Secondary Oral Squamous Cell Carcinoma following Haematopoietic Stem Cell Transplantation.

We report 10 cases of oral squamous cell carcinoma (SCC) post-haematopoietic stem cell transplant (HSCT).. Median latency from HSCT to oral SCC diagnosis was 10 years (range: 4-17 years) with 90% reporting a history of chronic graft-versus-host disease (cGVHD) and 40% exhibited active severe manifestations of oral GVHD. Clinical findings at diagnosis included induration, ulceration, tenderness, bleeding, hyperkeratosis, speckling and lymphadenopathy. The tongue and buccal mucosa were the commonest sites affected. Disease stage at presentation ranged from T1N0M0 to T4N2M0. Management included surgical resection in 90% of cases ± chemo/radiotherapy. Median follow-up for the cohort was l years with 50% mortality rate. SCC-specific mortality was 30%. Our data highlight the importance of regular, active oral and cutaneous surveillance of post-HSCT patients in specialised dermatology clinics, irrespective of GVHD severity and length of iatrogenic immunosuppression.

Genetic Findings of Potential Donor Origin following Hematopoietic Cell Transplantation: Recommendations on Donor Disclosure and Genetic Testing from the World Marrow Donor Association.

Following hematopoietic cell transplantation (HCT), recipients are subjected to extensive genetic testing to monitor the efficacy of the transplantation and identify relapsing malignant disease. This testing is increasingly including the use of large gene panels, which may lead to incidental identification of genetic and molecular information of potential donor origin. Deciphering whether variants are of donor origin, and if so, whether there are clinical implications for the donor can prove challenging. In response to queries from donor registries and transplant centers regarding best practices in managing donors when genetic mutations of potential donor origin are identified, the Medical Working Group of the World Marrow Donor Association established an expert group to review available evidence and develop a framework to aid decision making. These guidelines aim to provide recommendations on predonation consenting, postdonation testing of recipients, and informing and managing donors when findings of potential donor origin are identified in recipients post-transplantation. It is recognized that registries will have different access to resources and financing structures, and thus whenever possible, we have made suggestions on how recommendations can be adapted.

Serious Stem Cell Donation Events and Recipient Adverse Reactions Related to Severe Acute Respiratory Syndrome Coronavirus 2: Review of Reports to the World Marrow Donor Association.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has deeply impacted hematopoietic stem cell (HSC) donation and transplantation. Numerous changes in practice have been introduced, and monitoring the impact of these changes on donations and transplantations is of vital importance. As part of a global response to this pandemic, the World Marrow Donor Association (WMDA) asked that its member registries and cord blood banks submit SARS-CoV-2-related adverse events to the WMDA-operated Serious Product Events and Adverse Reactions (SPEAR) database. Here we review SARS-CoV-2-related SPEAR events that occurred in 2020. The WMDA SPEAR Committee reviewed reports submitted via an online tool. The Committee reviewed each report following the European Union definitions of a serious adverse event or reaction and determined the imputability and its impact. Reports submitted in 2020 were included in this analysis. A TOTAL OF: 74 such reports were received, and events were classified as donor-related (n = 41; 55.4%), recipient-related (n = 3; 4.1%), technical issues (n = 31; 41.8%), or transport-related issues (n = 4; 5.4%). Five cases appeared in multiple categories. The most frequently reported adverse events were of cells being unused. Many of these cases were caused by the uncoupling of the donation and transplantation consequent on the cryopreservation of products, as well as technical issues related to cell viability. Experience in some registries suggests that these issues have become less frequent as transplantation centers have become used to the changes in practice. Lessons learned include the importance of confirming recipient eligibility before the start of donor mobilization or collection and of minimizing the time between cell collection and transplantation. Transplantation centers should familiarize themselves with the expected cell losses when peripheral blood stem cell and bone marrow products are cryopreserved and should have validated viability assays in place for quality assurance. Reassuringly, there were no reports of donors becoming severely unwell because of G-CSF or transmission of SARS-CoV-2 to recipients and only 1 report of complete failure of transport of a donation.

Predicting the Availability of Hematopoietic Stem Cell Donors Using Machine Learning.

Hematopoietic stem cell transplantation (HSCT) is firmly established as an important curative therapy for patients with hematologic malignancies and other blood disorders. Apart from finding HLA-matched donors during the HSCT process, donor availability remains a key consideration as the time taken from diagnosis to transplant is recognized to adversely affect patient outcome. In this study, we aimed to develop and validate a machine learning approach to predict the availability of stem cell donors. We retrospectively collected a data set containing 10,258 verification typing requests made during the HSCT process in the British Bone Marrow Registry (BBMR) between January 1, 2013, and December 31, 2018. Three machine learning algorithms were implemented and compared, including boosted decision trees (BDTs), logistic regression, and support vector machines. Area under the receiver operating characteristic curve (AUC) was primarily used to assess the algorithms. The experimental results showed that BDTs performed better in predicting the availability of BBMR donors. The overall predictive power of the model, using AUC on the test cohort of 2052 records, was found to be 0.826. Our findings show that machine learning can predict the availability of donors with a high degree of accuracy. We propose the use of the BDT machine learning approach to predict the availability of BBMR donors and use the predictive scores during the HSCT process to ensure patients with blood cancers or disorders receive a transplant at the optimum time.

Treatment stratification of respiratory syncytial virus infection in allogeneic stem cell transplantation.

