Graft-versus-host disease: a case report of a rare but reversible cause of constrictive pericarditis

Abstract Background Constrictive pericarditis (CP), although an uncommon cause of heart failure, requires specialist multidisciplinary input and multi-modality imaging to identify the underlying aetiology and treat potentially reversible causes. Case summary We report the case of a 74-year-old gentleman referred for assessment of progressive exertional dyspnoea and peripheral oedema, 30 months following treatment of acute myeloid leukaemia with high-dose chemotherapy and allogeneic stem cell transplantation. Clinical examination and cardiac imaging revealed a small pericardial effusion and pericardial thickening with constrictive physiology; however, no aetiology was identified despite diagnostic pericardiocentesis. The patient required recurrent hospital admissions for intravenous diuresis, therefore, following multidisciplinary discussions, surgical partial pericardectomy was performed. Histology suggested graft-vs.-host disease (GvHD) and post-operatively, the patient improved clinically. Following immunomodulatory therapy with ruxolitinib for both pericardial and pulmonary GvHD, his functional status improved further with no subsequent hospital admissions. Discussion Although pericardial disease in cancer patients is common, CP is unusual. Determining the underlying aetiology is important for subsequent management, and here, we describe the use of multi-modality imaging to diagnose a rare cause, GvHD, which responded to surgical treatment and immunomodulatory therapy.

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Randomized Trial of Filgrastim, Sargramostim, or Sequential Sargramostim and Filgrastim After Myelosuppressive Chemotherapy for the Harvesting of Peripheral-Blood Stem Cells

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.1.43 ◽

2000 ◽

Vol 18 (1) ◽

pp. 43-43 ◽

Cited By ~ 70

Author(s):

Charles H. Weaver ◽

Kevin A. Schulman ◽

Barbara Wilson-Relyea ◽

Robert Birch ◽

William West ◽

...

Keyword(s):

Stem Cells ◽

Peripheral Blood ◽

Hospital Admissions ◽

High Dose Chemotherapy ◽

High Dose ◽

Peripheral Blood Stem Cells ◽

Platelet Recovery ◽

Blood Stem Cells ◽

Sequential Regimen ◽

Chemotherapy Patients

PURPOSE: The purpose of this study was to compare the effects of filgrastim, sargramostim, or sequential sargramostim and filgrastim on CD34+ cell yields and morbidity after myelosuppressive mobilization chemotherapy (MC). PATIENTS AND METHODS: One hundred fifty-six patients were randomized to receive filgrastim (n = 51), sargramostim (n = 52), or sargramostim for 5 days followed by filgrastim (n = 53) after MC with either cyclophosphamide and etoposide (n = 75) or paclitaxel and cyclophosphamide (n = 81). RESULTS: Compared with those who received sargramostim, patients who received filgrastim had faster recovery of an absolute neutrophil count of 0.5 × 109/L or greater (a median of 11 v 14 days; P = .0001), with fewer patients requiring RBC transfusions (P = .008), fewer patients with fever (18% v 52%; P = 0.001), fewer hospital admissions (20% v 42%; P = .013), and less intravenous antibiotic therapy (24% v 69%; P = .001). Patients who received filgrastim yielded more CD34+ cells (median, 7.1 v 2.0 × 106/kg/apheresis; P = .0001), and a higher fraction achieved 2.5 × 106 (94% v 78%; P = .021) and 5 × 106 (88% v 53%; P = .001) or more CD34+ cells/kg with fewer aphereses (median, 2 v 3; P = .002) and fewer days of growth-factor treatment (median, 12 v 14; P = .0001). There were no major differences in outcomes between the filgrastim alone and the sequential regimens. After high-dose chemotherapy, patients who had peripheral-blood stem cells (PBSCs) mobilized with filgrastim or the sequential regimen received higher numbers of CD34+ cells and had faster platelet recovery (P = .015), with fewer patients (P = .014) receiving fewer platelet transfusions (P = .001) than patients receiving sargramostim-mobilized PBSCs. CONCLUSION: It was concluded that filgrastim alone or sequential sargramostim and filgrastim were superior to sargramostim alone for the mobilization of CD34+ cells and reduction of toxicities after MC.

