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Passenger Lymphocyte Syndrome and Autoimmune Hypothyroidism Following Hematopoietic Stem Cell Transplantation

Passenger Lymphocyte Syndrome and Autoimmune Hypothyroidism Following Hematopoietic Stem Cell... Hindawi Case Reports in Immunology Volume 2022, Article ID 1690489, 6 pages https://doi.org/10.1155/2022/1690489 Case Report Passenger Lymphocyte Syndrome and Autoimmune Hypothyroidism Following Hematopoietic Stem Cell Transplantation 1 2 2 3 Denis F. Noubouossie , Mohammed I. A. Zaanona, Luciano J. Costa, Huy P. Pham, 1 2 Marisa B. Marques , and Antonio Di Stasi Division of Laboratory Medicine, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA Division of Hematology and Oncology, Department of Medicine, O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA Be  e Match Seattle Collection Center, National Marrow Donor Program, Seattle, WA, USA Correspondence should be addressed to Denis F. Noubouossie; noubouossie75@yahoo.fr Received 8 June 2021; Revised 5 April 2022; Accepted 28 May 2022; Published 23 June 2022 Academic Editor: Ahmad Mansour Copyright © 2022 Denis F. Noubouossie et al. �is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We present the case of a 24-year-old male, who received a minor ABO-incompatible allogeneic hematopoietic stem cell transplant + + (HSCT, blood group O ⟶ A ) from an HLA-matched unrelated female donor, as consolidation therapy for relapsed precursor- B-cell acute lymphoblastic leukemia. �e donor had a known history of Hashimoto’s thyroiditis before HSCT. At day +10 posttransplant, the patient developed severe hemolysis, which required emergent red blood cell exchange. Additionally, about a year posttransplant, he had circulating antithyroglobulin antibodies, decreased free-T4 (fT4) and increased serum thyroid- stimulating hormone (TSH). �e potential causes of the posttransplant hemolytic episode and hypothyroidism are discussed. While the hemolysis was worsened by the transfusion of A red blood cells (RBCs) in the context of passenger lymphocyte syndrome, the thyroid dysfunction might be explained by an autoimmune disease transferred from the donor. �e case highlights the possibility of several non-relapse-related complications of HSCT occurring in the same patient. It is critical that such adverse outcomes are distinguished from classical graft-versus-host disease (GVHD) for adequate recipient counseling, posttransplant screening, and prompt treatment. Here, we report the case of a patient who received an 1. Introduction HSCTfrom an HLA-matched unrelated donor with a known Allogeneic hematopoietic stem cell transplantation (HSCT) history of chronic lymphocytic thyroiditis, also known as is a curative procedure for selected malignant and non- “Hashimoto’s thyroiditis” (HT). In the early posttransplant malignant hematological diseases [1]. Potential complica- period, he experienced sudden hemolysis in the context of tions include relapse of the disease intended to be cured and passenger lymphocyte syndrome (PLS) and symptomatic non-relapse-related toxicities, which altogether contribute hypothyroidism a year after transplant. to reduced quality of life and signiœcant mortality [2–5]. �e potential mechanisms that led to acute hemolysis Non-relapse-related adverse outcomes include toxicity of and autoimmune hypothyroidism are discussed in order to peritransplant therapies and graft-versus-host disease highlight the importance of assessing transplant donors (GVHD) due to the attack of recipient’s tissue by donor for autoimmune conditions. Proper patient counseling, eŸector cells. posttransplant screening, and timely treatment of 2 Case Reports in Immunology these complications are essential to long-term success of During the transfusion reaction workup, anti-A was HSCTs. newly identified in the patient’s plasma at a titer 8, which was present in both samples collected immediately before and following the transfusion implicated in the reaction. A 2. Case Presentation posttransfusion urinalysis showed moderate (3+) hemo- )e patient was a 24-year-old white male without pre- globinuria and 3–10 red blood cells/40x field, and both of transplant autoimmune conditions, diagnosed with precur- which were absent in a urine sample collected before the sor-B-cell acute lymphoblastic leukemia (ALL) in 2008. transfusion of the triggering iRBC unit on day +10. Blood Cytogenetic analysis demonstrated near hypertriploid kar- urea and creatinine both rose from normal values pre- yotype with trisomy 4, 10, and 17. After being treated with transfusion to abnormally high values postreaction (Table 1). multiagent chemotherapy according to the AALL0232 pro- )e workup collectively indicated an acute hemolytic tocol, he achieved complete remission. Six years later, he transfusion reaction with acute kidney injury, likely due to relapsed and was treated with the pediatric R3 protocol, anti-A from the donor reacting with transfused and patient’s achieving a second complete morphologic remission. He then own group A RBCs. In addition to receiving corticosteroids, received consolidation with cyclophosphamide 70 mg/m and an emergent red blood cell exchange was performed. During the procedure, approximately 70% of the patient’s circu- total body irradiation (TBI, 1000 cGy) followed by an allo- geneic HSCT from an HLA-matched unrelated female donor lating red cells were replaced with seven units of group O in February of 2015. Prophylaxis of GVHD consisted of a iRBCs to achieve a final hematocrit of 24%. Following the single dose of posttransplant cyclophosphamide (50 mg/Kg), exchange, the patient’s clinical condition improved gradu- tacrolimus, and mycophenolate mofetil. Donor and Recipient ally, including his kidney function and hemoglobin level, ∗ ∗ ∗ HLA type was A 03 : 01/24 : 02, B 07 : 02/50 : 01, C 07 : 02/ which rose and remained above 7 g/dL. )e haptoglobin ∗ ∗ 06 : 02, Bw6, DRB1 04 : 01/07 : 01, and DQB1 03 : 01/02 : 02. returned to normal within 48 hours, and his blood type )e dose of infused total nucleated cells was 1.18 ×10 cells/kg converted to group O by day +94. 