Predictors for Autoimmune Cytopenias after Allogeneic Hematopoietic Cell Transplantation in Children

Abstract

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.

Autoimmune cytopenias following allogeneic hematopoietic stem cell transplant in pediatric patients: Response to therapy and late effects

“…Curiously, this is inconsistent with prior reports. 16,22,24 Likewise, in the prior literature, 20,25 viral reactivation has been suggested to be a trigger in AICs, but this was not observed in our cohort.…”

“…This is comparable to the incidences of 2.1%-7.8% previously reported in similar pediatric patient populations. 4,5,8,20,21 The association of nonmalignant disease with the development of AIC has been widely reported. 4,7,[20][21][22][23] Because prior studies identified primary nonmalignant disease and unrelated donor as risk factors for post-transplant AIC, we chose to match our control group based on these variables.…”

“…5,6 Prior studies have identified several risk factors for AIC development including nonmalignant transplant indications, chemotherapy naivety, unrelated donors, cord blood stem cell source, graft-vs-host disease (GVHD), reduced-intensity preparative regimens, serotherapy, and cytomegalovirus (CMV) reactivation. [7][8][9][10] Corticosteroids and rituximab are the most common first-line therapies for AICs. 11 However, these interventions have side effects and long-term consequences.…”

Treatment of immune-mediated cytopenias in patients with primary immunodeficiencies and immune regulatory disorders (PIRDs)

“…Autoimmune cytopenias for patients with secondary immunodeficiency, such as after allogeneic HSCT or after organ transplantation, are among the most difficult to diagnose and treat. Recent studies and reviews that address this topic specifically [29][30][31] provide more in-depth guidelines than this present work focusing on SIC in primary immunodeficiencies. In brief, autoimmune cytopenias in secondary immunodeficiencies such as post-transplantation settings may be caused by a complex mix of underlying pathomechanisms such as imbalanced immune reconstitution with preponderance or insufficient elimination of autoreactive T-or B-cell clones, calcineurin inhibitor-facilitated skewing of the immune system, drug-induced thrombotic microangiopathy or sinusoidal obstruction syndrome, and virustriggered conventional autoimmune reactions, to list a few.…”

Consensus opinion on immune-mediated cytopenias after hematopoietic cell transplant for inherited metabolic disorders

“…Furthermore, there are no clear guidelines on the diagnosis and management of IMC after transplantation. Since IMD itself appears to be an independent risk factor for IMC or has a relatively higher incidence of IMC [10][11][12][13][14], a multinational panel of physician experts in the treatment of IMD was convened, with the primary aim to identify the strategies for effective and timely diagnosis and develop a management strategy for IMC in this patient population. The panel included experts in HCT for IMDs from centers with experience in treating these disorders as well experts in nonmalignant disorders and transplant immunology.…”