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A Case Report of the Benefit of Cannabidiol (Cannabidiol (CBD)-Predominant Medical Cannabis Preparation) in the Management of Refractory Skin Graft Vs Host Disease (GVHD)

Blood ◽

10.1182/blood-2019-122715 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5687-5687

Author(s):

Tsiporah B. Shore ◽

Jessy B. Ryan ◽

Michael B. Samuel

Keyword(s):

Graft Versus Host Disease ◽

Oral Solution ◽

High Dose ◽

Medical Cannabis ◽

Host Disease ◽

Graft Versus Host ◽

Post Transplant ◽

Gvhd Prophylaxis ◽

Graft Vs Host Disease ◽

Anti Inflammatory

Cannabis sativa contains numerous cannabinoids, with D9-tetrahydrocannabinol (THC) and cannabidiol (CBD) the primary cannabinoids of medical interest. Both THC and CBD possess potent anti-inflammatory and immunosuppressive properties, but THC has significant psychoactive properties. In a phase 2 study of CBD plus standard GVHD prophylaxis,, Yeshrun et al found low rates of grade II - IV acute GVHD, and compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II - IV acute GVHD was .3 (P =.0002)1. Also, Kalytera Therapeutics announced promising results in a Phase 2a study evaluating the safety and efficacy of CBD, for the treatment of acute Grade III-IV GVHD, including 9/ 10 responses, of which 7 were complete remission (CR)2. We report a case of steroid refractory eczematous GVHD successfully treated with a CBD-predominant medical cannabis product. A 35 year old woman with T-cell Acute Lymphoblastic Leukemia (T-ALL) was treated on an MSKCC pediatric -inspired ALL protocol. She developed CNS involvement during induction therapy treated with intrathecal therapy with persistent CNS disease. She then received salvage therapy with HyperCVAD part B with high dose methotrexate, high dose cytarabine, with CR and underwent matched related donor (sister) stem cell transplant conditioned with Etoposide, TBI 1200 cGy. GvHD prophylaxis was Alemtuzumab, Tacrolimus. She developed a rash on day 126 post transplant involving face and scalp which spread to chest and back and within 1 week involved 100% of BSA with itching, facial and orbital swelling, ankle/feet swelling. Skin biopsy revealed an eczematous variant of GvHD which is considered to be very aggressive, difficult to control with immunosuppression3, and carries a poor prognosis. Phototherapy and steroid ointment was initiated with initial benefit and regression of rash but then rash and edema returned within 6 months. Ruxolitinib was given on expanded access protocol with no benefit. Systemic steroids were again initiated at 1 mg/kg/ day with minimal benefit. Insurance denied tociluzumab. Extracorporeal photopheresis was started with only minimal response and eventually ibrutinib was initiated. With steroids, photopheresis and ibrutinib she had marginal response but ongoing severe skin GvHD. She had numerous infectious complications including soft tissue skin infections requiring multiple admissions. At 16 months post transplant, the patient began a medical cannabis product manufactured by VIREO HEALTH, consisting of a high CBD:THC ratio (19:1) oral solution containing CBD 47.5mg/ml and THC 2.5mg/ml. A daily dose of 6 ml provided 285 mg CBD and 15mg THC daily comparable to the 300 mg CBD product in the Kalytera product. Toxicity was sleepiness; thus the patient took the dose in the evening. There was a definite response within 3 months, allowing discontinuation of ibrutinib and photopheresis. By 2 years post transplant, her skin issues had resolved with only mild itching and flakiness. She remains on this product at a dose of 6 ml daily. This case adds to the developing evidence regarding the potential anti- inflammatory and immunosuppressive effects of medical cannabis and its activity for the treatment of active GVHD. Both THC and CBD are anti-inflammatory via CB2 receptors and THC inhibits T-lymphocyte expansion in a murine BMT model.1 The THC component may have contributed therapeutic benefit but also explains the toxicity and was dose limiting. Further studies are warranted to explore the role of medical cannabis, the optimal dose of CBD and THC, in the prevention and management of GVHD. 1 Yeshurun, Moshe, et al. "Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study." Biology of Blood and Marrow Transplantation, vol. 21, no. 10, 2015, pp. 1770-1775., doi:10.1016/j.bbmt.2015.05.018. 2. Kalytera Therapeutics Announces Encouraging Results of a Phase 2a Clinical Study for the Treatment of Acute Graft versus Host Disease. Source: Kalytera Therapeutics, Inc.VANCOUVER, British Columbia, Feb. 22, 2017 (GLOBE NEWSWIRE) 3. Creamer D, Martyn-Simmons CL, Osborne G, et al. Eczematoid Graft-vs-Host Disease: A Novel Form of Chronic Cutaneous Graft-vs-Host Disease and Its Response to Psoralen-UV-A Therapy. Arch Dermatol.2007;143(9):1157-1162. doi:10.1001/archderm.143.9.1157 Figure Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: This is a medical cannabis product manufactured by VIREO HEALTH, consisting of a high CBD:THC ratio (19:1) oral solution containing CBD 47.5mg/ml and THC 2.5mg/ml. The drug was used to treat refractory graft versus host disease.