7 + with 92% viability, including 1.11 × 10 CD34 cells/kg and Around days +60 and +111, the patient developed acute 8 + 2.44 ×10 CD3 cells/kg of body weight. Full donor CD3, gastrointestinal and cutaneous GVHD, respectively. He CD20, and CD15 chimerism was attained by day +28. Of received systemic corticosteroids, immunosuppression with tacrolimus, and later, rituximab. As a steroid-sparing agent note, this was a minor ABO-incompatible HSCT as the pa- + + tient’s blood group was A , whereas the donor was O . and for poor compliance with tacrolimus, he was also started On day +3 post-HSCT, the patient developed a non- on mycophenolate mofetil. pruritic, erythematous rash on his chest, abdomen, and In light of the history of HT in the donor, the patient was extremities. A skin biopsy revealed interface dermatitis monitored with serum free-T4 (fT4) levels (Figure 1(b)), consistent with a drug reaction. He was transfused one unit thyroid-stimulating hormone (TSH) (Figure 1(c)) and the of irradiated iRBCs on each of day +3, +5, +7, +8, and +10 presence of autoantibodies directed against the thyroid. His (Figure 1(a)). )e blood type of the iRBC units was A, O, O, thyroid panel pretransplant was normal, including the O, and A, respectively. Additionally, two units of irradiated absence of detectable antibodies. On transplant day +3, he also had normal TSH and fT4 of 0.744 µIU/mL (reference apheresis platelets (iPLTs) were transfused on days +3 and +10. Shortly after receiving the iRBC unit on day +10, the range: 0.45–5.5 µIU/mL) and 1.25 ng/dL (reference range: 0.62–1.57 ng/dL), respectively. On re-evaluation on day patient complained of worsening back pain and was noted to have decreased urine output, which prompted a transfusion +46, TSH and T4 levels remained within the normal range reaction workup (Table 1). )e blood samples collected while antithyroglobulin (anti-TG) and antithyroid peroxi- before and after the transfusion were reported as A with dase (anti-TPO) were undetectable. However, on day +358, mixed-field reaction, consistent with the presence of group TSH was 0.047 µIU/ml and fT4 was 1.62 ng/dL suggesting O RBCs likely from his recent transfusions of O iRBCs. an initial hyperthyroid phase followed by a hypothyroid Although the plasma color posttransfusion was amber and phase from day +372 with a high TSH (79.6 µIU/mL). Anti- did not show overt hemolysis, the serum haptoglobin was TG was detected at a titer of 3 U (reference range:<0.5 U) at low and lactate dehydrogenase (LDH) and bilirubin levels this time indicating the development of autoimmune hy- pothyroidism. Concurrent decrease thyroid function and were higher than pretransfusion values. A posttransfusion direct agglutination test (DAT) was also microscopically the appearance of anti-TG antibodies in the serum suggest that complement-mediated injury may have also contrib- positive for IgG and C (1 ) compared with a DAT on his pretransfusion blood sample, which was negative for IgG uted the thyroid gland injury. )erefore, thyroid replace- ment therapy was initiated. An ultrasound on day +511 and microscopically positive for C . His antibody screen was negative both pre- and posttransfusion, indicating that a revealed a normal thyroid gland without evidence of non-ABO circulating alloantibody was unlikely present. At nodules or parenchymal abnormalities and no increased this point, it was evident that the blood bank had errone- blood flow. Grade 2 parenchymal echogenicity, high vas- ously issued a group A iRBC unit using the electronic cularity, and paratracheal lymph nodes enlargement typi- crossmatching method only. A serologic posttransfusion cally seen on thyroid ultrasound during hypothyroidism crossmatch could not be performed because the iRBC unit were missing possibly because the patient has already been on replacement therapy for several months and was in an was not returned to the laboratory. However, clerical checks confirmed that the most recently given iRBC unit was A . euthyroid state. Case Reports in Immunology 3 Anti-TG+ 4.0 Hemolytic reaction TSH HSCT 3.5 RBC Exchange 3.0 No compliance Start RT A+ O+ A+ to RT 2.5 RBC RBC RBC 2.0 8 1.5 1.0 0.5 0.0 0 2 4 6 8 10 12 14 0 500 1000 1500 2000 2500 Days post-HSCT Days HSCT (a) (b) 0 500 1000 1500 2000 2500 Days post-HSCT (c) Figure 1: Onset of severe immune hemolysis and autoimmune thyroiditis in a HSCT recipient. (a): Hemoglobin level and timeline of red blood cell (RBC) transfusions up to day +12 after HSCT. Note that a severe hemolytic transfusion reaction occurred after transfusion of group A iRBCs on day +10, which prompted an emergent red blood cell exchange. (b): Free-T4 (fT4) and (c) thyroid-stimulating hormone (TSH) levels up to day +2500 post-HSCT. Note the appearance of antithyroglobulin (Anti-TG) in the serum followed by the peak of TSH and the drop of fT4, indicating autoimmune thyroiditis. Further follow-up on day +813 showed normal thyroid has not been reported in the literature to date. Instead, there function and undetectable antithyroid antibodies. However, are case reports of patients who developed one [6–10] or the the patient was not compliant with his thyroid hormone other [11–14] following HSCT. Several mechanisms can potentially explain the occur- replacement therapy for a long period during which fT4 level was low and TSH was high (Figures 1(b) and 1(c)). During rence of hemolysis in minor ABO-incompatible HSCT. this period, the patient complained of fatigue and had two Isoagglutinins (anti-A in this case) contained in the graft and admissions to the hospital for sepsis for which he recovered. directed against the recipient’s ABO antigens can be pas- Following several sessions of patient education on the im- sively transferred during transplant, resulting in immediate portance of taking prescribed medications, the patient re- hemolysis. )is is more likely to occur if the donor has high sumed thyroid hormone replacement therapy and both fT4 titer isoagglutinins, the plasma volume in the HSCT product and TSH levels returned to normal values around day +2498 is large, and the recipient has a small body weight. However, posttransplant. Seven years later, the patient remains on it is unlikely that passive transfer of anti-A was responsible thyroid replacement therapy. )e latest posttransplant for the hemolytic reaction observed in this patient since course was complicated by oral and cutaneous chronic laboratory markers of hemolysis were not present until day GVHD. +10 before the transfusion of a group A iRBC unit. Of note, the patient was still typing as blood group A in a blood sample collected on day +10 prior to the triggering trans- 3. Discussion fusion event, indicating the presence of a significant number )is patient experienced immune hemolysis requiring red of recipient-type red cells before the transfusion. In addition blood cell exchange on day +10 