Passenger Lymphocyte Syndrome Research Articles

Immuno-Hematologic Complexity of ABO-Incompatible Allogeneic HSC Transplantation.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO incompatible. Immuno-hematologic investigations allow to estimate donor/recipient ABO mismatch and anti-A/B isohemagglutinin (IHA) titration in the pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can occur post HSCT. Some preventive measures take into consideration either decision-making algorithms based on the recipient's IHA titration or clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Product manipulation through red blood cell (RBC) and/or plasma depletion can also be taken into account. Currently, the best approach in the management of ABO-incompatible transplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHA titration are not standardized. A transfusion strategy must consider both the donor's and recipient's blood group systems until the RBC engraftment catches on and ABO conversion (forward and reverse typing) is confirmed on two consecutive and independent samples. Therefore, ABO incompatibility in HSCT represents a demanding immuno-hematologic challenge and requires all necessary preventive measures, including the appropriate selection of ABO blood components for transfusion.

Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.

Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath-Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.

Passenger lymphocyte syndrome, an unusual cause of anemia after liver transplantation

Passenger lymphocyte syndrome, an unusual cause of anemia after liver transplantation

High Rate of Passenger Lymphocyte Syndrome after ABO Minor Incompatible Lung Transplantation.

Rationale: Passenger lymphocyte syndrome (PLS) may complicate minor ABO mismatched lung transplantation (LuTX) via donor-derived red cell antibody-induced hemolysis.Objectives: To ascertain the incidence and specificity of PLS-relevant antibodies among the study population as well as the dynamics of hemolysis parameters and the transfusion requirement of patients with or without PLS.Methods: In this cohort study, 1,011 patients who received LuTX between January 2010 and June 2019 were studied retrospectively. Prospectively, 87 LuTX (July 2019 to June 2021) were analyzed. Postoperative ABO antibody and hemolytic marker determinations, transfusion requirement, and duration of postoperative hospital care were analyzed. Retrospectively, blood group A recipients of O grafts with PLS were compared with those without.Measurements and Main Results: PLS affected 18.18% (retrospective) and 30.77% (prospective) of A recipients receiving O grafts, 5.13% of B recipients of O grafts, and 20% of AB patients receiving O transplants. Anti-A and anti-A1 were the predominant PLS-inducing antibodies, followed by anti-B and anti-A,B. Significantly lower hemoglobin values (median, 7.4 vs. 8.3 g/dl; P = 0.0063) and an approximately twice as high percentage of patients requiring blood transfusions were seen in PLS. No significant differences in other laboratory markers, duration of hospital stay, or other complications after LuTX were registered.Conclusions: Minor ABO incompatible LuTX recipients are at considerable risk of developing clinically significant PLS. Post-transplant monitoring combining red cell serology and hemolysis marker determination appears advisable so as not to overlook hemolytic episodes that necessitate antigen-negative transfusion therapy.

Passenger lymphocyte syndrome from Transfusion Medicine's standpoint: Short Communication

Passenger lymphocyte syndrome from Transfusion Medicine's standpoint: Short Communication

Optimal blood transfusion strategy in ABO-incompatible sold organ transplantation patients: perspective of passenger lymphocyte syndrome

Optimal blood transfusion strategy in ABO-incompatible sold organ transplantation patients: perspective of passenger lymphocyte syndrome

Passenger Lymphocyte Syndrome in Post-Transplant Patients

Passenger Lymphocyte Syndrome in Post-Transplant Patients

Case Report: Passenger Lymphocyte Syndrome

Passenger Lymphocyte Syndrome is an hemolytic syndrome that can occur after a ABO nonidentical transplant. Lymphocytes derived from the donors organ stimulate an imune response against receptors red blood cells antigens, which lead to hemolysis. Passenger Lymphocyte Syndrome is often self-limited, solving itself within 3 months. In cases of severe anemia, blood transfution with the donos blood type is the ideal treatment. This article describes a case os Passenger Lymphocyte Syndrome occurred at Leforte Hospital, São Paulo, Brazil.

