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Nadine Shehata,
Alan Forster,
Le Li,
Deanna M Rothwell,
C David Mazer,
Gary Naglie,
Robert Fowler,
Jack V Tu,
Fraser D Rubens,
Steven Hawkens,
Kumanan Wilson
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ABSTRACT: BACKGROUND: Anemia is one of the most common complications of coronary artery bypass graft (CABG) surgery and has been shown to be associated with increased morbidity and mortality. The impact of anemia on hospital readmission after CABG, a potential measure of delayed complications, has not been addressed. STUDY DESIGN AND METHODS: We conducted a single-center retrospective study of 2102 patients who had CABG in Ontario to determine whether anemia at hospital discharge was associated with increased 30-day hospital readmissions, readmission secondary to cardiac disease, and 30-day mortality using administrative data. RESULTS: Of the 2102 patients, 224 patients (11%) were readmitted within 30 days of hospital discharge. Infection was the leading cause of readmissions (24%), followed by heart failure (13%), pulmonary disease (7%), and hemorrhagic disease (7%). Overall, 2.6% of patients were readmitted because of cardiac disease. Of patients discharged, 48% were discharged with a hemoglobin (Hb) level between 8 and 10 g/dL and 42% between 10 and 12 g/dL. Predischarge Hb concentration was not a significant independent predictor of 30-day readmission to the hospital due to all causes, readmission to the hospital due to cardiac causes, or 30-day mortality. A higher comorbidity score, adjusted odds ratio (OR) of 2.1 (95% confidence interval [CI], 1.3-3.6), leg and sternal wound infections OR of 1.9 (95% CI, 1.2-3.0), and postoperative renal failure OR of 1.4 (95% CI, 1.2-2.0) were associated with increased 30-day readmission rates. CONCLUSIONS: The predischarge Hb concentration after CABG was not associated with 30-day readmissions.
Transfusion 12/2012; · 3.22 Impact Factor
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ABSTRACT: Transfusion of allogeneic red blood cells (RBCs) is one of the main treatments of acute anemia secondary to blood loss and fluid resuscitation within the operating room. Decisions to transfuse blood are based largely on intermediate biological markers (hemoglobin, arterial oxygen saturation, blood pressure, heart rate) which may not accurately reflect inadequacy of tissue oxygen delivery. Based on experimental studies, we hypothesized that anemia-induced tissue hypoxia activates adaptive mechanisms which promote local vascular nitric oxide (NO) production to improve tissue perfusion and survival during acute anemia. Hemoglobin (Hb) oxidation to methemoglobin (MetHb) may be a byproduct of such local NO production. Therefore, we tested the hypothesis that MetHb is a biomarker of hypoxic-anemic stress during acute hemodilution associated with cardiopulmonary bypass.
With institutional ethics approval, routine laboratory arterial blood gas and co-oximetry values were obtained from 295 patients undergoing heart surgery during February 1 to September 30, 2010, and the values were assessed retrospectively. All samples with an arterial oxygen saturation value ≥ 90% were included (n = 1,421). The maximal change in Hb associated with hemodilution on cardiopulmonary bypass was determined within 48 hr of surgery (n = 180). A chart review was performed to determine the incidence of RBC transfusion and exogenous nitrate administration. All anonymous data were analyzed by linear regression to determine the relationship between Hb and MetHb. A Wilcoxon Signed Rank Test and Student's t test were used to determine changes in Hb, MetHb, and carboxyhemoglobin (CarboxHb) levels. All data are presented as mean and significance was assigned at P < 0.05.
A significant decrease in Hb [118 (20) g x L(-1) vs 94 (18) g x L(-1)] was associated with an increase in MetHb [0.88 (0.22)% vs 0.95 (0.24)%] (P < 0.001 for both), but not CarboxHb [1.08 (0.47)% vs 1.08 (0.49)%]. Regression analysis revealed a significant relationship between the change in Hb and MetHb (F = 40.3; P < 0.001) but not between the change in Hb and CarboxyHb (F = 0.2; P = 0.694). This correlation was not influenced by RBC transfusion or exogenous nitrate use.