and developed autoimmune to detecting anti-A in his plasma, his DAT was also positive hypothyroidism approximately a year after receiving a on the same blood sample, suggesting in vivo binding of the minor ABO-incompatible allogeneic HSCT. To our antibody to his red cells before the transfusion. )us, one can knowledge, this combination of immunologic complications reasonably speculate that transfusion of the wrong blood Hb (g/dL) µIU/mL fT4 (ng/dL) 4 Case Reports in Immunology Table 1: Laboratory parameters before and after the transfusion reaction. Parameters Before transfusion After transfusion Antibody screening Negative Negative ABO forward type A (mixed-field reaction) A (mixed-field reaction) Crossmatch Compatible (electronic) Incompatible Urine hemoglobin Negative 3+ (moderate) Urine RBCs @ 40x Negative 3–10/Field BUN (Ref:5–22 mg/dL) 7 mg/dL 30 mg/dL Creatinine (ref: 0.4–1.2 mg/dL) 0.5 mg/dL 1.6 mg/dL Haptoglobin (ref: 33–271 mg/dL) Not done 3 mg/dL LDH (ref: 120–240 IU/L) Not done 858 IU/L Indirect bilirubin 0.5 mg/dL 7.5 mg/dL RBC: red blood cell; BUN: blood urea nitrogen; LDH: lactate dehydrogenase. Ref: reference range; IU: international unit. reduction nor pre-HSCT red blood cell exchange was per- type exacerbated an already ongoing, subclinical, or im- minent hemolytic process. formed in this patient. Instead, the patient had a post- Indeed, this patient should not have received a group A hemolysis exchange with group O iRBCs, to which he iRBCs. Although the standard operating procedure in our responded well. institution at the time of this event allowed the release of About a year after HSCT, the patient developed a RBC units based on the patient’s historic blood type when symptomatic hypothyroidism and has been dependent on the antibody screen was negative, an exception to this rule thyroid hormone replacement therapy. )e presence of symptoms with laboratory evidence of decreased thyroid should have been applied for allogeneic HSCT recipients. When the error occurred, the blood bank staff had to function concurrently with the appearance of anti-TG an- tibodies in the serum suggests that the thyroid disease is manually check the patient’s status and the type of ABO incompatibility, and issue compatible iRBC units according autoimmune. Although more specific antithyroxin peroxi- to a table [15]. If this step had occurred, the patient would dase antibodies were below detection level at Day +46 have received group O iRBCs. Since this event, an electronic posttransplant, the presence of HT in donor raises the process to ensure that the appropriate blood type of RBCs is possibility of transferred HT to the patient. Similarly to other released to HSCT recipients every time has replaced the examples of HT post-HSCT previously reported [11–14], the manual check. disease was present in the donor before HSC collection but Passenger lymphocyte syndrome (PLS) is the most likely absent in the recipient before HSCT. )is latency time is underlying condition that predisposed the patient to the consistent within the range of 12 to 48 months previously described. Both overt and subclinical hypothyroidism have severe hemolysis observed following the transfusion of A iRBCs. PLS occurs when viable B-lymphocytes in the graft been reported, and most patients received thyroid hormone replacement. Several reported cases experienced acute produce incompatible antibodies directed against the re- cipient’s red cell antigens. In this case, B-lymphocytes from GVHD, and a few developed chronic GVHD. TBI was part the donor produced anti-A (and anti-B) which reacted with of the conditioning regimen in several cases. the A iRBCs transfused. Hemolysis associated with PLS )e pathogenesis of transferred autoimmune thyroiditis occurs usually five to 15 days posttransplant and rarely after in the context of HSCT is not well-understood. A large eight weeks [15–17]. While clinically significant hemolysis cohort study from China suggested that the most significant occurs in only 10–15% of minor ABO-incompatible HSCT triggering event was the transfer of donor lymphocytes and [16], severe and fatal hemolysis has been reported [7]. PLS their effect on the recipient’s thyroid [20]. Other significant risk factors include transplant from unrelated or non-HLA- risk factors identified in the cohort study from China in- cluded the use of a female donor, HSCT for chronic myeloid matched sibling donors, recipient of blood group A, HSC apheresis product, and usage of calcineurin inhibitors leukemia, the HLA B46, DR9 loci, and the A2B46DR9 haplotype [20]. Indeed, there is a strong genetic suscepti- without methotrexate as immunosuppressive regimen posttransplant [15, 18]. Some of these risk factors were bility associated with HT [21]. Polymorphisms in major present in our patient. immune-regulatory genes including HLA, cytotoxic Besides requirements for blood products, no guidelines T-lymphocyte antigen-4, and Protein Tyrosine Phosphatase exist to prevent hemolytic reaction following HSCT in minor Nonreceptor-Type 22 gene have also been linked to HT [21]. ABO incompatibility. However, reduction of plasma volume Pretransplant HLA showed that the donor and the patient ∗ ∗ of the graft is performed in some institutions to minimize had the DRB1 04-DQB1 0301 haplotype which is report- the transfer of isoagglutinins to the recipient [15, 19]. Other edly associated with HT in Caucasians [22]. Other predis- authors have performed pretransplant red blood cell ex- posing HLA alleles not present in this patient have also been change to replace recipient’s red cells with group O RBCs. associated with HT, including DR3, DR5, DQ7, and DQw7 However, hyperhemolysis involving donor’s O RBCs may [21]. Since gene polymorphisms can modulate mature im- occur due to adsorption of antigen-expressing microvesicles mune cell functions, it is speculated that HT’s susceptibility from the recipient’s red cells [18]. Neither graft plasma could be transferred from the donor to the recipient through Case Reports in Immunology 5 [6] J.-P. Salmon, S. Michaux, J.