High CD34-positive cell dose in matched unrelated donor allogeneic hematopoietic stem cell transplant is not associated with graft-versus-host disease or mortality.

BACKGROUND: CD34+ stem cells serve as the primary graft source for allogeneic transplants, with a minimum of 2-4 × 106 cells/kg needed for engraftment. There are conflicting data on outcomes at high stem cell doses, with studies limited by few patients receiving doses far above the minimum target. STUDY DESIGN AND METHODS: In this retrospective, single-center study of patients with hematologic malignancies who underwent matched unrelated donor transplants, we assessed outcomes for engraftment, survival, relapse, and graft-versus-host disease (GVHD) for the highest CD34+ dose quintile (>13 × 106 cells/kg, n = 36) compared to the remaining patients (n = 139). Similar analysis was performed correlating T cell dose and outcomes. RESULTS: There was no difference between the groups in neutrophil engraftment, with a trend toward faster platelet engraftment. There was no significant difference in mortality (adjusted risk ratio [aRR] = 1.02, 95% confidence interval [CI] = 0.85-1.22), relapse (aRR = 1.10, 95% CI = 0.85-1.42), or overall survival by Kaplan-Meier analysis (p = .44). High CD34+ dose was not associated with higher incidence of acute GVHD (aRR = 0.99 grades II-IV, aRR = 1.18 grades III-IV) or chronic GVHD (aRR = 0.87 overall, RR = 1.21 severe). There was limited correlation between CD34+ and T cell dose (R2 = .073), and there was no significant difference in survival, relapse, or GVHD in the highest T cell dose quintile (n = 33) compared to the remaining quintiles (n = 132). DISCUSSION: We found no difference in survival, relapse, or GVHD incidence or severity in patients receiving CD34+ doses above prior cutoffs reported in the literature. These data do not support the routine use of graft CD34+ dose reduction.

Interventional antibiotic treatment replacing antibiotic prophylaxis during allogeneic hematopoietic stem cell transplantation is safe and leads to a reduction of antibiotic administration.

Patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) face an elevated risk of infection-related mortality, particularly during the pre-engraftment period. Although systemic antibiotic prophylaxis (SAP) is commonly employed during neutropenia, it is linked to disruptions in the intestinal microbiome, increasing the risk of graft-versus-host disease (GVHD), Clostridium difficile infection (CDI), and colonization with multi-drug resistant (MDR) bacteria. In our retrospective analysis, we evaluated the safety and efficacy of an exclusively interventional antibiotic treatment (IAT) compared to SAP in adult alloHSCT patients. In comparison to SAP, IAT resulted in a significantly reduced duration of antibiotic therapy (24 vs. 18 days, p < 0.001), although the cumulative incidence (CI) of bloodstream infections (BSI) by day + 100 post-HSCT was significantly higher in the IAT group compared to SAP (40% vs. 13%, p < 0.001). However, this did not lead to a significant increase in ICU transfers (13% vs. 6%, p = ns) or a higher CI of non-relapse mortality (NRM) at 3 years (11% vs. 10%, p = ns). With a median follow-up of 1052 days, the 3-year overall survival (OS) rates were 69% and 66% for the SAP and IAT cohorts, respectively (p = ns). The CI of acute GVHD grade II-IV (30% vs. 39%) at 100 days or chronic GVHD of any grade (50% vs. 45%) at 3 years did not differ significantly between the SAP and IAT groups. There was a tendency towards a higher CI of severe chronic GVHD in the SAP cohort (28% vs. 13%, p = 0.08). Our single center experience in conducting alloHSCT without antibiotic prophylaxis but with stringent guidelines for prompt antibiotic intervention demonstrated no disadvantages in terms of OS and NRM. IAT led to significantly reduced consumption of cefotaxime, carbapenem, and glycopeptide antibiotics. In conclusion, our findings suggest that replacing SAP with the proposed IAT procedure is both safe and feasible.

Graft Versus Host Disease: Management Issues in the Intensive Care Unit.

Graft versus host disease (GVHD) in acute and chronic forms is a frequent post-transplant complication and seen in 50% of patients in acute and up to 70% cases in chronic GVHD setting. Patients with multiorgan involvement and those who are steroid refractory, frequently present with complications arising from this post-transplant complication. These GVHD patients are frequently managed in the Intensive care unit for treatment of air leaks, effusions, management of hypoxemia due to lung GVHD or infections. Close coordination between hematologists and Pulmonary medicine specialists is critical for timely management of these complications to improve patient outcomes.

