Autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (HSCT): A retrospective analysis and a proposal of treatment on behalf of the Grupo Español De Trasplante de Medula Osea en Niños (GETMON) and the Grupo Español de Trasplante Hematopoyetico (GETH)

González‐Vicent, Marta; Sanz, Jaime; Fuster, José Luís; Cid, Joan; Heredia, Cristina Díaz de; Morillo, Daniel; Fernández, José Marı́a; Pascual, Antonia; Badell, Isabel; Serrano, David; Fox, Laura; Serna, Javier de la; Benito, Ana; Couselo, José Miguel; Molina, Blanca; Díaz, Miguel Ángel; Sanz, Miguel Á.

doi:10.1016/j.tmrv.2018.02.005

Cited by 37 publications

(66 citation statements)

References 22 publications

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“…Development of AIC after HCT has been associated with graft-versus-host-disease (GVHD), higher risk of relapse, T cell depletion, and HCT from unrelated donors, suggesting that immune dysregulation or impaired immune reconstitution may be involved [7][8][9][10]. Other studies have reported age at transplant, viral reactivations, HCT for nonmalignant indications, cord blood (CB) stem cell source, conditioning, and interval time from primary diagnosis to HCT as predictors for AIC [4,9,[11][12][13]. Furthermore, Kruizinga et al [14] and Gonz alez-Vicent et al [11] studied the immune status at AIC diagnosis.…”

Section: Introductionmentioning

confidence: 99%

“…Other studies have reported age at transplant, viral reactivations, HCT for nonmalignant indications, cord blood (CB) stem cell source, conditioning, and interval time from primary diagnosis to HCT as predictors for AIC [4,9,[11][12][13]. Furthermore, Kruizinga et al [14] and Gonz alez-Vicent et al [11] studied the immune status at AIC diagnosis. Kruizinga et al [14] found that cytokine profiles of patients at the time of AIC diagnosis were skewed toward a more pronounced Th 2 response compared with control subjects.…”

Section: Introductionmentioning

confidence: 99%

“…Kruizinga et al [14] found that cytokine profiles of patients at the time of AIC diagnosis were skewed toward a more pronounced Th 2 response compared with control subjects. Gonz alez-Vicent et al [11] showed in a very large registry analysis (n > 4000) that most patients at the time of AIC diagnosis were lymphopenic (median, 882 lymphocytes/mL), including very low regulatory T cells, suggesting that deep immune deficiency is a predictor. These associations with AIC might give more insight in the pathogenesis of AIC and may eventually help in early diagnosis and thus treatment of AIC.…”

Section: Introductionmentioning

confidence: 99%

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Predictors for Autoimmune Cytopenias after Allogeneic Hematopoietic Cell Transplantation in Children

Szanto

Langenhorst

Koning

et al. 2020

Biology of Blood and Marrow Transplantation

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of autoimmune cytopenia (AIC) after allogeneic hematopoietic cell transplantation (HCT) is a serious complication requiring urgent intensification of immunosuppressive therapy. The pathophysiology and predictors of AIC are not completely understood. In this retrospective cohort analysis of 380 pediatric patients, we evaluated the incidence, outcomes, and related various variables, including immune reconstitution markers to AIC. Three hundred eighty patients (median age, 7.4 years; range, .1 to 22.7) were included, of which 30 patients (7.8%) developed AIC in 1 (n = 6), 2 (n = 6), or 3 (n = 16) cell lineages at a median of 133 days (range, 46 to 445) after HCT. Using multivariate analysis we found that chemo-naivety before HCT, acute graft-versus-host disease (aGVHD) grades II to IV, and serotherapy were associated with the development of AIC. Development of AIC was preceded by increased levels of IgM, IgA, and IgG. Immune profiles of total absolute lymphocytes were very similar between AIC patients and control subjects. However, CD3-CD16 + CD56 + natural killer cells, CD3 + T cells, CD3 + CD4 + T cell subset, and CD3 + CD8 + T cell subset were lower in AIC patients. Overall survival was good, at 83% (similar between AIC patients and control subjects). In conclusion, we identified chemo-naivety before HCT, preceding aGVHD grades II to IV, and serotherapy as predictors for development of AIC. Increasing levels of IgM, IgA, and IgG preceded AIC development. These data provide clues to further study the biology of AIC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predictors for Autoimmune Cytopenias after Allogeneic Hematopoietic Cell Transplantation in Children