-P. Hermanne et al., “Delayed the engrafted HSCs. Supporting this hypothesis, the trans- massive immune hemolysis mediated by minor ABO in- mission of HT has been reported following the transplant of compatibility after allogeneic peripheral blood progenitor cell selected CD34 peripheral blood stem cells [14]. Other transplantation,” Transfusion, vol. 39, no. 8, pp. 824–827, potential contributing factors to thyroid dysfunction post- HSCT include the effect of conditioning chemotherapy, [7] C. D. Bolan, R. W. Childs, J. L. Procter, A. J. Barrett, and radiation damage to the thyroid before transplantation, S. F. Leitman, “Massive immune haemolysis after allogeneic graft-versus-host disease, and the general immune dysre- peripheral blood stem cell transplantation with minor ABO gulation associated with the transplant [12]. incompatibility,” British Journal of Haematology, vol. 112, In summary, HSCTcan potentially transfer humoral and no. 3, pp. 787–795, 2001. cellular immune effectors and susceptibility genes for au- [8] A. Toren, Y. Dacosta, N. Manny, G. Varadi, R. Or, and toimmune diseases from the donor to the recipient. While A. Nagler, “Passenger B-lymphocyte-induced severe hemo- minor ABO incompatibility and the diagnosis of HT do not lytic disease after allogeneic peripheral blood stem cell preclude donor suitability for donation, they increase the transplantation [letter],” Blood, vol. 87, no. 2, pp. 843-844, risk of non-relapse-related complications of HSCT. )ey must be recognized for donors’ evaluation [23], recipient [9] H. J. Lee, A. Gulbis, L. De Padua Silva et al., “Rituximab for counseling, posttransplant screening, prompt treatment, and passenger lymphocyte syndrome associated with allogeneic SCT,” Bone Marrow Transplantation, vol. 42, no. 1, pp. 67–69, differential diagnosis from classic GVHD manifestations and other toxicities, requiring specific therapeutic measures. [10] M. Reed, M. Yearsley, D. Krugh, and M. S. Kennedy, “Severe Some of such manifestations can be considered under the hemolysis due to passenger lymphocyte syndrome after he- GVHD spectrum. matopoietic stem cell transplantation from an HLA-matched related donor,” Archives of Pathology & Laboratory Medicine, Data Availability vol. 127, no. 10, pp. 1366–1368, 2003. [11] B. Vialettes, D. Maraninchi, M. P. San Marco et al., “Auto- )e laboratory results supporting our conclusion were ob- immune polyendocrine failure - type 1 (insulin-dependent) tained from the Electronic Medical Record System of UAB, diabetes mellitus and hypothyroidism - after allogenic bone with patient’s informed consent. marrow transplantation in a patient with lymphoblastic leukaemia,” Diabetologia, vol. 36, no. 6, pp. 541–546, 1993. [12] D. T. Wyatt, L. G. Lum, J. Casper, J. Hunter, and B. Camitta, Conflicts of Interest “Autoimmune thyroiditis after bone marrow transplanta- )e authors declare that there are no conflicts of interest tion,” Bone Marrow Transplantation, vol. 5, pp. 357–361, regarding the publication of this article. 1990. [13] W. Lee, E. Oh, C. Min et al., “Changes in autoimmune thyroid disease following allogeneic bone marrow transplantation,” Acknowledgments Bone Marrow Transplantation, vol. 28, no. 1, pp. 63–66, 2001. [14] M. Karthaus, T. Gabrysiak, G. Brabant et al., “Immune Dr. Marisa B. Marques’ professional development fund was thyroiditis after transplantation of allogeneic CD34+ selected used to support this submission. peripheral blood cells,” Bone Marrow Transplantation, vol. 20, no. 8, pp. 697–699, 1997. References [15] J. Daniel-Johnson and J. Schwartz, “How do I approach ABO- incompatible hematopoietic progenitor cell transplantation? [1] R. F. Duarte, M. Labopin, P. Bader et al., “Indications for (CME),” Transfusion, vol. 51, no. 6, pp. 1143–1149, 2011. haematopoietic stem cell transplantation for haematological [16] G. S. Booth, E. A. Gehrie, C. D. Bolan, and B. N. Savani, diseases, solid tumours and immune disorders: current “Clinical guide to ABO-incompatible allogeneic stem cell practice in Europe, 2019,” Bone Marrow Transplantation, transplantation,” Biology of Blood and Marrow Transplanta- vol. 54, no. 10, pp. 1525–1552, 2019. tion, vol. 19, no. 8, pp. 1152–1158, 2013. [2] C. Zuanelli Brambilla, S. M. Lobaugh, J. D. Ruiz et al., “Relapse [17] S. Rowley, “Hematopoietic stem cell transplantation between after allogeneic stem cell transplantation of acute myeloge- red cell incompatible donor-recipient pairs,” Bone Marrow nous leukemia and myelodysplastic syndrome and the im- Transplantation, vol. 28, no. 4, pp. 315–321, 2001. portance of second cellular therapy,” Transplantion and Cell [18] J. Gajewski, L. Petz, L. Calhoun et al., “Hemolysis of trans- &erapy, vol. 27, pp. 771.e1–771.e10, 2021. fused group O red blood cells in minor ABO- incompatible [3] J. Cheon, Y. J. Lee, J. C. Jo et al., “Late complications and unrelated-donor bone marrow transplants in patients re- quality of life assessment for survivors receiving allogeneic ceiving cyclosporine without posttransplant methotrexate,” hematopoietic stem cell transplantation,” Supportive Care in Blood, vol. 79, no. 11, pp. 3076–3085, 1992. Cancer: Official Journal of the Multinational Association of [19] Roback, “AABB technical manual,” https://scholar.google. Supportive Care in Cancer, vol. 29, no. 2, pp. 975–986, 2021. com/scholar_lookup?hl�en&publication_ [4] N. S. Majhail, “Long-term complications after hematopoietic year�2011&author�Roback+J.D.&author�Grossman+B.J. cell transplantation,” Hematology/Oncology and Stem Cell &author�Harris+T.&author�Hillyer+C.D. &erapy, vol. 10, no. 4, pp. 220–227, 2017. &title�AABB+Technical+Manual. [5] J. R. Wingard, N. S. Majhail, R. Brazauskas et al., “Long-term survival and late deaths after allogeneic hematopoietic cell [20] W. Y. Au, A. K. W. Lie, A. W. C. Kung, R. Liang, B. R. Hawkins, and Y. L. Kwong, “Autoimmune thyroid transplantation,” Journal of Clinical Oncology, vol. 29, no. 16, pp. 2230–2239, 2011. dysfunction after hematopoietic stem cell transplantation,” 6 Case Reports in Immunology Bone Marrow Transplantation, vol. 35, no. 4, pp. 383–388, [21] K. Zaletel and S. Gaberscek, “Hashimotos thyroiditis: from genes to the disease,” Current Genomics, vol. 12, no. 8, pp. 576–588, 2011. [22] A. Petrone, G. Giorgi, C. A. Mesturino et al., “Association of DRB1∗04-DQB1∗0301 haplotype and lack of association of two polymorphic sites at CTLA-4 gene with hashimoto’s thyroiditis in an Italian population,” &yroid, vol. 11, no. 2, pp. 171–175, 2001. [23] N. Worel, A. Buser, H. T. Greinix et al., “Suitability criteria for adult related donors: a consensus statement from the worldwide network for blood and marrow transplantation standing committee on donor issues,” Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation, vol. 21, pp. 2052–2060, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Immunology Hindawi Publishing Corporation