The Onset of Puberty Presents Unique Management Issues in Penile Chronic Graft-versus-Host Disease Requiring Circumcision in Male Pediatric Patients.

Chronic GvHD of the penile tract in male pediatric patients has not been described well in the literature and is often under-diagnosed. We report three cases of penile chronic GvHD in adolescent male patients who received HSCT before the onset of puberty. Their penile cGvHD became symptomatic upon the onset of penile growth associated with puberty in combination with the fibrotic changes in the foreskin. Symptoms did not respond to systemic chronic GvHD medication but require circumcision for alleviation of symptoms. This case series highlights the need for frequent monitoring of the prepubertal pediatric HSCT patient who has the presence of sclerotic cGvHD and enters puberty. This population is particularly reluctant to allow a thorough examination of the genitalia. In addition, optimization of systemic and topical immunosuppression treatment for patients with chronic GvHD of the penile tract potentially with the introduction of novel agents that target the tissue repair and fibrosis pathway is needed to prevent circumcision as the only option in the future.

[Pathogenesis and novel therapies for chronic GVHD].

Treatment for chronic graft-versus-host disease, the most important long-term complication of allogeneic hematopoietic cell transplantation, has changed significantly over the past decade. Development of novel targeted therapies has advanced as objective criteria for the diagnosis and evaluation of chronic GVHD have been established and understanding of the biological pathways to pathogenesis has increased. This paradigm shift is driving chronic GVHD practice significantly toward individualized therapy while minimizing exposure to steroids. Treatment using a variety of novel agents, tailored to each individual patient's condition, is expected to improve quality of life and overall survival by preventing chronic GVHD, controlling disease progression, and maintaining motor and occupational functions. This article reviews the pathogenesis of chronic GVHD and discusses prospects for the treatment of chronic GVHD, along with recently approved drugs and promising drugs in development.

Pre-transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft-versus-host disease.

The role of the gastrointestinal microbiome in predisposing to chronic graft-versus-host disease (cGVHD), an immune-mediated haematopoietic cell transplant (HCT) complication, is not well defined. We examined the relationship of the host faecal microbiome with subsequent cGVHD development by analysing baseline stool samples as well as post-HCT changes in microbiome composition and metabolite pathway analyses. We analysed pre-transplant baseline samples from 11 patients who subsequently developed cGVHD compared to 13 controls who did not develop acute GVHD or cGVHD at any time. We found a significant differential abundance of multiple taxa at baseline between cGVHD versus controls, including the Actinobacteria phylum and Clostridium genus. A subgroup analysis of longitudinal samples within each patient revealed a greater loss of alpha diversity from baseline to post-engraftment in patients who subsequently developed cGVHD. Metabolic pathways analysis revealed that two pathways associated with short-chain fatty acid metabolism were enriched in cGVHD patient microbiomes: ß-oxidation and acyl-CoA synthesis, and γ-aminobutyrate shunt. In contrast, a tryptophan catabolism pathway was enriched in controls. Our findings show a distinct pattern of baseline microbiome and metabolic capacity that may play a role in modulating alloreactivity in patients developing cGVHD. These findings support the therapeutic potential of microbiome manipulation for cGVHD prevention.

CSF-1R inhibitor PLX3397 attenuates peripheral and brain chronic GVHD and improves functional outcomes in mice.

Graft-versus-host disease (GVHD) is a serious complication of otherwise curative allogeneic haematopoietic stem cell transplants. Chronic GVHD induces pathological changes in peripheral organs as well as the brain and is a frequent cause of late morbidity and death after bone-marrow transplantation. In the periphery, bone-marrow-derived macrophages are key drivers of pathology, but recent evidence suggests that these cells also infiltrate into cGVHD-affected brains. Microglia are also persistently activated in the cGVHD-affected brain. To understand the involvement of these myeloid cell populations in the development and/or progression of cGVHD pathology, we here utilized the blood-brain-barrier permeable colony stimulating factor-1 receptor (CSF-1R) inhibitor PLX3397 (pexidartinib) at varying doses to pharmacologically deplete both cell types. We demonstrate that PLX3397 treatment during the development of cGVHD (i.e., 30 days post-transplant) improves disease symptoms, reducing both the clinical scores and histopathology of multiple cGVHD target organs, including the sequestration of T cells in cGVHD-affected skin tissue. Cognitive impairments associated with cGVHD and neuroinflammation were also attenuated by PLX3397 treatment. PLX3397 treatment prior to the onset of cGVHD (i.e., immediately post-transplant) did not change in clinical scores or histopathology. Overall, our data demonstrate significant benefits of using PLX3397 for the treatment of cGVHD and associated organ pathologies in both the periphery and brain, highlighting the therapeutic potential of pexidartinib for this condition.

