Impact of tailored patient education on adherence of patients with chronic myeloid leukaemia to tyrosine kinase inhibitors: a randomized multicentre intervention study.

AIMS: The aim of this study was to evaluate the influence of tailored patient education on adherence to tyrosine kinase inhibitor medication among patients with chronic myeloid leukaemia. BACKGROUND: Management of chronic myeloid leukaemia has changed dramatically during the last decade. While medication adherence is crucial to clinical response, little is known about how to improve patients' adherence. DESIGN: Randomized multicentre intervention study. METHODS: The study was conducted between June 2012-August 2014. Eighty-six patients with chronic myeloid leukaemia who had been on tyrosine kinase inhibitor medication for at least six months from eight hospitals were randomized into intervention and control groups. Intervention combined nurse-conducted medication counselling, an information booklet, video and website and text message reminders. Patients were interviewed to assess medication adherence using Morisky's 8-Item Medication Adherence Scale at baseline and nine months. RESULTS: Medication adherence improved with the adherence aids used. At nine months, 51% of patients were highly adherent in the intervention group, compared with 21% in the control group. Adherence improved for a higher proportion of patients in the intervention group than the control group (49% vs. 18%). Morisky's score decreased in almost half of control group cases. Patients were most satisfied with face-to-face counselling (86%) and the information booklet (83%) and least satisfied with text messages (9%). CONCLUSION: Tailored patient education improved the medication adherence of patients with chronic myeloid leukaemia. Without this, adherence behaviour tended to decline. Personal communication with a nurse proved to be an essential part of adherence support and should not be ignored.

Chronic myeloid leukemia patients' adherence to peroral tyrosine kinase inhibitors compared with adherence as estimated by their physicians.

PURPOSE: To evaluate chronic myeloid leukemia (CML) patients' adherence to peroral tyrosine kinase inhibitors in Finland and to compare this with adherence as estimated by their physicians. Other aspects studied included how patients' knowledge of the disease and its treatment influence adherence. MATERIALS AND METHODS: A total of 120 CML patients were contacted between June 2012 and September 2013 in eight secondary or tertiary care hospitals in Finland. Of these, 86 participated in the study. This covers approximately 20% of all Finnish CML patients. The mean age was 57.8 years and 52% were male. Of the patients, 79.1% were using imatinib, 10.5% dasatinib, and 10.5% nilotinib. The patient-reported adherence (experienced adherence) was evaluated using the eight-item Morisky Medication Adherence Scale (MMAS). In addition, the treating physicians were asked to give their subjective opinion on their patients' adherence (observed adherence). The experienced adherence was compared with the observed adherence using a three-level rating system (high, medium, low). All patients were personally interviewed and their demographic data collected. The statistical analysis of the data was based on descriptive statistics presented as frequencies, percentages, means, and medians. The kappa coefficient was calculated between the patient's and the doctor's assessment of adherence. RESULTS: A total of 23% (20/86) of the patients were fully adherent according to the MMAS, while physicians evaluated 94% (80/86) of the patients as fully adherent. The physicians' estimate was too optimistic in 73% of cases. The discrepancy was confirmed by a kappa value of -0.004. The patients' knowledge of the disease and its treatment was poor in all adherence levels. CONCLUSION: The patient-reported adherence to tyrosine kinase inhibitor treatments in Finland was found to be the same as that found in the majority of previous studies. However, there seems to be a very weak agreement between the patient's and the physician's assessment of adherence. This study suggests that physicians overestimate the adherence of CML patients and base their assessment primarily on the clinical treatment response.

Leukocyte transfusions revisited: stem cell graft stimulation in graft failure.

BACKGROUND: The aim was to evaluate the role of leukocyte transfusions (LTX) in relation to graft function during prolonged neutropenia after stem cell transplantation (SCT). PROCEDURE: In 1989-2005, 22 SCT patients have received LTX in our unit. In all patients severe infection with profound neutropenia (<0.2 x 10(9)/L) preceded LTX. 13/22 had multi-organ failure or thrombotic microangiopathy. Irradiated leukocytes from pooled random donor products at 1.0 x 10(10) leukocytes/m(2)/day for a minimum of 3 days were used. Myeloid recovery and clinical benefit were analyzed. RESULTS: Engraftment defined as an absolute neutrophil count (ANC) of >0.5 x 10(9)/L on three consecutive days was observed in 15/22 (68%) patients at median of 6 (range 2-25) days after LTX, and sustained engraftment (ANC of >0.5 x 10(9)/L for 4 weeks) in 11/22 (50%) patients. Clinical benefit was observed in 6/22 (27%) patients with a prolonged antecedent neutropenia, who still demonstrated rapid sustained engraftment after LTX. Ongoing thrombotic microangiopathy was associated with persistent graft failure. CONCLUSIONS: LTX from random donors was associated with a rapid recovery of myeloid function in severely ill SCT patients. We speculate that allostimulation by LTX may have a role.