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Intra-Arterial Catheter Directed Immunosuppressive Therapy for Steroid Resistant or Dependent Graft vs. Host Disease (GVHD).

Blood ◽

10.1182/blood.v110.11.4960.4960 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4960-4960

Author(s):

Michael Y. Shapira ◽

Allan I. Bloom ◽

Reuven Or ◽

Igor B. Resnick ◽

Memet Aker ◽

...

Keyword(s):

Partial Response ◽

Median Time ◽

Steroid Therapy ◽

Local Therapy ◽

Complete Response ◽

Arterial Catheter ◽

High Dose ◽

Steroid Resistant ◽

Host Disease ◽

Graft Vs Host Disease

Abstract Introduction: Prolonged treatment of graft vs. host disease (GVHD) is extremely immunosuppressive. Local therapy with intra-arterial (IA) injection of steroids may induce remission with lower extent of systemic immune suppression. Here, we present our experience with IA treatment of gastrointestinal (GI) and/or hepatic steroid resistant/dependent GVHD with 2 consecutive protocols. Patients and methods: Thirty five patients (37 GVHD events (hepatic, n=15), (GI, n=16), (combined, n=6)) were treated with 53 IA sessions. Most side effects were minor. Results: We found that IA steroid therapy was associated with partial and complete remission among patients with steroid resistant/dependent hepatic or GI GVHD. Hepatic partial response was observed in 14 (66.6%) patients among whom 7 (33.3%) reached complete response. GI partial response was observed in 19 (86.4%) patients among whom 12 (54.4%) reached complete response. Early administration of the local therapy, female gender, myeloid basic disease, and a non-active status of the basic disease at the day of transplantation were found related for predicting a better response for the intra-arterial treatment. The use of high dose steroids in the hepatic IA protocol from was at least as good as intermediate dose steroids with methotrexate (table 1, figure 1) and may be safer. Conclusions: Intra-arterial catheter guided steroid therapy is safe and effective in steroid resistant/dependent GVHD. Hepatic artery treatment with methotrexate can be safely substituted with high dose IA methylprednisolone. Further research is warranted characterizing the patients benefit most. Table 1 - comparison between 1st and 2nd hepatic IA treatment protocols 1st protocol 2nd protocol Significance Median age (range) 25 years (7–42) 32 years (18–59) P=0.09 Sex (M:F) 6:1 8:5 NS family donor vs MUD 6:1 9:4 NS Median time in days SCT-GVHD (range) 27 (13–133) 45 (13–248) NS Median time in days GVHD-IA (range) 15 (6–218) 190 (12–2615) P=0.09 Median peak GVHD grade (range) 3 (3–4) 3 (2–4) NS Highest pre-IA treatment bilirubin level (in mmol/L; normal<17) (range) 186 (138–321) 225.5 (83–672) NS Median time to initial response in days (range) 14.5 (4–100) 8 (1–31) P=0.073 Median time to complete response in days (range) 130.5 (35–226) 49 (17–80) Figure 1A, Figure 1B Figure 1A, Figure 1B.

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Constrictive pericarditis

The ESC Textbook of Cardiovascular Imaging ◽

10.1093/med/9780198703341.003.0038 ◽

2015 ◽

pp. 520-535

Author(s):

Jérôme Garot ◽

Frank Rademakers

Keyword(s):

Differential Diagnosis ◽

Constrictive Pericarditis ◽

Clinical Findings ◽

Respiratory Cycle ◽

Atrial Pressure ◽

Pericardial Disease ◽

Multiple Modalities ◽

Pericardial Syndromes ◽

Very High ◽

Pericardial Thickening

The diagnosis of constrictive pericarditis (CP) generally requires both the demonstration of an appropriate physiology and evidence of pericardial thickening. Differential diagnosis in pericardial disease remains difficult and challenging to the clinician. The pathophysiologic characteristics of the various pericardial syndromes can be studied with different imaging modalities, but it is crucial to register morphology, function and flow during the different phases of the respiratory cycle. When a discrepancy exists between clinical findings and hemodynamic evaluation with imaging, multiple modalities should be combined and, if a very low or very high atrial pressure is suspected, an intervention to increase or lower this pressure can be required to unmask characteristic findings during respiration with respect to ventricular interdependence.