A negative correlation was observed between the change in Hb and MetHb in patients undergoing cardiac surgery and cardiopulmonary bypass. These data support the previously unreported hypothesis that MetHb may be a marker of anemic stress associated with reduced tissue perfusion during acute hemodilution in humans. Further prospective studies are needed to determine if these changes in MetHb are linked to adverse outcomes in patients undergoing cardiac surgery.
Canadian Anaesthetists? Society Journal 01/2012; 59(4):348-56. · 2.31 Impact Factor
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ABSTRACT: It is important to determine the optimal hemoglobin (Hb) concentration for red blood cell (RBC) transfusion for patients undergoing cardiac surgery because increased mortality has been associated with the severity of anemia and exposure to RBCs. Because a definitive trial will require thousands of patients, and because there is variability in transfusion practices, a pilot study was undertaken to determine adherence to proposed strategies.
A single-center parallel randomized controlled pilot trial was conducted in high-risk cardiac patients to assess adherence to two transfusion strategies. Fifty patients were randomly assigned either to a "restrictive" transfusion strategy (RBCs if their Hb concentration was 70 g/L or less intraoperatively during cardiopulmonary bypass [CPB] and 75 g/L or less postoperatively) or a "liberal" transfusion strategy (RBCs if their Hb concentration was 95 g/L or less during CPB and less than 100 g/L postoperatively).
The percentage of adherence overall was 84% in the restrictive arm and 41% in the liberal arm. Twenty-two (88%) patients were transfused 99 units of RBCs in the liberal group compared to 13 patients who were transfused 50 units in the restrictive group (p<0.01). There were no significant differences in individual adverse outcomes; however, more adverse events occurred in the restrictive group (38 vs. 15, p<0.01).
Adherence to the evaluated interventions is vital to all randomized controlled trials as it has the potential to affect outcomes. Further pilot studies are required to optimize enrollment and transfusion adherence before a definitive study is conducted.
Transfusion 07/2011; 52(1):91-9. · 3.22 Impact Factor
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ABSTRACT: Treatment with human platelet antigen (HPA)-matched platelets (PLTs) is the optimal therapy for bleeding secondary to neonatal alloimmune thrombocytopenia. Recent advances in high-throughput DNA-based blood group and PLT antigen genotyping have made it possible to screen plateletpheresis donors for potential HPA-matched PLT transfusion.
This prospective study evaluated genomic DNA from plateletpheresis donors for single-nucleotide polymorphisms (SNPs) associated with HPA-1, -2, -3, -4, -5, and -15 to determine whether high-throughput multiplex genomic DNA PCR and oligonucleotide extension technology can be used for mass-scale PLT antigen genotyping. Genotyping using SNP technology was confirmed using sequence-specific polymerase chain reaction (SSP-PCR).
Of the 748 donors screened, 277 were found to be negative for antigens implicated in alloimmune thrombocytopenia. In addition, two donors were homozygous for HPA-1b/b and -2b/b, six donors for HPA-1b/b and -3b/b, one for HPA-2b/b and -3b/b, one for HPA-1b/b and -5b/b, 10 for HPA-1b/b and -15 b/b, four for HPA-5b/b and -15b/b, and one for HPA-2b/b and -15b/b. Retesting using SSP-PCR was conducted for 60 donors. Discrepant results occurred between SNP and SSP-PCR in less than 20% of samples for HPA-1b/1b/HPA-3b/3b, HPA-5b/5b, and HPA-15b/b.
High-throughput multiplex PCR SNP and confirmatory molecular genotyping are useful for mass-scale screening of apheresis PLT donors to provide antigen-negative genotypes. Refinements to mass-scale multiplex analysis technology would reduce further the confirmatory testing needed.
