Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] post-haploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as GVHD prophylaxis. A liver biopsy confirmed the diagnosis of GVHD, while other possible etiologies were excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment, we decided to administer 1,000 mg/m2 (1,600 mg) of cyclophosphamide (\"pulse Cy\"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized (\"complete response\") within 55 days without relapses. The patient remains in good health with no recurrence of hepatic GVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting.

Extracorporeal photopheresis (ECP) has proven effective in the treatment of several diseases, including acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. In its standard version, ECP requires leukapheresis to obtain a fraction of mononuclear cells. The possibility of using leukapheresis is limited by the requirements for vascular access and the somatic status of the patient. We have developed a new ECP method that does not require leukapheresis. This paper presents a description of two clinical cases of severe refractory GVHD treated by micro-ECP.

Neuronal surface antibody syndromes (NSAS) encompass a growing set of autoimmune neurological disorders, with their predominant clinical presentation being autoimmune encephalitis (AE). The most extensively documented form within NSAS is anti-N-methyl-D-aspartate receptor (NMDAR) autoimmunity. In contrast, other NSAS, such as anti-metabotropic glutamate receptor-5 (mGluR5) autoimmunity, are less common and less comprehensively characterized, particularly in pediatric cases.
In this instance, we present the case of a 7-year-old girl who exhibited abnormal behaviors following hematopoietic stem cell transplantation (HSCT). She received a diagnosis of anti-mGluR5 AE, and her Electroencephalogram (EEG) displayed an increased number of generalized slow waves during wakefulness. Treatment involved intravenous administration of gamma globulin and methylprednisolone, followed by oral prednisone tablets. Levetiracetam was introduced as an antiepileptic therapy during the pulse steroid therapy. Notably, the abnormal behaviors exhibited significant improvement after treatment.
To the best of our knowledge, this is the first report of rare pediatric NSAS involving anti-mGluR5 AE following HSCT. Enhancing our understanding and characterization of this condition may facilitate its recognition and treatment in children. Serum antibody testing could enable early identification and treatment of anti-mGluR5 AE.

Patients receiving allogeneic hematopoietic stem cell transplant may experience graft-versus-host disease (GVHD) in which donor immune cells cause an immune reaction in host tissues. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are highly effective in prevention of severe coronavirus-2019 (COVID-19) disease, but the vaccine can result in immune activation and GVHD. Herein, we report 4 cases of oral manifestations that may have been stimulated by COVID-19 or vaccination with Pfizer or Moderna vaccines. We believe this study is the first to report oral changes driven by an inflammatory/immune mechanism leading to oral symptomatic cGVHD. The clinical impact of this study is early recognition and appropriate management of oral symptomatic cGVHD following COVID-19 disease or SARS-CoV-2 vaccination.

Burkitt lymphoma (BL) is the most common tumor of non-Hodgkin\'s lymphoma (NHL) in children, accounting for about 40% of cases. Although different combined short-course chemotherapies have achieved a good effect, refractory/relapsed BL has a poor prognosis with cure rates less than 30%. Chimeric antigen receptor T cell (CAR-T) therapy has developed rapidly in recent years and achieved excellent results in acute lymphoblastic leukemia (ALL). However, in some cases, there is a failure to produce autologous CAR-T cells because of T-cell dysfunction. In such cases, allogeneic CAR-T therapy has to be considered.
A 17-year-old boy with stage II BL did not respond to extensive chemotherapy and sequential autologous CAR-T therapy. Lentiviral vectors containing anti-CD20-BB-ζ (20CAR) and anti-CD22-BB-ζ (22CAR) transgenes were used to modify the T cells from an HLA-identical matched unrelated donor. Flow cytometry was used to assess the cytokine analyses and CAR-T cell persistence in peripheral blood, enumerated by qPCR as copies per ug DNA. Informed consent for autologous/allogeneic CAR-T therapy was obtained from the patient and his legal guardian.
Unedited HLA-matched allogeneic CD20 and CD22 CAR-T cells were infused after lymphodepletion chemotherapy with cyclophosphamide and fludarabine. The patient experienced Grade IV cytokine release syndrome (CRS) and went into complete remission (CR) after anti-inflammatory treatment including tocilizumab. Because of persistent pancytopenia and full donor chimerism, the same donor\'s conditioning-free peripheral blood stem cells were successfully transplanted 55 days post CAR-T. Neutrophils were engrafted at day +11 and platelets were rebuilt at day +47 without obvious acute graft-versus-host disease (GVHD), but there was mild chronic GVHD in the skin and eyes. Currently, active anti-rejection therapy is still underway.
Unedited HLA-matched allogeneic CAR-T cell therapy could be an innovative, effective, and safe treatment for children with refractory/relapse BL without obvious acute GVHD. Conditioning-free allogeneic hematopoietic stem cell transplantation (HSCT) from the same donor is feasible for a patient with full donor T-cell chimerism after allogeneic CAR-T. It cannot be ignored that close GVHD monitoring is needed post HSCT.