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Calcified pericardial band at the level of right ventricle causing midventricular obstruction: a case report of constrictive pericarditis

Journal of College of Medical Sciences-Nepal ◽

10.3126/jcmsn.v7i4.6813 ◽

2012 ◽

Vol 7 (4) ◽

pp. 58-62

Author(s):

MP Gautam ◽

D Sharma ◽

G Subramanyam ◽

S Gautam ◽

U Ghimire

Keyword(s):

Constrictive Pericarditis ◽

Young Female ◽

Medical Sciences ◽

Pericardial Disease ◽

Management Journal ◽

Antituberculous Treatment ◽

Atrioventricular Groove ◽

The Right ◽

Pericardial Thickening ◽

Midventricular Obstruction

Constrictive pericarditis is a debilitating but potentially curable disease. Diffuse pericardial thickening and calcification is a classic feature described; localized pericardial constrictions are very rare. Here we report a case of a young female who had presented with constrictive pericarditis and had localized calcific constrictive band located at the level distal to atrioventricular groove which had caused right midventricular obstruction. In many patients the cause of the pericardial disease is undetermined, and in them an asymptomatic or forgotten bout of viral or tubercular pericarditis, acute or idiopathic, may have been the inciting event. Our patient had pulmonary tuberculosis during childhood and received antituberculous treatment. Investigations revealed the presence of thickened pericardium and a thickened calcific constrictive band around the right ventricles at midventricle level causing midventricular obstruction. She was referred to another centre for further surgical management. Journal of College of Medical Sciences-Nepal,2011,Vol-7,No-4, 58-62 DOI: http://dx.doi.org/10.3126/jcmsn.v7i4.6813

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Cost-Benefit Analysis of Primary Prophylaxis with Granulocyte Colony Stimulating Factor (GCSF) in Reducing Hospital Admissions with Febrile Neutropenia in Patients Undergoing High Dose Chemotherapy for Non-Hodgkin Lymphoma (NHL).

Blood ◽

10.1182/blood.v114.22.4764.4764 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4764-4764

Author(s):

Sophie Lee ◽

Hilary Blacklock ◽

Samar Issa

Keyword(s):

Febrile Neutropenia ◽

Hospital Admissions ◽

Cost Benefit Analysis ◽

Cost Benefit ◽

Cost Effective ◽

Primary Prophylaxis ◽

High Dose Chemotherapy ◽

High Dose ◽

Benefit Analysis ◽

Non Hodgkin Lymphoma

Abstract Abstract 4764 Introduction High dose chemotherapy for lymphoma is known to be associated with significant risk of febrile neutropenia (FN), especially in elderly patients. FN is a major dose-limiting toxicity of high dose chemotherapy and can lead to delay in treatment. In addition, FN also causes significant patient morbidity and has an adverse impact on quality of life. Although a meta-analysis of 12 randomised trials with Hodgkin disease(HD) and non-Hodgkin lymphoma (NHL) patients has shown that prophylactic GCSF significantly reduces the relative risk of FN (Bohlius J, et al: Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database of Systematic Reviews CD003189, 2004), it is not known whether primary prophylaxis is also cost-effective. Since December 2007, we implemented guidelines in our haematology department for the use of primary GCSF prophylaxis in patients age >65 years undergoing high dose chemotherapy treatment for NHL. We studied the impact on the incidence of FN as well as cost-effectiveness of this approach. Patients and Methods A cohort of 62 patients who underwent high dose chemotherapy for NHL from December 2006 to May 2009 was identified. Patient demographics, type of lymphoma, chemotherapy regimen, details of GCSF prophylaxis, hospital admissions due to FN, and outcome of treatment at last follow up were recorded. Cost-benefit analysis was carried out using the actual cost of hospital admissions and numbers needed to treat (NNT). Chi-square test was used to calculate p-value. Results GCSF was given in a dose of 300 mcg subcutaneously daily, for an average of 7 days. The median age of the cohort was 63 years (IQR 54, 70). Fifty three patients received CHOP based regimen. Forty one patients had diffuse large B cell lymphoma. Overall, patients who received primary GCSF therapy had significantly less FN compared to those who did not [8% vs 56%, p<0.0001, absolute risk reduction (ARR) 48% (95% confidence interval(C.I.) 25% to 66%) with NNT of 2 (95% C.I. 2 to 4)]. In subgroup analysis, even patients aged '65 years appeared to receive benefit from primary GCSF prophylaxis in reduction of FN [4.8% vs 66.7%, p=0.005, ARR 62%(95% C.I. 34%-90%), NNT 2(95% C.I. 1-3)]. In patients who underwent CHOP-based chemotherapy, the benefit of primary GCSF prophylaxis appeared to be greater compared to the cohort [11% vs 68%, p<0.0001, ARR 58%(C.I. 30%-76%) with NNT of 2 (95% C.I. 1-3) – table 1. There was no difference in treatment outcomes such as achieving at least PR or CR, and no difference in mortality, either from disease or all cause combined, during the study period. The average cost of hospital admission with FN was calculated to be NZD$6753.31. Using the NNT value obtained, primary GCSF prophylaxis appeared to be cost effective, leading to saving of $1991.22 per patient. Conclusion Our study shows that primary GCSF prophylaxis is effective in preventing FN in patients undergoing high dose chemotherapy and that it is highly cost-effective; hence primary GCSF prophylaxis is recommended in this patient group. Disclosures: No relevant conflicts of interest to declare.

