Involvement of ocular surface in graft-versus-host disease: An update from immunopathogenesis to treatment.

Graft-versus-host disease is a common complication of hematopoietic stem cell transplantation and the ocular surface is a main target of inflammatory reaction.

Engraftment Syndrome and Acute Graft-versus-Host Disease: A Meta-Analysis.

Engraftment syndrome (ES) has been associated with the surge of neutrophils and cytokines, which is similar to the presumed underlying pathophysiology behind acute graft-versus-host disease (aGVHD). However, there has been no meta-analysis to evaluate the association; therefore, the team attempted to verify an association between ES and aGVHD through meta-analysis. The team searched for titles of articles in MEDLINE (PubMed), the Cochrane Library, and the EMBASE database up until December 2018 that evaluated the association between ES and aGVHD and conducted a random effect meta-analysis of 8 studies involving a total of 1,945 participants to report the pooled odds ratio (OR) for association of ES and aGVHD. The team found a significantly increased odds of developing aGVHD in patients with ES with the pooled OR of 2.76 (95% confidence interval [CI]: 1.64-4.63) and an I2= 64.5%. In conclusion, patients with ES have significantly higher odds of developing aGVHD compared to patients without ES.

Kinetics and Risk Factors of Relapse after Allogeneic Stem Cell Transplantation in Children with Leukemia: A Long-Term Follow-Up Single-Center Study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment for high-risk hematological malignancies in the pediatric population, but relapse remains the leading cause of death. We analyzed risk factors associated with relapse. Data from 353 allo-HSCTs from 1989 to 2015 in our center were studied retrospectively. We performed a multivariate analysis of pre- and postransplantation variables and developed a predictive risk score for relapse using the significant factors in this training cohort. The results were confirmed in a validation cohort of 90 allo-HSCTs done in our institution from 2016 to the present. A total of 104 patients relapsed after allo-HSCT, with a relapse cumulative incidence of 31 ± 2%. In multivariate analysis, only 2 variables influenced relapse: disease phase (advanced versus early, HR, 2.84; 95% CI, 1.76 to 4.57; P = .001) and presence of chronic graft-versus-host disease (GVHD) (acute GVHD versus chronic GVHD [HR, 4.27; 95% CI, 1.99 to 9.15; P = .0001] and no GVHD versus chronic GVHD [HR, 6.86; 95% CI, 3.63 to 12.97] P = .0001]. Applying the personalized risk score (0 to 3), the relapse cumulative incidence was 70 ± 5% in patients with a score of 3 (without GVHD and in the advanced phase) compared with 6 ± 4% in patients with a score of 0 (with chronic GVHD and in an early phase). This score has been verified in the validation set. With a median follow-up of 54 months, the disease-free survival (DFS) and overall survival rate were 37 ± 3% and 45 ± 4%, respectively. The association of GVHD with the graft-versus-leukemia effect is clearly established in our study, and the form of GVHD associated with less relapse and the best DFS is the classical form of chronic GVHD according to the National Institutes of Health classification. The proposed relapse risk score was validated in an independent cohort and allows personalization of the prognosis.

Impact of the 2014 NIH chronic graft-versus-host disease scoring criteria modifications assessed in a large cohort of severely affected patients.

In 2005, the National Institutes of Health (NIH) chronic graft-versus-host disease (cGVHD) consensus project provided diagnosis and staging criteria, based mostly on clinical experience and expert opinion. These criteria were revised in 2014, aiming to provide enhanced specificity and clarity. However, the impact of 2014 changes to the original NIH cGVHD severity scoring criteria has not been reported. In this study, 284 patients, prospectively enrolled on the National Cancer Institute's cross-sectional cGVHD natural history study, were scored using the 2005 NIH cGVHD criteria and then rescored according to the 2014 modifications. In comparing the two criteria, 2014 cGVHD global severity scoring resulted in a tendency toward being categorized as milder scores (75 vs. 72% of severe score per 2014, p = 0.0009), with a statistically significant shift in NIH liver and lung scores toward milder categories (p < 0.0001). 2005 and 2014 NIH global severity scores showed a significant association with reduced grip strength (p < 0.0001), reduced joint range of motion (p = 0.0003), and the subspecialist evaluation score (p < 0.0001). Poor survival prediction of the severe NIH lung score is also retained in the new criteria (p = 0.0012). These findings support the use of 2014 cGVHD scoring criteria in continuous efforts to develop better classification systems.

