Allogeneic Human Mesenchymal Stem Cell Therapy (Remestemcel-L,Prochymal) as a Rescue Agent for Severe Refractory Acute Graft-versus-Host Disease in Pediatric Patients

Severe steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal stem cells (hMSCs) in pediatric patients with severe aGVHD resistant to multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile of remestemcel-L (Prochymal), a third-party, off-the-shelf source of hMSCs, as a rescue agent for treatment-resistant aGVHD in pediatric patients. Children with grade B-D aGVHD failing steroids and, in most cases, other immunosuppressive agents were eligible for enrollment. Patients received 8 biweekly i.v. infusions of 2 × 10⁶ hMSCs/kg for 4 weeks, with an additional 4 weekly infusions after day +28 for patients who achieved either a partial or mixed response. The enrolled patients compose a very challenging population with severe disease that was nonresponsive to the standard of care, with 88% of the patients experiencing severe aGVHD (grade C or D). Seventy-five patients (median age, 8 yr; 58.7% male; and 61.3% Caucasian) were treated in this study. Sixty-four patients (85.3%) had received an unrelated hematopoietic stem cell graft, and 28 patients (37.3%) had received a cord blood graft. At baseline, the distribution of aGVHD grades B, C, and D was 12.0%, 28.0%, and 60.0%, respectively. The median duration of aGVHD before enrollment was 30 d (range, 2 to 1639 d), and patients failed a median of 3 immunosuppressive agents. Organ involvement at baseline was 86.7% gastrointestinal, 54.7% skin, and 36.0% liver. Thirty-six patients (48.0%) had 2 organs involved, and 11 patients (14.7%) had all 3 organs involved. When stratified by aGVHD grade at baseline, the rate of overall response (complete and partial response) at day +28 was 66.7% for aGVHD grade B, 76.2% for grade C, and 53.3% for grade D. Overall response for individual organs at day +28 was 58.5% for the gastrointestinal system, 75.6% for skin, and 44.4% for liver. Collectively, overall response at day +28 for patients treated for severe refractory aGVHD was 61.3%, and this response was correlated with statistically significant improved survival at day +100 after hMSC infusion. Patients who responded to therapy by day +28 had a higher Kaplan-Meier estimated probability of 100-d survival compared with patients who did not respond (78.1% versus 31.0%; P < .001). Prochymal infusions were generally well tolerated, with no evidence of ectopic tissue formation.     

A meta-analysis of the use of typical antipsychotic agents in bipolar disorder.

BACKGROUND: The potential benefits of typical antipsychotic agents in bipolar disorder are offset by serious treatment-associated side effects. Despite these concerns and the availability of mood stabilizing agents, the treatment of bipolar disorder with typical antipsychotic agents appears to be widespread. METHODS: A Medline search identified 16 publications that outlined medication use among 2378 bipolar disorder patients. Meta-analysis was used to estimate a weighted average of the relative proportions of the treatment use, where the weights were the reciprocals of the estimated variances for each study. RESULTS: Overall, 84.7% of bipolar patients received typical antipsychotic agents, with a loading toward a greater in-patient (90.7%) relative to out-patient (65.3%) use. Monotherapy accounted for 53.8% of typical antipsychotic use, and typical antipsychotic/mood stabilizer combination therapy accounted for 47.4%. In four studies where length of treatment data were available, the median of minimum typical antipsychotic use was 2.5 months, with 96.0% of the patients receiving typical antipsychotic agents. LIMITATIONS: The meta-analytic technique employed in this analysis is limited by the possible inclusion of studies with unreliable study designs or biased treatment practices, publication bias in which some studies may not have been reported, and possible lack of identification of all relevant studies. CONCLUSIONS: Typical antipsychotic agents are commonly used in the treatment of bipolar disorder, possibly due to dissatisfaction with mood stabilizer monotherapy especially in psychotic mania, the high prevalence of psychotic symptoms in acute mania, inappropriate continuation of typical antipsychotic agents after initial stabilization, and/or unavailability or unfamiliarity with new treatments. These findings also suggest that typical antipsychotics may have not only antipsychotic effects in mania but perhaps also antimanic properties.     

