Safety and impact of donor-type red blood cell transfusion before allogeneic peripheral blood progenitor cell transplantation with major ABO mismatch

BACKGROUND: Changes within the ABO system are regularly observed phenomena in allogeneic bone marrow transplantation (BMT) and peripheral blood progenitor cell transplantation (PBPCT). Major ABO mismatch can lead to different clinical problems including acute hemolysis after infusion of the allograft, delay of red blood cell (RBC) engraftment, or even manifestation of pure red cell aplasia (PRCA). STUDY DESIGN AND METHODS: This retrospective study demonstrates the safety and the impact of donor-type RBC transfusion before allogeneic PBPCT in major ABO settings as routinely performed at our transplantation unit. This study reports on transfusion of mismatched RBCs at the end of the conditioning period in 35 patients who underwent allogeneic PBPCT, which led to a decrease in isoagglutinin titers in most cases. RESULTS: A decrease of isoagglutinin titer after donor-type RBC transfusion can significantly reduce the demand of RBC transfusion between transplantation and Day +30 (p = 0.003). Interestingly, patients who developed PRCA were not observed, a complication being regularly documented by other groups. CONCLUSION: A decrease of isoagglutinin titers by in vivo immunoadsorption before allogeneic PBPCT does not only lack severe complication but also leads to a reduction in demand of RBC transfusion after engraftment and may reduce the incidence of PRCA in these patients.     

Impact of ABO incompatibility on allogeneic peripheral blood progenitor cell transplantation after reduced intensity conditioning

BACKGROUND: Most studies indicate that ABO incompatibility has no effect on the clinical outcome after allogeneic peripheral blood progenitor cell (PBPC) transplantation (allo-PBPCT). However, it carries additional risks of hemolytic reactions, delayed red blood cell (RBC) engraftment, and pure red cell aplasia (PRCA). Data on these events after reduced intensity conditioning (RIC) regimens are limited, but recent studies have suggested a higher transplant-related mortality (TRM) and morbidity in this setting. STUDY DESIGN AND METHODS: We investigated the impact of ABO-matching on the outcome of 77 patients included in a prospective RIC allo-PBPCT protocol, focusing on engraftment, transfusion requirements, graft-versus-host disease, TRM, and survival. RESULTS: There were 17 (22%) minor and 8 (10%) major ABO-incompatible transplants. No graft failures were observed. After major ABO-incompatible grafts, RBC engraftment was delayed, longer thrombocytopenia periods were documented, and transfusion requirements increased. A transient mild hemolysis occurred in 10 patients, 7 (41%) minor and 3 (37%) major ABO-mismatched. A PRCA was observed in a O+ patient with a pretransplant anti-Jka, grafted from an A + Jka+ donor. Graft-versus-host disease, disease progression, and TRM were not affected by ABO matching. CONCLUSION: ABO incompatibility was not associated with clinically relevant hemolysis after the RIC protocol used and did not impair the clinical outcome. PRCA was only observed in one patient, with a non-ABO RBC allo-antibody.     

After major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation, erythroid engraftment occurs later in patients with donor blood group A than donor blood group B

BACKGROUND: Isohemagglutinins directed against the donor blood group frequently delay erythroid engraftment after major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation (HPCT). Graft-versus-host reactions are capable of accelerating the clearance of isohemagglutinins. Whether immunogenicity of the A- and B-antigen is important in this process is unknown. PATIENTS AND METHODS: Data of 807 patients from three centers were screened for patients with major or bidirectionally ABO-mismatched donors. Clinical data and red blood cell (RBC) transfusion support were analyzed retrospectively. RESULTS: A total of 158 patients with major or bidirectionally mismatched donors were identified. After major mismatched HPCT, patients with anti-A directed against the donor blood group required RBC transfusion support for a median of 109 days (range, 0-324 days) compared to 21 days (range, 2-98 days) for patients with anti-B directed against donor blood group (log-rank test, p = 0.0001). Other risk factors associated with prolonged RBC transfusion support in univariate analysis were age (p = 0.024), cytomegalovirus infection (p = 0.016), hemolytic anemia (p = 0.027), and chronic bleeding disorders (p = 0.038). The independent influence of donor blood group and recipient age were confirmed in a multivariate analysis. CONCLUSION: These results indicate that the immunogenicity of the ABO antigen plays an important role for the kinetics of erythroid engraftment after ABO-mismatched HPCT.     

