Massive hemorrhage after percutaneous liver biopsy in a pediatric patient with graft-versus-host disease; a successful angiographic embolization

Most cases of bleeding that develop after percutaneous liver biopsies can be managed with follow-up and supportive treatment. In life-threatening situations, however, open surgery or minimally invasive methods are required. This case report describes the clinical course of an 11-year-old patient with a diagnosis of Wiskott-Aldrich syndrome who experienced a major hemorrhage following a percutaneous liver biopsy. Clinical findings, imaging, interventions, and results were evaluated. Allogeneic hematopoietic stem cell transplantation was performed without any problem. The patient's bilirubin level started to increase on the 20th day after transplantation. Profuse watery diarrhea started on the 24th day. Graft-versus-host disease of the gastrointestinal tract and liver was considered as his diarrhea continued to the 29th day. An ultrasound-guided Tru-cut® liver biopsy (Merit medical, South Jordan, UT, USA) was performed with an 18-gauge needle on the 52nd day after transplantation. In the fourth hour after the procedure, the general condition of the patient started to deteriorate. Active bleeding was detected in the patient with computed tomography, and he was hypotensive and tachycardic. The patient was urgently transferred to the angiography unit and a successful angiographic embolization was performed. Angiographic embolization is an intervention with high success rates in cases of bleeding where the patient is hemodynamically stable. However, it can also be successfully applied in selected patients who are hemodynamically unstable.

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Prophylaxis of Graft-Versus-Host Disease in Unrelated Donor Transplantation With Pentostatin, Tacrolimus, and Mini-Methotrexate: A Phase I/II Controlled, Adaptively Randomized Study

Journal of Clinical Oncology ◽

10.1200/jco.2010.30.6357 ◽

2011 ◽

Vol 29 (3) ◽

pp. 294-302 ◽

Cited By ~ 21

Author(s):

Simrit Parmar ◽

Borje S. Andersson ◽

Daniel Couriel ◽

Mark F. Munsell ◽

Marcelo Fernandez-Vina ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Randomized Study ◽

Dose Finding ◽

Unrelated Donor ◽

Success Rates ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Grade 3 ◽

Prevention Methods

Purpose Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression. We hypothesized that addition of pentostatin to GVHD prophylaxis with tacrolimus and mini-methotrexate may improve outcomes, and we conducted a Bayesian adaptively randomized, controlled, dose-finding study, taking into account toxicity and efficacy. Patients and Methods Success was defined as the patient being alive, engrafted, in remission, without GVHD 100 days post-HSCT and no grade ≥ 3 GVHD at any time. Patients were randomly assigned to pentostatin doses of 0, 0.5, 1.0, 1.5, and 2.0 mg/m2 with drug administered on HSCT days 8, 15, 22, and 30. Eligible patients were recipients of mismatched related (n = 10) or unrelated (n = 137) donor HSCT. Results Median age was 47 years. Thirty-seven, 10, 29, 61, and 10 patients were assigned to the control and four treatment groups, respectively, with comparable baseline characteristics. Pentostatin doses of 1.0 and 1.5 mg/m2 had the highest success rates (69.0% and 70.5%) versus control (54.1%). The posterior probabilities that the success rates were greater with 1.5 mg/m2 or 1.0 mg/m2 versus control are 0.944 and 0.821, respectively. Hepatic aGVHD rates were 0%, 17.2%, and 11.1%, respectively, for 1.5 mg/m2, 1.0 mg/m2, and control groups. No grades 3 to 4 aGVHD occurred in 11 HLA-mismatched recipients in the 1.5 mg/m2 group. Conclusion Pentostatin increased the likelihood of success as defined here, and should be further investigated in larger randomized, confirmatory studies.

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Effect of Early Post-Transplantation Tacrolimus Concentration on the Risk of Acute Graft-Versus-Host Disease in Allogenic Stem Cell Transplantation

Cancers ◽

10.3390/cancers13040613 ◽

2021 ◽

Vol 13 (4) ◽

pp. 613

Author(s):

Nidhi Sharma ◽

Qiuhong Zhao ◽

Bin Ni ◽

Patrick Elder ◽

Marcin Puto ◽

...

Keyword(s):

Stem Cell ◽

Graft Versus Host Disease ◽

Tacrolimus Concentration ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

The Impact ◽

Risk Of Relapse ◽

Acute Graft

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.

