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

Autoimmune cytopenias (AIC) following allogeneic hematopoietic stem cell transplantation (HSCT) may cause significant morbidity and mortality and are often challenging to treat. We present a case of a pediatric patient with primary myelofibrosis of infancy caused by VPS45 protein deficiency, who developed severe refractory hemolytic anemia and immune‐mediated thrombocytopenia 3.5 months following HSCT. After the failure of several treatments, he received daratumumab, an anti‐CD38 specific antibody, and demonstrated fast and sustained response. The only side effect was delayed recovery of humoral immunity. Daratumumab, by targeting antibody‐producing plasma cells, may be a valid treatment option for refractory post‐HSCT AIC.

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confidence: 93%

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confidence: 99%

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confidence: 99%

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Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia

Even‐Or

NaserEddin

Shadur

et al. 2019

“…Daratumumab has been reported to be successfully used in other pediatric patients with similar complications. 9,33 Lastly, we investigated the late effects and consequences of AICdirected therapies. Short-and long-term effects of the most frequently used AIC treatments (steroids and rituximab) and supportive care measures (transfusions) are well established in various populations.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Koo

Giller

Quinones

et al. 2020

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.

Characteristics and outcomes of autoimmune hemolytic anemia after pediatric allogeneic stem cell transplant

Hillier

Harris

Berbert

et al. 2021

Background Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplant (HSCT) is a rare but complex and serious complication. Detailed descriptions of cases and management strategies are needed due to lack of prospective trials. Objectives Describe the incidence, clinical characteristics, and management of AIHA after HSCT in a pediatric cohort. Methods This is a retrospective cohort study of 33 pediatric patients with AIHA after HSCT at an academic tertiary care center from 2003 to 2019. Results The overall incidence of AIHA after allogeneic HSCT was 3.8% (33/868). AIHA was significantly more common after transplant for nonmalignant versus malignant diagnoses (7.0% [26/370] vs. 1.4% [7/498], p < .0001). AIHA developed at a median of 4.7 months (range 1.0–29.7) after transplant. Sixteen of 33 patients (48.5%) required new AIHA‐directed pharmacologic therapy; 17 (51.5%) were managed on their current immunosuppression and supportive care. Patients managed without additional therapy were significantly older, more likely to have a malignant diagnosis, and tended to develop AIHA at an earlier time point after transplant. Patients received a median of two red blood cell transfusions within the first 2 weeks of diagnosis and a median of one AIHA‐directed medication (range one to four), most commonly corticosteroids and rituximab. Conclusions AIHA after HSCT is rare but occurs more commonly in patients transplanted for nonmalignant diagnoses. While some pediatric patients who develop AIHA after transplant can be managed on current immunosuppression and supportive care, many require AIHA‐directed therapy including second‐line medications.