Guidelines for the Standardization of Acute Graft-Versus-Host Disease Clinical Data Collection: An International Consensus Report

Abstract Clinical GVHD staging varies between centers and is not agreed upon by independent reviewers (Weisdorf, BBMT 2003). These inconsistencies help explain why promising GVHD treatments from single center studies have not reproduced in multicenter trials. To address this issue, our international GVHD research consortium has developed guidance that has been refined through consensus following case discussions, resulting in uniform and reproducible GVHD clinical symptom reporting. We record all raw target organ symptom data and apply staging based upon this data (Table 1). Only areas of erythema, bullae and desquamation are quantified because other skin changes are not typical of active GVHD rash. Upper GI symptoms must meet thresholds to diagnose GVHD: anorexia with associated weight loss, nausea and/or 2+ vomiting episodes/day lasting 3+ days. For lower GI GVHD we collect stool volumes excluding formed/mostly-formed stools. Unquantified episodes are counted at 200 ml per episode (3 ml/kg for children <50kg) based upon a chart review of 300 patients with post-BMT diarrhea from any cause. Non-GVHD rectal bleeding that results in flecks or streaks of blood in the stool are ignored for staging. We use the highest daily stool output in the 3 days prior to the diagnosis of lower GI GVHD to determine onset stage and, when available, a 3-day average stool volume for subsequent staging to smooth daily variability. We classify biopsy report interpretation into four standardized categories: Positive (unequivocal presence of GVHD), Equivocal (findings suggestive of GVHD, but the pathologist cannot confirm the diagnosis), Non-diagnostic (no abnormalities or subtle findings insufficient to determine etiology), and Non-GVHD etiology (definitive evidence of another diagnosis without concomitant features suggestive of GVHD). We then combine the biopsy interpretation with clinical decision making to assign an overall confidence level to the diagnosis of GVHD in each target organ (Table 2): Confirmed (positive biopsy, regardless of clinician treatment decision), Probable (GVHD diagnosis is sufficiently favored that treatment is given without a positive biopsy), Possible (symptoms present without a positive biopsy; not treated as GVHD), Negative (no symptoms or symptoms are present but a GVHD diagnosis is not entertained and a non-GVHD etiology is identified). Uniform clinical data collection is essential for future GVHD trials and requires application of clear guidance. While still subject to refinement, these guidelines, in use for 2 years by an international research consortium, are designed to be clear, easy to apply, and for clinical trial use. Table 1. GVHD Target Organ Staging Stage Skin (active erythema only) Liver (bilirubin) Upper GI Lower GI (stool output/day) 0 No active (erythematous) GVHD rash < 2 mg/dl No or intermittent nausea, vomiting or anorexia Adult: < 500 ml/day or <3 episodes/day Child: < 10 ml/kg/day or <4 episodes/day 1 Rash < 25% BSA 2-3 mg/dl Persistent nausea, vomiting or anorexia Adult: 500-999 ml/day or 3-4 episodes/day Child: 10 -19.9 ml/kg/day or 4-6 episodes/day 2 Rash 25 - 50% BSA 3.1-6 mg/dl - Adult: 1000-1500 ml/day or 5-7 episodes/day Child: 20 - 30 ml/kg/day or 7-10 episodes/day 3 Rash > 50% BSA 6.1-15 mg/dl - Adult: >1500 ml/day or >7 episodes/day Child: > 30 ml/kg/day or >10 episodes/day 4 Generalized rash (>50% BSA) and bullous formation or desquamation > 5% BSA >15 mg/dl - Severe abdominal pain with or without ileus, or grossly bloody stool (volume independent) Table 2. Confidence Levels Pathologic evidence Clinician assessment Treatment for acute GVHD Comments Confirmed Unequivocal evidence of GVHD GVHD is the etiology for symptoms Not required GVHD is clearly present even if other etiologies co-exist simultaneously Probable Not required (includes equivocal and non-diagnostic biopsies) GVHD most likely etiology for symptoms Yes GVHD is most likely present but other etiologies may also explain the symptoms and there insufficient evidence to make a confirmed diagnosis Possible GVHD in differential diagnosis (but no treatment is being provided) No GVHD may be present, but other etiologies are favored Negative Unequivocal evidence of a diagnosis other than GVHD (e.g., drug rash) GVHD is not considered as an explanation for the symptoms No and the symptoms resolve without GVHD treatment A "negative" biopsy (e.g., normal skin) is not unequivocal evidence of a diagnosis other than GVHD Disclosures Devine: Genzyme: Research Funding. Chen:Bayer: Consultancy, Research Funding. Porter:Novartis: Patents & Royalties, Research Funding. Levine:Novartis: Consultancy.