Etanercept as Treatment of Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Patients

Corticosteroids are the standard of care for first-line treatment of patients who develop grade II-IV of acute graft-versus-host disease (aGVHD), but the optimal second-line treatment has not yet been determined. We prospectively evaluated the use of the anti-TNFα monoclonal antibody etanercept (ET) as second-line treatment in children with steroid-refractory (SR) aGVHD. Twenty-five children with either malignant or nonmalignant diseases experiencing grade II-IV SR aGVHD received ET as second-line treatment. ET was administered after a median of 14days (range, 5 to 135 days) from the onset of aGVHD. Seventeen out of 25 patients (68%) developed a complete response (CR) or partial response (PR) to ET. The overall response rate (CR plus PR) was 78% in patients with cutaneous SR aGVHD, 78% in those with gastrointestinal aGVHD, and 57% in those with hepatic aGVHD. On day +100 after the start of ET, 52% of the children were in CR, 16% were in PR, and the remaining 32% failed to respond. Overall survival was 76.5% in responders and 16.7% in nonresponders (P?=?.004). Transplantation-related mortality at 5years was 34.1% (95% confidence interval, 18.6% to 57.1%). In our experience, ET has proven to be effective as second-line treatment in children with SR aGVHD.     

Treatment of inflammatory myopathy: emerging therapies and therapeutic targets

Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy and myositis-associated interstitial lung disease. Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. First-line conventional immunosuppressive drugs include either methotrexate or azathioprine, and when they fail, more aggressive therapy includes mycophenolate mofetil, tacrolimus or cyclosporine, intravenous immunoglobulin, rituximab, or cyclophosphamide, used alone or in various combinations. Further investigations are required to assess the role of more novel therapies in the treatment of myositis and myositis-associated interstitial lung disease.     

Alemtuzumab for Severe Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease

Acute graft-versus-host disease (aGVHD) still remains the main cause of morbidity and mortality after allogeneic stem cell transplantation. Moreover, patients who did not respond to first-line treatment with glucocorticosteroids have a very poor outcome. Some studies suggested that alemtuzumab (a humanized monoclonal antibody against the CD52 antigen) might be effective for treatment of refractory aGVHD. Here we report a single-center experience with alemtuzumab in refractory gastrointestinal aGVHD. From September 2009 to April 2012 at the Grenoble medical university center, 24 patients who had presented a refractory gastrointestinal aGVHD to corticosteroid, or after another immunosuppressive drug, were retrospectively analyzed. Most patients (n = 19) presented stage 4 gastrointestinal aGVHD. Response to treatment (either complete or partial) was observed in 15 patients (62.4%). The overall survival rate at 1 year for all patients was 33.3% (95% confidence interval [CI], 15.9% to 51.9%) and for responders, 53.3% (95% CI, 26.3% to 74.4%). Two patients died from infection, 5 patients from recurrent GVHD, and 1 from an uncontrolled post-transplant lymphoproliferative disorder.     

Transcriptomic studies in tolerance: Lessons learned and the path forward

Immunosuppression after solid organ transplantation is a delicate balance of the immune response and is a complex phenomenon with many factors involved. Despite advances in the care of patients receiving organ transplants the adverse effects associated with immunosuppressive agents and the risks of long-term immunosuppression present a series of challenges and the need to weigh the risks and benefits of either over or under-immunosuppression. Ideally, if all transplant recipients could develop donor-specific immunological tolerance, it could drastically improve long-term graft survival without the need for immunosuppressive agents. In the absence of this ideal situation, the next best approach would be to develop tools to determine the adequacy of immunosuppression in each patient, in a manner that would individualize or personalize therapy. Despite current genomics-based studies of tolerance biomarkers in transplantation there are currently, no clinically validated tools to safely increase or decrease the level of IS that is beneficial to the patient. However, the successful identification of biomarkers and/or mechanisms of tolerance that have implications on long-term graft survival and outcomes depend on proper integration of study design, experimental protocols, and data-driven hypotheses. The objective of this article is to first, discuss the progress made on genomic biomarkers of immunological tolerance and the future avenues for the development of such biomarkers specifically in kidney transplantation. Secondly, we provide a set of guiding principles and identify the pitfalls, advantages, and drawbacks of studies that generate genomic data aimed at understanding transplant tolerance that is applicable to all solid transplants.     