A Case Report of Passenger Lymphocyte Syndrome Following Bidirectional ABO-mismatched Kidney Transplantation

A Case Report of Passenger Lymphocyte Syndrome Following Bidirectional ABO-mismatched Kidney Transplantation

S3145 Severe Transplantation-Mediated Alloimmune Thrombocytopenia After Liver Transplant Treated Successfully With Efgartigimod

Introduction: Transplantation-mediated alloimmune thrombocytopenia (TMAT) is a rare form of passenger lymphocyte syndrome in which lymphocytes from the donor organ produce antibodies against recipient platelets resulting in thrombocytopenia. We describe a novel treatment of TMAT with efgartigimod, a human IgG1 Fc antibody fragment, in a patient with severe, refractory thrombocytopenia following liver transplantation. Case Description/Methods: A 70-year-old man with cirrhosis secondary to non-alcoholic steatohepatitis complicated by hepatocellular carcinoma underwent deceased donor orthotopic liver transplantation. He required emergent retransplantation on post-operative day 7 for acute hepatic artery thrombosis. Seven days after retransplantation, the patient developed severe thrombocytopenia with platelets <1 × 109/L. He responded poorly to platelet transfusion, and two days later developed severe intra-abdominal bleeding requiring exploratory laparotomy. No active bleeding was found, and splenectomy was performed. Testing for heparin induced thrombocytopenia was negative, and the working diagnoses were post transfusion purpura and idiopathic thrombocytopenic purpura. Over the next 8 weeks, the patient had persistent, severe thrombocytopenia despite platelet transfusions and treatment with intravenous immunoglobulin, plasmapheresis, rituximab, romiplostim, and eltrombopag. Notably, two patients who received lung and kidney transplants from the same donor also developed severe thrombocytopenia. Ultimately, testing revealed the presence of serum antibodies to human platelet antigen (HPA) 1a. Genetic testing revealed the genotypes HPA 1a/1b and HPA 1b/1b in the patient and donor respectively, consistent with a mismatch and TMAT. The patient received weekly efgartigimod for 4 doses, and after his third infusion developed sustained improvement in platelets to >100 × 109/L without need for transfusion. Discussion: TMAT is a rare disorder after solid organ transplantation that can lead to severe thrombocytopenia with life threatening bleeding and even death. Although TMAT generally resolves a few months after transplantation as donor lymphocytes are cleared from the circulation, initial management is challenging. Efgartigimod is a novel treatment approved by the food and drug administration for myasthenia gravis that leads to degradation of IgG by binding to the neonatal Fc receptor and should be considered for severe TMAT.

Long-Term Persisting Donor-Derived Human Leukocyte Antigen Antibody as a Possible Passenger Lymphocyte Syndrome Following Lung Transplantation: A Case Report

Herein, we reported the transfer of donor-derived antihuman leukocyte antigen (HLA) antibodies in 2 recipients after lung transplantation. Case 1: A 39-year-old woman with pleuroparenchymal fibroelastosis underwent a single brain-dead donor lung transplantation. Antibody screening 36 days after transplantation demonstrated high levels of de novo nondonor HLA class I-specific antibodies. The antibody screening in the donor serum revealed that the donor demonstrated a largely overlapping antibody profile. Importantly, the donor serum also included high-level HLA-specific antibodies against the recipient HLA-specific antigens, which were not detected in the recipient sera after transplantation. Donor-derived anti-HLA antibodies were still detected in the recipient 39 months after transplantation, without causing any complications such as graft-vs-host disease. Case 2: A 47-year-old woman underwent living-donor lobar lung transplantation for pulmonary complications after bone marrow transplantation with a right lower lobe from her husband and the left lower lobe from her sister. On postoperative day 39, the recipient's anti-HLA-class I antibody profile was found to be similar to that of the highly sensitized left lung donor. These donor-derived anti-HLA antibodies remained to be produced in the recipient 66 months after transplantation, without the development of complications.

Passenger lymphocyte syndrome following small bowel transplantation.

Passenger lymphocyte syndrome following small bowel transplantation.