The influence of blood group differences in allogeneic hematopoietic peripheral blood progenitor cell transplantation

BACKGROUND: Severe immunohematologic complications after ABO-mismatched allogeneic blood peripheral blood progenitor cell (PBPC) transplantation (PBPCT), including pure red cell aplasia and immune hemolysis, have been described. Although several studies have addressed this issue, the clinical influence of blood group differences on transfusion requirements and survival is still discussed controversially, especially in the case of PBPCT. STUDY DESIGN AND METHODS: This single-center study is based on 143 patients receiving PBPCT after standard or reduced-intensity conditioning. The influence of blood group differences in the ABO, Rh, and Kell systems on red blood cell, platelet, and plasma transfusion requirements; length of hospitalization in transplantation unit; survival; and occurrence of graft-versus-host disease was investigated. Additionally, the influence of the conditioning regimen and irregular antibodies on the measures mentioned above was analyzed. RESULTS: Multivariate analysis demonstrated that minor and bidirectional ABO mismatch (p = 0.028) and Rh difference (p = 0.020) independently led to poorer survival. The Kell difference did not show significant influences on the measures mentioned above. A clinically relevant influence of blood group differences on transfusion requirements could not be demonstrated. Irregular antibodies also did not show significant influences. CONCLUSION: These findings indicate an influence of blood group differences in PBPCT on survival and must be studied in further detail.     

Clinically significant anti‐A1 in a presumed ABO‐identical hematopoietic stem cell transplant recipient: a case report

BACKGROUND: Subgroups of the blood group A (ABO) are generally not considered ABO incompatible for hematopoietic progenitor cell (HPC) transplant. CASE REPORT: A 54‐year‐old female presented for HPC transplantation for acute leukemia. No HLA‐matched donor was identified, so she received a peripheral blood stem cell graft from an HLA‐mismatched unrelated donor. On pretransplant testing, both the donor and the recipient typed as blood group A. On Day +67 after transplant, the recipient had a transfusion reaction consisting of an increase in temperature, rigors, and shaking chills during infusion of a unit of group A red blood cells (RBCs). A transfusion reaction workup revealed an ABO discrepancy with both anti‐A (1+) and anti‐B (3+) identified in the patient's serum as well as a positive direct antiglobulin test with monoclonal anti‐IgG antisera. Anti‐A₁ were identified serologically and in an eluate. Hemolysis was clinically significant, requiring blood transfusion. No ABO typing discrepancies were found on pretransplant testing in either the recipient or the donor. DNA sequencing for blood group A subgroups performed after the transfusion reaction on blood collected before the transplant showed the donor to be type A₁ and the recipient as A₂. Unfortunately, the patient experienced graft failure requiring reconditioning and reinfusion of additional cells from the original HPC donor. On Day +94 after the second transplant, the patient died with severe acute gastrointestinal graft‐versus‐host disease. CONCLUSION: This report describes a blood group A₂ patient who developed an anti‐A₁ causing clinically significant hemolysis after HPC transplant from an A₁ donor.     

TRANSPLANTATION AND CELLULAR ENGINEERING: Prolonged isolated red blood cell transfusion requirement after allogeneic blood stem cell transplantation: identification of patients at risk

BACKGROUND: Delayed donor red blood cell chimerism (DRCC), pure red blood cell aplasia (PRCA), and autoimmune hemolytic anemia (AIHA) are poorly documented complications after hematopoietic cell transplantation (HCT). The clinical variable “prolonged isolated red blood cell transfusion requirement” (PRTR) was evaluated as a trigger for an extended diagnostic workup. STUDY DESIGN AND METHODS: PRTR was defined as the need for red blood cell (RBC) transfusions beyond Day 60 after HCT. We analyzed 487 patients transplanted between 2000 and 2006. Median age was 37 years (range, 0‐70 years). Peripheral blood stem cells (n = 344), marrow (n = 138), and cord blood (n = 5) from 278 unrelated and 209 family donors were used. RESULTS: Univariate analysis identified age (incidence of 18.3% among elderly patients, 10.5% in adults, and 2.0% among children [p = 0.002]), ABO incompatibility (16.4% after major incompatible, 2.9% after minor incompatible, and 9.4% after ABO‐compatible transplantations [p = 0.003]), conditioning (15.2% after reduced‐intensity regimens vs. 7.3% after myeloablative conditioning; p = 0.006), donor type (13.2% after HLA‐matched unrelated, 13.6% after mismatched unrelated, 5.7% after matched related, and 0.0% after mismatched related grafts; p = 0.026), and acute graft‐versus‐host disease (aGVHD; 7.1% with aGVHD vs. 12.5% without aGVHD; p = 0.046) as predisposing factors. In multivariate analysis minor ABO incompatibility (odds ratio [OR] = 0.2, p = 0.01), younger age (OR = 0.1, p = 0.02), and matched related HCT (OR = 0.4, p = 0.02) remained independent protective factors. CONCLUSIONS: PRTR could serve as a trigger for a standardized screening for DRCC, PRCA, and AIHA after HCT.     