Low incidence of severe acute and chronic graft-versus-host disease in a long-term retrospective study with ATG Grafalon routine use.

Since 2006, combined graft-versus-host disease (GVHD) prophylaxis with ATG Grafalon has been our department's base of peri-transplant supportive care. This recent retrospective study included 398 patients who underwent their first allogeneic hematopoietic stem cell transplantation after receiving a defined dose of ATG Grafalon. Our observations recorded reduced incidence of severe acute and chronic GVHD without negative impact on overall survival in a nonselected group with standard and uniform GVHD prophylaxis.

The oral histopathological and immunological characteristics of a xenogeneic mouse chronic graft-versus-host disease model.

BACKGROUND: Oral lesions are important clinical manifestations of chronic graft-verse-host disease (cGVHD). However, the oral characteristics of cGVHD mouse model are not yet clear. This study aims to demonstrate oral histopathological and immunological characteristics of a xenogeneic cGVHD mouse model. MATERIALS AND METHODS: 2.5 × 106 , 5.0 × 106 , 7.5 × 106 , and 10.0 × 106  human peripheral blood mononuclear cells (hPBMCs) were intravenously transplanted into NCG mice to induce cGVHD. After transplantation, clinical observations were recorded. Tissue samples from salivary glands and oral mucosa were stained with H&E, Masson Trichrome, and immunofluorescence, and the histopathology of oral tissues was scored according to our modified criteria. RESULTS: NCG mice showed signs of cGVHD onset after transplantation. The oral histopathological lesion incidences in each group were 37.50%, 50.00%, 62.50%, and 75.00%, respectively. Oral histopathological lesion incidence and histopathological scores were positively correlated with the amount of infused hPBMCs. Epithelial atrophy, epithelial cells vacuolar degeneration, and basal cells liquefaction denaturation were observed in oral mucosa, and acinar destruction and collagen deposition were observed in the salivary glands. Human CD45+ , CD4+ , CD8+ , IL-17+ , and FoxP3+ cells infiltrated into oral tissues. In the 5.0 × 106  hPBMCs group, oral histopathological changes mainly began between days 30 and 45 post-transplantation, and became more severe after day 45. The oral histopathological scores also gradually increased. CONCLUSION: Inflammation in oral mucosa epithelium and salivary glands, and CD4+ and CD8+ T cells dominating infiltration are the main oral features in the xenogeneic cGVHD mouse model. The severity of oral histopathological lesions shows a dose and time correlation. These may be helpful to oral cGVHD research.

How does transfusion-associated graft-versus-host disease compare to hematopoietic cell transplantation-associated graft-versus-host disease?

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare life-threatening complication of blood transfusion caused by donor T cells that escape rejection by the recipient immune system. These donor T cells drive recipient tissue damage in response to host antigens. On the other hand, GVHD occurring after allogeneic hematopoietic cell transplantation (HCT-GVHD) is also caused by donor T cells, but its pathophysiology is more complex and differs due to the effects of tissue damage caused by pre-HCT conditioning and profound immunosuppression. Both TA-GVHD and HCT-GVHD can be fatal; however, mortality is higher with TA-GVHD due to the paucity of treatment options. Here, we compare and summarize the presentation, diagnosis, pathophysiology, prevention, and treatment of TA-GVHD and HCT-GVHD.

Early reconstitution of lymphocytes after allogenic hematopoietic stem cell transplantation affects chronic graft-versus-host disease.