Passenger Lymphocyte Syndrome and Autoimmune Hypothyroidism Following Hematopoietic Stem Cell Transplantation

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Copyright © 2022 Denis F. Noubouossie et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract

Hindawi Case Reports in Immunology Volume 2022, Article ID 1690489, 6 pages https://doi.org/10.1155/2022/1690489 Case Report Passenger Lymphocyte Syndrome and Autoimmune Hypothyroidism Following Hematopoietic Stem Cell Transplantation 1 2 2 3 Denis F. Noubouossie , Mohammed I. A. Zaanona, Luciano J. Costa, Huy P. Pham, 1 2 Marisa B. Marques , and Antonio Di Stasi Division of Laboratory Medicine, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA Division of Hematology and Oncology, Department of Medicine, O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA Be  e Match Seattle Collection Center, National Marrow Donor Program, Seattle, WA, USA Correspondence should be addressed to Denis F. Noubouossie; noubouossie75@yahoo.fr Received 8 June 2021; Revised 5 April 2022; Accepted 28 May 2022; Published 23 June 2022 Academic Editor: Ahmad Mansour Copyright © 2022 Denis F. Noubouossie et al. �is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We present the case of a 24-year-old male, who received a minor ABO-incompatible allogeneic hematopoietic stem cell transplant + + (HSCT, blood group O ⟶ A ) from an HLA-matched unrelated female donor, as consolidation therapy for relapsed precursor- B-cell acute lymphoblastic leukemia. �e donor had a known history of Hashimoto’s thyroiditis before HSCT. At day +10 posttransplant, the patient developed severe hemolysis, which required emergent red blood cell exchange. Additionally, about a year posttransplant, he had circulating antithyroglobulin antibodies, decreased free-T4 (fT4) and increased serum thyroid- stimulating hormone (TSH). �e potential causes of the posttransplant hemolytic episode and hypothyroidism are discussed. While the hemolysis was worsened by the transfusion of A red blood cells (RBCs) in the context of passenger lymphocyte syndrome, the thyroid dysfunction might be explained by an autoimmune disease transferred from the donor. �e case highlights the possibility of several non-relapse-related complications of HSCT occurring in the same patient. It is critical that such adverse outcomes are distinguished from classical graft-versus-host disease (GVHD) for adequate recipient counseling, posttransplant screening, and prompt treatment. Here, we report the case of a patient who received an 1. Introduction HSCTfrom an HLA-matched unrelated donor with a known Allogeneic hematopoietic stem cell transplantation (HSCT) history of chronic lymphocytic thyroiditis, also known as is a curative procedure for selected malignant and non- “Hashimoto’s thyroiditis” (HT). In the early posttransplant malignant hematological diseases [1]. Potential complica- period, he experienced sudden hemolysis in the context of tions include relapse of the disease intended to be cured and passenger lymphocyte syndrome (PLS) and symptomatic non-relapse-related toxicities, which altogether contribute hypothyroidism a year after transplant. to reduced quality of life and signiœcant mortality [2–5]. �e potential mechanisms that led to acute hemolysis Non-relapse-related adverse outcomes include toxicity of and autoimmune hypothyroidism are discussed in order to peritransplant therapies and graft-versus-host disease highlight the importance of assessing transplant donors (GVHD) due to the attack of recipient’s tissue by donor for autoimmune conditions. Proper patient counseling, eŸector cells. posttransplant screening, and timely treatment of 2 Case Reports in Immunology these complications are essential to long-term success of During the transfusion reaction workup, anti-A was HSCTs. newly identified in the patient’s plasma at a titer 8, which was present in both samples collected immediately before and following the transfusion implicated in the reaction. A 2. Case Presentation posttransfusion urinalysis showed moderate (3+) hemo- )e patient was a 24-year-old white male without pre- globinuria and 3–10 red blood cells/40x field, and both of transplant autoimmune conditions, diagnosed with precur- which were absent in a urine sample collected before the sor-B-cell acute lymphoblastic leukemia (ALL) in 2008. transfusion of the triggering iRBC unit on day +10. Blood Cytogenetic analysis demonstrated near hypertriploid kar- urea and creatinine both rose from normal values pre- yotype with trisomy 4, 10, and 17. After being treated with transfusion to abnormally high values postreaction (Table 1). multiagent chemotherapy according to the AALL0232 pro- )e workup collectively indicated an acute hemolytic tocol, he achieved complete remission. Six years later, he transfusion reaction with acute kidney injury, likely due to relapsed and was treated with the pediatric R3 protocol, anti-A from the donor reacting with transfused and patient’s achieving a second complete morphologic remission. He then own group A RBCs. In addition to receiving corticosteroids, received consolidation with cyclophosphamide 70 mg/m and an emergent red blood cell exchange was performed. During the procedure, approximately 70% of the patient’s circu- total body irradiation (TBI, 1000 cGy) followed by an allo- geneic HSCT from an HLA-matched unrelated female donor lating red cells were replaced with seven units of group O in February of 2015. Prophylaxis of GVHD consisted of a iRBCs to achieve a final hematocrit of 24%. Following the single dose of posttransplant cyclophosphamide (50 mg/Kg), exchange, the patient’s clinical condition improved gradu- tacrolimus, and mycophenolate mofetil. Donor and Recipient ally, including his kidney function and hemoglobin level, ∗ ∗ ∗ HLA type was A 03 : 01/24 : 02, B 07 : 02/50 : 01, C 07 : 02/ which rose and remained above 7 g/dL. )e haptoglobin ∗ ∗ 06 : 02, Bw6, DRB1 04 : 01/07 : 01, and DQB1 03 : 01/02 : 02. returned to normal within 48 hours, and his blood type )e dose of infused total nucleated cells was 1.18 ×10 cells/kg converted to group O by day +94. 