Abstract. Acute graft versus host disease (aGVHD) remains the second leading cause of death following allogeneic hematopoietic stem cell transplant (AHSCT
Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients. MRD and URD recipients received 4 days of busulfan and 4 days of fludarabine. HRD recipients received low-dose cyclophosphamide for 2 days, fludarabine for 5 days, 2 to 3 days of busulfan depending on cytogenetics, and 200 cGy total body irradiation. MRD and URD recipients received tacrolimus and short-course methotrexate for graft-versus-host disease (GVHD) prophylaxis. HRD recipients received high-dose post-transplant cyclophosphamide (PTCy) followed by tacrolimus and mycophenolate mofetil. At a median follow-up of 24 months (range, 9 to 50), 19 of 22 patients were alive with reversal of the disease phenotype and correction of the myelodysplastic syndrome, including eradication of cytogenetic abnormalities. Three patients died: 1 from refractory acute myelogenous leukemia, 1 from GVHD, and 1 from sepsis. There was a 26% incidence of grades III to IV acute GVHD in the MRD and URD groups and no grades III to IV acute GVHD in the HRD cohort. Similarly, there was a 46% incidence of chronic GVHD in the MRD and URD cohorts, whereas only 28% of HRD recipients developed chronic GVHD. Despite excellent overall disease-free survival (86%), GVHD remains a limitation using standard prophylaxis for GVHD. We are currently extending the use of PTCy to the MRD and URD cohorts to reduce GVHD.
Lung cancer is the leading cause of cancer-related death in males, and the second leading cause of death in females worldwide (1). Non-small cell lung cancer (NscLc) accounts for 85% to 90% of all lung cancer. There are different subtypes of NscLc that are grouped together because, until recently, the approach to treatment as well as prognosis was often similar. These subtypes are squamous cell carcinoma (sqNscLc), adenocarcinoma, large cell carcinoma and more poorly differentiated variants (2). squamous cell carcinoma constitutes about 25-30% of all lung cancer. it originates from the bronchial lining, and is often linked to a history of smoking. Adenocarcinoma represents around 40% of lung cancer. it emerges from mucus-secreting cells. While this type of cancer occurs mainly in current and former smokers, it is the most common type of lung cancer occurring in non-smokers. Large-cell carcinoma accounts for about 10% to 15% of lung cancer and tends to grow and spread quickly (1).Treatment options for NscLc have evolved tremendously over the past 15 years, especially with the advent of genetic and molecular techniques to characterize the driver mutations at the cellular level. overall survival (os) rates from lung cancer have been increasing slowly over the past decade for both men and women. This is mainly due to reduction in smoking over the past 50 years, although the decline in the rates of lung cancer in men started significantly before that in women (3). several treatment modalities are being used including surgery, radiation therapy, chemotherapy, targeted therapy, laser therapy, photodynamic therapy, radiofrequency ablation, cryosurgery, electrocautery, and watchful waiting. New modalities are being tested in clinical trials and they include immunotherapy, combination therapies and chemoprevention (4). To date, there are no studies that evaluate the best sequence of available therapies, and as such, the choice of therapy is highly personalized and likely depends on the setting in which available drugs were investigated, stage of disease, cytogenetic or molecular profile, performance status, toxicities, and medical comorbidities.For a long time, lung cancer has been considered to be non-immunogenic. However, after the success of immunotherapies in melanoma (5), there has been great interest and investigation in the immune checkpoint inhibitors in NscLc. These immune inhibitors have shown promising results in front-line therapy and after failure of multiple lines, as well as in monotherapy and combination 377Τhis article is freely accessible online.Correspondence to: imad Tabbara, MD,
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