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Mesenchymal stem cells (MSC) delays the occurrence of graft-versus-host disease(GVHD) in the inhibition of hematopoietic stem cells in major histocompatibility complex semi-consistent mice by regulating the expression of IFN-γ/IL-6

Bioengineered ◽

10.1080/21655979.2021.1955549 ◽

2021 ◽

Vol 12 (1) ◽

pp. 4500-4507

Author(s):

Ying Wang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Major Histocompatibility Complex ◽

Hematopoietic Stem Cells ◽

Graft Versus Host Disease ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Histocompatibility Complex ◽

Ifn Γ

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Mast Cell Involvement in Fibrosis in Chronic Graft-Versus-Host Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22052385 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2385

Author(s):

Ethan Strattan ◽

Gerhard Carl Hildebrandt

Keyword(s):

Wound Healing ◽

Mast Cell ◽

Mast Cells ◽

Graft Versus Host Disease ◽

Chronic Gvhd ◽

Fibrotic Disease ◽

Acute Leukemias ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host

Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead to fibrotic disease. Interestingly, in chronic GVHD, aberrant wound healing mechanisms lead to pathological fibrosis, but the cellular etiology driving this is not well-understood, although some studies have implicated mast cells. Given this novel role, we here review the literature for studies of mast cell involvement in the context of chronic GVHD. While there are few publications on this topic, the papers excellently characterized a niche for mast cells in chronic GVHD. These findings may be extended to other fibrosing diseases in order to better target mast cells or their mediators for treatment of fibrotic disease.

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Sustained remission after haploidentical bone marrow transplantation in a child with refractory systemic juvenile idiopathic arthritis

Pediatric Rheumatology ◽

10.1186/s12969-021-00523-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Guillaume Morelle ◽

Martin Castelle ◽

Graziella Pinto ◽

Sylvain Breton ◽

Matthieu Bendavid ◽

...

Keyword(s):

Bone Marrow ◽

Juvenile Idiopathic Arthritis ◽

Graft Versus Host Disease ◽

Immune Thrombocytopenia ◽

Systemic Juvenile Idiopathic Arthritis ◽

Sustained Remission ◽

Refractory Disease ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host

Abstract Background Some patients with systemic juvenile idiopathic arthritis (SJIA) and severe, refractory disease achieved remission through intensive immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (HSCT). However, disease relapsed in most cases. More recently selected SJIA patients received allogenic HSCT from a HLA-identical sibling or a HLA matched unrelated donor. While most transplanted patients achieved sustained SJIA remission off-treatment, the procedure-related morbidity was high. Case report A girl presented SJIA with a severe disease course since the age of 15 months. She was refractory to the combination of methotrexate and steroids to anti-interleukin (IL)-1, then anti-IL-6, tumor necrosis factor alpha inhibitors, and thalidomide. Given the high disease burden and important treatment-related toxicity the indication for a haploidentical HSCT from her mother was validated, as no HLA matched donor was available. The patient received a T replete bone marrow graft at the age of 3.7 years. Conditioning regimen contained Rituximab, Alemtuzumab, Busulfan, and Fludarabine. Cyclophosphamide at D + 3 and + 4 post HSCT was used for graft-versus-host-disease prophylaxis, followed by Cyclosporin A and Mycophenolate Mofetil. Post HSCT complications included severe infections, grade 3 intestinal graft-versus-host-disease, autoimmune thyroiditis, and immune thrombocytopenia. Three years after HSCT, the child is alive and well, notwithstanding persistent hypothyroidy requiring substitution. Immune thrombocytopenia had resolved. Most importantly, SJIA was in complete remission, off immunosuppressive drugs. Conclusion Allogenic HSCT may be a therapeutic option, even with a HLA haplo-identical alternative donor, in patients with inflammatory diseases such as SJIA. Despite increased experience with this treatment, the risk of life-threatening complications restrains its indication to selected patients with severe, refractory disease.