7 + with 92% viability, including 1.11 × 10 CD34 cells/kg and Around days +60 and +111, the patient developed acute 8 + 2.44 ×10 CD3 cells/kg of body weight. Full donor CD3, gastrointestinal and cutaneous GVHD, respectively. He CD20, and CD15 chimerism was attained by day +28. Of received systemic corticosteroids, immunosuppression with tacrolimus, and later, rituximab. As a steroid-sparing agent note, this was a minor ABO-incompatible HSCT as the pa- + + tient’s blood group was A , whereas the donor was O . and for poor compliance with tacrolimus, he was also started On day +3 post-HSCT, the patient developed a non- on mycophenolate mofetil. pruritic, erythematous rash on his chest, abdomen, and In light of the history of HT in the donor, the patient was extremities. A skin biopsy revealed interface dermatitis monitored with serum free-T4 (fT4) levels (Figure 1(b)), consistent with a drug reaction. He was transfused one unit thyroid-stimulating hormone (TSH) (Figure 1(c)) and the of irradiated iRBCs on each of day +3, +5, +7, +8, and +10 presence of autoantibodies directed against the thyroid. His (Figure 1(a)). )e blood type of the iRBC units was A, O, O, thyroid panel pretransplant was normal, including the O, and A, respectively. Additionally, two units of irradiated absence of detectable antibodies. On transplant day +3, he also had normal TSH and fT4 of 0.744 µIU/mL (reference apheresis platelets (iPLTs) were transfused on days +3 and +10. Shortly after receiving the iRBC unit on day +10, the range: 0.45–5.5 µIU/mL) and 1.25 ng/dL (reference range: 0.62–1.57 ng/dL), respectively. On re-evaluation on day patient complained of worsening back pain and was noted to have decreased urine output, which prompted a transfusion +46, TSH and T4 levels remained within the normal range reaction workup (Table 1). )e blood samples collected while antithyroglobulin (anti-TG) and antithyroid peroxi- before and after the transfusion were reported as A with dase (anti-TPO) were undetectable. However, on day +358, mixed-field reaction, consistent with the presence of group TSH was 0.047 µIU/ml and fT4 was 1.62 ng/dL suggesting O RBCs likely from his recent transfusions of O iRBCs. an initial hyperthyroid phase followed by a hypothyroid Although the plasma color posttransfusion was amber and phase from day +372 with a high TSH (79.6 µIU/mL). Anti- did not show overt hemolysis, the serum haptoglobin was TG was detected at a titer of 3 U (reference range:<0.5 U) at low and lactate dehydrogenase (LDH) and bilirubin levels this time indicating the development of autoimmune hy- pothyroidism. Concurrent decrease thyroid function and were higher than pretransfusion values. A posttransfusion direct agglutination test (DAT) was also microscopically the appearance of anti-TG antibodies in the serum suggest that complement-mediated injury may have also contrib- positive for IgG and C (1 ) compared with a DAT on his pretransfusion blood sample, which was negative for IgG uted the thyroid gland injury. )erefore, thyroid replace- ment therapy was initiated. An ultrasound on day +511 and microscopically positive for C . His antibody screen was negative both pre- and posttransfusion, indicating that a revealed a normal thyroid gland without evidence of non-ABO circulating alloantibody was unlikely present. At nodules or parenchymal abnormalities and no increased this point, it was evident that the blood bank had errone- blood flow. Grade 2 parenchymal echogenicity, high vas- ously issued a group A iRBC unit using the electronic cularity, and paratracheal lymph nodes enlargement typi- crossmatching method only. A serologic posttransfusion cally seen on thyroid ultrasound during hypothyroidism crossmatch could not be performed because the iRBC unit were missing possibly because the patient has already been on replacement therapy for several months and was in an was not returned to the laboratory. However, clerical checks confirmed that the most recently given iRBC unit was A . euthyroid state. Case Reports in Immunology 3 Anti-TG+ 4.0 Hemolytic reaction TSH HSCT 3.5 RBC Exchange 3.0 No compliance Start RT A+ O+ A+ to RT 2.5 RBC RBC RBC 2.0 8 1.5 1.0 0.5 0.0 0 2 4 6 8 10 12 14 0 500 1000 1500 2000 2500 Days post-HSCT Days HSCT (a) (b) 0 500 1000 1500 2000 2500 Days post-HSCT (c) Figure 1: Onset of severe immune hemolysis and autoimmune thyroiditis in a HSCT recipient. (a): Hemoglobin level and timeline of red blood cell (RBC) transfusions up to day +12 after HSCT. Note that a severe hemolytic transfusion reaction occurred after transfusion of group A iRBCs on day +10, which prompted an emergent red blood cell exchange. (b): Free-T4 (fT4) and (c) thyroid-stimulating hormone (TSH) levels up to day +2500 post-HSCT. Note the appearance of antithyroglobulin (Anti-TG) in the serum followed by the peak of TSH and the drop of fT4, indicating autoimmune thyroiditis. Further follow-up on day +813 showed normal thyroid has not been reported in the literature to date. Instead, there function and undetectable antithyroid antibodies. However, are case reports of patients who developed one [6–10] or the the patient was not compliant with his thyroid hormone other [11–14] following HSCT. Several mechanisms can potentially explain the occur- replacement therapy for a long period during which fT4 level was low and TSH was high (Figures 1(b) and 1(c)). During rence of hemolysis in minor ABO-incompatible HSCT. this period, the patient complained of fatigue and had two Isoagglutinins (anti-A in this case) contained in the graft and admissions to the hospital for sepsis for which he recovered. directed against the recipient’s ABO antigens can be pas- Following several sessions of patient education on the im- sively transferred during transplant, resulting in immediate portance of taking prescribed medications, the patient re- hemolysis. )is is more likely to occur if the donor has high sumed thyroid hormone replacement therapy and both fT4 titer isoagglutinins, the plasma volume in the HSCT product and TSH levels returned to normal values around day +2498 is large, and the recipient has a small body weight. However, posttransplant. Seven years later, the patient remains on it is unlikely that passive transfer of anti-A was responsible thyroid replacement therapy. )e latest posttransplant for the hemolytic reaction observed in this patient since course was complicated by oral and cutaneous chronic laboratory markers of hemolysis were not present until day GVHD. +10 before the transfusion of a group A iRBC unit. Of note, the patient was still typing as blood group A in a blood sample collected on day +10 prior to the triggering trans- 3. Discussion fusion event, indicating the presence of a significant number )is patient experienced immune hemolysis requiring red of recipient-type red cells before the transfusion. In addition blood cell exchange on day +10 and developed autoimmune to detecting anti-A