Long-Term Persisting Donor-Derived Anti-Human Leukocyte Antigen (HLA) Antibody as a Possible Passenger Lymphocyte Syndrome Following Lung Transplantation

<h3>Introduction</h3> A routine screening for the presence of HLA-specific antibodies after solid organ transplantation, produced by recipient B cells or plasma cells, is important for the management of antibody-mediated rejection. A novel possibility has recently been suggested in a few clinical case reports, where some de novo HLA-specific antibodies could continue to be produced by donor passenger B lymphocytes/plasma cells. We herein report the transfer of donor-derived anti-HLA antibodies in two recipients following lung transplantation. <h3>Case Report</h3> Case 1: A 39‐year‐old woman with pleuroparenchymal fibroelastosis underwent single lung transplantation with a left lung from a brain-dead donor. Antibody screening 36 days after transplant showed high levels of de novo non-donor HLA class I-specific antibodies. Then antibody screening in the donor serum identified that the donor showed a largely overlapping antibody profile to that found in the recipient. Importantly, the donor serum also included high-level HLA-specific antibodies against the recipient HLA-specific antigens, which were not detected in the recipient sera after transplantation. The donor-derived anti-HLA antibodies have still been detected in the recipient at 39 months after transplantation, which have never caused any complications such as graft-versus-host disease (GVHD). Case 2: A 47‐year‐old woman underwent living donor lobar lung transplantation for pulmonary complications after bone marrow transplantation with the right lower lobe from her husband and the left lower lobe from her sister. On postoperative day 39, the recipient anti- HLA-class I antibody profile was found to be similar to that of the high-sensitized left lung donor. These donor-derived anti-HLA antibodies have remained to be produced in the recipient at 66 months after transplantation without development of complications such as GVHD. <h3>Summary</h3> This case report suggests that alloreactive passenger B cells or plasma cells located within the highly sensitized donor lungs could lead to the early production of de novo anti-HLA-specific antibodies in the lung transplant recipients. Although there have been no overt clinical manifestations in either of the patients so far, the clinical significance of transfer of donor HLA-specific allosensitization should be elucidated.

Blood banking in solid organ transplantation

: Over 150,000 organ transplants are performed annually worldwide, and transfusion medicine support is crucial for each patient. Liver transplants have posed the greatest challenge for transfusion support, including 4–9% rates of preoperative red blood cell (RBC) alloimmunization, and higher-end blood use is associated with adverse outcomes. However, with effective patient blood management, means/medians of 4–9 allogeneic RBC units per case and 75th percentiles of 7–12 units or lower are reported. Heart or lung transplant RBC transfusions averaged around 3 units, but COVID-19 lung transplants needed a median 8 units (75th percentile 15) due to dense adhesions. Passenger lymphocyte syndrome due to donor anti-A/B induce hemolysis after 6% of ABO-unmatched kidneys, 19% of livers and 29% of intestinal transplants. ABO-incompatible transplants are achieved by desensitization, A subgroup organs, or tolerance in infants. However, interlaboratory reproducibility of anti-A/B titers in these patients remains problematic. ABH structures are predominantly type 2 in RBCs and hearts, type 4 in kidneys and secretor-dependent type 1 in liver bile ducts and arteries. These anatomic differences suggest that anti-A/B assessments and therapeutic adsorptions might be improved by using organ-tailored ABH glycans. Therapeutic plasma exchange (TPE) and extracorporeal photopheresis (ECP) are widely employed for antibody removal and rejection treatment. As organ transplantation expands globally, transfusion medicine will continue to be integral to patient care.

Haploidentical Peripheral Blood Stem Cell Transplantation (Haplo-PBSCT) with Cyclophosphamide Pos Transplant (CyPost) in High-Risk Hematologic Malignancies. Results of 5 Years in Transplant Center in Northeast of Mexico