A defect of regulatory T cells in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic recessive disease characterized by autoimmunity against multiple tissues, offers a unique possibility to study the breakdown of self-tolerance in humans. It is caused by mutations in the autoimmune regulator gene (AIRE), which encodes a transcriptional regulator. Work using Aire(-/-) mice suggests that Aire induces ectopic expression of peripheral Ags and promotes their presentation in the thymus. We have explored reasons for the difference between the comparatively mild phenotype of Aire-deficient mice and human APECED patients. We provide evidence that, unlike in the Aire(-/-) mice, in the patients a key mediator of active tolerance, the CD4(+)CD25(+) regulatory T (Treg) cell subset is impaired. This was shown by significantly decreased expression of FOXP3 mRNA and protein, decreased function, and alterations in TCR repertoire. Also, in the normal human thymus a concentric accumulation of AIRE(+) cells was seen around thymic Hassall's corpuscles, suggesting that in the patients these cells may be involved in the observed Treg cell failure. In Aire(-/-) mice the expression of FoxP3 was normal and even increased in target tissues in parallel with the lymphocyte infiltration process. Our results suggest that a Treg cell defect is involved in the pathogenesis of APECED and emphasize the importance of active tolerance mechanisms in preventing human autoimmunity.

Prognostic value of pretransplantation host thymic function in HLA-identical sibling hematopoietic stem cell transplantation.

Thymic function is critical for immune reconstitution after hematopoietic stem cell transplantation (HSCT). We evaluated recipient thymic function before HSCT by quantifying T-cell receptor excision circles (TRECs) in pretransplantation peripheral blood lymphocytes from 102 patients who received HSCs from an HLA-identical sibling for malignant (n = 87) or nonmalignant diseases (n = 15). Median TREC value before transplantation was 257 TRECs per 150,000 CD3+ cells (range, 0-42,746). We assessed 172 TRECs per 150,000 CD3+ cells as the most discriminating TREC value for survival in a first cohort of patients (n = 62). This cut-off was validated in a second independent prospective group of 40 patients. In the 102 patients, a TREC value greater than or equal to 172 was associated with a better survival (P < .000 01), a decreased incidence of grade II-IV acute graft-versus-host disease (GVHD; P = .017), chronic GVHD (P = .023), and bacterial (P = .003) and cytomegalovirus (CMV) infection (P = .024). In a multivariate analysis, low pretransplantation TREC values were associated with a higher incidence of CMV infection (hazard ratio [HR] = 2.0, P = .06) and severe bacterial infections (HR = 2.8, P = .036). Finally, high TREC values (HR = 6.6, P = .002) and ABO compatibility (HR = 2.7, P = .02) were associated with a better survival. Therefore, recipient host thymic function assessment could be helpful in predicting HSCT outcome and identifying patients who require a close immunologic monitoring.

A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation.

Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study was designed to evaluate T-cell reconstitution using combined approaches of phenotyping, analysis of alphabeta T-cell receptor (TCR) diversity, and assessment of ex vivo thymic function by measuring TCR rearrangement excision circles (TRECs). Ten patients who underwent CB transplantation for high-risk hematologic disorders were compared to a reference group of 19 age- and GVHD-matched patients who underwent transplantation with non-T cell-depleted bone marrow from an HLA-identical sibling donor. TREC values correlated with the relative number of naive T cells and with TCR repertoire polyclonality. During the first year after transplantation, TCR repertoires were highly abnormal and TREC values low in both groups. Notably, 2 years after transplantation onward TREC values as well as TCR diversity were higher in CB recipients than in recipients of bone marrow transplants. These data indicate an efficient thymic regeneration pathway from CB lymphoid progenitors despite the low number of cells infused compared to bone marrow, arguing for a complete clinical immune recovery after CB transplantation.