Current Practice in Diagnosis and Treatment of Acute Graft-versus-Host Disease: Results from a Survey among German-Austrian-Swiss Hematopoietic Stem Cell Transplant Centers

To assess current clinical practice in diagnosis and treatment of acute graft-versus-host disease (aGVHD), we performed a survey among German, Austrian, and Swiss allogeneic hematopoietic stem cell transplantation (allo-HSCT) centers. Thirty-four of 72 contacted centers (47%) completed both the diagnostic and therapeutic sections of the survey, representing 65% of allo-HSCT activity within the participating countries in 2011. Three pediatric centers answered as requested only the diagnostic part of the survey. In the presence of diarrhea and decreased oral intake after engraftment, only 4 centers (12%) do not perform any endoscopy before the start of immunosuppressive treatment. In case of a skin rash with the differential diagnosis of drug reaction, only 12 centers (35%) perform a skin biopsy up front, whereas 19 do so after failure of systemic steroids. In the presence of rapidly increasing cholestasis occurring without any other signs of aGVHD, 11 centers (32%) perform a liver biopsy up front and 14 only after failure of steroid treatment, whereas 9 centers do not perform a liver biopsy at all. Twenty centers (59%) use a percutaneous approach, 12 a transvenous approach, and 1 mini-laparoscopy for liver biopsies. First-line treatment of cutaneous aGVHD stage 1 consists of topical treatment alone in 17 of 31 responding centers (61%), whereas isolated cutaneous aGVHD stage III is treated with systemic steroids (prednisolone below 0.5 mg/kg/day n = 2, 0.5 to 1.0 mg/kg/day n = 10, above 1.0 to 2.5 mg/kg/day n = 19) without or with topical agents (steroids n = 10; calcineurin inhibitors n = 3). In gastrointestinal manifestations of aGVHD, 9 centers (29%) add topical to systemic steroids, and 3 consider topical steroids as the only treatment for mild gastrointestinal and cutaneous aGVHD. The choice of agent for second-line treatment as well as the sequence of administration are extremely heterogeneous, most likely due to a lack of convincing data published. Most frequently used are mycophenolate mofetil (n = 14) and extracorporeal photopheresis (n = 10). Our survey also demonstrates that clinicians chose salvage therapies for steroid-refractory aGVHD based on their centers' own clinical experience.     

肾移植术后乳腺癌研究进展

随着器官移植技术的提高和免疫抑制剂的广泛应用,移植器官或受者移植物的存活率增加,同时移植术后恶性肿瘤发生的风险也升高。 由于其治疗需同时考虑到恶性肿瘤和移植器官功能,且有关此类群体的临床研究较少,其治疗方案尚未形成共识,亟需积累针对性的大规模临床观察和研究。本文拟探讨和总结近年来肾移植术后乳腺癌的临床特点、免疫抑制剂应用、治疗等相关因素。     

Oral beclomethasone dipropionate in gastrointestinal graft-versus-host disease

Beclomethasone dipropionate is a corticosteroid with topical activity for inflammatory disorders at mucosal surfaces. Oral beclomethasone dipropionate (orBec^®) has demonstrated activity in gastrointestinal acute graft-versus-host disease (aGVHD) associated with hematopoietic cell transplantation. Since the GI tract is the dominant aGVHD target in many patients, oral beclomethasone dipropionate reduces the requirement for systemic immunosuppressive drugs in treating aGVHD. In this patient population, reduced exposure to systemic corticosteroids is associated with fewer infections and, possibly, preserved graft-versus-tumor effects, yielding a statistically significant improvement in survival in a randomized, multicenter clinical trial.     

Secondary treatment of acute graft-versus-host disease: a critical review

Management of steroid-resistant or steroid-refractory acute graft-versus-host disease (aGVHD) poses one of the most vexing and difficult problems faced by transplantation physicians. In the current study, we used 10 criteria to evaluate 67 reports describing secondary treatment of patients with aGVHD. The goal of this exercise was not only to provide a critical summary of the literature but also to offer suggestions that could improve future studies. Areas especially in need of improvement include the use of a consistent treatment regimen, the assessment of response at a consistent prespecified time point, consideration of concomitant treatment in assessing response, documentation that selection bias was minimized, and the use of methods that test a formal statistical hypothesis based on a contemporaneous or historical benchmark. Our results suggest that previous published reports collectively offer little guidance in discerning the most effective treatments for patients with steroid-resistant or steroid-refractory aGVHD. Adherence to the proposed criteria in future reports would enable meaningful comparisons across studies and thereby accelerate progress in evaluating new treatments for patients with aGVHD.     