BACKGROUND: Due to paucity of evidence to guide management of allogeneic haematopoietic stem cell transplantation (allo-HSCT) patients with respiratory syncytial virus (RSV) infections national and international guidelines make disparate recommendations. METHODS: The outcomes of allo-HSCT recipients with RSV infection between 2015 and 2017 were assessed using the following treatment stratification; upper respiratory tract infections (URTI) being actively monitored and lower respiratory tract infections (LRTI) treated with short courses of oral ribavirin combined with intravenous immunoglobulin (IVIG, 2 g/kg). RESULTS: During the study period 49 RSV episodes were diagnosed (47% URTI and 53% LRTI). All patients with URTI recovered without pharmacological intervention. Progression from URTI to LRTI occurred in 15%. Treatment with oral ribavirin given until significant symptomatic improvement (median 7 days [3-12]) and IVIG for LRTI was generally well tolerated. RSV-attributable mortality was low (2%). CONCLUSIONS: In this cohort study, we demonstrate that active monitoring of allo-HSCT patients with RSV in the absence of LRTI was only associated with progression to LRTI in 15% of our patients and therefore appears to be a safe approach. Short course oral ribavirin in combination with IVIG was effective and well-tolerated for LRTI making it a practical alternative to aerosolised ribavirin. This approach was beneficial in reducing hospitalisation, saving nursing times and by using oral as opposed to nebulised ribavirin.

UK consensus statement on the use of plerixafor to facilitate autologous peripheral blood stem cell collection to support high-dose chemoradiotherapy for patients with malignancy.

Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte-colony stimulating factor [G-CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re-mobilization after a failed mobilization attempt with G-CSF, and rescue or pre-emptive mobilization in patients in whom mobilization with G-CSF is likely to fail. Pre-emptive use has the advantage that it avoids the need to re-schedule the transplant procedure, with its attendant inconvenience, quality-of-life issues for the patient and cost of additional admissions to the transplant unit. UK experience from 2 major centers suggests that pre-emptive plerixafor is associated with an incremental drug cost of less than £2000 when averaged over all patients undergoing peripheral blood stem cell (PBSC) transplant. A CD34+ cell count of <15 µl-1 at the time of recovery after chemomobilization or after four days of G-CSF treatment, or an apheresis yield of <1 × 106 CD34+ cells/kg on the first day of apheresis, could be used to predict the need for pre-emptive plerixafor.

Partial engraftment following plerixafor rescue after failed sibling donor peripheral blood stem cell harvest.

BACKGROUND: Rarely, healthy donors fail adequate peripheral blood stem cell (PBSC) mobilization. If the recipient has already received conditioning chemotherapy, this can result in the donor undergoing urgent marrow harvest under general anesthesia. Plerixafor is a novel CXCR4 antagonist, licensed for autologous PBSC harvest (PBSCH) in patients who failed mobilization with granulocyte-colony-stimulating factor (G-CSF) alone. Experience using plerixafor in healthy allogeneic donors failing G-CSF mobilization is scarce. CASE REPORT: A 65-year-old patient was referred for a reduced-intensity conditioning sibling allograft for relapsed follicular lymphoma. She received fludarabine, melphalan, and alemtuzumab conditioning. Her 68-year-old brother was fully HLA matched. PBSCH was planned on Day -1 after 4 days of 10 µg/kg G-CSF. Day 1 PBSCH collected an inadequate number of CD34+ 0.35 × 10(6) /kg cells. Despite increasing G-CSF (16 µg/kg), Day 2 yielded 0.33 × 10(6) /kg CD34+ cells, giving a suboptimal total dose. He proceeded to a third PBSCH day after plerixafor (0.24 mg/kg) and G-CSF (16 µg/kg) were given the evening before. A total of 1.79 × 10(6) /kg CD34+ cells were harvested, giving a total dose of 2.46 × 10(6) /kg CD34+ cells. After initial neutrophil engraftment on Day +13, the patient's neutrophils gradually decreased to 0.02 × 10(9) /L by Day +74. A marrow aspirate on Day +81 was markedly hypocellular. Total white blood cell chimerism was near 100% donor on Days +32, +74, and +102. Despite chimeric-only engraftment, the patient remains platelet and red blood cell transfusion dependent. CONCLUSION: Rescue plerixafor to assist PBSCH in healthy allogeneic donors has been effective in terms of CD34+ cell number mobilized. It is unclear whether the partial engraftment seen was coincidental or related to a difference in PBSC quality.

Malignancy: Human T-Cell Lymphotropic Virus Type I and Adult T-Cell Leukaemia/Lymphoma.

Adult T-cell leukaemia/lymphoma (ATLL) was first identified in Japan in 1977 [1,2]. The causative agent, the human T-lymphotropic virus type I (HTLV-I), was isolated 3 years later by Gallo's group from a patient initially diagnosed as having mycosis fungoides but subsequently reclassified as a case of ATLL [3]. Since this time, much has been discovered about the molecular pathogenesis of the disease. Despite this, treatment of ATLL remains disappointing and the prognosis of acute and lymphoma types poor. In the United Kingdom, cases of ATLL are mainly restricted to people of Afro-Caribbean descent but the disease is of general importance because ATLL has also been reported in non-endemic areas and may possibly spread into other populations via blood transfusion as blood donors in the UK are currently not screened for HTLV-I.