BACKGROUND: Lymphocyte reconstitution after hematopoietic stem cell transplantation (HSCT) is important for the prevention of infections, as well as for the reduction of recurrence, by its graft versus tumor effect. However, these lymphocytes may also play a role in the development of graft-versus-host disease (GVHD). Few studies have investigated the association between lymphocyte reconstitution and clinical outcomes after HSCT. METHODS: This issue was investigated by retrospectively analyzing pediatric patients who received their first allogeneic-HSCT using a newly developed parameter, the LD-index, which evaluates both the intensity and duration of lymphopenia. A total of 101 patients underwent allo-HSCT from April 2007 to August 2019 in our hospital. Excluding patients who died before lymphocyte recovery or underwent multiple HSCT, 78 patients were analyzed for associations between the LD-index with various factors relating to HSCT. RESULTS: A significantly high association was observed between a low LD-index and the incidence of chronic GVHD (P = 0.0019). Analysis of predictive factors for chronic GVHD was carried out using univariate analysis. Lower LD-index, donor source and duration of lymphopenia were found to be significant factors associated with chronic GVHD. Multivariate analysis, however, only identified an association between a lower LD-index and an increased incidence of chronic GVHD (P = 0.00081). CONCLUSIONS: Early reconstitution of lymphocytes after allo-HSCT is associated with a higher incidence of chronic GVHD.

Graft-versus-host disease in the female genital tract: a prospective cohort study.

BACKGROUND: Graft-versus-host disease (GVHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD in the female genital tract can cause sinusorrhagia, dyspareunia, synechia, and even complete vagina occlusion. PURPOSE: This prospective study aimed to evaluate the clinical characteristics and effects of preventive and prompt treatment for genital GVHD in females undergoing HSCT (n = 40). RESULTS: Genital GVHD was diagnosed in 11 of 40 patients (27.5%), and the most common complaint was vaginal dryness (54.6%). The majority of patients (63.6%) presented mild genital GVHD (clinical score 1), with interlabial fissures and lichen-like lesions, while a minority of patients (9.1%) presented advanced genital GVHD (clinical score 3) with the fusion of the small and large lips. The median time of onset of genital GVHD signs was 10 months after HSCT, concomitant with GVHD in the skin and oral cavity. Personalized and topical therapy was effective in most cases (81.8%), and no patient required surgical intervention. CONCLUSION: We confirmed that female genital GVHD affects approximately one-third of females undergoing HSCT, highlighting the importance of periodic gynecological monitoring for early detection and treatment to improve care for these females.

Thymic stromal lymphopoietin levels after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an immunoregulatory, Th2-polarizing cytokine produced by epithelial cells. We hypothesized that TSLP affects immune reconstitution after hematopoietic stem cell transplantation (HSCT) leading to increased alloreactivity. METHODS: We measured plasma TSLP by ELISA in 38 patients and assessed the immune reconstitution by flow cytometry. RESULTS: TSLP levels rose after initiation of the conditioning to peak at day +21 after HSCT (p = .03), where TSLP levels correlated with counts of neutrophils (rho = 0.36, p = .04), monocytes (rho = 0.58, p = .006), and lymphocytes (rho = 0.59, p = .02). Overall absolute TSLP levels were not associated with acute or chronic graft-vs-host disease (a/cGvHD). However, patients mounting a sustained increase in TSLP levels at day +90 had a higher risk of cGvHD compared to patients who had returned to pre-conditioning levels at that stage (cumulative incidence: 77% vs. 38%, p = .01). CONCLUSION: In conclusion, this study suggests a role of TSLP in immune reconstitution and alloreactivity post-HSCT. lymphopoietin (TSLP) is an immunoregulatory, Th2-polarizing cytokine produced by epithelial cells. We hypothesized that TSLP affects immune reconstitution after hematopoietic stem cell transplantation (HSCT) leading to increased alloreactivity. We measured plasma TSLP by ELISA in 38 patients and assessed the immune reconstitution by flow cytometry.

Thalidomide as treatment of crohn-like disease occurred after allogeneic hematopoietic stem cell transplantation in a pediatric patient.