Introduction: Haploidentical peripheral blood stem cell transplantation ( Haplo-PBSCT) is a curative option in patient with hematology malignancy. In Mexico is very difficult to find an identical HLA donor , for this reason Haplo PBSCT it is an option in our public Health institution.Materials and methods: we aimed a retrospective study since (2017 -2021) in our Hospital Unidad Médica de alta Especialidad 25, Instituto Mexicano del Seguro Social (IMSS UMAE 25) Monterrey, Mexico. We include patients over 15 years of age who were undergo Haplo PBSCT with hematolgy malignancies . We performed Analysis of Overall and Relapse-free survival with kaplan meier curves and incidence of acute and chronic graft versus host disease (GVHD) and percentage of Transplant-Related Mortality (TRM).Results: we analized a 38 patients, the median age was 35 years (range 15-64). Of the total , 25 were male (65%) and 13 famale (34%). The rest of baseline data is described in table 1.The median time of neutrophil engrafment was days 17 ( 11-26 ) and platelets was 19.5 days ( 12-38 ). The Incidence of Primary Graft failure was 18 % ( seven patients). Patients with graft had 99-100% chimerism at day 100. The Incidence of aGVHD was 26 % and the cGVHD was 16%. DLI was used in four patients to treat passenger lymphocyte syndrome (2 patients) and ( 2 patients) with severe graft rejection.The principal cause of death was sepsis in eleven patients (29%). Two patients with acute leukemia (AML and ALL) died after development of post transplant lymphoproliferative disease. The TRM was 28.2%. There were no relapse-related deaths during follow-up after Haplo-PBSCT.The median of survival was 4.5 months ( range 1-44) with Overall Survival (OS) of 42 % at 3 years ( figure 1).Conclusion: Our analysis shows results that were comparable with those published in first world international transplant centers . Relapse remains the major cause of transplant failure, in our population the antigenic disparity between donor and recipient can strengthen the immune response versus disease. Haplo-PBSCT is a feasible transplantation method in patients with hematological malignancies in developing countries with limited resources. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Passenger lymphocyte syndrome presented as hemolytic anemia after small bowel transplantation: a case report

Passenger lymphocyte syndrome presented as hemolytic anemia after small bowel transplantation: a case report

P-17: Transplant Associated Thrombotic Microangiopathy and Immune Haematological Complications Following Intestine Containing Organ Transplantation: Experience from Over 100 Consecutive Cases

Descriptions of passenger lymphocyte syndrome (PLS), immune cytopenias and transplant associated thrombotic microangiopathy (TA-TMA) in patients with intestine-containing grafts remains scarce. We describe our experience of these complications in a retrospective chart review from 2007-2019. 96 patients received 103 transplants. PLS occurred in 9 (9%) patients (median 12 days post-transplant); all due to ABO antibodies. There were 31 minor ABO mismatch transplants. No patient required change in immunosuppression. Immune cytopenias (excluding PLS) occurred in 6 patients at an incidence of 1.6/100 years follow-up; 3 immune haemolysis, 1 immune thrombocytopenia, 1 acquired Glanzmann’s and 1 immune neutropenia; 50% occurred with other cytopenias. All cases responded to treatment, with a median of 5 treatments (range 1–8) and 5/6 required rituximab. 1 patient with immune haemolysis required bortezomib. Complications of infection or thrombosis were common. In 3/6 cases a secondary cause for the immune cytopenia was evident. Switching from tacrolimus to ciclosporin wasn’t necessary. There were 5 cases of TA-TMA (1.3/100 patient years) requiring calcineurin inhibitor withdrawal; 2 cases associated with acute rejection. 2 cases were managed with plasma exchange and 1 with eculizumab. We describe extensive experience for this patient group, in the largest published series, where further research collaboration or a research registry is needed.

Passenger Lymphocyte Syndrome in a Pediatric Lung Transplant Recipient with Previous Bone Marrow Transplantation

