Role of folinic acid in methotrexate-based prophylaxis of graft-versus-host disease following hematopoietic stem cell transplantation.

Methotrexate (MTX) is one of the main therapeutic agents currently used for the prophylaxis of graft-versus-host disease (GvHD) following hematopoietic stem cell transplantation. However, it is associated with significant toxicity and considerable side effects in many patients, which lead to either early withdrawal or dose reductions that may expose patients to the risk of GvHD and graft failure. Folinic acid (FA) can bypass the inhibitory effects of MTX on folate availability and control MTX toxicity. However, concerns that FA might inhibit the anti-GvHD effect of MTX and limited reports on its clinical usefulness have led to reluctance in its inclusion in standard GvHD prophylaxis regimens. Additionally, universal dosing and timing guidelines are lacking. I discuss the available literature and evaluate the evidence for the effect of FA on MTX toxicity and its safety regarding GvHD development and graft rejection in both adult and pediatric patients. Although FA administration appears to be safe, its efficacy for routine use in all types of transplants in adult patients is unproven and further research is required to confirm its MTX toxicity-lowering effect, identify the individual parameters that influence its usefulness in clinical practice, and evaluate its potential when developing a personalized prophylaxis regimen.

Re-infection with a different SARS-CoV-2 clade and prolonged viral shedding in a hematopoietic stem cell transplantation patient.

Immunocompromised patients who have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection pose many clinical and public health challenges. We describe the case of a hematopoietic stem cell transplantation patient with lymphoma who had a protracted illness requiring three consecutive hospital admissions. Whole genome sequencing confirmed two different SARS-CoV-2 clades. Clinical management issues and the unanswered questions arising from this case are discussed.

Clinical course and outcomes of COVID-19 in hematopoietic cell transplant patients, a regional report from the Middle East.

The coronavirus disease-2019 (COVID-19) caused by SARS Coronavirus 2 (SARS-CoV-2) is a potentially lethal infection. Cancer patients, and specifically hematopoietic cell transplant (HCT) recipients are severely immunocompromised and may be at a higher risk of a complicated course with this infection. We aimed to study the COVID-19 outcomes and severity in post HCT patients. We retrospectively reviewed post-HCT patients diagnosed with COVID-19 between March 15, 2020, and December 1, 2020 at 10 transplant centers across the Middle East. We identified 91 patients with confirmed SARS-CoV-2 infection across 10 transplant centers. The median age upon presentation with COVID-19 was 35. Fifty two patients were post allo-HCT while the remaining 39 patients were post auto-HCT. The median time from transplant was 14.9 months. Mortality rate was 4.4%. Hospital admission rate was 53%. ICU admission rate was 14%. Mechanical ventilation rate was 10%. Oxygen supplementation rate was 18%. Time from HCT to COVID-19 >6 months was associated with lower admission rates and lower rates of the "severity" composite endpoint. Antibody responses was seen 67% of evaluable patients. In this series of HCT recipients, we report overall favorable clinical outcomes for patients with COVID-19 and provide preliminary insights into the clinical course of this disease in this specific population.

What is the minimum adequate busulfan dose for patients with sickle cell disease undergoing reduced intensity conditioning with fludarabine, busulfan, and anti-thymocyte globulin?

Fludarabine busulfan anti-thymocyte globulin is a common conditioning chemotherapy with reduced toxicity used for transplantation in sickle cell disease (SCD). The dose of busulfan used in this protocol is variable across studies and centers. The minimum dose that maintains long-term donor chimerism is not well established. We hypothesized that a lower, less-toxic dose could be used to maintain adequate long-lasting chimeras, which might allow for the inclusion of older or comorbid patients with this disease. In our retrospective study of 11 patients, 8-9.6 mg/kg was adequate to maintain chimerism in six patients. A 6 mg/kg dose resulted in transplant rejection in two patients. This suggests that 0.8 mg/kg IV busulfan every 6 h for 8-12 doses (total 8-9.6 mg/kg) is the minimum adequate busulfan dose required to maintain long-lasting chimeras, facilitating the successful withdrawal of immunosuppression in SCD patients who receive this protocol.

Dose-adjusted bendamustine as a replacement for carmustine in autologous stem cell transplant conditioning for patients with relapsed lymphoma: A retrospective single-center study.

BEAM conditioning regimen (carmustine [BCNU], etoposide, cytarabine, and melphalan) has been widely used for autologous stem cell transplantation in patients with relapsed or refractory lymphoma. However, BCNU-associated toxicities have prompted research to explore other options. This study aimed to assess the feasibility of bendamustine as an alternative to BCNU. We compared 71 patients who received either bendamustine (Benda-EAM group) or BCNU (BEAM group) conditioning. Considering previous reports of increased cardiotoxicity, nephrotoxicity, and mucositis, we adopted a lower bendamustine dose of 160 mg/m2/day administered for 2 days. There was no increase in nephrotoxicity and cardiotoxicity. Further, positive results were also obtained for neutrophil and platelet engraftment, appearing earlier in patients treated with Benda-EAM (10 vs. 14 days and 16 vs. 27 days, respectively). However, caution is warranted because an increased frequency of Grade 3 mucositis was observed in the Benda-EAM group (82.4% vs. 48%). This was accompanied by an increased need for parenteral nutrition. Despite the lower dose of bendamustine, the overall and progression-free survival rates were comparable between the Benda-EAM and BEAM groups. In conclusion, a lower dose of bendamustine may be an attractive alternative to BCNU as a tolerable treatment modality for patients with relapsed/refractory lymphoma.