We describe a 9-year-old boy who developed generalised erythematous lesions 12 months after haematopoietic stem cell transplant (HSCT). Histopathology showed both features of psoriasis and graft-versus-host disease (GVHD). The lesions responded well to secukinumab, suggesting that IL-17A monoclonal antibody might be a treatment option for GVHD.

UNASSIGNED: The incidence of kidney disease is high in patients after allogeneic hematopoietic cell transplantation (aHCT). Although rarely performed, kidney biopsy may be useful to make a precise diagnosis because several mechanisms and risk factors can be involved, and to adjust the treatment accordingly. This case series aimed to report the spectrum of biopsy findings from patients with kidney injury after aHCT.
UNASSIGNED: Single-center retrospective case series.
UNASSIGNED: All individuals who underwent a native kidney biopsy, among all adult patients who received aHCT in a tertiary hospital in Montreal (Canada) from January 1, 2010, to December 31, 2020, were identified, and the clinical data were extracted from their medical records.
UNASSIGNED: A total of 17 patients were included. Indications for biopsy included acute kidney injury (n=6), chronic kidney disease (n=5), nephrotic syndrome (n=4), and subnephrotic proteinuria (n=2). Pathologic findings from the kidney biopsy were heterogenous: 10 patients showed evidence of thrombotic microangiopathy (TMA), 5 of acute tubular injury, and 4 of membranous nephropathy. Cases of acute interstitial nephritis, BK virus nephropathy, immune complex nephropathy, focal and segmental glomerulosclerosis, minimal change disease, and karyomegalic-like interstitial nephritis were also described.
UNASSIGNED: There was no systematic kidney biopsy performed for all patients with kidney injury after aHCT. Only a small proportion of patients with kidney damage underwent biopsy, making the results less generalizable.
UNASSIGNED: Kidney biopsy is useful in patients with kidney disease after aHCT to make a precise diagnosis and tailor therapy accordingly. This series is one of the few published studies describing pathologic findings of biopsies performed after aHCT in the context of acute kidney injury and chronic kidney disease. TMA was widely present on biopsy even when there was no clinical suspicion of such a diagnosis, suggesting that the current clinical criteria for a diagnosis of TMA are not sensitive enough for kidney-limited TMA.

Patients planned for hematopoietic stem cell transplantation (HSCT) routinely undergo dental evaluation. Conditioning before HSCT engenders immunosuppression that may lead to flares of oral infections. Before transplantation, the dental provider should educate the patient on the oral complications of HSCT and identify and treat dental needs as appropriate to the patient\'s medical status. Dental evaluation and treatment must be performed in close coordination with the patient\'s oncology team.

Acute gastrointestinal graft-versus-host disease (GI GVHD) is a complication after hematopoietic stem cell transplant with high morbidity and mortality. In particular, steroid-refractory GI GVHD can be difficult to treat. Recent investigations have revealed that patients after transplant can experience intestinal dysbiosis contributing to the progression of GVHD. Modulation of the gut microbiome through dietary intake could potentially improve the intestinal dysbiosis in GI GVHD. In this case series, we present 3 patients where dietary therapy was used in conjunction with immunosuppression to achieve clinical remission of GI GVHD.

Hyperacute GVHD (HaGVHD) is a rare complication of hematopoietic stem cell transplantation (HSCT) occurring before engraftment, a syndrome commonly involving skin and/or gut and/or liver, with increased morbidity and mortality. Myeloablative conditioning (MAC) regimes and mismatched donor transplants have an increased risk for HaGVHD. There is a higher chance of steroid-refractoriness and chronic GVHD in those who develop HaGVHD. There is limited literature about HaGVHD, especially in the paediatric age group. This retrospective single-centre case series included five paediatric patients who underwent HSCT between 1st April 2013 and 31st July 2015 at a tertiary care centre in South India, who fulfilled the criteria for HaGVHD as per criteria by Kim et al. and whose follow up data was available. We noted their risk factors, clinical course and prognosis. There were five paediatric HaGVHD patients. The risk factors noted among them were MAC regimen in three and mismatched unrelated donor sources in three. Two had steroid-refractory disease, four went on to develop chronic GVHD and three died of GVHD or treatment-related complications. A high index of suspicion is necessary to recognize HaGVHD, especially in patients with known risk factors developing a fever with rash post-HSCT.