BackgroundMycosis fungoides (MF) is a subtype of T‐cell lymphoma that is characterised by the infiltration of malignant T cells into the skin. Treatment approaches usually include skin‐directed therapies for early‐stage disease and, additionally, systemic therapies for advanced stages. Chlormethine hydrochloride gel is recommended as a first‐line treatment option for adult patients with MF, with previous studies demonstrating its efficacy. Due to the rarity of this disease, available literature on the optimal treatment of MF with chlormethine gel is limited, creating challenges for making informed clinical decisions. Thus, we share our individual clinical experiences of selected patients on chlormethine combination treatments to increase the real‐world evidence for chlormethine gel in patients with MF.Case PresentationWe present the cases of five male and two female Caucasian patients above the age of 48 with Stage I–IV MF, presenting with symptoms of skin plaques and lesions. All patients were treated with chlormethine hydrochloride gel in combination with other skin‐directed and systemic therapies, including bexarotene, methotrexate, topical steroids, extracorporeal photopheresis, donor lymphocyte infusion and interferon‐α (IFN‐α) 2a. In most cases, chlormethine combination treatment resulted in disease control, e.g., plaque reduction, stable disease, and partial or complete response. The combination regimens were generally well tolerated, with associated adverse events being inflammation, pruritus and erythema.ConclusionsThis case series reports on the efficacy and safety of chlormethine hydrochloride gel in combination with other topical and systemic therapies in reducing the skin lesion severity in patients with Stage I–IV MF in different real‐world settings.

A phase 1b study on the safety of Wharton's jelly mesenchymal stromal cells in the treatment of acute graft-versus-host disease.

Chronic GvHD is a major cause of non-relapse morbidity and mortality after hematopoietic cell transplantation. Its incidence has increased due to more frequent use of unrelated and/or mismatched donors, reduced intensity conditioning regimens or intensified regimens and PBSC grafts. The first-line therapy for chronic GvHD is systemic corticosteroids associated with either CNI or sirolimus, as a steroid sparing agent. Since children are more susceptible to the long-term steroid side effects, development of steroid-free strategies for front-line therapy is crucial. Sirolimus seems to be an interesting choice due to its capacity of inhibiting T-cells preserving the Tregs cells and antifibrotic, antineoplastic and antiviral activities. FAM regimen (Fluticasone, Azitromycin and Montelucaste) is recommended in combination with systemic steroids for initial treatment of bronchiolitis obliterans. For steroid-refractory chronic GvHD, ruxolitinib is the standard of care, while extracorporeal photopheresis can be combined for better results, however treatment costs are limitations. Extracorporeal photopheresis, treatment that preserves graft-versus-leukemia effect due to its steroid sparing and immunomodulatory actions, and mesenchymal stem cells, another non-pharmacological strategy that can be combined with the options mentioned above in severe chronic GvHD. Since access to novel drugs and extracorporeal photopheresis or mesenchymal stem cells is tough, other options approved for the third line and beyond are ibrutinib, belumosudil and axatilimab. Conventional agents could be used such as imatinib, low dose-MTX, rituximab, however the expected response rates are lower. We reviewed clinical studies and published recommendations on pediatric chronic GVHD that were presented in debate rounds with GvHD experts of the Pediatric group of the Sociedade Brasileira de Terapia Celular e Transplante de Medula Óssea (SBTMO). The goal of this consensus is to standardize the prophylaxis, diagnosis, grading and treatment of chronic GvHD among Brazilian pediatric HCT centers, to improve post-transplant outcomes.

Mechanisms of immune modulation by therapeutic plasma exchange.

BackgroundCheckpoint inhibition induced immune-related adverse events (irAE) may be steroid-dependent or steroid-refractory and are associated with increased morbidity, mortality and potentially compromised anti-tumor immunity. Extracorporeal photopheresis (ECP) has emerged as an alternative for salvage therapy, however, evidence remains scarce.MethodsThis monocenter retrospective study included patients with either irColitis or irHepatitis, who received ECP after failure or dependence on high-dose corticosteroids + infliximab/vedolizumab or mycophenolate mofetil/tacrolimus. Clinical activity was quantified at least weekly (stool frequency for colitis; AST/ALT for hepatitis) and primary endpoint was change in irAE activity over time. Secondary analyses included steroid-sparing, overall safety, and melanoma-specific outcomes. Spearman’s correlation assessed irAE severity reduction.ResultsSix patients were included in this study (irColitis n = 4; irHepatitis n = 2; CTCAE ≥ 3). Extracorporeal photopheresis was started after initial therapy with corticosteroids and immunosuppression was not successful. All ECP cycles included two consecutive treatment days. irAE activity declined promptly after ECP across patients: irColitis showed strong negative correlation with time since ECP (rs range -0.88 to -0.97); irHepatitis displayed parallel ALT/AST declines (rs ≥ -0.92). Corticosteroids were tapered following ECP start with a median corticosteroid reduction across all patients to 25% of baseline dose (IQR: 20.7 - 33.3) by week 4 and to <5% of baseline dose by week 9 (IQR: 1.6 - 4.7). No ECP-related adverse events were observed. Accelerated disease progression was not observed during or after ECP.Conclusions and relevanceThis study of six patients with irColitis or irHepatitis provides evidence that use of ECP is associated with clinical remission and steroid sparing, while demonstrating an excellent safety profile and not compromising disease control. Our data supports the use of ECP as salvage therapy for steroid- and immunosuppression- refractory irAE in cancer patients.