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Constrictive pericarditis after high-dose chemotherapy

The Lancet ◽

10.1016/s0140-6736(05)64017-2 ◽

1997 ◽

Vol 350 (9091) ◽

pp. 1601 ◽

Cited By ~ 11

Author(s):

JE Tulleken ◽

CGHM Kooiman ◽

TS van der Werf ◽

JG Zijlstra ◽

EGE de Vries

Keyword(s):

Constrictive Pericarditis ◽

High Dose Chemotherapy ◽

High Dose

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Phase I trial of cyclosporine-induced autologous graft-versus-host disease in patients with multiple myeloma undergoing high-dose chemotherapy with autologous stem-cell rescue.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.2.667 ◽

1997 ◽

Vol 15 (2) ◽

pp. 667-673 ◽

Cited By ~ 30

Author(s):

S Giralt ◽

D Weber ◽

M Colome ◽

M Dimopoulos ◽

R Mehra ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Graft Versus Host Disease ◽

Clinical Signs ◽

High Dose Chemotherapy ◽

High Dose ◽

Host Disease ◽

Graft Versus Host ◽

Autologous Graft ◽

Level Group

PURPOSE To determine the feasibility and toxicity of inducing autologous graft-versus-host disease (GVHD) with cyclosporine in patients with multiple myeloma undergoing autologous stem-cell transplantation. PATIENTS AND METHODS Fourteen multiple myeloma patients with a median age of 50 years (range, 41 to 63) were enrolled. The median time from diagnosis to transplant was 651 days (range, 229 to 3,353). Ten patients had primary refractory disease, two were in first remission, and two were responsive to salvage therapy. The preparative regimen consisted of thiotepa, busulfan, and cyclophosphamide. Cyclosporine was administered daily for 28 days after the stem-cell infusion, and the dose was adjusted to maintain whole-blood cyclosporine levels between 50 and 150 ng/dL in the first seven patients (low-level group) and between 150 and 300 ng/dL in the other seven patients (high-level group). RESULTS All patients achieved neutrophil engraftment a median of 11 days after transplant. Four patients developed > or = grade 2 hepatic toxicity, six developed > or = grade 2 nephrotoxicity, and four developed reversible cardiac toxicity. Only one treatment-related death occurred. Cyclosporine was withheld in seven patients for a median of 6 days because of renal and/or liver dysfunction. One patient developed clinical skin GVHD, which responded to corticosteroid therapy. Six patients developed histologic evidence of GVHD without clinical signs of GVHD (subclinical GVHD). The incidence of clinical and subclinical GVHD was similar in both cyclosporine groups. Three of 11 patients assessable for response achieved remissions. Three patients experienced disease progression 80, 160, and 354 days after transplant. Ten patients are alive without progression between 56 and 444 days after transplant. CONCLUSION Induction of autologous GVHD by posttransplant cyclosporine is feasible and well tolerated in patients with multiple myeloma.

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