Successful treatment of severe refractory autoimmune hemolytic anemia after hematopoietic stem cell transplant with abatacept

Hess, Judith; Su, Leon; Nizzi, Frank; Beebe, Kristen; Magee, Kyrie; Salzberg, Dana; Stahlecker, Jennifer; Miller, Holly; Adams, Roberta H.; Ngwube, Alexander

doi:10.1111/trf.14907

Cited by 16 publications

(10 citation statements)

References 24 publications

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“…The next line of treatment he received was abatacept, a fusion protein composed of the Fc region of the immunoglobulin IgG1 fused to the extracellular domain of cytotoxic T‐lymphocyte antigen‐4, which inhibits T‐cell costimulation by binding to CD80/CD86 on antigen‐presenting cells . Starting on day +230, four doses of abatacept (10 mg/m 2 ) once every 2 weeks were given, and showed no therapeutic effect.…”

Section: Case Descriptionmentioning

confidence: 99%

“…9 The child was transplanted with a peripheral blood stem cell (PBSC) collected graft inhibits T-cell costimulation by binding to CD80/CD86 on antigenpresenting cells. 12 Starting on day +230, four doses of abatacept (10 mg/m 2 ) once every 2 weeks were given, and showed no therapeutic effect. On day +254, a pulse of high-dose solumedrol (3 days of 10 mg/kg/day) was given, followed by a second course of rituximab, again without any improvement.…”

Section: Case Descriptionmentioning

confidence: 99%

“…Other reported treatment options include calcineurin inhibitors, sirolimus, mycophenolate mofetil, abatacept, and bortezomib. Additional therapeutic modalities include plasmapheresis; chemotherapeutic agents such as 6-mercaptopurin, azathioprine, cyclophosphamide, and vincristine; and in some refractory cases even splenectomy or a second transplant [1][2][3][4]12,13.…”

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confidence: 99%

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Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia

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NaserEddin

Shadur

et al. 2019

Pediatric Blood & Cancer

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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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Section: Case Descriptionmentioning

confidence: 99%

Section: Case Descriptionmentioning

confidence: 99%

mentioning

confidence: 99%

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Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia

Even‐Or

NaserEddin

Shadur

et al. 2019

Pediatric Blood & Cancer

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“…Given that BOS is explicitly characterized by disturbance of B cell homeostasis with increased CD19 + CD21 -B cells and excess of B cell activation factor (BAFF) [38], abatacept might target Tfh cells in this context, which would at least partially explain the particular improvement of patients with BOS in our study. In addition, we observed a complete response in a steroid and rituximab refractory AIHA patient as previously described [39]. Despite not meeting NIH diagnostic criteria for cGvHD, we included this patient in our analysis since it has recently been reported that based on biomarker profiles, patients with signs of immune mediated damage not diagnostic for cGvHD do not significantly differ from those showing diagnostic signs of cGvHD suggesting that the current NIH diagnostic criteria may not involve all targets of cGvHD [40,41].…”

Section: Discussionmentioning

confidence: 72%

Abatacept as salvage therapy in chronic graft-versus-host disease—a retrospective analysis

et al. 2021

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The immunomodulatory fusion protein abatacept has recently been investigated for the treatment of steroid-refractory chronic graft-versus-host disease (cGvHD) in a phase 1 clinical trial. We analyzed the safety and efficacy of abatacept for cGvHD therapy in a retrospective study with 15 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and received abatacept for cGvHD with a median age of 49 years. Grading was performed as part of the clinical routine according to the National Institute of Health’s (NIH) consensus criteria at initiation of abatacept and 1, 3, 6, 9 and 12 months thereafter. The median time of follow-up was 191 days (range 55–393 days). Best overall response rate (ORR) was 40%. In particular, patients with bronchiolitis obliterans syndrome showed significant clinical improvement and durable responses following abatacept treatment with a response rate of 89% based on improvement in lung severity score (n = 6) or stabilized lung function (n = 4) or both (n = 3). Infectious complications CTCAE °III or higher were observed in 3/15 patients. None of the patients relapsed from the underlying malignancy. Thus, abatacept appears to be a promising treatment option for cGvHD, in particular for patients with lung involvement. However, further evaluation within a phase 2 clinical trial is required.

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“…Finally, a recent study showed the efficacy of the T-cell inhibitor abatacept in 3 post-allo-HSCT AIHA cases 50. Abatacept is a fusion protein formed by linking extracellular domain of cytotoxic T-lymphocyte antigen 4 with the Fc region of immunoglobulin G (IgG) and inhibits T-cell activation through competitive binding of CD80 and CD86 on antigen-presenting cells, thus blocking the required CD28 costimulatory interaction.…”

Section: Emerging Treatments For Post-allo-hsct Aihamentioning

confidence: 99%

<p>Management of refractory autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: current perspectives</p>

Barcellini¹,

Fattizzo²,

Zaninoni³

2019

JBM

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Autoimmune hemolytic anemia (AIHA) is increasingly observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a reported incidence between 4% and 6%. The disease is generally severe and refractory to standard therapy, with high mortality, and there are neither defined therapies, nor prospective clinical trials addressing the best treatment. Most of the knowledge on the therapy of AIHAs derives from primary forms, which are highly heterogeneous as well, further complicating the management of post-allo-HSCT forms. The review addresses the risk factors associated with post-allo-AIHA, including unrelated donor, the development of chronic extensive graft-versus-host disease, CMV reactivation, nonmalignant diagnosis pre-HSCT, and alemtuzumab use in conditioning regimens. Regarding therapy, we describe standard treatments, such as corticosteroids, intravenous immunoglobulin, splenectomy, rituximab, cyclophosphamide, and plasma exchange, which have lower response rates than those reported in primary forms. New therapeutic options, including sirolimus, bortezomib, abatacept, daratumumab and complement inhibitors, are promising tools for this detrimental complication occurring after allo-HSCT.

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Successful treatment of severe refractory autoimmune hemolytic anemia after hematopoietic stem cell transplant with abatacept

Abstract: Abatacept may provide significant clinical benefit in the management of AIHA after HSCT.

Cited by 16 publications

References 24 publications

Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia

Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia

Abatacept as salvage therapy in chronic graft-versus-host disease—a retrospective analysis

<p>Management of refractory autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: current perspectives</p>

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