Introduction Passenger lymphocyte syndrome (PLS) is a rare complication following solid organ transplantation (SOT). It consists of immune-mediated hemolysis due to antibodies produced by donor B-lymphocytes against recipient red blood cells [1]. Incidence across all SOT is as low as 0.5% in adults, with the highest rates being in lung and heart [2,3,4]. There have been no cases reported in children post-lung transplantation to our knowledge. Case Report A 12-year-old female received a double lung transplantation for bronchiolitis obliterans due to graft versus-host disease (GHVD). She had undergone allogeneic BMT 6 years prior for myelodysplastic syndrome (MDS). Her post-BMT course was complicated by lung, skin, and gastrointestinal GVHD. Lung transplant was uncomplicated: with donor blood group O+, recipient blood group A+, and crossmatch negative. On post-operative day 13, there was an acute drop in hemoglobin: from 131 g/L day 7, to 87 g/L day 13, to 66 g/L the same day. Septic workup was negative. Direct antiglobulin test was positive. Hemolysis markers were present with high LDH, high unconjugated bilirubin, and low haptoglobin. Eluate test was positive for anti-A1 antibody, consistent with a diagnosis of PLS. She received donor-type (O+) red cells, and was given IVIG 600 mg/kg for hypogammaglobulinemia. Hemoglobin recovered after day 21. Given her BMT history, concern around recurrent MDS was also raised. A chimerism study was sent on day 22 for this with the added benefit of examining for circulating lung-donor lymphocytes. No MDS was revealed. FISH revealed all cells were chromosomally XX (recipient had received BMT from a female donor), indicating no persistent circulating lung-donor lymphocytes since lung donor was male. Summary We report PLS following lung transplant in a 12-year-old post-BMT. Risk factors included minor ABO mismatch and organ type transplanted, with a high lymphocyte burden in lungs compared to other organs [3,4]. It is unclear whether prior allogeneic BMT and GVHD were added risk factors. Given higher PLS rates post-BMT [5], one could postulate that this may have also predisposed to PLS in this case. Albeit self-limiting, transfusion with donor blood group is necessary to prevent further hemolysis. Finally, a chimerism study for MDS has the added benefit of searching for lung-donor lymphocytes, if still present in circulation.

Transmitted Donor Immunology Not Infection: Common Persistence of Donor Hepatitis C Antibody Production in Aviremic Lung Transplant Recipients

Since 2018 The American Society of Transplant has recommended that Hepatitis C Virus seropositive positive, non-viremic donors (HCVAb+/NAT-) be considered non-infectious and safe for transplantation. This report describes clinical outcomes and HCV serological and virological outcomes following lung transplantation (LTx) utilizing such donors. This retrospective cohort study describes seven HCVAb+/NAT- donors used for bilateral LTx. Donor information was sourced from the national organ donation service and recipient information from the institutional LTx database. Seven deceased donors (three female, median age 53, range 37-63 years) acquired HCV from injecting drug use (n=4), blood products (n=1), unknown (n=1). Four donors had been previously treated and cleared of HCV (sustained virological response at 24 weeks) before death. Seven recipients (2 female, median age 56, range 51-71 years), with pulmonary fibrosis (n=4), re-do LTx (n=3), were waitlisted a median of 87 days (range 8-362). At post-LTx follow up, six of seven are alive with excellent graft function at a median 1625 days (range 779-2582). No patient developed clinical, biochemical or virological evidence of HCV infection, however five recipients demonstrated persistent HCVAb+ (all consistently NAT-) for a median 414 days (range 332-872) post-LTx. Two patients HCVAb sero-reverted at d731 and d1461. Two other recipients remained HCVAb- at d1621 and d1398 on repeat testing. There was no evidence of HCV transmission to seven LTx recipients from HCVAb+/NAT- life-saving lung donors, however persistent HCV Ab positivity was seen in 5 LTx recipients with two demonstrating remote sero-reversion. We postulate this may be a form of Passenger Lymphocyte Syndrome.

Passenger Lymphocyte Syndrome; a Review of the Diagnosis, Treatment, and Proposed Detection Protocol

Passenger lymphocyte syndrome (PLS) is caused by the transfer of B-lymphocytes present in the donor graft into the recipient circulation following solid organ or hematopoietic stem cell transplantation. These cells may produce antibodies against the recipient's red blood cells, thereby triggering antibody dependent cytotoxicity and erythroid clearance, with potential resulting hemolysis and jaundice. Although uncommon, the true incidence is unknown because many cases are subclinical, with only serologic findings or with non significant levels of hemolysis detectable clinically or by laboratory monitoring. Thus, these cases may not be detected in the immediate perioperative period. No standardized consensus exists on screening for PLS in patients. Through a review of the literature from 2009 to 2019, we aim to approximate the incidence of this condition in different solid organ transplant settings, as well as to streamline recognition, detection, and management of PLS early in the disease course to prevent adverse outcomes and minimize invasive therapy. The resultant literature review yielded 22 case reports and 8 case series comprising 71 solid organ transplant patients. Hematopoietic stem cell transplant cases were excluded, as PLS cases related to solid organ transplant were the primary focus of this review. Our institution has traditionally handled PLS on a case-by-case basis, although we hope to improve this process through an introduction of an algorithm based on review of the literature and formalized communication with primary caregivers.