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Prognostic Factors and Outcomes of Severe Gastrointestinal Graft Versus Host Disease after Allogeneic Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood.v112.11.4341.4341 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4341-4341

Author(s):

Cristina Castilla-LLorente ◽

Richard A. Nash ◽

George B McDonald ◽

Barry E. Storer ◽

Paul J. Martin

Keyword(s):

Abdominal Pain ◽

Multivariable Analysis ◽

High Dose ◽

Upper Gi ◽

Gi Symptoms ◽

Days Of Therapy ◽

Stage 1 ◽

Dose Prednisone ◽

Steroid Refractory ◽

Stool Volume

Abstract Introduction: Treatment of severe GI GVHD poses a challenge, as little progress has been made in developing better treatments and survival remains poor. One problem is that it is difficult to know the ultimate severity of GVHD and the outcome at the onset of symptoms. We analyzed patients with peak stage 3–4 GI GVHD to identify factors within 2 weeks of the onset of GVHD that predicted the eventual outcome. This information could be useful in initial patient management and to inform the design of clinical trials. Patients and methods: We reviewed the records of 117 consecutive patients transplanted between 2000–2005 who developed stages 3–4 GI GVHD. Data were collected for more than 20 parameters, including stool volume, abdominal pain, melena, upper GI symptoms, serum albumin, number of GVHD treatments, visual findings at endoscopy and histopathologic grade of GI biopsies. Clinical parameters were measured as the peak value during each 14 day period starting from 2 weeks before the diagnosis of GI GVHD to the resolution of symptoms, loss of follow-up or patient death. Patients had been treated with myeloablative or reduced intensity conditioning regimens and received either marrow or growth factor-mobilized blood cells from related or unrelated HLA-matched donors. All patients received prophylactic pharmacologic immunosuppression for GVHD. Results: Median onset of symptoms was day 28 (range 4 – 113); 11 (9.6%) patients presented after day 80. Mean daily stool volume at diagnosis was 1494 ±1450 mL/day. At onset of GI symptoms, 75% of patients had ≥ stage 1 skin GVHD and 65% had ≥ stage 1 liver GVHD. At onset, 78% had upper GI symptoms (nausea and vomiting); less than 50% of patients presented with severe abdominal pain. Within the first 2 weeks after the diagnosis of GI GVHD, 52 (44.8%), 45 (38.7%), 7 (6.2%) and 12 (10.3%) patients had a peak GI stage of 4, 3, 2 and 1 respectively. All patients received high dose prednisone/prednisolone as initial treatment; 67 received 2nd line therapy; and 32 received three or more lines of treatment. Steroid refractoriness was defined as worsening GI symptoms after 3 days of high-dose steroid therapy, or non-response after 7 days, or only partial response after 14 days of therapy. Patients who developed stage 3 or 4 GI GVHD while receiving high dose prednisone for skin or liver GVHD were also considered steroid refractory. Non-relapse mortality was 71% and 41% at 1 year after transplant in patients with steroid-refractory and steroid-responsive GVHD, respectively. Overall survival was 30% at 1 year after HCT and 26% at 2 years. Thirteen patients relapsed, and all but 1 died subsequently. Adult patients who had steroid-refractory GVHD within 2 weeks of onset had a 1-year survival of 16% compared to 88% among steroid refractory pediatric patients. During the 14 day periods immediately before or after the onset of GI symptoms, these risk factors for overall mortality were identified by multivariable analysis: All patients, no endoscopy result considered (N=117) Factor Hazard Ratio p-value Adult age 3.2 .007 Jaundice (bilirubin >3.1 mg/dL) 1.97 .006 Albumin ≤1.6 g/dL 1.91 .01 Steroid refractory 1.76 .02 In a subgroup of patients who underwent endoscopy (N=73), a finding of ulcerated mucosa was predictive of mortality (HR 2.52, p=0.02). Conclusions: Within 2 weeks of GI symptom onset, mortality in patients with GVHD can be predicted by age, jaundice, hypoalbuminemia, response to prednisone, and presence of ulcerated mucosa at endoscopy. More effective early treatment in GI GVHD patients at risk for mortality is likely to be more useful than salvage therapy for steroid-refractory patients.

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Patient Perception of OxbrytaTM Treatment Benefit

Blood ◽

10.1182/blood-2020-143120 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 26-27

Author(s):

Modupe Idowu ◽

Anam Haque ◽

Elisa M. Williams

Keyword(s):

Sickle Cell Disease ◽

Data Collection ◽

Board Of Directors ◽

Clinical Improvement ◽

Sickle Cell ◽

Clinical Data ◽

Research Funding ◽

Substantial Improvement ◽

Cell Disease ◽

Advisory Committees

Background: Sickle cell disease (SCD) is an inherited disorder in which sickle hemoglobin (HbS) polymerization triggers red blood cell sickling, chronic hemolysis, anemia and episodic vaso-occlusion. Complications include cumulative organ damage and disability as well as accelerated mortality. OxbrytaTM is a first-in-class therapy that increases hemoglobin (Hb) levels and reduces markers of hemolysis and is FDA-approved for treatment of SCD in patients 12 years of age or older. We report here the single-center experience of patient-perceived benefit in 27 consecutive patients treated with OxbrytaTM tablets for at least 8 weeks. Methods: We collected clinical data on 27 consecutive patients with SCD at The University of Texas Comprehensive Sickle Cell Center under an approved data collection protocol for standard-of-care clinical data. All patients with at least 8 weeks of data collection are included. The Standing Data Collection Protocol was amended to allow collection of Patient Global Impression - Improvement scale (PGI-I) data. Four patients did not have complete laboratory and PGI-I data. Data analysis was done on 23 patients for whom there is information on Hb, retic %, CGI-I, and PGI-I. Seventeen of the patients had complete laboratory data while 23 patients provided PGI-I information. Laboratory test frequency was limited by COVID-19 pandemic restrictions. Results: Twenty-three patients whose data were analyzed ranged in age from 20 to 66 years, with 65 % being female. HbS genotypes were 91 % SS and 9 % Sβ°-thalassemia. No patient had Sβ+-thalassemia or hemoglobin SC. Table 1 shows the impact of OxbrytaTM on key laboratory parameters. The Hb improved with treatment to a degree comparable to that seen in the HOPE Trial. The healthcare provider assessed each patient for improvement with OxbrytaTM treatment using the 7-point Clinical Global Impression - Improvement scale (CGI-I). In addition, each patient provided an assessment of improvement with OxbrytaTM treatment using the 7-point PGI-I scale. Figure 1 shows the results of these assessments. Most patients report substantial improvement which correlates with the clinician impression. We noticed that for some of the patients who reported significant clinical improvement (very much better or much better symptoms) hemoglobin values declined or improved only slightly from baseline (Figure 2). Hence, Hb increase of > 1 g/dL is not needed for clinical improvement. About 30% of the patients reported mild to moderate diarrhea, that was managed with reduction in OxbrytaTM dose until diarrhea improved followed by titration back to recommended dose. For more severe diarrhea, OxbrytaTM was interrupted for 2 to 3 days followed by restart at a lower dose. Conclusions: This study is the first to utilize the 7-point PGI-I scale and CGI-I to assess SCD improvement with OxbrytaTM treatment. Figure 1 shows patient and clinician assessment of change in symptoms or clinical status with OxbrytaTM therapy. Most patients report substantial improvement, which correlates with the clinician impression. The majority of patients (16/23; 70%) reported much improved or very much improved symptoms while 22% reported minimally improved and only 8% reported no change in symptoms. The clinician impression correlated well with patients' impression of their improvement. Most of the responses, (19/23; 83%), were much improved and very much improved; whereas, 13% were minimally improved and 4% no change. Some patients also mentioned that their energy level improved significantly and that they had less pain at their typical sites of chronic pain while on OxbrytaTM therapy. In this study, patient hemoglobin values improved with treatment to a degree comparable to that seen in the HOPE Trial. Figure 2 shows that clinical improvement can occur for patients whose hemoglobin declined or improved only slightly from baseline. Our data collection is limited due to COVID-19 pandemic restrictions; most of the patients were unable to have laboratory assessments as frequently as desired. In summary, our study suggests that most sickle cell disease patients perceive benefit with OxbrytaTM therapy in terms of improvement in their condition and level of functioning. Disclosures Idowu: Cyclerion Therapeutics, Inc: Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Enterogastric Reflux: an Uncommon Diagnosis Analyzed by Hepatobiliary Imaging

Journal of Case Reports in Medicine ◽

10.25149/jcrm.v8i2.178 ◽

2019 ◽

Vol 8 (2) ◽

Author(s):

Peter Wang

Keyword(s):

Abdominal Pain ◽

Digestive Enzymes ◽

Gallbladder Disease ◽

Hepatobiliary Scintigraphy ◽

Hepatobiliary Imaging ◽

Upper Gi ◽

Gi Symptoms ◽

Upper Abdominal ◽

Enterogastric Reflux

Enterogastric reflux (EGR) is the reflux of bile and digestive enzymes from the small bowel into the stomach. While it is a normal physiologic process in small amounts, excessive reflux and chronic EGR can cause upper GI symptoms often mimicking more common diseases such as gallbladder disease and GERD that often leads to its underdiagnosis. Identifying EGR is significant as it has been associated with the development of gastroesophogeal pathology including gastritis, esophagitis, ulcers, and mucosal metaplasia. This article presents a 22-year-old male with enterogastric reflux causing upper abdominal pain and will discuss the role of hepatobiliary scintigraphy in its diagnosis.

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Experience of Coding Ambulatory Visits to Outpatient Clinics

Health Information Management ◽

10.1177/183335839602600314 ◽

1996 ◽

Vol 26 (3) ◽

pp. 141-144 ◽

Cited By ~ 1

Author(s):

K Gibson ◽

J Ives ◽

M Wilson ◽

D Richardson

Keyword(s):

Data Collection ◽

Clinical Data ◽

Discharge Summary ◽

Tertiary Hospital ◽

Outpatient Clinics

Clinical data for all current outpatients at a large tertiary hospital has been collected for analysis. Patient diagnoses for selected “key” clinics have been coded to ICD-9-CM standards. Methods to reduce the volume of coding required for such data collection are discussed, and include short-lists of codes, default assignment of diagnoses codes according to the nature of visit, and producing a “discharge” summary for outpatients, similar to that routinely produced for inpatients.

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Reliability and validity of a modified questionnaire of upper GI symptoms utilized in a disease management program of patients on chronic acid suppression

Gastroenterology ◽

10.1016/s0016-5085(03)82556-8 ◽

2003 ◽

Vol 124 (4) ◽

pp. A505

Author(s):

Braden Kuo ◽

Timothy Ferris

Keyword(s):

Disease Management ◽

Disease Management Program ◽

Reliability And Validity ◽

Management Program ◽

Acid Suppression ◽

Upper Gi ◽

Gi Symptoms

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The Early Identification of Beginning Stuttering I

American Journal of Speech-Language Pathology ◽

10.1044/1058-0360.0103.43 ◽

1992 ◽

Vol 1 (3) ◽

pp. 43-53 ◽

Cited By ~ 16

Author(s):

Pearl A. Gordon ◽

Harold L. Luper

Keyword(s):

Data Collection ◽

Young Children ◽

Clinical Data ◽

Early Identification ◽

Future Research ◽

Speech Language Pathologists ◽

Companion Article

Speech-language pathologists often struggle with the differentiation of stuttering from normal disfluencies in young children. Differential diagnostic protocols are frequently used to aid clinicians in this complex clinical task. In this article the general format and criteria, clinical data collection procedures, documentation, and relative use of quantification in six protocols are examined and discussed. In a forthcoming companion article, we will discuss problems encountered with the use of differential diagnostic protocols and offer suggestions for future research and the use of these protocols.

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Collecting clinical data in primary ciliary dyskinesia- challenges and opportunities

F1000Research ◽

10.12688/f1000research.9323.1 ◽

2016 ◽

Vol 5 ◽

pp. 2031 ◽

Cited By ~ 3

Author(s):

Israel Amirav ◽

Mary Roduta Roberts ◽

Huda Mussaffi ◽

Avigdor Mandelberg ◽

Yehudah Roth ◽

...

Keyword(s):

Data Collection ◽

Clinical Research ◽

Clinical Data ◽

Primary Ciliary Dyskinesia ◽

Completion Rates ◽

End User ◽

Revision Process ◽

Data Collection And Analysis ◽

Challenges And Opportunities ◽

Ciliary Dyskinesia

Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.

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