Transfusion 03/2011; 51(9):2028-33. · 3.22 Impact Factor
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JAMA The Journal of the American Medical Association 01/2011; 305(4):357-8; author reply 358-9. · 30.03 Impact Factor
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Nadine Shehata,
Valerie Palda,
Tom Bowen,
Elie Haddad,
Thomas B Issekutz,
Bruce Mazer,
Robert Schellenberg,
Richard Warrington,
David Easton,
David Anderson,
Heather Hume
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ABSTRACT: The standard treatment for patients with primary antibody deficiency is immunoglobulin (IG), but the care of these patients is complex. These guidelines, initiated by the Canadian Blood Services and the National Advisory Committee on Blood and Blood Products, have been developed to facilitate and standardize the care of these patients by the various physician specialties that are responsible for their care. A panel of national expert immunologists and methodologists developed salient clinical questions; and a systematic, expert, and bibliography literature search up to July 2008 was conducted. One thousand eighty-seven citations were retrieved, and 102 reports were used in the preparation of this guideline. The recommendations provide guidance (1) on the complexity of the treatment of these patients; (2) the established benefits of IG on morbidity and mortality; (3) dosage, routes of administration, and management of reactions; (4) the various IG formulations available; (5) vaccination of these patients; and (6) research priorities.
Transfusion medicine reviews 01/2010; 24 Suppl 1:S28-50. · 3.61 Impact Factor
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Nadine Shehata,
Valerie A Palda,
Ralph M Meyer,
Tom D Blydt-Hansen,
Patricia Campbell,
Carl Cardella,
Steven Martin,
Peter Nickerson,
Kevork Peltekian,
Heather Ross,
Tom K Waddell,
Lori West,
David Anderson,
John Freedman,
Heather Hume
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ABSTRACT: This guideline for the use of immunoglobulin (IG) for sensitized patients undergoing solid organ transplantation (SOT) is an initiative of the Canadian Blood Services and the National Advisory Committee on Blood and Blood Products of Canada to (1) provide guidance for Canadian practitioners involved in the care of patients undergoing SOT and transfusion medicine specialists on the use of IG and (2) standardize care, limit adverse events, and optimize patient care. A systematic expert and bibliography literature search up to July 2008 was conducted, with 791 literature citations and 45 reports reviewed. To validate the recommendations, the guideline was sent to physicians involved in SOT in Canada and a patient representative. The recommendations identify (1) sensitized patients undergoing SOT that would have a better survival and decreased morbidity by receiving IG preoperatively, postoperatively, and for the treatment of organ rejection; (2) patients who may not have any benefit from receiving IG; and (3) potential adversities to IG.
Transfusion medicine reviews 01/2010; 24 Suppl 1:S7-S27. · 3.61 Impact Factor
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ABSTRACT: The significance of ABO matching for platelet (PLT) transfusion has not been clearly defined. The primary objective of this report is to assess whether ABO-identical PLT transfusion is associated with improved mortality and/or morbidity for patients with hematologic/oncologic disorders.
A systematic review to January 2009 was conducted. Data on mortality, morbidity, PLT refractoriness, and PLT increment after transfusion were abstracted.
A total of 100 citations were identified. Nineteen studies were included in the systematic review. A total of 1502 patients from three randomized controlled trials and 16 observational studies were included. Survival, bleeding events, and transfusion reactions were only considered as secondary outcomes in the reports reviewed. The PLT count increment was the primary outcome of several studies and was consistently higher with ABO-identical PLT transfusion. The largest difference in increment between ABO-identical and nonidentical PLT transfusion was 4 x 10(9)/L. No consistent benefit in clinical outcomes was noted. Survival was assessed in three reports with conflicting results. Although two studies described bleeding as an outcome, the assessment of hemorrhage was considered inadequate. In six studies, ABO-nonidentical PLT transfusion was not associated with transfusion reactions, and the results from four studies addressing the impact of ABO-identical PLT transfusion on PLT and red blood cell utilization were conflicting.
ABO-identical PLT transfusion results in a higher PLT increment. Randomized controlled trials are required to definitely determine the effect of ABO-identical PLT transfusion on survival, bleeding events, or transfusion reactions.