BACKGROUND: Autoimmune diseases may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and inflammatory bowel disease (IBD or Crohn disease) is rarely described. We describe a child who developed CD after allo-HSCT, successfully treated with thalidomide. CASE REPORT: A child affected by mucopolysaccharidosis type I received two allogeneic HSCTs for rejection after the first one. After cutaneous and intestinal chronic GvHD and 6 months after HSCT, the patients developed a trilinear autoimmune cytopenia successfully treated with rituximab and sirolimus. Due to persisting intestinal symptoms, colonoscopies were performed and histological findings demonstrated a picture of CD. Based on this observation and according to the recommendations for the treatment of CD, thalidomide was started. A complete stable clinical response was obtained 8 weeks after start of thalidomide. Colonoscopy performed 4.8 years later demonstrated a complete endoscopic and histological remission of CD. DISCUSSION: In this case, the diagnosis of CD after HSCT was based on histological findings. Indeed, repeated colonscopies were necessary for diagnosis, since both clinical and endoscopic features are often common to chronic GvHD and CD. Thalidomide was started at the dose of 1.7 mg/Kg/day, and it was well tolerated. Mild peripheral neurotoxicity occurred 5 years later but disappeared completely with the dose reduction. Currently, the patient is in complete remission from CD, despite the discontinuation of all the immunosuppressive therapies. CONCLUSIONS: Thalidomide could represent a therapeutic option to treat CD as autoimmune disease after allogeneic HSCT.

Oral white lesion in patients post-hematopoietic stem cell transplantation: a case series demonstrating the diagnostic dilemma.

The current National Institutes of Health (NIH) consensus paper excluded "white hyperkeratotic plaque" from the diagnostic criteria for oral chronic graft-versus-host disease (cGVHD) in order to ensure malignant transformation is not overlooked. Therefore, an isolated oral white plaque is recommended to be subjected to biopsy and pathologic examination. The cases described in this paper shed a new light on the clinical approach to oral white plaque post-hematopoietic stem cell transplantation. The objectives of this article are to demonstrate that a white plaque does not contradict a diagnosis of oral cGVHD, and to highlight the clinical considerations for taking a biopsy.

Development of iron deficiency anemia in patients undergoing extracorporeal photopheresis: Comparison of the UVAR and CELLEX instruments.

INTRODUCTION: Extracorporeal photopheresis (ECP) is a procedure used to influence T-cell activity in patients suffering from immune-mediated cellular damage secondary to activated lymphocytes. Although well-tolerated, iron deficiency anemia (IDA) has been described. The goal herein is to describe IDA in patients who received extracorporeal photopheresis (ECP) treatment using UVAR (Therakos Inc) and CELLEX (Therakos Inc) instruments. DESIGN AND METHODS: Patients treated with ECP from 2015 to 2019 were retrospectively analyzed. IDA was defined by a decrease in hemoglobin following treatment with concomitant decrease in mean cell volume, mean corpuscular hemoglobin concentration, increased RBC distribution width, and/or iron studies compatible with IDA. RESULTS: During the four-year study period, thirty-four patients received ECP. Thirteen (38%) underwent treatment with the previous UVAR device while 21 (62%) received treatment on the newer CELLEX instrument. Nineteen (56%) of the cohort developed clinical and laboratory evidence of IDA with an average of 3.2 g/dL decrease in hemoglobin. Patients who developed IDA treated on the CELLEX instrument experienced a significantly greater drop in hemoglobin (P = .04) than those treated on the UVAR. Examining the CELLEX-treated patients, those who received the procedure at greater frequency experienced significantly greater drops in hemoglobin (P = .03). CONCLUSIONS: IDA is a risk of chronic ECP therapy and is likely secondary to retained blood components in the instrument. The temporal relationship between anemia and ECP treatment has a direct correlation with the treatment schedule. Patients undergoing ECP treatment should be closely monitored for the development of IDA.