[Harmonization of data coding in post-transplant follow-up - "GVHD, complications and additional treatments": Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Harmonisation du codage des données difficiles du post-greffe « GVHD, complications et traitements additionnels ¼ : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

The quality of the information provided in post-transplant follow-up is necessary to obtain a coherent and exploitable database. Since the beginning of 2017, three forms (Med-B-allograft) have been available: the first month (Day 0), Day 100 (second report) and an annual follow-up report. Recommendations for follow-up were addressed in the 2014 harmonization workshop, "Harmonization of Data Coding…". However, it is sometimes difficult to determine which data to specify in ProMISe for post-transplantation. The objective of this workshop was to clarify certain situations and/or items.

Simple, Reproducible, and Efficient Clinical Grading System for Murine Models of Acute Graft-versus-Host Disease.

Acute graft-versus-host disease (aGVHD) represents a challenging complication after allogeneic hematopoietic stem cell transplantation. Despite the intensive preclinical research in the field of prevention and treatment of aGVHD, and the presence of a well-established clinical grading system to evaluate human aGVHD, such a valid tool is still lacking for the evaluation of murine aGVHD. Indeed, several scoring systems have been reported, but none of them has been properly evaluated and they all share some limitations: they incompletely reflect the disease, rely on severity stages that are distinguished by subjective assessment of clinical criteria and are not easy to discriminate, which could render evaluation more time consuming, and their reproducibility among different experimenters is uncertain. Consequently, clinical murine aGVHD description is often based merely on animal weight loss and mortality. Here, we propose a simple scoring system of aGVHD relying on the binary (yes or no) evaluation of five important visual parameters that reflect the complexity of the disease without the need to sacrifice the mice. We show that this scoring system is consistent with the gold standard histological staging of aGVHD across several donor/recipient mice combinations. This system is also a strong predictor of survival of recipient mice when used early after transplant and is highly reproducible between experimenters.

[Cutaneous graft-versus-host disease]. / Kutane Graft-versus-Host-Erkrankung.

BACKGROUND: Graft-versus-host disease (GvHD) is a complex multiorgan disease, which can occur as a complication following allogeneic stem cell transplantation. Involvement of the skin represents the most common appearance of GvHD. The role of the dermatologist is critical for diagnosis and initiation of treatment. OBJECTIVES: The aim of this article is to provide a comprehensive review of the cutaneous types of GvHD and to present the most recent data on diverse therapy options for its acute and chronic form allowing the clinician to establish a definite diagnosis and to initiate proper therapy. MATERIALS AND METHODS: Possible clinical appearances and recommended criteria to assist in making the right diagnosis are presented by means of expert recommendations. RESULTS AND CONCLUSION: GvHD is still a complex entity whose diagnosis is often associated with challenges due to its variable presentation. Proper diagnosis and subsequent therapy is paramount for the optimal clinical outcome.

Validation of International Chronic Ocular Graft-Versus-Host Disease (GVHD) Group Diagnostic Criteria as a Chronic Ocular GVHD-Specific Metric.

PURPOSE: To validate the International Chronic Ocular GVHD Consensus Group (ICCGVHD) diagnostic criteria for chronic ocular chronic graft-versus-host disease (GVHD), by comparing results with comprehensive ophthalmic evaluation after allogeneic hematopoietic stem cell transplantation. METHODS: A single-institution retrospective chart review was conducted on patients who underwent hematopoietic stem cell transplantation at Vanderbilt University Medical Center in Nashville, TN, from January 1, 2002, through April 17, 2014. A total of 344 patients were eligible for the study. Data collected include the Schirmer test score, corneal fluorescein staining, Ocular Surface Disease Index, conjunctival injection, and presence or absence of systemic GVHD. The diagnosis of chronic ocular GVHD in each participant and determination of the overall severity score were determined based on the newly proposed ICCGVHD diagnostic criteria and compared with the best clinical practice (BCP) score. RESULTS: Chronic ocular GVHD was diagnosed in 141/344 (41%) participants, of these, 86 (61%) had complete charts. Based on the BCP score, 1.2% had none, 38.4% mild, 47.7% moderate, and 12.8% had severe chronic ocular GVHD. Based on the ICCGVHD, 34.8% had none, 59.3% mild/moderate, and 5.8% had severe chronic ocular GVHD. The clinical diagnostic stages of chronic ocular GVHD by BCP and ICCGVHD criteria had slight agreement (kappa statistic 0.187, with 95% confidence interval 0.049-0.321), with a higher correlation seen in those with severe chronic ocular GVHD. CONCLUSIONS: The newly proposed ICCGVHD diagnostic criteria can be used reproducibly for the diagnosis and determination of severity of chronic ocular GVHD. However, larger prospective studies are needed to further validate it.