Hematopoietic stem cell transplantation in Saudi Arabia between 1984 and 2016: Experience from four leading tertiary care hematopoietic stem cell transplantation centers.

Saudi Arabia is the largest of the Arabian Gulf countries with a total population of 33.41 million as of 2017. This report summarizes the experience from four leading tertiary care hematopoietic stem cell transplantation (HSCT) centers in Saudi Arabia representing more than 90% of all HSCTs performed in the country. Between 1984 and 2016, a total of 6,184 HSCTs were performed. Of these, 3,586 HSCTs were performed in adults and 2,598 HSCTs were performed in pediatric patients. Malignancy was the main indication for transplantation (47%). While most transplants were performed from an identical sibling donor, HSCTs from cord blood, unrelated and, more recently, haploidentical donors have also been performed. Relative shortage of HSCT bed capacity is perceived to be a limiting factor in Saudi Arabia. Lately, more HSCT centers are emerging with rapid growth, which may significantly improve the access to HSCT in the country in the near future.

Physical therapy pathway and protocol for patients undergoing hematopoietic stem cell transplantation: Recommendations from The Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) Group.

BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) are often referred for physical therapy (PT) to help improve their quality of life. However, to our knowledge there is no clear PT pathway to guide therapists and patients before, during, and after HSCT. METHODS: A comprehensive literature review was carried out exploring the role and benefits of PT in HSCT patients. The current evidence was comlimented with recommendations and opinions from the experts in the field, which included PT's and hematology consultants from PTAGVHD and the EMBMT group. RESULT: A clear pathway and protocol as a working guide for rehabilitation professionals working with the HSCT patient's was developed. CONCLUSION: This paper not only reviews the current evidence on safe PT practice but also puts forward a protocol and pathway for HSCT rehabilitation, highlights the importance of individualized exercise intervention for HSCT patients, and outlines safe practice guidelines for the physical therapists working in this field.

Abundant expression of BMI1 in follicular lymphoma is associated with reduced overall survival.

Although generally indolent, follicular lymphoma (FL) sometimes pursues a more aggressive course leading to early death. B-cell-specific Mo-MLV insertion site-1 (BMI1) is a member of the polycomb group (PcG) proteins that confer stem cell properties through gene silencing. We used multi-channel immunofluorescence and automated image analysis to quantify BMI1 selectively in the nuclei of FL-derived B-cells in routine biopsy specimens. Applying this assay to 109 pretreatment FL biopsy samples demonstrates a significant association between abundant BMI1 and reduced overall survival (p = .001); the statistically significant association with mortality persists in a Cox proportional hazards model that includes Follicular Lymphoma International Prognostic Index (FLIPI) score, histological grade, and the presence of a component of diffuse large B-cell lymphoma in the biopsy sample. Ascertaining BMI1 over-expression may be useful in identifying patients who might benefit from novel therapies directed at reversing the chromatin-modifying functions of BMI1.

Inclusion body myositis in a patient with chronic myeloid leukemia treated with dasatinib: a case report.

INTRODUCTION: Chronic myelogenous leukemia is often treated using tyrosine kinase inhibitors such as dasatinib. Here we describe a rare case of inflammatory myopathy in a patient with chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. CASE PRESENTATION: A 69-year-old Caucasian man with imatinib-resistant chronic myelogenous leukemia achieved complete molecular remission in response to dasatinib therapy. However, from a normal initial serum creatine kinase level, he developed elevated serum creatine kinase levels and gradual-onset progressive muscle weakness after dasatinib therapy was initiated. Our patient was eventually diagnosed with inclusion body myositis. However, we were unable to determine the mechanism underlying the dasatinib-associated muscle weakness. Given the efficacy of dasatinib in the treatment of chronic myelogenous leukemia and our patient's mild symptoms of inclusion body myositis, he continued to receive dasatinib under close clinical and laboratory observation. CONCLUSION: Despite the wide use of dasatinib and its documented safety, we report a case of severe muscle injury of unknown etiology. Therefore, patients with chronic myelogenous leukemia receiving dasatinib and perhaps all tyrosine kinase inhibitors should be carefully monitored for signs of muscle injury, especially if this is associated with significant elevations in serum creatine kinase levels.

Acquired factor V inhibitor in a patient with mantle cell lymphoma presenting with hematuria followed by thrombosis: a case report.

Acquired factor V inhibitor is a rare hemostatic disorder that presents with hemorrhagic manifestations in the vast majority of patients. Factor V inhibitor may develop through a variety of mechanisms involving development of alloantibodies or autoantibodies specific to Factor V. Autoantibodies, in particular, have been reported in a number of conditions. In this report, we describe a case of acquired factor V inhibitor in a patient with mantle cell lymphoma who presented with hematuria. Seven weeks after diagnosis and successful management, the patient developed deep vein thrombosis in the right lower extremity. The patient's factor V levels were normalized, and the inhibitor was successfully eradicated using corticosteroids. Here, we discuss this rare disorder, its unusual manifestation, and provide a mini-review of the current literature regarding factor V inhibitors.