Oral beclomethasone dipropionate for the treatment of gastrointestinal acute graft-versus-host disease (GVHD).

Acute graft-versus-host disease (aGVHD) remains one of the most severe complications after allogeneic transplantation; in particular, the presence of gut involvement has been related to increased mortality and poorer response. The use of systemic steroids remains the standard for first-line treatment despite its severe secondary effects. Beclomethasone dipropionate (BDP) is a topically active corticosteroid with low absorption, thereby avoiding many of the deleterious side effects associated with systemic steroids. In the present study we analyzed the efficacy of BDP in a series of 26 patients who were diagnosed with grade 1 and 2 gastrointestinal aGVHD. Twenty patients (77%) responded to BDP treatment, 17 (65.5%) reached complete remission (CR), and 3 (11.5%) showed partial response. Among those patients who reached CR, 5 relapsed, although 1 of them reached second CR after a second course of BDP; therefore, 13 (50%) of the 26 patients did not require systemic steroids to treat gastrointestinal aGVHD. CR rates in those showing gastrointestinal symptoms were 68% for patients with persistent nausea, 50% for those with vomiting, and 54% for those with diarrhea (P=.2). No patient included in the study developed any symptom related to adrenal axis suppression. Thirteen patients (50%) developed >or=1 infectious episode during the first 100 days after transplantation. Transplant-related mortality was 0% at 100 days, and overall transplant-related mortality was 30%, with only 2 patients dying due to infectious complications. Therefore, our study shows that monotherapy with oral BDP is an effective initial therapeutic approach for mild to moderate intestinal GVHD, which avoids complications related to systemic steroids.     

Risk Factors for and Management of Post-Transplantation Cardiovascular Disease

The mortality rates due to cardiovascular disease (CVD) in transplant recipients are greater than in the general population. CVD is a major cause of both graft loss and patient death in renal transplant recipients, and improving cardiovascular health in transplant recipients will presumably help to extend both patient and graft survival. Further studies are needed to better evaluate the effectiveness of risk modification on subsequent CVD morbidity and mortality. There is no reason to consider risk factors for CVD such as hyperlipidaemia, hypertension and diabetes mellitus in transplant recipients differently from in the general population. In addition, there are specific transplantation risk factors such as acute rejection episodes and the use of immunosuppressive drugs. It is obvious that several of the immunosuppressive agents used today have disadvantageous influences on risk factors for CVD such as hyperlipidaemia, hypertension and post-transplantation diabetes mellitus (PTDM), but the relative importance of immunosuppressant-induced increases in these risk factors is basically unknown. This may be a strong argument for the selective use and individual tailoring of immunosuppressive agents based upon the risk factor profile of the patient, without jeopardising the function of the graft. Hyperlipidaemia is common after transplantation, and immunosuppression with corticosteroids, cyclosporin, or sirolimus (rapamycin) causes different types of post-transplantation hyperlipidaemia. However, to date, no studies have demonstrated that lipid lowering strategies significantly reduce CVD morbidity or mortality and improve allograft survival in transplant recipients. Several studies using preventive or interventional approaches are ongoing and will be reported in the near future. Post-transplantation hypertension appears to be a major risk factor determining graft and patient survival, and immunosuppressive agents have different effects on hypertension. Controlled studies support the opinion that post-transplantation hypertension must be treated as strictly as in a population with essential hypertension, diabetes mellitus, or chronic renal failure. As increasing numbers of immunosuppressive agents become available for use, we may be in a better position to tailor immunosuppressive therapy to the individual patient, avoiding the use of diabetogenic drugs, drug combinations, or inappropriate doses in patients susceptible to PTDM. Multiple acute rejection episodes have also been demonstrated to be a risk factor for CVD — a strong argument for the use of immunosuppressive drugs to reduce acute rejection. Until we have a better understanding from ongoing landmark studies on the management of CVD, presently available therapy to reduce risk factors needs to be used together with individual tailoring of immunosuppressive therapy with the aim of reducing CVD in these patients.     