Classification systems for chronic graft-versus-host disease.

Chronic graft versus host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Clinically, chronic GVHD is a pleiotropic, multiorgan syndrome involving tissue inflammation and fibrosis that often results in permanent organ dysfunction. Chronic GVHD is fundamentally caused by replacement of the host's immune system with donor cells, although the heterogeneity of clinical manifestations suggests that patient, donor, and transplant factors modulate the phenotype. The diagnosis of chronic GVHD and determination of treatment response largely rely on clinical examination and patient interview. The 2005 and 2014 National Institutes of Health Consensus Development Projects on Criteria for Clinical Trials in Chronic GVHD standardized the terminology around chronic GVHD classification systems to ensure that a common language and procedures are being used in clinical research. This review provides a summary of these recommendations and illustrates how they are being used in clinical research and the potential for their use in clinical care.

Acute and chronic Graft-versus-host disease after hematopoietic stem cell transplantation.

graft-versus-host disease (GVHD) is one of the main complications of hematopoietic stem cell transplantation, affecting about 50% to 80% of the patients. Acute GVHD and its clinical manifestations are discussed in this article, as well as the new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both chronic and acute GVHD is an important field of discussion, as there is no proven superiority for the majority of therapies used after primary treatment has failed. Hence, this review is meant to be a useful consultation tool for hematologists dealing with this complex transplantation procedure complication.

Acute and chronic Graft-versus-host disease after hematopoietic stem cell transplantation / Doença do enxerto contra o hospedeiro aguda e crônica após transplante de células-tronco hematopoiéticas

ABSTRACT graft-versus-host disease (GVHD) is one of the main complications of hematopoietic stem cell transplantation, affecting about 50% to 80% of the patients. Acute GVHD and its clinical manifestations are discussed in this article, as well as the new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both chronic and acute GVHD is an important field of discussion, as there is no proven superiority for the majority of therapies used after primary treatment has failed. Hence, this review is meant to be a useful consultation tool for hematologists dealing with this complex transplantation procedure complication.

RESUMO A doença do enxerto contra hospedeiro (DECH) é uma das principais complicações do transplante de células-tronco Hematopoéticas, acometendo cerca de 50% a 80% dos pacientes. A DECH aguda e suas manifestações clínicas são discutidas neste artigo, bem como a classificação revisada do NIH para diagnóstico e classificação da DECH crônica. A terapêutica para DECH aguda e crônica é um importante campo de discussão uma vez que não há superioridade comprovada para a maioria das terapêuticas utilizadas após o tratamento primário. Assim, esta revisão pretende ser instrumento de consulta para hematologistas transplantadores que lidam com esta complexa complicação do procedimento.

Prognostic factors for survival of patients with newly diagnosed chronic GVHD according to NIH criteria.

Chronic graft versus host disease (cGvHD) is the most common cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated the impact of NIH classification on outcome of patients at our center. Primary endpoint was overall survival at 5 years. Two hundred one patients with cGVHD according to NIH were included. Platelets <100,000/µl on day of diagnosis of cGvHD (HR 2.97, 95 % CI 1.7-5.3, p < 0.001), female donor (HR 1.78, 95 % CI 1.0-3.2, p = 0.05), and reduced intensity conditioning (HR 1.95, 95 % CI 1.0-3.8, p = 0.05) impacted overall survival. Non-relapse mortality (NRM) was higher for patients with low vs. high platelets: 26 % (95 % CI 14-40) vs. 6 % (95 % CI 2-10), p < 0.001, and tended to be higher for female vs. male donor: 14 % (95 % CI 7-23) vs. 7 % (95 % CI 3-13), p = 0.08. Relapse tended to be higher for recipients of reduced intensity conditioning (RIC) vs. myeloablative conditioning (MAC): 33 % (95 % CI 23-43) vs. 20 % (95 % CI 10-31), p = 0.06. After excluding patients with myeloma and lymphoma, IgG serum levels at diagnosis of cGvHD of 122 patients were correlated with survival. IgG levels above normal were associated with worse 2-year overall survival (OS), p = 0.04, compared to normal or low IgG levels. Platelet count at diagnosis remains the most valid prognostic factor for survival of patients with cGvHD even in the era of NIH grading. High IgG level at diagnosis of cGVHD represents a potential negative prognostic parameter that deserves further investigation.