Disability Related to Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) is a heterogenous syndrome whose symptoms and treatment are often associated with decreases in functional status and quality of life among survivors of transplantation. We explored definitions of cGVHD-related disability and factors associated with disability in cGVHD. We analyzed 371 patients with cGVHD requiring a new systemic therapy with enrollment and 18-month assessments through the Chronic GVHD Consortium, evaluating disability as a composite endpoint including any 1 of 5 impairments previously defined by Fatobene et al [1] (score 2 or 3 keratoconjunctivitis sicca, score 2 or 3 scleroderma, any diagnosis of bronchiolitis obliterans, score 2 or 3 joint/fasciae involvement, or score 3 esophageal stricture requiring dilation). We also evaluated disability, defined as an ≥8-point decline in a human activity profile (HAP) score or a ≥20% decline in Karnofsky Performance Status (KPS) from enrollment to 18 months. At enrollment, 47% of patients had at least 1 of the 5 Flowers disability features, with 50% of this group acquiring additional impairments at 18 months. Of the 197 patients (53%) with no Flowers disability at enrollment, 50% progressed with disability features at 18 months. We found that any progressive Flowers impairment was associated with a decline in HAP/KPS as well as with increased National Institutes of Health severity scores at 18 months. Enrollment mouth scores and patient-reported eye and skin scores were significantly associated with progressive impairment at 18 months. Progressive disability at 18 months did not predict subsequent nonrelapse mortality. Additional studies to define chronic GVHD related-disability and risk factors are needed to develop this important patient-centered outcome.

A Prospective, Longitudinal Observation of the Incidence, Treatment, and Survival of Late Acute and Chronic Graft-versus-Host Disease by National Institutes of Health Criteria in a Japanese Cohort.

To prospectively validate the incidence, manifestations, and outcomes of graft-versus-host disease (GVHD) by National Institutes of Health criteria, we recruited 406 hematopoietic stem cell transplantation recipients at 16 transplant centers in Japan from May 2012 to June 2014. The 2-year cumulative incidence of late acute and chronic GVHD was 3.2% (n = 13) and 35.4% (n = 145), with a median onset of 3.6 and 4.7 months after transplant, respectively. The global severity at onset was mild in 30.3%, moderate in 43.5%, and severe in 26.2%. Eighty-two patients were followed up for 2 years, with 79.3% still manifesting GVHD symptoms, and 80.6% (n = 117) of the patients received systemic immunosuppressive treatment (IST), with a 2-year cumulative incidence of IST termination of 33.1%. Severe patients showed a significantly lower rate of IST termination than those with mild and moderate severities (mild, 38.5%; moderate, 40.9%; and severe, 17.2%). The 2-year incidence of nonrelapse mortality (NRM) and relapse was not significantly different according to the severity at onset (NRM: mild [16.6%] versus moderate [8.7%] versus severe [16.1%]; relapse: mild [14.9%] versus moderate [14.7%] versus severe [5.3%]). As a result, 2-year overall survival (OS) and GVHD-specific survival (GSS) were equivalent according to the severity at onset (mild: OS = 81.0%, GSS = 85.7%; moderate: OS = 84.2%, GSS = 92.5%; severe: OS = 83.9%, GSS = 89.2%). Our study helped identify the characteristics of late acute and chronic GVHD in Japanese patients. Further investigation is needed to identify an optimal endpoint for survival prediction.

The impact of donor full-length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT.

BACKGROUND: Killer Ig-like receptor 2DS4 (KIR2DS4) is the most prevalent activating killer Ig-like receptor gene. It is divergent and encodes either full-length or deleted allele variants. The studies of donor killer KIR2DS4 in unrelated allogeneic hematopoietic stem cell transplantations were limited. METHODS: KIR and HLA genotyping were determined in 75 pairs of Chinese pediatric hematologic malignancy patients. RESULTS: Among the 75 donor-recipient pairs, 77.3% (58/75) of the donors were positive for full-length KIR2DS4 and 22.7% (17/75) were negative. Patients who had donors positive for full-length KIR2DS4 had higher cumulative incidence of aGVHD than patients whose donor negative for full-length KIR2DS4 (86.2% versus 76.5%, P = .038). Multivariate analysis showed full-length KIR2DS4 was the significant factor for I-IV aGVHD (HR = 2.166, 95% CI: 1.01-4.26, P = .025). Subgroup analysis showed that AML and CML patients who received donors negative for full-length KIR2DS4 have a higher cumulative incidences of cGVHD (75% vs 62%, P = .008). There were no significant effects of full-length KIR2DS4 on overall survival (P = .13), relapse-free survival (P = .14), CMV reactivation (P = .52), and relapse (HR = 0.38, 95% CI: 0.09-1.6, P = .1875). CONCLUSIONS: Our findings indicated a significant correlation of donor full-length KIR2DS4 on aGVHD and cGVHD. These results suggested that combining KIR and HLA genotyping may help make a better sense of transplants in these patients.

Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval, .388 to .673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost.