The aim of this review is to update the current status of allogeneic hemopoietic stem cell transplants (HSCT) for patients with myelofibrosis (MF). We have first summarized the issue of an indication for allogeneic HSCT, discussing several prognostic scoring systems, developed to predict the outcome of MF, and therefore to identify patients who will benefit of an allogeneic HSCT. Patients with low risk MF are usually not selected for a transplant, whereas patients with intermediate or high risk MF are eligible. A separate issue, is how to predict the outcome of HSCT: we will outline a clinical molecular myelofibrosis transplant scoring system (MTSS), which predicts overall survival, ranging from 90% for low risk patients, to 20% for very high risk patients. We will also discuss transfusion burden and spleen size, as predictors of transplant outcome. The choice of a transplant platform including the conditioning regimen, the stem cell source and GvHD prophylaxis, are crucial for a successful program in MF, and will be outlined. Complications such as poor graft function, graft failure, GvHD and relapse of the disease, will also be reviewed. Finally we discuss monitoring the disease after HSCT with donor chimerism, driver mutations and hematologic data. We have made an effort to make this review as comprehensive and up to date as possible, and we hope it will provide some useful data for the clinicians.
Secondary antibody deficiency (SAD) is a frequent manifestation of chronic lymphocytic leukemia (CLL) that increases the risk of infections. However, no formal guideline are available regarding the eligibility for prophylaxis or the delivery method, dosage, frequency of administration and duration of immunoglobulin replacement therapy (IgRT). The aim of this study was to assess the efficacy and safety of subcutaneous IgRT (SCIg) and its impact on quality of life (QoL) of CLL pts in the Covid‐19 era. Ten CLL pts with SAD were treated with subcutaneous IgRT (SCIg) at our institution between October 2019 and December 2020. Median age was 66 years and five patients had comorbidities. Seven patients were receiving therapy for CLL when treatment with SCIg was initiated. All pts received 10 g total dose hyaluronidase‐free SCIg independently from body weight. The IgG level and CD4/CD8, CD19 and CD16/56 lymphocytes subset were recorded at baseline and every 3 months. No patient experienced infectious events nor Covid‐19 mediated interstitial pneumonia while on SCIg therapy. All patients tolerated well the therapy and experienced an increase of IgG levels, which was then stable in time. We conclude that SCIg administration in CLL pts with SAD is efficacious and safe as infectious prophylaxis. This route of administration appears particularly advantageous in the Covid‐19 era, because of the self‐administration at home which results in improvement in the QoL and reduced treatment expenditures.
Measurable residual disease (MRD) is defined as the presence of residual cancer cells after treatment in patients with clinically undetectable disease, who would otherwise be considered in complete remission. It is a highly sensitive parameter which indicates the disease burden and predicts survival in this setting of patients. In recent years, MRD has gained a role in many hematological malignancies as a surrogate endpoint for clinical trials: undetectable MRD has been correlated to longer progression free survival (PFS) and overall survival (OS). New drugs and combinations have been developed with the aim to achieve MRD negativity, which would indicate favorable prognosis. Different methods to measure MRD have also been devised, which include flow cytometry, polymerase chain reaction (PCR) and next generation sequencing (NGS), with different sensitivity and accuracy in evaluating deep remission after treatment. In this review, we will analyze the current recommendations for the detection of MRD, with particular focus on its role in Chronic Lymphocytic Leukemia (CLL), as well as the different detection methods. Moreover, we will discuss the results of clinical trials and the role of MRD in new therapeutic schemes with inhibitors and monoclonal antibodies. MRD is not currently used in the clinical practice to evaluate response to treatment, due to technical and economical limitations, but it’s gaining more and more interest in trials settings, especially since the introduction of venetoclax. The use of MRD in trials will likely be followed by a broader practical application in the future. The aim of this work is to provide a reader-friendly summary of the state of art in the field, as MRD will soon become an accessible tool to evaluate our patients, predict their survival and guide physician’s therapeutic choices and preferences.
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