Background: The aim of this study was to investigate the effects of chronic graft-versus-host disease (cGVHD) and its treatment with cyclosporine and extracorporeal photopheresis (ECP) on salivary caries risk factors. Methods: In this exploratory single-centre cross-sectional pilot study, saliva samples from 22 cGVHD patients were analysed for flow rate, pH, buffering capacity, and counts of Streptococcus mutans and Lactobacillus. A detailed dental examination assessed plaque, carious lesions, and their progression. Caries risk was determined based on general health and diet questionnaires and clinical findings. Results: Patients receiving a combination of cyclosporine and ECP had significantly fewer carious teeth, affected tooth surfaces, and non-cavitated carious lesions compared with those treated with ECP alone (Bonferroni test, p = 0.004, p = 0.002, and p < 0.001, respectively). Patients treated with ECP had more carious teeth and affected surfaces than those who did not receive either ECP or cyclosporine (p = 0.008 and p = 0.002), whereas patients treated with cyclosporine only had more non-cavitated lesions than those receiving both cyclosporine and ECP (p < 0.001). A negative correlation was observed between cyclosporine dose and stimulated salivary flow (R = −0.672, p = 0.0486), and a positive correlation between cyclosporine dose and caries risk (R = 0.640, p = 0.0461). Conclusions: The disease and its treatment were associated with reduced salivary flow and increased caries risk. Patients’ oral health should be monitored regularly and managed with care to prevent further deterioration.

BackgroundGraft-versus-host disease (GvHD) is a serious complication of allogeneic hematopoietic cell transplantation, and the major cause of post-transplant mortality and morbidity. If steroid treatment as first-line therapy fails, treatment options are limited. Ruxolitinib (Ruxo) as well as extracorporeal photopheresis (ECP) showed high efficacy in the treatment of steroid-refractory (SR) acute and chronic GvHD.MethodsWe interrogated data from 68 adult and pediatric patients with SR acute and chronic GvHD, between 2017 and 2024, who received either Ruxo plus ECP (Ruxo + ECP, n = 31) or Ruxo alone (Ruxo, n = 37). Endpoints were to compare the overall response rates (ORRs) including complete response (CR) and partial response (PR) of acute and chronic GvHD at last encounter, and the percentage of patients with history of acute GvHD, who progressed to chronic GvHD at 1 year, 1-year non-relapse mortality (NRM), graft-versus-host disease relapse-free survival (GRFS) and survival outcomes at 3 years.ResultsPatient, disease, and transplant characteristics were well balanced, except for more severe acute GvHD in Ruxo + ECP arm (66.6% vs. 18.5%, P = 0.007) and longer Ruxo treatment in Ruxo alone arm (11 vs. 7 months, P = 0.05). The ORRs were 58% for Ruxo + ECP arm compared to 49% in Ruxo alone arm (P = 0.002) at last encounter and the duration of response was 17.6 versus 9 months (P = 0.3171), respectively. In both arms, 87% and 93% of patients could taper steroids rapidly by 50% and 16%. At 1 year, cumulative incidence of chronic GvHD was higher after Ruxo versus Ruxo + ECP, being 55% (95% CI: 42-69%) vs. 26% (95% CI: 22-64%) (P = 0.018). No statistically significant difference in 1-year NRM, relapse, and GRFS and survival at 3 years was observed.ConclusionOur data suggest improved long-term control of acute and chronic GvHD by combining Ruxo plus ECP compared with Ruxo alone.

Graft-versus-host disease after liver transplantation: A global review of pathogenesis, diagnosis, and treatment strategies.