主要ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍

目的 研究主要ABO血型不合异基因造血干细胞移植（allo-HSCT）后患者纯红细胞再生障碍（PRCA）的发病情况及危险因素。方法 分析移植后患者PRCA的发病危险因素，比较抗A凝集素与抗B凝集素对红系造血恢复的影响。结果 100例ABO血型主要及主次要均不合allo-HSCT患者中，12例发生PRCA。A供O者9例，A供B者1例，B供O者2例。有抗A凝集素的患者（10例）较有抗B凝集素的患者（2例）易发生PRCA（P〈0．05）。PRCA的发生不影响急性移植物抗宿主病（GVHD）或巨细胞病毒（CMV）感染的发生。发生PRCA时血型转换的中位时问为150．5d，显著长于无PRCA发生患者（60．0d）（P〈0．05）；红系恢复的中位时间为203．5d，显著长于无PRCA发生患者（76．0d）（P〈0．05）。有抗A凝集素的患者血型转换中位时间为90．0d，显著长于有抗B凝集素的患者（55．0d）（P〈0．05）；红系恢复中位时间为98．0d，长于有抗B凝集素者（80．0d）（P〉0．05），但差异无统计学意义。结论 PRCA是ABO血型不合移植的合并症之一。A供O是主要ABO血型小合allo-HSCT后PRCA发病的危险因素。     

ABO血型不合的异基因骨髓移植

目的 探讨ＨＬＡ 相合,ＡＢＯ 血型不合的异基因骨髓移植（ａｌｌｏＢＭＴ） 中存在的免疫及造血问题。方法 对本所３８ 例ＡＢＯ 血型主要不合,２３ 例次要不合的ＨＬＡ 相合的ａｌｌｏＢＭＴ 受者进行分析,并选用同期ＡＢＯ 血型相合的ａｌｌｏＢＭＴ 患者作配对比较。结果ＡＢＯ 血型不合的ａｌｌｏＢＭＴ患者,输注骨髓后无一例发生急性溶血。经配对ｔ 检验及χ２ 检验,ＡＢＯ 血型不合对骨髓植活、血小板恢复,ＧＶＨＤ 及５ 年无病生存率均无影响; 在ＡＢＯ 血型主要不合组, 红系开始恢复时间明显延迟,使红细胞输用量明显增多;其中５ 例患者发生纯红细胞再生障碍（ 纯红再障） ,持续约７ ～２４ 个月。发生纯红再障者均为“Ｏ”型血受者,红系恢复与血型抗体滴度具有相关性。结论ＡＢＯ 血型不合可以进行ａｌｌｏＢＭＴ,但对发生纯红再障高危的患者宜慎重。     

Severe immune hemolysis after minor ABO-mismatched allogeneic peripheral blood progenitor cell transplantation occurs more frequently after nonmyeloablative than myeloablative conditioning

BACKGROUND: Hemolysis as a result of donor-recipient minor ABO mismatching is a complication of allogeneic peripheral blood progenitor cell (PBPC) transplantation (PBPCT). The increased B-lymphocyte content of PBPC grafts and immunosuppressive regimens without methotrexate (MTX) may increase incidence and severity of this event. STUDY DESIGN AND METHODS: A total of 93 patients were analyzed after allogeneic PBPCT. In 25 (27%) cases, minor (n=21) or bidirectional (n=4) ABO mismatching was present. Of these, 15 patients received myeloablative and 10 received nonmyeloablative conditioning regimens. For GVHD, prophylaxis cyclosporin A (CsA) alone (n=2) or CsA with MTX (n=13) was given after myeloablative conditioning and CsA with mycophenolate mofetil (MMF) after nonmyeloablative conditioning (n=10). RESULTS: Hemolysis occurred in 4 out of 25 (16%) patients with minor or bidirectional ABO mismatching only. Three patients underwent nonmyeloablative conditioning and were given CsA with MMF, and one patient underwent myeloablative conditioning and was given CsA alone for GVHD prophylaxis. Hemolysis began 7 to 10 days after transplantation, and donor type alloantibodies were detectable concomitantly with recipients type RBCs. CONCLUSION: Patients receiving minor or bidirectional ABO-mismatched PBPC grafts and GVHD prophylaxis without MTX are at risk of hemolysis. Prophylactic interventions in patients before minor ABO-mismatched PBPCT not receiving MTX should be taken into consideration. Careful monitoring of hemolysis parameters during the first 15 days after PBPCT transplantation is mandatory.     

