What is the outcome in patients with acute leukaemia who survive severe acute graft‐versus‐host disease?

Ringdén, Olle; Labopin, Myriam; Sadeghi, Behnam; Mailhol, Audrey; Beelen, Dietrich; Fløisand, Yngvar; Ghavamzadeh, Ardeshir; Finke, Jürgen; Ehninger, Gerhard; Volin, Liisa; Socié, Gèrard; Stuhler, Gernot; Ganser, Arnold; Schmid, Christoph; Giebel, Sebastian; Mohty, Mohamad; Nagler, Arnon

doi:10.1111/joim.12695

Cited by 11 publications

(12 citation statements)

References 44 publications

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“…These are unfortunate yet expected complications after HCT. Patients who survived acute GVHD have an reduced risk of leukemic relapse (101). The graft-versus-leukemia (GVL) effect did not prevent relapse in this girl with high risk B-ALL.…”

Section: Discussionmentioning

confidence: 77%

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Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease

2020

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Mesenchymal stromal cells (MSCs) are rare precursors in all organs of the body. MSCs have profound anti-inflammatory effects and reduce alloreactivity in vitro and in vivo. In pediatric allogeneic hematopoietic cell transplantation (HCT), MSCs have mainly been used to treat acute graft-versus-host disease (GVHD). MSCs are commercially available for this indication in Canada, Japan, and New Zeeland. More rare indications for MSCs in pediatric patients include graft failure and chronic GVHD. MSCs from bone marrow, adipose tissue, umbilical cord, Wharton's jelly, placenta tissue, and decidua have been used, but the optimal clinical stromal cell source has not been compared in clinical trials. More experimental clinical indications using MSCs, such as sepsis, acute respiratory distress syndrome, hemorrhages, pneumo-mediastinum, and neuroinflammation have primarily been explored in animal models or adult HCT patients. MSCs have almost no if any side-effects. In this pilot study we report the outcome of six children treated with decidua stromal cells (DSCs) for steroid refractory acute GVHD. At 6 months, complete response was seen in four patients and partial response in two patients. One child with high-risk ALL died from relapse and a boy with sickle cell disease died from a cerebral hemorrhage. Five-year survival was 67% and all survivors showed a Lansky score of 100%. To conclude, MSCs from various organs are well-tolerated and have shown an encouraging outcome for acute GVHD in pediatric patients.

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Section: Discussionmentioning

confidence: 77%

“…Children have a relatively low risk of chronic GVHD (104,105). However, there is an increased risk of chronic GVHD in patients who survive acute GVHD (101). Children have a better outcome than adults after HCT and this is striking in patients with severe acute GVHD (6).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease

2020

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“…With our current protocol (corresponding to group 2), the survival of patients with steroid‐refractory acute GVHD was similar to that in all the patients who underwent HSCT at our center in the last 5 years. It should be noted that patients who survived severe acute GVHD, treated with conventional immunosuppressive therapy, have a significantly worse outcome than all other HSCT patients . In contrast, patients who were treated with DSCs for severe acute GVHD had much better survival.…”

Section: Discussionmentioning

confidence: 99%

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease

Ringdén¹,

Baygan²,

Remberger

et al. 2018

Stem Cells Translational Medicine

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Severe acute graft‐versus‐host disease (GVHD) is a life‐threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta‐derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM‐MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21). The viability of cells was higher when thawed in albumin rather than AB plasma (p < .001). Group 1 received a higher cell dose (p < .001), cells of lower passage number (p < .001), and fewer infusions (p = .002) than group 2. The GVHD response (no/partial/complete) was 7/5/5 in group 1 and 0/10/11 in group 2 (p = .01). One‐year survival in the two groups was 47% (95% confidence interval [CI] 23–68) and 76% (95% CI 51–89), respectively (p = .016). For the SR patients, 1‐year survival was 73% (95% CI 37–90) in SR group 2 (n = 11), which was better than 31% (95% CI 11–54) in SR group 1 (n = 13; p = .02), 20% (95% CI 5–42) in BM‐MSC treated (n = 15; p = .0015), and 3% (95% CI 0–14) in historic controls (n = 32; p < .001). DSCs are a promising new treatment for severe acute GVHD. Prospective randomized trials are needed for evaluation of efficacy. (Clinical trial NCT‐02172937.) stem cells translational medicine 2018;7:325–332

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“…7,16 Not ideal, this therapy is associated with severe side effects, and in patients with acute GVHD of grade II or higher, durable response rates are dismal varying from 30% to 50%. [17][18][19] Outcomes in severe cases of acute GVHD are poor, leading to increased risk of chronic GVHD, increased nonrelapse mortality (NRM), and decreased overall survival (OS). 19 Given the incidence of acute GVHD and its highly debilitating consequences, efforts to better comprehend and abate this clinical syndrome are ongoing.…”

mentioning

confidence: 99%

“…[17][18][19] Outcomes in severe cases of acute GVHD are poor, leading to increased risk of chronic GVHD, increased nonrelapse mortality (NRM), and decreased overall survival (OS). 19 Given the incidence of acute GVHD and its highly debilitating consequences, efforts to better comprehend and abate this clinical syndrome are ongoing. Although it is recognized that several advances in the realm of pathophysiology have been made by others, discussion of this topic is outside the scope of this review.…”

mentioning

confidence: 99%

Acute Graft‐versus‐Host Disease: Emerging Insights and Updates into Detection, Prevention, and Treatment

DiMaggio

2020

Pharmacotherapy

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Acute graft‐versus‐host disease remains a devastating complication following hematopoietic cell transplantation, resulting in increased morbidity and mortality. Vast research efforts continue to refine or develop new means of prediction, assessment, prevention, and treatment of this syndrome. Recent updates in acute graft‐versus‐host disease include more definitive guidance and definitions for its grading and diagnosis. Biomarker use is being incorporated into early stages following hematopoietic cell transplantation to aid in the detection and prediction of long‐term outcomes. New preventive strategies under investigation include the use of vedolizumab or tocilizumab as upfront prophylaxis. Finally, although steroids remain the backbone of therapy once treatment is warranted, the efficacy of several agents including vedolizumab, tocilizumab, ruxolitinib, and α1 antitrypsin are being evaluated as potential therapeutic options.

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What is the outcome in patients with acute leukaemia who survive severe acute graft‐versus‐host disease?

Abstract: HSCT patients who survive severe aGVHD have higher risk of developing extensive cGVHD, a higher NRM, a lower relapse probability, and lower LFS than other HSCT patients. This study is a platform for outcome analysis in patients treated with novel therapies for acute GVHD.

Cited by 11 publications

References 44 publications

Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease

Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease

Acute Graft‐versus‐Host Disease: Emerging Insights and Updates into Detection, Prevention, and Treatment

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