Safe discontinuation of nilotinib in a patient with chronic myeloid leukemia: a case report

Case presentation. We report the case of a 64-year-old Caucasian man diagnosed with chronic-phase chronic myeloid leukemia in April 2005. After 4 years of treatment with imatinib, he became intolerant to the drug and was switched to nilotinib. Two years later, he decided to stop nilotinib. Undetectable molecular response persisted for 30 months after discontinuation of the drug. Introduction. Although there is a considerable amount of data in the literature on safe discontinuation of first-generation tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia, little is known about discontinuation of second-generation tyrosine kinase inhibitor therapy. Most previous studies have been focused on dasatinib, and the few cases of nilotinib withdrawal that have been reported had a median follow-up of 12 months. To the best of our knowledge, the present report is the first to describe nilotinib withdrawal with 30 months of follow-up. Conclusion: Our present case suggests that nilotinib withdrawal is safe for patients with chronic myeloid leukemia who achieve a stable undetectable molecular response. Our patient was homozygous for killer immunoglobulin-like receptor haplotype A, previously reported to be a promising immunogenetic marker for undetectable molecular response. We recommend additional studies to investigate patient immunogenetic profiles and their potential role in complete response to therap

Bone marrow homing and engraftment defects of human hematopoietic stem and progenitor cells

Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process. In this overview, we analyze the characteristics of stem cells (SCs) with particular emphasis on their plasticity and ability to find their way home to the bone marrow. We also address the problem of graft failure which remains a significant contributor to morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Within this context, we discuss non-malignant and malignant hematological disorders treated with reduced-intensity conditioning regimens or grafts from human leukocyte antigen (HLA)-mismatched donor

Early Death in Two Patients with Acute Promyelocytic Leukemia Presenting the bcr3 Isoform, FLT3-ITD Mutation, and Elevated WT1 Level

Despite major advances in the treatment of acute promyelocytic leukemia (APL), the problem of early death (ED) remains unsolved. Alongside the currently known clinical and hematological risk factors, prognostic significance has been attributed to internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD), hypogranular variant morphology, and the bcr-3 isoform of PML-RARα. We describe premature death of two patients with the hypogranular variant of APL who presented remarkably high expression levels of Wilms' tumor gene (WT1). Our results point to WT1 as an important prognostic factor of ED that needs to be promptly evaluated in all newly diagnosed cases of APL

Clinical course and features of persistent polyclonal B-cell lymphocytosis with BCL-6 amplification during pregnancy

Background: Persistent polyclonal B-cell lymphocytosis is a rare nonmalignant disorder characterized by mild persistent lymphocyte proliferation with possible evolution to aggressive lymphoma. Its biology is not well known, but it is characterized by a specific immunophenotype with rearrangement of the BCL-2/IGH gene, whereas amplification of the BCL-6 gene has rarely been reported. Given the paucity of reports, it has been hypothesized that this disorder is associated with poor pregnancy outcomes. Case report: To our knowledge, only two successful pregnancies have been described in women with this condition. We report the third successful pregnancy in a patient with PPBL and the first with amplification of the BCL-6 gene. Conclusions: PPBL is still a poorly understood clinical condition with insufficient data to demonstrate an adverse effect on pregnancy. The role of BCL-6 dysregulation in the pathogenesis of PPBL and its prognostic significance are still unknown. Evolution into aggressive clonal lymphoproliferative disorders is possible and prolonged hematologic follow-up is warranted in patients with this rare clinical disorder

Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

Background: Beta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent. Discussion: Thalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy or accept the high mortality risk of HSCT in the hope of obtaining complete recovery. Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome. Summary: Only if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients

Adherence to treatment in patients with solid and hematological cancers. Could spiritual and psychological support facilitate optimal adherence?

ABSTRACT – Objective: Cancer-related diseases pose a substantial public health challenge; however, recent treatments have enhanced patient outcomes. Adherence to therapy is crucial, and research focuses on elucidating the factors that influence it. Limited information exists on medication adherence in cancer patients. This study aims to identify risk factors for non-adherence in a cohort of people with solid and hematological tumors. Participants and Methods: This is a cross-sectional study in which participants were recruited from two Oncologic hospital units in Italy. The inclusion criteria were age ≥ 18 years, confirmed malignant neoplasm, and active treatment. Data included sociodemographic and clinical-oncological factors. Treatment adherence was assessed through a clinician-based dichotomous scale. Health-related quality of life (HRQoL) was evaluated with the Short Form Health Survey – 12 items (SF-12), satisfaction with care was measured using the Treatment Perception Questionnaire. Results: A total of 263 participants (132 females, 50.2%) was involved in this study. The mean age was 61.2±13.8. Non-adherence frequency was 9.9%. Factors associated with non-adherence were shorter time since care initiation (<6 months), receiving palliative care, having a solid cancer diagnosis. Non-adherence was higher in solid cancer (12.4%) compared to hematologic cancer (1.6%). In the combination of risk factors, a significant association was found between unemployment/high level of education and non-adherence. Conclusions: The study found a low non-adherence rate to oncological treatments, possibly due to strong psychological and spiritual support. However, individuals with higher education and unemployment showed specific non-adherence risk, necessitating attention to their emotional challenges while facing canc

Low adherence to therapy and co-morbid depressive episodes are independent determinants of early death in people with cancer

Objective: The demanding nature of oncological therapies may affect treatment motivation and adherence, leading to an increased risk of premature death. Exploring the interaction between depressive episodes and treatment adherence is essential, considering how depression may influence patients' willingness to continue treatment. This study aims to investigate the association between depressive episodes, low treatment adherence, and premature death in individuals with cancer. The study also assessed whether low adherence to therapy acted as a mediator in the relationship between depression and the risk of early death. Participants and Methods: This is a 9-month cohort study in which participants were enrolled in two Italian Oncology hospital units. The Patient Health Questionnaire (PHQ-9) was used for depression screening. Stratified analyses were conducted to explore the relationship between depression, low adherence, and premature death. Results: Out of 263 subjects, depressive episode frequency was 48.2% and low adherence was 9.9%. After 9 months, 13.7% had died. There was a significative association between experiencing a depressive episode (RR=2.14, 95% CI: 1.08-4.39) and low adherence (RR=2.2, 95% CI: 1.01-4.48) upon cohort entry and being deceased at month 9 of observation. The risk associated with depression was found to persist even after accounting for the level of adherence to therapy through standardization (MH-OR=3.11; 95% CI: 1.52-6.34). Conclusions: Individuals with cancer who experience a depressive episode or demonstrate low adherence to therapy are at risk for premature death. Early intervention targeting depressive symptoms and treatment adherence may improve oncological-related outcomes