Apheresis-related enrichment of CD26++ T lymphocytes: phenotypic characterization and correlation with unfavorable outcome in autologous hematopoietic progenitor cell transplantation

BACKGROUND: The lymphocyte surface glycoprotein CD26 anchors adenosine deaminase to the lymphocyte surface and possesses dipeptidyl peptidase IV activity. A distinct subset of CD26++ lymphocytes in autologous hematopoietic progenitor cell transplants (HPCTs) was investigated with regard to clinical outcome after autologous HPCT. The phenotype of these cells was characterized in more detail. STUDY DESIGN AND METHODS: Forty‐two eligible patients (multiple myeloma, n = 31; Hodgkin's disease, n = 3; non‐Hodgkin's lymphoma, n = 6; peripheral neuroectodermal tumor, n = 1; acute myeloid leukemia, n = 1) were included in a retrospective analysis. Distinct cellular subsets, including CD26+/? and CD26++ subpopulations, were analyzed for correlations with kinetics of engraftment, progression‐free survival, and overall survival. RESULTS: The numbers of CD26++ T lymphocytes in the autograft correlated inversely with progression‐free survival (p = 0.013). CD26++ T lymphocytes transfused per kg of body weight were predictive for the occurrence of disease progression or relapse (p = 0.006). Importantly, the numbers of CD26++ cells showed a highly variable degree of enrichment in the autograft, but no significant variations in the peripheral blood before apheresis. The characterization of CD26++ cells revealed that CD26++/CD8+ cells form a homogeneous population with a distinct T memory cell phenotype (CD45RO+, CD161++, interleukin‐18Rα++, CCR7?). CONCLUSION: CD26++ lymphocytes define a discrete phenotype of T memory cells with known chemoresistance and T‐cell‐repopulating capacity. Their enrichment during apheresis and corresponding depletion from the circulation are associated with an adverse outcome in autologous HPCT.     

Significance of isoagglutinin titer in ABO‐incompatible kidney transplantation

ABO‐incompatible (ABO‐i) kidney transplantation (KT) has emerged for overcoming the shortage of organ donors. Although this technique initially achieved only low graft survival due to isoagglutinin, recently developed desensitization protocols have improved survival to levels that are comparable to ABO‐compatible KT. However, isoagglutinin is still regarded as a major obstacle to ABO‐i KT. In this study, we evaluate the impact of isoagglutinin titer on clinical outcomes as well as factors that may influence isoagglutinin titers. In total, data from 95 patients who underwent ABO‐i KT were analyzed. Preoperatively, rituximab administration and plasmapheresis were performed until the titer was reduced to ≤1:4. Retrospective analysis included blood group; timing and dosage of rituximab; isoagglutinin titer; number of plasmapheresis; and clinical outcomes including graft survival and serum creatinine. Graft survival was 95.8% (n = 91) and average serum creatinine at 1‐ and 1.5‐year post‐ABOi‐KT was 1.3. Three patients died of sepsis. The identified predictors of titer‐rebound after transplant were short interval (<7 days) between rituximab and first plasmapheresis (P = 0.004); high initial titer (≥256) (P = 0.023); low titer‐reduction rate (P < 0.001); and blood group O (P < 0.001). One patient who experienced a rebound developed antibody‐mediated rejection. With low‐dose (200 mg) rituximab, the change in isoagglutinin titer‐rebound was not significant and the infection rate was significantly decreased (P = 0.001). In conclusion, isoagglutinin titer‐rebound within the first 2 weeks after KT may be a risk factor for rejection. The factors identified as affecting titer‐rebound after KT were high initial isoagglutinin titer, low titer‐reduction rate, short interval, and blood group O. J. Clin. Apheresis 29:243–250, 2014. © 2013 Wiley Periodicals, Inc.     