in his plasma, his DAT was also positive hypothyroidism approximately a year after receiving a on the same blood sample, suggesting in vivo binding of the minor ABO-incompatible allogeneic HSCT. To our antibody to his red cells before the transfusion. )us, one can knowledge, this combination of immunologic complications reasonably speculate that transfusion of the wrong blood Hb (g/dL) µIU/mL fT4 (ng/dL) 4 Case Reports in Immunology Table 1: Laboratory parameters before and after the transfusion reaction. Parameters Before transfusion After transfusion Antibody screening Negative Negative ABO forward type A (mixed-field reaction) A (mixed-field reaction) Crossmatch Compatible (electronic) Incompatible Urine hemoglobin Negative 3+ (moderate) Urine RBCs @ 40x Negative 3–10/Field BUN (Ref:5–22 mg/dL) 7 mg/dL 30 mg/dL Creatinine (ref: 0.4–1.2 mg/dL) 0.5 mg/dL 1.6 mg/dL Haptoglobin (ref: 33–271 mg/dL) Not done 3 mg/dL LDH (ref: 120–240 IU/L) Not done 858 IU/L Indirect bilirubin 0.5 mg/dL 7.5 mg/dL RBC: red blood cell; BUN: blood urea nitrogen; LDH: lactate dehydrogenase. Ref: reference range; IU: international unit. reduction nor pre-HSCT red blood cell exchange was per- type exacerbated an already ongoing, subclinical, or im- minent hemolytic process. formed in this patient. Instead, the patient had a post- Indeed, this patient should not have received a group A hemolysis exchange with group O iRBCs, to which he iRBCs. Although the standard operating procedure in our responded well. institution at the time of this event allowed the release of About a year after HSCT, the patient developed a RBC units based on the patient’s historic blood type when symptomatic hypothyroidism and has been dependent on the antibody screen was negative, an exception to this rule thyroid hormone replacement therapy. )e presence of symptoms with laboratory evidence of decreased thyroid should have been applied for allogeneic HSCT recipients. When the error occurred, the blood bank staff had to function concurrently with the appearance of anti-TG an- tibodies in the serum suggests that the thyroid disease is manually check the patient’s status and the type of ABO incompatibility, and issue compatible iRBC units according autoimmune. Although more specific antithyroxin peroxi- to a table [15]. If this step had occurred, the patient would dase antibodies were below detection level at Day +46 have received group O iRBCs. Since this event, an electronic posttransplant, the presence of HT in donor raises the process to ensure that the appropriate blood type of RBCs is possibility of transferred HT to the patient. Similarly to other released to HSCT recipients every time has replaced the examples of HT post-HSCT previously reported [11–14], the manual check. disease was present in the donor before HSC collection but Passenger lymphocyte syndrome (PLS) is the most likely absent in the recipient before HSCT. )is latency time is underlying condition that predisposed the patient to the consistent within the range of 12 to 48 months previously described. Both overt and subclinical hypothyroidism have severe hemolysis observed following the transfusion of A iRBCs. PLS occurs when viable B-lymphocytes in the graft been reported, and most patients received thyroid hormone replacement. Several reported cases experienced acute produce incompatible antibodies directed against the re- cipient’s red cell antigens. In this case, B-lymphocytes from GVHD, and a few developed chronic GVHD. TBI was part the donor produced anti-A (and anti-B) which reacted with of the conditioning regimen in several cases. the A iRBCs transfused. Hemolysis associated with PLS )e pathogenesis of transferred autoimmune thyroiditis occurs usually five to 15 days posttransplant and rarely after in the context of HSCT is not well-understood. A large eight weeks [15–17]. While clinically significant hemolysis cohort study from China suggested that the most significant occurs in only 10–15% of minor ABO-incompatible HSCT triggering event was the transfer of donor lymphocytes and [16], severe and fatal hemolysis has been reported [7]. PLS their effect on the recipient’s thyroid [20]. Other significant risk factors include transplant from unrelated or non-HLA- risk factors identified in the cohort study from China in- cluded the use of a female donor, HSCT for chronic myeloid matched sibling donors, recipient of blood group A, HSC apheresis product, and usage of calcineurin inhibitors leukemia, the HLA B46, DR9 loci, and the A2B46DR9 haplotype [20]. Indeed, there is a strong genetic suscepti- without methotrexate as immunosuppressive regimen posttransplant [15, 18]. Some of these risk factors were bility associated with HT [21]. Polymorphisms in major present in our patient. immune-regulatory genes including HLA, cytotoxic Besides requirements for blood products, no guidelines T-lymphocyte antigen-4, and Protein Tyrosine Phosphatase exist to prevent hemolytic reaction following HSCT in minor Nonreceptor-Type 22 gene have also been linked to HT [21]. ABO incompatibility. However, reduction of plasma volume Pretransplant HLA showed that the donor and the patient ∗ ∗ of the graft is performed in some institutions to minimize had the DRB1 04-DQB1 0301 haplotype which is report- the transfer of isoagglutinins to the recipient [15, 19]. Other edly associated with HT in Caucasians [22]. Other predis- authors have performed pretransplant red blood cell ex- posing HLA alleles not present in this patient have also been change to replace recipient’s red cells with group O RBCs. associated with HT, including DR3, DR5, DQ7, and DQw7 However, hyperhemolysis involving donor’s O RBCs may [21]. Since gene polymorphisms can modulate mature im- occur due to adsorption of antigen-expressing microvesicles mune cell functions, it is speculated that HT’s susceptibility from the recipient’s red cells [18]. Neither graft plasma could be transferred from the donor to the recipient through Case Reports in Immunology 5 [6] J.-P. Salmon, S. Michaux, J.