ABSTRACTChronic graft‐versus‐host disease (cGVHD) remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Many cGVHD patients require prolonged systemic immunosuppression with corticosteroids, which carry significant adverse effects, and alternative therapies are often required. Extracorporeal photopheresis (ECP) has historically shown promise as a cGVHD treatment, but recent efficacy data have been limited and inconsistent. To evaluate the efficacy of ECP as a treatment for cGVHD patients according to the 2014 NIH Consensus Criteria. We retrospectively analyzed 53 patients treated with ECP for cGVHD at our center from 2010 to 2024. ORR was 51%, with 3 CRs (5.7%) and 24 PRs (45.3%). Highest organ‐specific responses were seen in the gastrointestinal tract (70%) and liver (69.2%), and lowest in joints/fascia (15.4%) and lung (21.4%). A total of 23 (43.4%) patients experienced at least one treatment‐related complication (TRC), with a median time to first TRC of 29.3 weeks (IQR = 7.4–55.2). The estimated 1‐ and 3‐year OS was 79.2% (95% CI = 65.7%–87.9%) and 70.1% (95% CI = 55.0%–80.9%), respectively. The estimated 1‐ and 3‐year FFS was 75.5% (95% CI = 61.5%–84.9%) and 43.1% (95% CI = 28.6%–56.9%), respectively. Of the 37 patients who were on corticosteroids at the start of ECP, 22 (59.5%) were able to decrease their daily dose by ≥ 50% by the time of ECP discontinuation. Multivariable analyses revealed that patients on tacrolimus and other non‐steroid immunosuppressive treatments (ISTs) had better outcomes in clinical benefit, steroid‐sparing, overall survival, and failure‐free survival. ECP was a safe and effective treatment for cGVHD in our population and showed promising efficacy when used in combination with tacrolimus or other ISTs.

Abstract Purpose of Review Extracorporeal photopheresis (ECP) is an immunomodulatory treatment in which an apheresis machine isolates mononuclear cells from whole blood that are then treated with psoralen and ultraviolet-A light and reinfused into the patient. ECP has been approved for use in cutaneous T-cell lymphoma (CTCL) for 30 years; it has also been shown to be effective for graft-versus-host disease, solid organ transplant rejection, and various autoimmune diseases. Nonetheless, ECP is relatively underutilized, perhaps due to knowledge gaps and resource limitations. Here, we review ECP indications and techniques, as well as the data supporting its use in clinical settings. Recent Finding Recent clinical studies have emphasized the durability of ECP in CTCL, both as monotherapy and in combination with topical and other systemic CTCL treatment modalities. New insights into the mechanism of action underlying ECP have illuminated its effects on both cellular and humoral immunity. Specific clinical and laboratory findings have been identified as potential predictors of ECP response. Summary ECP is a well-tolerated and effective treatment option for a growing list of indications. In CTCL, ECP can achieve durable responses with longer treatment courses and should be considered as a first-line option for erythrodermic disease and Sézary syndrome.

Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard first-line therapy; however, many patients develop steroid-refractory or steroid-dependent disease, underscoring the need for more effective and better-tolerated treatments. Ruxolitinib has emerged as the most evidence-supported option for steroid-refractory cGVHD, with the phase 3 REACH3 trial demonstrating higher response rates, durable disease control, and clinically meaningful improvements in symptom burden compared with best available therapy. Belumosudil and axatilimab have also shown encouraging efficacy and safety in heavily pretreated populations. The addition of novel agents to standard corticosteroid-based therapy has been explored in clinical trials. Interest in combination strategies, such as ruxolitinib with extracorporeal photopheresis or belumosudil, is increasing, though prospective studies are required to define their role. Key challenges include optimizing long-term safety, mitigating infectious complications, and preserving the graft-versus-leukemia effect. This review summarizes current therapeutic strategies and discusses evolving treatment algorithms, emphasizing practical considerations in therapy selection. Approaches targeting specific pathogenic mechanisms, combining agents with distinct mechanisms of action, and incorporating biomarker-driven strategies are expected to further improve outcomes and quality of life for patients with cGVHD.

Persistent racial disparities in Sézary syndrome outcomes despite use of modern therapies: A single-center analysis

Multicenter real-world experience of belumosudil treatment in heavily pretreated patients with steroid-refractory chronic graft-versus-host disease: Clinical outcomes and risk factor analysis for failure-free survival.