Transfusion policy: when to stop the use of extremely rare blood for an allogeneic hematopoietic progenitor cell transplant recipient with a history of red cell alloimmunization

BACKGROUND: Decisions for when to select, and when to discontinue, antigen-negative blood in hematopoietic progenitor cell transplantation (HPCT) recipients with red blood cell (RBC) antibodies can be confusing. In HPCT performed for sickle cell anemia patients who require extremely rare antigen-negative blood, the balance of caution and practicality is further complicated. CASE REPORTS: Four sickle cell anemia patients with current or historic RBC antibodies underwent allogeneic HPC transplantation. One required extremely rare (group O D-, hr(B)-) blood. None of the antibodies caused significant hemolysis after transplant. In the case requiring rare blood, antigen-negative blood was requested after donor RBC engraftment because of incomplete donor white blood cell (WBC) chimerism. CONCLUSIONS: RBC antibodies derived from a recipient of allogeneic HPCT rarely cause significant hemolysis, in contrast to the more severe picture sometimes seen with donor-derived antibodies. When donor WBC chimerism is delayed past the time of donor RBC engraftment, there can be concern for the possibility of future recipient-type antibody production. Even 100 percent donor lymphocyte chimerism is no guarantee of total host plasma cell ablation. Immunoglobulin allotyping, when informative, can suggest chimerism for several years. Recipient-type blood, when extremely rare, may not be available for that duration.     

主要ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍

20例主要ABO血型不合异基因造血干细胞移植（allo-HSCT)患中，6例发生纯红细胞再生障碍（PRCA）。PRCA对中性粒细胞和血小板植入以及Ⅱ-Ⅳ度aGVHD并无影响。6例PRCA患血型均为O型，而供血型5例为A型，1例B型，提示供／受血型A／O是主要ABO血型不合allo-HSCT后PRCA发生的高危因素。4例除给予RBC输注无其它特殊治疗，随着凝集素滴度降至＜8，红系造血自然恢复，而另2例尽管给予重组人红细胞生成素（rhEPO）治疗红系再障仍持续＞300天，经供型血浆置换而红系恢复造血。在本组病例，环孢菌素在PRCA发生中并无作用，而GVHD发生则可促进红系造血恢复。     

ABO血型不合的非清髓异基因外周血干细胞移植

为了探讨ABO血型不合对HLA相合的非清髓异基因外周血干细胞移植(NAST)的影响,回顾分析了15例ABO血型主要不舍,9例次要不合的HLA相合的NAST的临床特点,并选用同期ABO血型相合的NAST作成组比较。结果显示：24例ABO血型不合的NAST受者在输入供者外周血千细胞悬液时无1例发生急性溶血,但有2例发生迟发性溶血。统计学分析表明,ABO血型不合对NAST骨髓植活、血小板恢复、GVHD、疾病复发及无病生存均无影响。在ABO血型主要不合组,红系开始恢复时间明显延迟,其中1例“0”型血受者发生纯红细胞再生障碍,持续5个月。结论：ABO血型不合不是NAST的障碍,仅在ABO血型主要不合时．红系恢复时间延迟。     

Impact of ABO mismatching on the outcomes of allogeneic related and unrelated blood and marrow stem cell transplantations for hematologic malignancies: IPD-based meta-analysis of cohort studies

BACKGROUND: The impact of donor-recipient ABO matching on outcomes after allogeneic stem cell transplantation has been a matter of controversy.
STUDY DESIGN AND METHODS: Individual patient data–based meta-analysis was conducted with a pooled data set provided through six published and one unpublished cohorts. Outcomes in recipients of peripheral blood or bone marrow transplantation for hematologic malignancies were evaluated. A multivariate Cox model was used to adjust differences in outcomes of patients receiving ABO-matched grafts with those receiving major, minor, or bidirectional mismatched grafts. Considering multiple testing, p values of less than 0.05 and 0.001 were considered significant for the primary and secondary endpoints, respectively.
RESULTS: In all, 1208 cases, including 697 ABO-matched and 202 major, 228 minor, and 81 bidirectional mismatched transplants, were analyzed. Overall, adverse impact of ABO matching on overall survival (OS), as a primary endpoint, was not observed (adjusted hazard ratios [95% confidence intervals]: major, 1.03 [0.82-1.30], p = 0.81; minor, 1.19 [0.97-1.47], p = 0.10; bidirectional, 1.25 [0.91-1.72], p = 0.17). Among related stem cell recipients, ABO matching had no significant influence on OS, while the minor and bidirectional mismatched groups among unrelated stem cell recipients exhibited lower OS with marginal significance, especially in patients with acute leukemia, patients who received transplants after 1998, and patients who underwent transplants at Asian centers.
CONCLUSIONS: Our meta-analysis demonstrates no adverse association between any ABO mismatching and survival. However, marginally lower OS found in recipients of minor or bidirectional mismatched grafts from unrelated donors suggested the need for larger studies focusing on unrelated transplants.     

