusion in the program (p<0.000), number of levels fused (Odds Ratio: 1.143, p=0.010), and number of autologous red blood cells donated (Odds Ratio: 1.906, p<0.000). CONCLUSIONS: The preoperative autologous blood donation program designed in our hospital was effective for reducing allogeneic transfusion in mostly young patients under major elective spinal surgery. However and as expected, their inclusion in the program increased the risk to be transfused.

Significance of increased blastic-appearing cells in bone marrow following myeloablative unrelated cord blood transplantation in adult patients.

An abnormal increase of nonleukemic blastic-appearing lymphocytes in bone marrow (BM) specimens has been reported after unrelated cord blood transplantation (UCBT). This study analyzed the incidence, chronology, biological features, and clinical significance of elevated numbers of these cells in a series of 165 consecutive adult patients demonstrating myeloid engraftment after myeloablative UCBT in a single institution. The patients' BM samples were routinely evaluated by cytomorphology at different time points after UCBT. When ≥5% of blastic-appearing cells were detected by cytomorphology in the BM, samples were also evaluated by multiparametric flow cytometry to characterize these cells. Systematic chimerism analyses of BM samples using PCR amplification of short tandem repeat markers were performed. Forty-three patients (cumulative incidence, 26.1%) demonstrated ≥5% of nonmalignant blastic-appearing cells in BM after a median of 101 days after UCBT (range, 28-377 days). All of these patients had full-donor chimerism and a clinical course without leukemic relapse. Multiparametric flow cytometry analyses performed in 36 of the 43 patients showed a polyclonal expansion of B lymphocytes with a broad spectrum of maturation stages. An increased number of nonmalignant blastic-appearing cells was significantly associated with a high number of lymphocytes infused at the time of UCBT and with low rates of acute and chronic extensive graft-versus-host disease, suggesting a potential immunoregulatory role of these cells. The observation of ≥5% nonmalignant blastic-appearing cells in BM samples after myeloablative UCBT is frequent, and these should be distinguished from malignant blasts.

Passenger lymphocyte syndrome in liver transplant recipients: a description of 12 cases.

BACKGROUND: Passenger lymphocyte syndrome is an important cause of immune haemolysis after solid organ transplantation. It mainly occurs in minor ABO and Rh mismatched transplants. The haemolysis is usually mild and self-limited. We present our experience in passenger lymphocyte syndrome and liver transplantation and review the literature. MATERIALS AND METHODS: We reviewed liver transplants performed in our centre from January 2002 to September 2013, searching for ABO or Rh incompatibility and serological findings of haemolysis. A direct antiglobulin test was systematically performed in each pre-transfusion assessment. RESULTS: A total of 1,217 liver transplants were performed and 12 passenger lymphocyte syndromes were detected: of the 56 cases with minor ABO incompatibility, ten patients developed passenger lymphocyte syndrome (17.9%) and of 147 cases with minor Rh incompatibility, two patients developed the syndrome (1.40%). All patients with passenger lymphocyte syndrome had haemolysis, a decrease of haemoglobin (median 6.8 g/dL) and an increase of bilirubin (median 5.15 mg/dL). The treatment of passenger lymphocyte syndrome consisted of increasing the dose of corticosteroids that the patients were receiving as post-transplantation immunosuppressive therapy and, in the majority of cases, transfusion of donor compatible red blood cells. DISCUSSION: Passenger lymphocyte syndrome in liver transplantation has significant clinical consequences. It is, therefore, important to make the diagnosis rapidly, performing pre-transfusion direct antiglobulin tests, and manage the problem correctly with donor compatible red blood cell transfusions and/or immunosuppressive treatment.

Transfusion of ABO non-identical platelets does not influence the clinical outcome of patients undergoing autologous haematopoietic stem cell transplantation.