Study 275: Updated Expanded Access Program for Remestemcel-L in Steroid-Refractory Acute Graft-versus-Host Disease in Children

Clinical outcomes in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD) are generally poor, with a high mortality rate and limited therapeutic options. Here we report our updated investigational experience with mesenchymal stromal cell (MSC) therapy with remestemcel-L in a multicenter expanded access protocol (ClinicalTrials.gov identifier NCT00759018) in 241 children with aGVHD who failed to respond to steroids with or without other secondary and tertiary immunosuppressive therapies. A total of 241 children with grade B-D SR-aGVHD were enrolled at 50 sites in 8 countries and received 8 biweekly i.v. infusions of human MSCs, 2 × 10⁶ per kg for 4 weeks, with an option for an additional 4 weekly infusions after day +28 for subjects who achieved either a partial response (PR) or mixed response. The mean age of the subjects was 9.6 years; 39% were female, and 60% were white. Most of the subjects had grade C (30%) or grade D (50%) disease, and in most cases, the subjects had failed to respond to other immunosuppressive agents after failing steroids. The primary endpoint was overall response (OR; the sum of complete response [CR] and PR) at day +28. Across all subjects, a 28-day OR was observed in 157 patients (65.1%), with 34 (14.1%) achieving CR and 123 (51.3%) achieving PR. Stratified by aGVHD grade at baseline, the OR rate at day +28 was 72.9% for patients with aGVHD grade B, 67.1% for those with aGVHD grade C, and 60.8% for those with aGVHD grade D. Survival through day +100, a secondary endpoint of the study, was 66.9% (n = 160 of 239). Importantly, survival through day +100 was significantly greater in subjects who achieved a day +28 OR compared with nonresponders (82.1% versus 38.6%; P < .001, log-rank test). Remestemcel-L safety was generally well tolerated, with no infusional toxicity and no identified safety concerns. In summary, this update to the remestemcel-L expanded access program confirms the reported clinical and survival benefits of remestemcel-L therapy in children with aGVHD who have exhausted all conventional therapeutic options.     

Overall and comparative safety of biologic and immunosuppressive therapy in inflammatory bowel diseases

ABSTRACT

Introduction: Efficacy and safety are key aspects when choosing therapies for patients with inflammatory bowel diseases (IBD). While several randomized trials and indirect comparisons have informed the comparative efficacy of medications, there has been a limited synthesis of safety of different agents.

Areas covered: We focus on the overall and comparative risk of serious and opportunistic infections and malignancy of biologic and immunosuppressive therapy in IBD, based on randomized trials, open-label extension and registry studies, and real-world comparative observational studies.

Expert opinion: TNFα antagonists may be more immunosuppressive than non-TNF-targeted biologic agents and increase the risk of systemic infections. Most consistent risk factors for serious infections include use of combination therapy with immunosuppressive agents and/or corticosteroids, moderate to severe disease activity, and older age. TNFα antagonists may also be associated with an increased risk of lymphoma, especially when combined with thiopurines. Real-world comparative safety studies, especially with newer biologic agents, are warranted to inform decision-making. Comparative safety of pharmacotherapy for IBD should be viewed in conjunction with efficacy and in the context of treatment strategies/approach, rather than in the context of specific agents used.     

Management of uveitis

Uveitis is a group of inflammatory eye diseases that cause substantial visual disability and present challenges to diagnosis and treatment. Immune-mediated subtypes of uveitis must be distinguished from infections and malignant forms of the disease, and systemic associations of an ocular inflammation must be recognized. Clinical examination, rather than screening by a series of laboratory and radiological investigations, is generally the key to making the correct diagnosis. Treatment of many forms of immune-mediated uveitis involves immunosuppressive agents, which may be administered locally or systemically. The introduction of biological agents and novel methods for drug delivery are providing further therapeutic options for patients with recalcitrant disease. This review focuses on the common specific forms of uveitis, and describes current and potential future treatment practices.     

Developments in Inhaled Immunosuppressive Therapy for the Prevention of Pulmonary Graft Rejection