脐血血浆体外对造血祖细胞增殖的影响

目的：探讨脐血血浆对造血细胞增殖的刺激作用。方法：用细胞培养的方法以集落形成单位（ＣＦＵ）为指标，观察了脐血血浆体外对脐血和骨髓造血祖细胞增殖的影响。结果：①脐血血浆使脐血ＣＦＵ总和增加了２．２３±０．５２倍，在一定范围内，ＣＦＵ总和增加幅度与培养体系中脐血血浆含量呈剂量依赖关系，并发现脐血细胞和脐血血浆ＡＢＯ血型不同时刺激作用更为明显。②脐血血浆对骨髓造血祖细胞集落形成的刺激作用与ＡＢＯ血型有关，血型相同者，无刺激作用，血型不同者ＣＦＵ总和增加了１．５５±０．４３倍。③细胞因子可使脐血ＣＦＵ总和增加，联合应用细胞因子与脐血血浆，ＣＦＵ总和增加更为明显。④成人外周血血浆对脐血和骨髓造血细胞增殖的影响与胎牛血清相比无差异。结论：脐血血浆中含有刺激造血细胞增殖的因子，这种（些）因子对造血细胞的刺激作用具有一定的选择性；并提示脐血干细胞移植时同时输注脐血血浆可能更为有利。     

Passenger lymphocyte syndrome with severe hemolytic anemia due to an anti-Jk(a) after allogeneic PBPC transplantation

BACKGROUND: After allogeneic peripheral blood progenitor cell (PBPC) transplantation, a patient developed a severe hemolytic transfusion reaction due to passenger lymphocyte syndrome. CASE REPORT: A 50-year-old woman with secondary acute myeloid leukemia transforming from a myelodysplastic syndrome received an ABO-compatible PBPC graft from her HLA-identical sister. For prophylaxis of GVHD, the patient was treated with cyclosporine and methotrexate. Eighteen days after the transplant, the patient experienced a severe hemolytic transfusion reaction due to an alloantibody (anti-Jk(a)) produced by donor lymphocytes. RESULTS: The patient was typed as group A, Jk(a+) before transplantation; the donor was typed as group A, Jk(a-). On Day 18 after transplantation, the immunohematologic screening revealed a positive DAT (C3d 3+) and an alloanti-Jk(a). Hemolysis in the patient at that time was indicated by a drop in the Hb and an increase in the LDH level (maximum, 592 IU/L on Day 23). CONCLUSION: The course of hemolysis and the time of appearance of an alloantibody in this patient meet the criteria for passenger lymphocyte syndrome. In most cases, this syndrome is triggered by ABO system antibodies. This is the first reported case of passenger lymphocyte syndrome after PBPC transplantation that was due to an alloantibody that did not belong to the ABO system.     

Prophylactic red blood cell exchange for prevention of severe immune hemolysis in minor ABO-mismatched allogeneic peripheral blood progenitor cell transplantation after reduced-intensity conditioning

BACKGROUND: Delayed severe immune hemolysis due to donor-derived passenger lymphocytes is observed in minor and/or bidirectional ABO-mismatched transplants, especially after reduced-intensity conditioning (RIC). The incidence is reported in up to 30 percent of patients and can result in multiorgan failure (MOF) and death. STUDY DESIGN AND METHODS: A first group of 32 patients (historical control) underwent RIC followed by allogeneic hematopoietic peripheral blood progenitor cell transplantation at our institution. In 5 of 10 patients with a minor and/or bidirectional ABO-mismatched graft, severe immune hemolysis was observed, leading to death in 3 of them. Therefore, we initiated a protocol with prophylactic red blood cell (RBC) exchange in minor and/or bidirectional ABO mismatch of a second group of patients (study group) and investigated the incidence of hemolysis, transplant-related mortality (TRM), and overall survival (OS) and compared these data with the historical control group. Twenty-two of 80 patients in the study group had a minor and/or bidirectional ABO-mismatched donor. RESULTS: In 20 patients, a prophylactic RBC exchange was performed. Three patients showed mild to moderate citrate reactions, and in 1 patient the procedure had to be stopped because of hypotension. Eighteen of 20 patients engrafted uneventfully, 1 patient rejected his graft, and another 1 showed signs of mild hemolysis. In the minor and/or bidirectional ABO-mismatched setting patients in the study group had a lower risk for TRM at 1 year compared to patients in the historical control group (16% vs. 53%, p < 0.05) and a better 1-year OS (65% vs. 40%, p < 0.05). CONCLUSION: RBC exchange is a safe procedure, reducing the incidence of delayed severe immune hemolysis and thus the risk of TRM in minor and/or bidirectional ABO-mismatched cases.     

Alterations of platelet function and clot formation kinetics after in vitro exposure to anti‐A and ‐B

BACKGROUND: ABO‐mismatched platelets (PLTs) are commonly transfused despite reported complications. We hypothesized that because PLTs possess A and B antigens on their surface, ABO‐mismatched transfused or recipient PLTs could become activated and/or dysfunctional after exposure to anti‐A or ‐B in the transfused or recipient plasma. We present here in vitro modeling data on the functional effects of exposure of PLTs to ABO antibodies. STUDY DESIGN AND METHODS: PLT functions of normal PLTs of all ABO types were assessed before and after incubation with normal saline, ABO‐identical plasma samples, or O plasma samples with varying titers of anti‐A and anti‐B (anti‐A/B). Assays used for this assessment include PLT aggregation, clot kinetics, thrombin generation, PLT cytoskeletal function, and mediator release. RESULTS: Exposure of antigen‐bearing PLTs to O plasma with moderate to high titers of anti‐A/B significantly inhibits aggregation, prolongs PFA‐100 epinephrine closure time, disrupts clot formation kinetics, accelerates thrombin generation, reduces total thrombin production, alters PLT cytoskeletal function, and influences proinflammatory and prothrombotic mediator release. CONCLUSIONS: Our findings demonstrate a wide range of effects that anti‐A/B have on PLT function, clot formation, thrombin generation, PLT cytoskeletal function, and mediator release. These data provide potential explanations for clinical observations of increased red blood cell utilization in trauma and surgical patients receiving ABO‐nonidentical blood products. Impaired hemostasis caused by anti‐A/B interacting with A and B antigens on PLTs, soluble proteins, and perhaps even endothelial cells is a potential contributing factor to hemorrhage in patients receiving larger volumes of ABO‐nonidentical transfusions.     

Delayed massive immune hemolysis mediated by minor ABO incompatibility after allogeneic peripheral blood progenitor cell transplantation

BACKGROUND: Bone marrow transplantation with minor ABO incompatibility may be followed by moderate delayed hemolysis of the recipient's red cells by donor-derived ABO antibodies. This reaction may be more severe after transplantation of peripheral blood progenitor cells (PBPCs). CASE REPORT: A 16-year-old boy underwent an allogeneic PBPC transplant from his HLA-mismatched mother as treatment for acute myeloblastic leukemia that had proved resistant to induction chemotherapy. Transfusion of the unmanipulated PBPCs proceeded without any complication, despite the difference in ABO blood group (donor, O Rh-positive; recipient, A Rh-positive). On Day 7, a rapid drop in hemoglobin to 4 g per dL was observed, which was attributed to a massive hemolysis. All the recipient's group A red cells were destroyed within 36 hours. This delayed and rapidly progressive hemolytic anemia was not associated with the transfusion of the donor's plasma. Rather, the anti-A titer increased in parallel with marrow recovery, which suggested an active synthesis of these antibodies by immunocompetent cells from the donor against the recipient's red cells. The mother's anti-A titer was retrospectively found to be 2048. Her unusually high titer is probably due to prior sensitization during pregnancies. On Day 12, the patient developed grade IV graft-versus-host disease, which proved resistant to all treatments instituted and led to his death on Day 35. CONCLUSION: PBPC transplantation with minor ABO incompatibility may be associated with significant risk of massive delayed hemolysis.