Transfusion 11/2009; 49(11):2442-53. · 3.22 Impact Factor
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ABSTRACT: The effectiveness of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with non-myeloid hematological malignancies needs to be assessed as the response to their administration is not uniform and their cost is high. We conducted a systematic review (SR) of the literature to identify reports of the effect of ESAs on survival, quality of life (QOL), transfusion requirements, and anemia. The entries to MEDLINE, EMBASE, and the Cochrane Library databases, and abstracts published in the proceedings of the annual meetings of the American Society of Clinical Oncology and the American Society of Hematology were searched. Seventeen reports and five abstracts of randomized trials fulfilled prospective criteria for inclusion. Five trials reported on survival; three failed to detect differences between groups and two demonstrated inferior survival in patients allocated to an ESA. Seven trials and three abstracts reported on QOL with four articles and three abstracts describing improvements in patients allocated to erythropoietin. However, important methodologic limitations were identified in these reports. Seven randomized controlled trials reported a reduction in the proportion of patients transfused. The absolute risk reduction in transfusions ranged from 15% to 24%. This is the only SR that assesses the use of erythropoiesis-stimulating agents specifically in patients with hematological malignancies. We conclude that available data evaluating ESAs in patients with hematologic malignancies demonstrate that these agents reduce transfusion requirements. Limitations of these data preclude conclusions that these agents improve QOL. More data are required to confirm the inferior survival associated with ESAs.
Annals of Hematology 12/2008; 87(12):961-73. · 2.62 Impact Factor
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ABSTRACT: To ensure the safety of the blood supply, it is necessary to permanently defer blood donors with a repeat-reactive transmissible disease test result. The purpose of this study was to explore the permanent deferral experience from the donor's perspective.
A qualitative study was conducted with donors from two Canadian blood centers who received written notice of permanent deferral in six deferral categories: human immunodeficiency virus-1 and/or -2 and hepatitis C virus and/or hepatitis B virus (negative, indeterminate, or positive). Telephone interviews were conducted with a semistructured questionnaire. Interview transcripts were coded and central themes were identified. The data were then modeled to illustrate the relationships between the themes.
Twenty-eight permanently deferred donors were interviewed and described a variety of negative emotional and behavioral responses including confusion, shock, disbelief, panic, fear, anger, stigmatization, and loss. A conceptual model was developed illustrating the phases that a deferred donor goes through (identifying as a healthy donor, receiving notification, experiencing emotional and behavioral reactions, trying to make sense of what happened, and taking action) as they travel along the path to becoming either a "reconciled" or "not reconciled" permanently deferred donor. Participants offered constructive suggestions for modifying the notification process including revising the letter, providing follow-up, and educating family physicians.
To our knowledge, this is the first study to use qualitative research methodology to explore the experience of permanent blood donor deferral. More studies are needed to validate and expand this preliminary conceptual model.
Transfusion 02/2008; 48(1):64-72. · 3.22 Impact Factor
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Transfusion Medicine Reviews 11/2007; 21(4):317-36. · 3.58 Impact Factor
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ABSTRACT: Hospital variation in transfusion practices has been described previously but the proportion of variation attributable to the hospital has not. The objective of this report was to quantify hospital variation in red cell transfusion decisions perioperatively for patients undergoing coronary artery bypass surgery (CABG).
We used a cross-sectional study design using pretested self-administered mailed questionnaires sent to all anesthesiologists and cardiac surgeons involved in CABG in Canada.
Responses were received from anesthesiologists from all 32 hospital sites and from cardiac surgeons from 30/32 sites (94%). There was variation attributable to the hospital in transfusion triggers selected (P<0.0001). For patients who had uncomplicated CABG surgery, the range of transfusion triggers among hospitals for the intraoperative and postoperative case scenarios were 61 to 80 gxL(-1) and 64 to 80 gxL(-1), respectively. The hospital accounted for 20% of the variation in the transfusion practice intraoperatively and postoperatively. The remainder of the variation was attributable to the individual physician. Academic affiliation and the number of surgical cases performed at the hospital were not significant factors impacting on the transfusion triggers selected
This is the first study to quantify the variation in red cell transfusion practices according to individual physicians and the hospital. The variation attributed to the hospital is significant. The explanation for the variation in transfusion decisions that relate to the hospital needs to be explored further in order to help optimize transfusion practice.
Canadian Journal of Anaesthesia 11/2007; 54(11):902-7. · 2.35 Impact Factor
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Transfusion Medicine Reviews 11/2006; 20(4):294-314. · 3.58 Impact Factor
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ABSTRACT: A high proportion of patients having cardiac bypass surgery receive erythrocyte transfusions. Decisions about when to transfuse patients having surgery for coronary artery disease may impact on erythrocyte utilization and patient morbidity and mortality. There are no published data about the factors that influence physicians' decisions to transfuse erythrocytes to these patients. The objectives of this study were to determine the hemoglobin concentration for transfusion and the factors that influence physicians' perioperative transfusion decisions for coronary artery bypass patients.
The authors conducted a cross-sectional study using pretested, self-administered, mailed questionnaires sent in 2004 to all cardiac surgeons and anesthesiologists in Canada who participate in coronary artery bypass surgery. The questionnaire included four intraoperative and four postoperative vignettes. Factors assessed included patient age, sex, cardiac index, and myocardial ischemia.
The response rates were 70% (345 of 489) for the intraoperative and 61% (297 of 489) for the postoperative case scenarios. The mean hemoglobin concentrations for transfusion were 7.0 g/dl for the intraoperative case scenarios and 7.2 g/dl for the postoperative case scenarios. Older age, the presence of myocardial ischemia, and a low cardiac index were factors that increased the hemoglobin concentration for transfusion (P < 0.0001). Physicians ranked myocardial ischemia as the most significant factor affecting their transfusion decisions.
Factors such as the presence of a low cardiac index, myocardial ischemia, and older age increase the hemoglobin concentrations at which physicians transfuse coronary bypass surgery patients. Future studies are required to elucidate whether transfusions based on these variables affect patient morbidity and mortality.
Anesthesiology 08/2006; 105(1):19-27. · 5.36 Impact Factor
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Canadian Journal of Anaesthesia 05/2006; 53(4):331-5. · 2.35 Impact Factor
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ABSTRACT: The cost-effectiveness of four blood donor screening strategies for malaria was estimated to determine whether transmission by transfusion can be reduced.
A decision analysis model was developed to compare 1) not screening allogeneic blood donors for malaria (Strategy 1); 2) using the standard questionnaire (Strategy 2); 3) using the standard questionnaire followed by testing blood donors with risk factors for malaria with PCR (Strategy 3); and 4) screening all blood donors using PCR (Strategy 4). The expected costs and the number of cases of malaria for each strategy were compared and incremental cost-effectiveness ratios were calculated as the cost per case of malaria averted. All costs are in Canadian dollars.
Strategies 2 and 3 had the same effectiveness but different costs, with Strategy 3 being less costly. Compared to Strategy 1, the incremental cost effectiveness ratio was 6463 dollars per case of malaria averted for Strategy 3. Strategy 4 resulted in less transmission of malaria (0.4/million donors), but the cost compared to Strategy 3 was 3,972,624 dollars per case of malaria averted.
The addition of PCR to the standard screening questionnaire is economically attractive compared to the current standard screening questionnaire.
Transfusion 03/2004; 44(2):217-28. · 3.22 Impact Factor
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ABSTRACT: Apheresis has developed into a common therapeutic modality. The evidence for the clinical benefit of apheresis, however, is generally from uncontrolled and nonrandomized trials. Although the effectiveness of therapeutic apheresis may be established from uncontrolled trials, well-designed, randomized controlled trials provide the best evidence for a clinical benefit because this type of trial design minimizes bias. We assess the evidence for the use of apheresis, the optimal schedules for apheresis, and the replacement solutions used, based on randomized controlled trials. The databases, MEDLINE and EMBASE, and reference lists from relevant articles were searched. The literature search was restricted to articles published in English and included adult patients only. Two of the authors (NS, CK) independently reviewed the citation list to identify reports for retrieval, and the kappa statistic was used to quantify agreement between the reviewers. Articles were included if they used apheresis as an intervention and had clinical endpoints. The quality of the studies was assessed by using a validated instrument. Five hundred and ninety-two citations were identified, and a total of 85 reports were included in this review. There are only a few well-established indications for therapeutic apheresis. Randomized, controlled trials have clearly shown a benefit for patients treated with apheresis who have Guillain-Barre syndrome and patients who have thrombotic thrombocytopenic purpura. A clinical benefit has not been shown for a variety of conditions, including systematic lupus erythematosus, polyarteritis nodosa/Churg-Strauss syndrome, and for the treatment of renal allograft rejection. The effectiveness of apheresis needs to be clarified for several other diseases. As better-designed, randomized trials are performed, the role of apheresis for these indications will be further elucidated.