Clinical features and outcomes of patients with non-erythrodermic mycosis fungoides with high blood tumor burden

Real-world monotherapy and combination usage of mogamulizumab among patients with mycosis fungoides or Sézary syndrome in the United States

Outcomes of stem cell transplantation in pediatric and adolescent/young adult patients with trisomy 21: A single-center experience

345 Extracorporeal photopheresis (ECP) in cutaneous T-cell lymphoma – a systematic literature review of the impact of ECP on clinical and non-clinical outcomes

Abstract Advances in pediatric hemato-oncology and transplantation have markedly improved outcomes for children with hematologic malignancies, immunodeficiencies, and organ failures. Nonetheless, complications such as graft-versus-host disease (GVHD), multi-organ dysfunction, and therapy-related toxicities often require extracorporeal support. Extracorporeal therapies – including photopheresis, plasma exchange, red cell exchange (RCE), leukapheresis, thrombocytapheresis, continuous renal replacement therapy (CRRT), and extracorporeal membrane oxygenation (ECMO) – play essential roles in immune modulation, metabolic control, and organ support. Extracorporeal photopheresis promotes immune tolerance and improves steroid-refractory GVHD outcomes, whereas plasma exchange and RCE aid in desensitization, antibody removal, and hemoglobinopathy management. Leukapheresis enables rapid cytoreduction in hyperleukocytosis and facilitates peripheral stem cell collection for hematopoietic stem cell transplant, chimeric antigen receptor therapy (CAR-T), and for advanced cellular therapies, including donor lymphocyte infusion, memory T-cell, and natural killer (NK) cell therapies. CRRT ensures hemodynamic stability and continuous clearance in acute kidney injury, whereas ECMO serves as a life-saving bridge in reversible cardiorespiratory failure. Although technically demanding, these modalities are generally safe with multidisciplinary expertise, individualized protocols, and vigilant monitoring. Early and judicious application of extracorporeal support improves survival and recovery in critically ill children, reinforcing their indispensable role in modern pediatric hemato-oncology and transplant critical care.

Background/AimInduction of immune tolerance by the activation of regulatory T (Tregs) cells after extracorporeal photopheresis (ECP) appears to influence the response to treatment in patients with chronic graft-versus-host disease (cGvHD). This study examined the activation mechanisms of Tregs and their potential link to the expression of FOXP3, TP53, and SELPLG genes. Results were compared with the therapeutic response to ECP.Materials and MethodsThe study included six patients with cGvHD who underwent at least four cycles of ECP. The samples were collected from peripheral blood (PB) and from apheresis material before and after ECP, which was then used to establish cell cultures. The percentage of Tregs and their subpopulations were assessed using multicolor flow cytometry. Gene expression levels were evaluated using quantitative PCR (qPCR).ResultsA statistically significant increase in the expression levels of TP53 gene was found in the fourth ECP cycle in patients with partial response (PR) compared to patients with stable disease (SD). Patients with PR were characterized by higher mRNA levels for the TP53 and SELPLG genes after 48 h of culture. Patients with PR had a statistically significant higher percentage of Tregs including activated HLA-DR+ Tregs.ConclusionPatients with PR demonstrated elevated gene expression levels in 48-h mononuclear cell cultures, which correlated with their clinical response to treatment. They also had a higher baseline percentage of Tregs, which did not correlate with elevated FOXP3 or other gene expression levels.

A significant challenge in extracorporeal photopheresis (ECP) in developing countries is the high cost of apheresis equipment. Additionally, obtaining proper IV access in pediatric patients is considerably more difficult than in adult patients. To address the limitations of applying ECP for pediatric patients, such as vein access difficulties, time constraints, and costs, the cryopreservation of mononuclear cells (MNCs) has been explored. Since cryopreservation reduces the need for repeated apheresis procedures, it offers potential convenience for pediatric patients and resource-limited settings, particularly in developing countries. Twenty-four pediatric patients with steroid-resistant or steroid-dependent acute or chronic GvHD participated in this study. All patients underwent offline apheresis. The viability and proliferation rates of fresh and thawed MNCs were assessed using flow cytometry and the CFSE assay. The clinical response was also evaluated at various time points over 21 months for all patients. There were no significant differences in annexin/PI analysis (p = 0.39) and CFSE assay (p = 0.8) between fresh and thawed samples using flow cytometry. Response to ECP after nine months in aGvHD revealed favorable results, with a complete response in 12 patients (60%) and a partial response in 8 patients (40%), which remained stable until 12 months after ECP therapy. In cGvHD, complete and partial responses were the same and occurred in 7 patients (46.6%). Cryopreserving MNCs for ECP in pediatric patients with steroid-resistant GvHD is a practical and effective method to overcome existing limitations. We propose that cryopreservation could be a more effective option than repeated apheresis for pediatric patients and in developing countries, as it reduces costs and eliminates the need for multiple apheresis sessions.