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1075. Absolute Lymphocyte Count as a Predictor of Cytomegalovirus (CMV) Infection and Recurrence in Hematopoietic Stem Cell Transplant (HSCT) Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1261 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S565-S565

Author(s):

Joanne Reekie ◽

Marie Helleberg ◽

Christina Ekenberg ◽

Mark P Khurana ◽

Isabelle P Lodding ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Lymphocyte Count ◽

Absolute Lymphocyte Count ◽

Cell Transplant ◽

Cmv Infection ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Increased Risk ◽

Acute Graft

Abstract Background Cytomegalovirus (CMV) is a serious complication following Hematopoietic Stem Cell Transplant (HSCT) and can lead to serious organ disease and mortality. This study aimed to investigate the association between absolute lymphocyte count (ALC) and CMV to determine whether ALC could help to identify those at an increased risk of CMV infection and recurrence Methods Adults undergoing HSCT between 2011 and 2016 at Rigshospitalet, Denmark were included. Cox proportional hazards models investigated risk factors, including ALC, for CMV infection in the first year post-transplant and recurrent CMV infection 6 months after clearance and stopping CMV treatment for the first infection. For the primary outcome ALC was investigated as a time-updated risk factor lagged by 7 days, and for recurrent CMV, ALC measured at the time at the time of stopping treatment for the first CMV infection was investigated (+/- 7 days). Results Of the 352 HSCT recipients included, 57% were male, 40% received myeloablative conditioning, 42% had high risk (D-R+) CMV IgG serostatus at transplant and the median age was 56 (IQR 43-63). 143 (40.6%) patients had an episode of CMV DNAemia a median of 47 days after transplant (IQR 35-62). A lower current ALC (≤ 0.3 x109/L) was associated with a higher risk of CMV infection in univariate analysis compared to a high current ALC (> 1 x109/L). However, this association was attenuated after adjustment, particularly for acute graft versus host disease (Figure). 102 HSCT recipients were investigated for risk of recurrent CMV of which 41 (40.2%) had a recurrent CMV episode a median of 27 days (IQR 16-50) after stopping CMV treatment for the first infection. A lower ALC (≤ 0.3 x109/L) at the time of stopping CMV treatment was associated with a significantly higher risk of recurrent CMV after adjustment (Figure). A higher peak viral load (> 1500 IU/ml) during the first episode of CMV infection was also associated with an increased risk of recurrent CMV (aHR 2.47, 95%CI 1.00-6.10 compared to < 750 IU/ml). Association between absolute lymphocyte count (ALC) and risk of CMV infection and recurrent CMV within 6 months. **First CMV infection multivariable model also adjusted for sex, CMV serostatus, age, year of transplant, Charlson Comorbidity Index, Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease (time-updated) *Recurrent CMV infection multivariable model also adjusted for conditioning regimen, sex, CMV serostatus, age, year of transplant Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease and peak CMV viral load during the first CMV infection Conclusion A lower ALC at the time of stopping treatment for the first CMV infection was associated with an increased risk of recurrent CMV and could be used to help guide decisions for augmented CMV surveillance and clinical awareness of CMV disease symptoms in these patients. Disclosures All Authors: No reported disclosures

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A Novel Secondary Neoplasm Following Allogeneic Hematopoietic Stem Cell Transplant: Mixed Donor-Recipient Primitive Mesenchymal Proliferation of the Liver

Pediatric and Developmental Pathology ◽

10.1177/10935266211001656 ◽

2021 ◽

pp. 109352662110016

Author(s):

Brian Earl ◽

Zi Fan Yang ◽

Harini Rao ◽

Grace Cheng ◽

Donna Wall ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Graft Versus Host Disease ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Post Transplant

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.

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Tissue immune profiles supporting response to mesenchymal stromal cell therapy in acute graft-versus-host disease—a gut feeling

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1449-9 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Caroline Gavin ◽

Erik Boberg ◽

Lena Von Bahr ◽

Matteo Bottai ◽

Anton Törnqvist Andrén ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Mesenchymal Stromal Cell ◽

Stromal Cell ◽

Immune Cell ◽

Therapeutic Potential ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Cell Profile ◽

Acute Graft

AbstractAcute graft-versus-host disease (aGvHD), post-allogeneic hematopoietic stem cell transplantation, is associated with high mortality rates in patients not responding to standard line care with steroids. Adoptive mesenchymal stromal cell (MSC) therapy has been established in some countries as a second-line treatment.Limitations in our understanding as to MSC mode of action and what segregates patient responders from non-responders to MSC therapy remain. The principal aim of this study was to evaluate the immune cell profile in gut biopsies of patients diagnosed with aGvHD and establish differences in baseline cellular composition between responders and non-responders to subsequent MSC therapy.Our findings indicate that a pro-inflammatory immune profile within the gut at the point of MSC treatment may impede their therapeutic potential. These findings support the need for further validation in a larger cohort of patients and the development of improved biomarkers in predicting responsiveness to MSC therapy.

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