Transfusion Medicine Reviews 08/2002; 16(3):200-29. · 3.58 Impact Factor
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Irwin Walker, Nadine Shehata,
Guy Cantin,
Felix Couture,
Nathalie Dhédin,
Rebecca Barty,
Ronan Foley,
Robert D Sutherland,
Christopher Sigouin,
Kirk R Schultz,
David Mitchell
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ABSTRACT: Canadian multicenter pilot study of haploidentical donor.
To assess (1) ability to collect suitable graft (CD34+ > or = 5 x 10(6)/kg and CD3 < 1 x 10(5)/kg recipient body weight), (2) toxicity, (3) survival to day +100. ELIGIBILITY: All hematological malignancies and ages; accrual to end after 20 transplants of patients with AML in remission and age less than 55 years.
Preparation: Modified Perugia regimen, chemotherapy alone; melphalan 140 mg/m2 day -9, thiotepa 10 mg/kg day -7, fludarabine 40 mg/m2 days -7 to -3, and ATG (Thymoglobulin, Sangstat) days -6 to -2 (total 10.5 mg/kg). Infection prophylaxis: Ganciclovir (GC) 5 mg/kg days 5-20 then x5/week until day +100 then x3/week until 210 (subjects 1-3), foscarnet (FC) 90 mg/kg days 4-21 then short course pre-emptive GC or FC (subjects 4-11); fluconazole; cotrimoxazole. Donors: G-CSF 16 microg/kg daily x5 until second pheresis day. T-cell depletion: CliniMACS (MiltenyiBiotec).
Eleven patients with AML have been transplanted from four centers, eight female, three male, median age 34 (range 19-60). Disease status, first CR 1/11, second CR 4/11, third CR1/11, relapse 5/11. Graft CD34+ > or = 5 x 10(6)/kg was achieved in all cases, median 13.72 x 10(6)/kg (Q1, Q3: 8.26, 17.72; min 5.59, max 22.22), and CD3+ was < 1 x 10(5)/kg in all cases, median of 0.49 x 10(4)/kg (Q1, Q3: 0.30, 2.20; min 0.22, max 4.10). Ten of the 11 patients have died, median survival 103.5 days (Q1, Q3: 61.0, 151.0; min 0, max 290.0). Survival to day +100 6/11 (55%). Four patients died of leukemic relapse, six of infection. Of six patients dying of infection, CMV was a definite cause in four. Of four dying with relapse, CMV was significant in one. Engraftment was assessed in 10 patients who survived >0 days. Granulocyte engraftment (> 0.5 x 10(9)/l) was achieved in all patients, median 11.5 days (Q1, Q3: 10, 17; min 8, max 70). Platelet engraftment (> 20 x 10(9)/l) was achieved in 8 of 10 patients, median 15 days (Q1, Q3: 9, 16; min 9, max 97). The two platelet non-engrafters died on days +45 and +61. Toxicity was low, with one toxic death (day 0), and the Bearman organ toxicity gradings were < or = grade 2 in all other patients. There were no instances of graft-vs.-host disease or graft rejection.
The problems of graft-vs.-host disease and graft rejection have been removed as barriers to haploidentical transplantation but the slow immune reconstitution limits its general application. Late referrals contribute to a high relapse rate and have delayed an optimal evaluation of the procedure.
Blood Cells Molecules and Diseases 33(3):222-6. · 2.35 Impact Factor