Szanto

Langenhorst

Koning

et al. 2020

Biology of Blood and Marrow Transplantation

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“…When identified early, initiation of first‐line therapy with corticosteroids is appropriate. Patients who do not respond to steroids should receive treatment with rituximab . Long‐term courses of corticosteroids should be avoided to minimize long‐term side effects, which may be more intensified in this patient population with significant underlying comorbidities and concomitant therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Previously proposed risk factors for the development of post‐HSCT AIC include nonmalignant disease as the indication for transplant, unrelated donor transplant, peripheral or cord blood stem cell source, and the presence of graft‐versus‐host disease (GvHD). These risk factors can theoretically contribute to loss of self‐tolerance and incomplete immune reconstitution post HSCT, leading to homeostatic expansion of autoreactive lymphocytes that can continue unchecked in the profoundly lymphodepleted host . Additionally, infections in an immunocompromised host can also lead to new autoimmunity …”

Section: Introductionmentioning

confidence: 99%

Autoimmune hemolytic anemia and immune thrombocytopenia following hematopoietic stem cell transplant: A critical review of the literature

Neunert

Despotovic

2018

Pediatric Blood & Cancer

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Autoimmune cytopenias (AIC) post‐hematopoietic stem cell transplant (HSCT) are rare but exceptionally challenging complication. We conducted a comprehensive literature review and identified a pooled incidence of post‐HSCT autoimmune hemolytic anemia and/or immune thrombocytopenia of 2.66% (SE = 0.27) in pediatric patients. Nonmalignant disease, unrelated donor transplant, peripheral or cord blood stem cell source, conditioning regimen without total body irradiation, and presence of chronic graft‐versus‐host disease were prominent risk factors. Treatment was highly variable, and cytopenias were commonly refractory. AIC represent a significant post‐HSCT complication. We report here the incidence, risk factors, and possible biology behind the development of AIC in pediatric post‐HSCT patients.

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The effect of HLA matching and donor relatedness on the risk of autoimmune haemolytic anaemia in haematopoietic stem cell transplant recipients: A systematic review and meta‐analysis

Kennedy

Jackson

2022

eJHaem

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Recent studies have identified autoimmune haemolytic anaemia (AIHA) as a haematopoietic stem cell transplant (HSCT) complication that represents a significant cause of morbidity and mortality for these patients. In order to understand this autoimmune phenomenon, emerging research has focused on the prognostic factors associated with the development of the disorder. These studies have identified numerous possible associations with often contrasting and conflicting results. A systematic review and meta-analysis were performed in order to determine the effect of human leucocyte antigen (HLA) matching and donor relatedness on the risk of AIHA post-HSCT. PubMed, SCOPUS and ProQuest were searched from 1 January 1995 to 1 August 2021 using a range of keywords. Meta-analysis was performed using OpenMeta-Analyst software using a random effects model and arcsine risk difference (ARD). Eight eligible articles were identified, and meta-analysis showed an increased risk of AIHA in those who received HLA-mismatched transplants (ARD −0.082; 95% confidence interval [CI] −0.157, −0.007; p = 0.031) and those who received donations from unrelated donor sources (ARD −0.097; 95% CI −0.144, −0.051; p < 0.001).Patients who receive HSCT from HLA-matched and related donor sources have a reduced risk of developing AIHA. Healthcare practitioners should be mindful of the risk of AIHA, especially in those who receive HLA-mismatched and unrelated donorsourced stem cells. While these findings provide further evidence for researchers investigating the pathogenesis of this HSCT complication, more studies are needed to fully understand the cause.

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Autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (HSCT): A retrospective analysis and a proposal of treatment on behalf of the Grupo Español De Trasplante de Medula Osea en Niños (GETMON) and the Grupo Español de Trasplante Hematopoyetico (GETH)

Cited by 37 publications

References 22 publications

Predictors for Autoimmune Cytopenias after Allogeneic Hematopoietic Cell Transplantation in Children

Predictors for Autoimmune Cytopenias after Allogeneic Hematopoietic Cell Transplantation in Children

Autoimmune hemolytic anemia and immune thrombocytopenia following hematopoietic stem cell transplant: A critical review of the literature

The effect of HLA matching and donor relatedness on the risk of autoimmune haemolytic anaemia in haematopoietic stem cell transplant recipients: A systematic review and meta‐analysis

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