BACKGROUND: There are ABO antigens on the surface of platelets, but whether ABO compatible platelets are necessary for transfusions is a matter of ongoing debate. We retrospectively reviewed the ABO matching of platelet transfusions in a subset of patients undergoing autologous haematopoietic progenitor cell transplantation during a 14-year period. Our aim was to analyse the characteristics and outcomes of patients who received platelet transfusions that were or were not ABO identical. MATERIAL AND METHODS: We analysed 529 consecutive patients with various haematological and non-haematological diseases who underwent 553 autologous progenitor stem cell transplants at the University Hospital la Fe between January 2000 and December 2013. We retrospectively analysed and compared transfusion and clinical outcomes of patients according to the ABO match of the platelet transfusions received. The period analysed was the time from transplantation until discharge. RESULTS: The patients received a total of 2,772 platelet concentrates, of which 2,053 (74.0%) were ABO identical and 719 (26.0%) ABO non-identical; of these latter 309 were compatible and 410 incompatible with the patients' plasma. Considering all transplants, 36 (6.5%) did not require any platelet transfusions, while in 246 (44.5%) cases, the patients were exclusively transfused with ABO identical platelets and in 47 (8.5%) cases they received only ABO non-identical platelet transfusions. The group of patients who received both ABO identical and ABO non-identical platelet transfusions had higher transfusion needs and worse clinical outcomes compared to patients who received only ABO identical or ABO non-identical platelets. DISCUSSION: In our hospital, patients undergoing autologous haematopoietic stem cell transplantation who received ABO identical or ABO non-identical platelet transfusions had similar transfusion and clinical outcomes. The isolated fact of receiving ABO non-identical platelets did not influence morbidity or survival.

[The "Seville" Consensus Document on Alternatives to Allogenic Blood Transfusion. Sociedades españolas de Anestesiología (SEDAR), Medicina Intensiva (SEMICYUC), Hematología y Hemoterapia (AEHH), Transfusión sanguínea (SETS) Trombosis y Hemostasia (SETH)]. / Documento «Sevilla¼ de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica.

The Consensus Document on Alternatives to Allogenic Blood Transfusion (AABT) has been drawn up by a panel of experts from 5 scientific societies. The Spanish Societies of Anesthesiology (SEDAR), Critical Care Medicine and Coronary Units (SEMICYUC), Hematology and Hemotherapy (AEHH), Blood Transfusion (SETS) and Thrombosis and Hemostasis (SETH) have sponsored and participated in this Consensus Document. Alternatives to blood transfusion have been divided into pharmacological and non-pharmacological, with 4 modules and 12 topics. The main objective variable was the reduction of allogenic blood transfusions and/or the number of transfused patients. The extent to which this objective was achieved by each AABT was evaluated using the Delphi method, which classifies the grade of recommendation from A (supported by controlled studies) to E (non-controlled studies and expert opinion). The experts concluded that most of the indications for AABT were based on middle or low grades of recommendation, "C", "D", or "E", thus indicating the need for further controlled studies.

Incidence of Wra antigen and anti-Wra in a Spanish population.

BACKGROUND: This study reports the incidence of Wr(a) antigen and anti-Wr(a) in Valencia, Spain. STUDY DESIGN AND METHODS: The incidence of the Wr(a) antigen in 110,000 healthy blood donors was estimated. Likewise, the incidence of anti-Wr(a) was analyzed in a population consisting of 730 healthy blood donors, 356 pregnant women, and 581 patients who received transfusions from the area of Valencia, Spain. RESULTS: The incidence of Wr(a) antigen was 1 in 785. Overall, anti-Wr(a) was found in 59 samples: 20 healthy blood donors (1/37), 18 pregnant women (1/20), and 21 patients who received transfusions (1/28). The most frequent immunoglobulin class of anti-Wr(a) in healthy blood donors was immunoglobulin M, either alone (8 cases) or plus immunoglobulin G (IgG; 8 cases); the IgG1 and IgG3 were the IgG subclasses most frequently detected in pregnant women (12 cases) and in patients who received transfusions (12 cases). Only 51 percent of the anti-Wr(a) appeared to have the potential to be clinically significant. CONCLUSION: These data show that the incidence of Wr(a) antigen and anti-Wr(a) among the population from Valencia is similar to that reported in other European areas and suggest that the development of anti-Wr(a) is facilitated by the presence of a hyperactive immune system. The clinical relevance of anti-Wr(a) is limited, however.