Cyclosporin is the main immunosuppressive treatment for lung and heart-lung transplantation. When combined with azathioprine and oral corticosteroids, repeated episodes of acute rejection are limited to a minority of transplant patients. Despite early successful transplantation, many patients developed a disabling and fatal condition called obliterative bronchiolitis. This is currently thought to be a result of chronic rejection. The principal risk factor for the development of obliterative bronchiolitis is undercontrolled acute rejection in the first 3 months after transplantation. Frequent early acute rejection increases the later risk of death and disability. A new approach to immunosuppressive therapy is needed to prevent this complication. Simply increasing the dosage of cyclosporin or oral corticosteroids results in the major complications of opportunistic infection and renal failure. Targeted immunosuppressive treatment delivered to the transplanted organ may offer certain advantages, since a high topical inhaled dosage should be relatively free from systemic complications. The lung as a transplanted organ is easily accessible to targeted therapy by means of inhalation. Inhaled nebulised corticosteroids have been shown to be effective in preventing obliterative bronchiolitis in patients at risk after heart-lung transplantation. Similarly, inhaled cyclosporin has also been reported to be more effective than oral administration, with substantially lower blood concentrations. Such new approaches to targeting immunosuppressive treatment could have specific advantages in long term therapy of lung and heart-lung transplant recipients. They might also be of use in other types of solid organ transplantation.     

Poverty and Mental Health: How Do Low‐Income Adults and Children Fare in Psychotherapy?

Poverty is associated with an increased risk for psychological problems. Even with this increased risk for mental health problems and need for care, many low‐income adults and families do not receive treatment because of logistical, attitudinal, and systemic barriers. Despite significant barriers to obtaining care, research suggests that low‐income individuals show significant benefit from evidence‐based mental healthcare. In this article, we review the link between poverty and mental health, common barriers to obtaining mental health services, and treatment studies that have been conducted with low‐income groups. Finally, we discuss the implications of the research reviewed and offer recommendations for clinicians working with low‐income children or adults, highlighting the importance of evidence‐based care, extensive outreach, and empathic respect.     

European concepts for the domestic transport of highly infectious patients

Highly infectious diseases involve clinical syndromes ranging from single to multiorgan infections and pose a constant threat to the public. In the absence of a definite treatment for most causative agents, patients benefit from maximum supportive care as clinical conditions may deteriorate in the short term. Hence, following initial case identification and isolation, rapid transportation to a specialized treatment unit must be considered in order to minimize the risk of secondary infections, but this is limited by available infrastructure, accessible care en route and the patient's clinical condition. Despite the development of consensus curricula for the clinical management of highly infectious patients, medical transportation lacks a common European approach. This article describes, as examples, three current European concepts for the domestic relocation of highly infectious patients by ground vehicles and aircraft with respect to national legislation and geography.     

Management of uveitis

Abstract. Uveitis is a group of inflammatory eye diseases that cause substantial visual disability and present challenges to diagnosis and treatment. Immune-mediated subtypes of uveitis must be distinguished from infections and malignant forms of the disease, and systemic associations of an ocular inflammation must be recognized. Clinical examination, rather than screening by a series of laboratory and radiological investigations, is generally the key to making the correct diagnosis. Treatment of many forms of immune-mediated uveitis involves immunosuppressive agents, which may be administered locally or systemically. The introduction of biological agents and novel methods for drug delivery are providing further therapeutic options for patients with recalcitrant disease. This review focuses on the common specific forms of uveitis, and describes current and potential future treatment practices.     

IL-17-producing T cells contribute to acute graft-versus-host disease in patients undergoing unmanipulated blood and marrow transplantation

The aim of this study was to investigate the effects of IL-17-producing T cells, including Th17 and Tc17 cells, on acute graft-versus-host disease (aGVHD) in patients who had undergone granulocyte colony-stimulating factor (G-CSF)-mobilised peripheral blood progenitor cell (PBPC) and G-CSF-primed bone marrow (G-BM) transplantation. Allografts from forty-one patients were analysed for IL-17-producing T cells with respect to aGVHD. Furthermore, ten patients with aGVHD onset were monitored for the presence of Th17 cells in the peripheral blood by flow cytometry. Patients who received a higher dose of Th17 cells in the G-BM (>8.5 × 10(4) /kg, p=0.005) or a higher dose of Tc17 cells in PBPC (>16.8 × 10(4) /kg, p=0.001) exhibited a higher incidence of aGVHD. An increased Th17 population (up to 4.99% CD4(+) T lymphocytes) was observed in patients with aGVHD onset. In contrast, the percentage of Th17 population decreased drastically in aGVHD patients following treatment to achieve partial and complete remission (p=0.013 and p=0.008, respectively). All percentages of Th17 and Tc17 cells were significantly reduced after in vivo G-CSF application. Our results suggested that IL-17-producing T cells contributed to aGVHD. The application of G-CSF in vivo aided in reducing the occurrence of aGVHD through a decrease in IL-17 secretion by T cells.