Correlation Between Tear Film Osmolarity and the Disease Score of the International Chronic Ocular Graft-Versus-Host-Disease Consensus Group in Hematopoietic Stem Cell Transplantation Patients.

PURPOSE: To evaluate tear film osmolarity (TFO) as a diagnostic tool for detecting chronic ocular graft-versus-host disease (GVHD) in patients after hematopoietic stem cell transplantation and to assess its correlation with the new international chronic ocular GVHD score. METHODS: A group of 204 consecutive patients who underwent hematopoietic stem cell transplantation at University Hospital Wuerzburg in Germany received an ophthalmologic examination after transplantation. TFO was measured and the chronic ocular GVHD score was calculated based on the Schirmer test, corneal fluorescein staining, conjunctival injection, Ocular Surface Disease Index questionnaire, and presence of systemic GVHD. RESULTS: A total of 172 patients showed no chronic ocular GVHD. Of the remaining 32 patients using the international chronic ocular GVHD score, 21 were classified as "probably" and 11 as "definite" chronic ocular GVHD. TFO was positively correlated with the new chronic ocular GVHD score (P < 0.01, r = 0.35). TFO differed significantly between patients with no ocular GVHD (300 ± 16.5 mOsm/L) and definite ocular GVHD (337 ± 36 mOsm/L)-a receiver operating characteristic analysis showed high discrimination capability (area under the curve: 0.91 ± 0.04) and suggested a threshold level of the TFO value of 312 mOsm/L yielding a sensitivity of 91% and a specificity of 82%. CONCLUSIONS: TFO can be used for detecting chronic ocular GVHD with high sensitivity and specificity as a noninvasive objective test in addition to traditional dry eye tests. It correlates positively with the diagnostic criteria of a recently established international consensus score for diagnosing the disease.

Changes in circulating endothelial cells count could become a valuable tool in the diagnostic definition of acute graft-versus-host disease.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is burdened by life-threatening complications, with graft-versus-host disease (GvHD) being the major cause of morbility and mortality. Recently, clinical and physiopathologic evidences showed that vascular endothelium can be a target of GvHD in the early phase and circulating endothelial cells (CECs) represent surrogate markers of endothelial damage. METHODS: Using the CellSearch System (Veridex LLC, Raritan, NJ), CECs were counted before (T1), after conditioning regimen (T2), at engraftment (T3), at GvHD onset (T4), and after steroid treatment (T5) in 40 patients (7 Hodgkin's Disease, 13 Acute Myeloblastic Leukemia, 5 Acute Lymphoblastic Leukemia, 8 Multiple Myeloma, 3 Chronic Lymphocytic Leukemia, 1 Non-Hodgkin Lymphoma, 1 Chronic Myeloid Leukemia, 2 Severe Aplastic Anemia) undergoing allo-HSCT. RESULTS: The median CEC per milliliter at T1 was 20 (n=33, range 4-718), in comparison to a value of 2 (range, 1-14) in controls (P<0.001). At T3, CEC per milliliter were 47 (range, 16-148) in GvHD patients and 92 (range, 23-276) in patients without GvHD (P=0.006). This difference remained significant in multivariate analysis (odds ratio, 0.97; 95% confidence interval, 0.96-0.99; P=0.02). At GvHD onset, the relative increase of CEC counts from time of engraftment (T4 vs. T3) was 44% (range, -43% to 569%) in GvHD patients versus 0% (range, -49% to 2%) in patients without GvHD (P=0.003), being confirmed as significant in multivariate analysis (odds ratio, 1.04; 95% confidence interval, 1.0-1.08; P=0.04). CONCLUSION: Changes in CEC count can represent a promising marker to monitor endothelial damage in patients undergoing allo-HSCT and could become a valuable tool in the diagnostic definition of GvHD.

Histopathologic diagnosis of chronic graft-versus-host disease of the oral mucosa according to the National Institutes of Health Consensus.

OBJECTIVE: To validate the minimal criteria of the histopathologic diagnosis of oral chronic graft-versus-host disease, based on the histopathologic classification of the National Institutes of Health and correlate them with clinical features. METHODS: Forty-one specimens containing both oral mucosa and salivary glands were analyzed in slides stained with hematoxylin-eosin. The histological specimens were blindly examined by two trained pathologists using criteria recommended for the histopathologic diagnosis of chronic graft-versus-host disease proposed by the National Institutes of Health Consensus. The clinical classification of chronic graft-versus-host disease was correlated with analysis of slides. RESULTS: Our data showed that the epithelium was involved in 39/41 specimens, presenting acanthosis (29/70.7%), exocytosis of lymphocytes (29/70.7%), thickening of basal lamina (29/70.7%), and apoptosis (15/36.6%). Connective tissue presented interstitial inflammatory infiltrate (38/92.7%). Minor salivary glands showed periductal fibrosis (38/92.7%), mixed periductal inflammatory infiltrate (32/78%), ductal ectasia (30/73.2%), lymphocytes around and into acinar units (30/73.2%), and interstitial fibrosis (29/70.7%). The most common clinical manifestations were lichenoid aspect (40/97.6%), complaints of sensitivity to oral feeding (38/92.7%), and dry mouth sensation (36/87.8%). CONCLUSION: This study validated the National Institutes of Health Consensus of minimal histologic criteria for diagnosis of oral chronic graft-versus-host disease and has not found an association between the severity of clinical manifestation and the histopathological stage.

Histopathologic diagnosis of chronic graft-versus-host disease of the oral mucosa according to the National Institutes of Health Consensus / Diagnóstico histopatológico da doença do enxerto contra hospedeiro crônica da mucosa oral conforme Consenso do National Institutes of Health

Objective To validate the minimal criteria of the histopathologic diagnosis of oral chronic graft-versus-host disease, based on the histopathologic classification of the National Institutes of Health and correlate them with clinical features. Methods Forty-one specimens containing both oral mucosa and salivary glands were analyzed in slides stained with hematoxylin-eosin. The histological specimens were blindly examined by two trained pathologists using criteria recommended for the histopathologic diagnosis of chronic graft-versus-host disease proposed by the National Institutes of Health Consensus. The clinical classification of chronic graft-versus-host disease was correlated with analysis of slides. Results: Our data showed that the epithelium was involved in 39/41 specimens, presenting acanthosis (29/70.7%), exocytosis of lymphocytes (29/70.7%), thickening of basal lamina (29/70.7%), and apoptosis (15/36.6%). Connective tissue presented interstitial inflammatory infiltrate (38/92.7%). Minor salivary glands showed periductal fibrosis (38/92.7%), mixed periductal inflammatory infiltrate (32/78%), ductal ectasia (30/73.2%), lymphocytes around and into acinar units (30/73.2%), and interstitial fibrosis (29/70.7%). The most common clinical manifestations were lichenoid aspect (40/97.6%), complaints of sensitivity to oral feeding (38/92.7%), and dry mouth sensation (36/87.8%). Conclusion This study validated the National Institutes of Health Consensus of minimal histologic criteria for diagnosis of oral chronic graft-versus-host disease and has not found an association between the severity of clinical manifestation and the histopathological stage. .

Objetivo Validar os critérios mínimos de diagnóstico histopatológico da doença do enxerto contra hospedeiro crônica oral, com base em critérios de classificação do National Institutes of Health, e correlacioná-los com as características clínicas. Métodos Quarenta e um espécimes contendo mucosa oral e glândulas salivares foram analisados em lâminas coradas por hematoxilina-eosina. Os espécimes histológicos foram avaliados de forma cega, por dois patologistas calibrados, utilizando os critérios recomendados para diagnóstico histopatológico de doença do enxerto contra hospedeiro crônica propostos pelo Consenso do National Institutes of Health. A classificação clínica da doença do enxerto contra hospedeiro crônica foi correlacionada após a análise das lâminas. Resultados Nossos resultados mostraram que o epitélio estava comprometido em 39/41 espécimes, apresentando acantose (29/70,7%), exocitose de linfócitos (29/70,7%), espessamento da lâmina basal (29/70,7%) e apoptose (15/36,6%). O tecido conjuntivo apresentou infiltrado inflamatório intersticial em 38 (92,7%) casos. Nas glândulas salivares menores, observaram-se fibrose periductal (38/92,7%), infiltrado inflamatório periductal misto (32/78%), ectasia ductal (30/73,2%), linfócitos em torno e migrando para dentro dos ácinos (30/73,2%), e fibrose intersticial (29/70,7%). As manifestações clínicas mais comuns foram mucosa de aspecto liquenoide (40/97,6%), queixa de sensibilidade bucal ao se alimentar (38/92,7%), e sensação de boca seca (36/87,8%). Conclusão Os critérios mínimos para o diagnóstico histopatológico da doença do enxerto contra hospedeiro crônica oral, com base no Consenso do National Institutes of Health, foram ...

Acute graft-versus-host disease in a nonhematopoietic stem cell transplantation candidate treated with decitabine followed by granulocyte colony-stimulating factor-primed peripheral blood stem cells infusion: a special entity of the disease?

BACKGROUND: With a well-developed strategy of acute graft-versus-host disease (aGVHD) prophylaxis, the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients who develop aGVHD has improved considerably. Meanwhile, transfusion-associated GVHD (TA-GVHD) can be fatal. Recent advancements in immune cellular therapy are being adopted in clinical practice, although many concerns including TA-GVHD remain. This report describes a 64-year-old male non-HSCT candidate diagnosed with acute myeloid leukemia who had received decitabine followed by an infusion of granulocyte-colony-stimulating factor-primed peripheral blood stem cells (G-PBSCs) from his daughter, who carried haploidentical human leukocyte antigen. The patient developed aGVHD on the 20th day after infusion. STUDY DESIGN AND METHODS: This study is a single case report of a non-HSCT candidate who developed skin aGVHD with mild clinical course after decitabine and G-PBSCs combination. The clinical course, chimerism, and aGVHD pathology studies are detailed. RESULTS: Compared with conventional aGVHD in allo-HSCT recipients and TA-aGVHD, the presentation of this case followed a self-limited clinical course without marrow aplasia or severe progression. However, the patient eventually died of leukemia without a significant graft-versus-leukemia effect. CONCLUSION: First, the results demonstrate the existence of aGVHD in elderly non-HSCT candidates receiving adoptive cellular immune therapy. Second, aGVHD occurring under these conditions is probably a unique entity of aGVHD compared to TA-aGVHD and the conventional pattern in allo-HSCT recipients with respect to clinical course and prognosis.

Validation of NIH consensus criteria for diagnosis and severity-grading of chronic graft-versus-host disease.

To validate the National Institutes of Health (NIH) consensus criteria for chronic GVHD, we retrospectively reviewed 143 patients who developed GVHD later than 100 days after allogeneic hematopoietic stem cell transplantation. Their GVHD was reclassified and the severity was graded according to the criteria. Only four patients (2.8 %) could not be reclassified into any type of GVHD. In the remaining 139 patients, reclassified subtypes were late acute GVHD in 52 patients (37.4 %), classic chronic GVHD in 33 (23.7 %), and overlap syndrome in 54 (38.8 %). Of 87 patients with classic chronic GVHD or overlap syndrome, the severity was graded as mild in 21 patients (24 %), moderate in 53 (61 %), and severe in 13 (15 %). The proportions of moderate (70 %) and severe (20 %) disease were significantly higher in patients with overlap syndrome than those with classic chronic GVHD (46 and 6 %, respectively; P < 0.001). Univariate and multivariate analyses of subtypes and severity did not identify any significant prognostic values in any of the transplant outcomes, such as transplant-related mortality, overall survival, GVHD-specific survival, or discontinuation of systemic immunosuppressants. These findings suggest that the NIH consensus criteria are useful for classification of chronic GVHD, but have limited significance in predicting clinical outcomes. The validity of these criteria remains inconclusive, and future prospective studies will be required to refine them.

National Institutes of Health chronic graft-versus-host disease staging in severely affected patients: organ and global scoring correlate with established indicators of disease severity and prognosis.

Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD. Out of 189 patients enrolled, 125 met the criteria for severe cGVHD on the NIH global score, 62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned average NIH organ score and the corresponding organ scores assigned by subspecialists were highly correlated (r = 0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale, 2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung involvement affected function and quality of life most significantly and showed the greatest correlation with outcome measures. The final Cox model with factors jointly predictive for survival included the time from cGVHD diagnosis (>49 versus ≤49 months, hazard ratio [HR] = 0.23; P = .0011), absolute eosinophil count at the time of NIH evaluation (0-0.5 versus >0.5 cells/µL, HR = 3.95; P = .0006), and NIH lung score (3 versus 0-2, HR = 11.02; P < .0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH organ and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex subspecialist examinations. In this population of severely affected patients, NIH lung score is the strongest predictor of poor overall survival, both alone and after adjustment for other important factors.