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

Abstract

Background Autoimmune cytopenias (AICs) are rare, but serious complications of allogeneic hematopoietic cell transplantation (allo‐HSCT). Procedure We performed a case‐control study using 20 pediatric AIC cases and 40 controls, matched by stem cell source and primary indication comparing clinical and transplant characteristics, treatment, outcomes, and late effects. Results Cases were more likely to be human leukocyte antigen mismatched (P = 0.04). There was no difference in conditioning regimen, serotherapy use, graft‐versus‐host disease (GVHD) prophylaxis, incidence of acute or chronic GVHD, ABO compatibility, infections, and donor engraftment. The median time to AIC onset was 219 days (range, 97‐1205 days) and AIC resolution was 365 days (range, 10 days to 2737.5 days). First‐line therapies for AIC patients most commonly included corticosteroids (75%) and rituximab (55%). Only 25% of patients responded to first‐line treatment. At a median of 611.5 days from last rituximab dose, 82.5% patients were still receiving intravenous immune globulin for hypogammaglobulinemia compared with 2.5% of controls (P < 0.0001). Iron overload was higher in AIC patients (P = 0.0004), as was avascular necrosis (P = 0.04). There was no difference in overall survival at one year after HSCT (85% vs 82.5%). Two patients with refractory autoimmune hemolytic anemia responded to daratumumab and had resolution of B‐cell aplasia. Conclusions In this study, we find poor initial responses to AIC‐directed therapies and significant late effects.

Targeting plasma cells with daratumumab aids in the treatment of post‐transplant autoimmune‐like hepatitis

“…Daratumumab was well tolerated in our patient post‐HCT, as has been observed in the emerging experience with daratumumab for autoimmune cytopenias in this population 14,15,17 . Beyond hematologic conditions, treatment with daratumumab has shown a reduction in autoantibodies 21 and is being investigated for other autoimmune conditions 22,23 .…”

“…Daratumumab, a CD38–targeted monoclonal antibody, was initially developed for use in multiple myeloma, 9–11 but it has also been effective in other plasma cell–mediated disorders as well. In the post‐HCT setting, the use of daratumumab has been described in pediatric and adult patients with delayed red blood cell engraftment after HCT, associated with major ABO mismatch between donor and the recipient 12,13 and for autoimmune cytopenias 14–17 . We report the novel use of daratumumab to treat post‐HCT autoimmune hepatitis in a pediatric patient after HCT for relapsed B cell acute lymphoblastic leukemia (B‐ALL).…”

The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease

“…Molecular studies did not further inform the diagnosis. As in our patient, the literature review highlighted the efficacy of daratumumab in several clinical settings, including multi-refractory CAD and wAIHA/Evans syndrome, mainly occurring after hematopoietic stem cell transplant (8)(9)(10)(11)(12)(13)(14)(15). Today, no effective second line treatment has been licensed for CAD and novel drugs targeting the complement cascade or the antibody producing B-cell clone are under active investigation.…”

“…Another interesting anti-MM treatment is daratumumab a human IgG1κ MoAb directed against the transmembrane glycoprotein CD38 (6,7). Several reports highlighted the efficacy of daratumumab in different settings, including refractory and post-transplant warm AIHA (8)(9)(10)(11)(12), CAD (13), and Evans' syndrome (i.e., association of AIHA and immune thrombocytopenia) (14,15). Besides these proofs of efficacy, the regulatory effect of daratumumab on immune response mediators such as cytokines is largely unknown.…”

Pathogenesis, risk factors and therapeutic options for autoimmune haemolytic anaemia in the post‐transplant setting

“…Koo et al . demonstrated a reduced number of CD4 and CD8 in children with post‐HSCT AIHA compared to controls 18 . Moreover, an imbalance in T cell reconstitution compared to B cells, with relative increase in B cell number, has been described 19,20 .…”