-P. Hermanne et al., “Delayed the engrafted HSCs. Supporting this hypothesis, the trans- massive immune hemolysis mediated by minor ABO in- mission of HT has been reported following the transplant of compatibility after allogeneic peripheral blood progenitor cell selected CD34 peripheral blood stem cells [14]. Other transplantation,” Transfusion, vol. 39, no. 8, pp. 824–827, potential contributing factors to thyroid dysfunction post- HSCT include the effect of conditioning chemotherapy, [7] C. D. Bolan, R. W. Childs, J. L. Procter, A. J. Barrett, and radiation damage to the thyroid before transplantation, S. F. Leitman, “Massive immune haemolysis after allogeneic graft-versus-host disease, and the general immune dysre- peripheral blood stem cell transplantation with minor ABO gulation associated with the transplant [12]. incompatibility,” British Journal of Haematology, vol. 112, In summary, HSCTcan potentially transfer humoral and no. 3, pp. 787–795, 2001. cellular immune effectors and susceptibility genes for au- [8] A. Toren, Y. Dacosta, N. Manny, G. Varadi, R. Or, and toimmune diseases from the donor to the recipient. While A. Nagler, “Passenger B-lymphocyte-induced severe hemo- minor ABO incompatibility and the diagnosis of HT do not lytic disease after allogeneic peripheral blood stem cell preclude donor suitability for donation, they increase the transplantation [letter],” Blood, vol. 87, no. 2, pp. 843-844, risk of non-relapse-related complications of HSCT. )ey must be recognized for donors’ evaluation [23], recipient [9] H. J. Lee, A. Gulbis, L. De Padua Silva et al., “Rituximab for counseling, posttransplant screening, prompt treatment, and passenger lymphocyte syndrome associated with allogeneic SCT,” Bone Marrow Transplantation, vol. 42, no. 1, pp. 67–69, differential diagnosis from classic GVHD manifestations and other toxicities, requiring specific therapeutic measures. [10] M. Reed, M. Yearsley, D. Krugh, and M. S. Kennedy, “Severe Some of such manifestations can be considered under the hemolysis due to passenger lymphocyte syndrome after he- GVHD spectrum. matopoietic stem cell transplantation from an HLA-matched related donor,” Archives of Pathology & Laboratory Medicine, Data Availability vol. 127, no. 10, pp. 1366–1368, 2003. [11] B. Vialettes, D. Maraninchi, M. P. San Marco et al., “Auto- )e laboratory results supporting our conclusion were ob- immune polyendocrine failure - type 1 (insulin-dependent) tained from the Electronic Medical Record System of UAB, diabetes mellitus and hypothyroidism - after allogenic bone with patient’s informed consent. marrow transplantation in a patient with lymphoblastic leukaemia,” Diabetologia, vol. 36, no. 6, pp. 541–546, 1993. [12] D. T. Wyatt, L. G. Lum, J. Casper, J. Hunter, and B. Camitta, Conflicts of Interest “Autoimmune thyroiditis after bone marrow transplanta- )e authors declare that there are no conflicts of interest tion,” Bone Marrow Transplantation, vol. 5, pp. 357–361, regarding the publication of this article. 1990. [13] W. Lee, E. Oh, C. Min et al., “Changes in autoimmune thyroid disease following allogeneic bone marrow transplantation,” Acknowledgments Bone Marrow Transplantation, vol. 28, no. 1, pp. 63–66, 2001. [14] M. Karthaus, T. Gabrysiak, G. Brabant et al., “Immune Dr. Marisa B. Marques’ professional development fund was thyroiditis after transplantation of allogeneic CD34+ selected used to support this submission. peripheral blood cells,” Bone Marrow Transplantation, vol. 20, no. 8, pp. 697–699, 1997. References [15] J. Daniel-Johnson and J. Schwartz, “How do I approach ABO- incompatible hematopoietic progenitor cell transplantation? [1] R. F. Duarte, M. Labopin, P. Bader et al., “Indications for (CME),” Transfusion, vol. 51, no. 6, pp. 1143–1149, 2011. haematopoietic stem cell transplantation for haematological [16] G. S. Booth, E. A. Gehrie, C. D. Bolan, and B. N. Savani, diseases, solid tumours and immune disorders: current “Clinical guide to ABO-incompatible allogeneic stem cell practice in Europe, 2019,” Bone Marrow Transplantation, transplantation,” Biology of Blood and Marrow Transplanta- vol. 54, no. 10, pp. 1525–1552, 2019. tion, vol. 19, no. 8, pp. 1152–1158, 2013. [2] C. Zuanelli Brambilla, S. M. Lobaugh, J. D. Ruiz et al., “Relapse [17] S. Rowley, “Hematopoietic stem cell transplantation between after allogeneic stem cell transplantation of acute myeloge- red cell incompatible donor-recipient pairs,” Bone Marrow nous leukemia and myelodysplastic syndrome and the im- Transplantation, vol. 28, no. 4, pp. 315–321, 2001. portance of second cellular therapy,” Transplantion and Cell [18] J. Gajewski, L. Petz, L. Calhoun et al., “Hemolysis of trans- &erapy, vol. 27, pp. 771.e1–771.e10, 2021. fused group O red blood cells in minor ABO- incompatible [3] J. Cheon, Y. J. Lee, J. C. Jo et al., “Late complications and unrelated-donor bone marrow transplants in patients re- quality of life assessment for survivors receiving allogeneic ceiving cyclosporine without posttransplant methotrexate,” hematopoietic stem cell transplantation,” Supportive Care in Blood, vol. 79, no. 11, pp. 3076–3085, 1992. Cancer: Official Journal of the Multinational Association of [19] Roback, “AABB technical manual,” https://scholar.google. Supportive Care in Cancer, vol. 29, no. 2, pp. 975–986, 2021. com/scholar_lookup?hl�en&publication_ [4] N. S. Majhail, “Long-term complications after hematopoietic year�2011&author�Roback+J.D.&author�Grossman+B.J. cell transplantation,” Hematology/Oncology and Stem Cell &author�Harris+T.&author�Hillyer+C.D. &erapy, vol. 10, no. 4, pp. 220–227, 2017. &title�AABB+Technical+Manual. [5] J. R. Wingard, N. S. Majhail, R. Brazauskas et al., “Long-term survival and late deaths after allogeneic hematopoietic cell [20] W. Y. Au, A. K. W. Lie, A. W. C. Kung, R. Liang, B. R. Hawkins, and Y. L. Kwong, “Autoimmune thyroid transplantation,” Journal of Clinical Oncology, vol. 29, no. 16, pp. 2230–2239, 2011. dysfunction after hematopoietic stem cell transplantation,” 6 Case Reports in Immunology Bone Marrow Transplantation, vol. 35, no. 4, pp. 383–388, [21] K. Zaletel and S. Gaberscek, “Hashimotos thyroiditis: from genes to the disease,” Current Genomics, vol. 12, no. 8, pp. 576–588, 2011. [22] A. Petrone, G. Giorgi, C. A. Mesturino et al., “Association of DRB1∗04-DQB1∗0301 haplotype and lack of association of two polymorphic sites at CTLA-4 gene with hashimoto’s thyroiditis in an Italian population,” &yroid, vol. 11, no. 2, pp. 171–175, 2001. [23] N. Worel, A. Buser, H. T. Greinix et al., “Suitability criteria for adult related donors: a consensus statement from the worldwide network for blood and marrow transplantation standing committee on donor issues,” Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation, vol. 21, pp. 2052–2060,

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Case Reports in ImmunologyHindawi Publishing Corporation

Published: Jun 23, 2022

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