The Benefits of the Post-Transplant Cyclophosphamide in Both Haploidentical and Mismatched Unrelated Donor Setting in Allogeneic Stem Cells Transplantation.

Allogeneic hematopoietic cell transplantation (alloHSCT) is a standard therapeutic approach for acute leukemias and many other hematologic malignancies. The proper choice of immunosuppressants applicable to different types of transplantations still requires strict and careful consideration, and data in this regard are divergent. For this reason, in this single-centered, retrospective study, we aimed to compare the outcome of 145 patients who received post-transplant cyclophosphamide (PTCy) for MMUD and haplo-HSCT or GvHD prophylaxis for MMUD-HSCT alone. We attempted to verify if PTCy is an optimal strategy in MMUD setting. Ninety-three recipients (93/145; 64.1%) underwent haplo-HSCT while 52 (52/145; 35.9%) underwent MMUD-HSCT. There were 110 patients who received PTCy (93 in haplo and 17 in MMUD group) and 35 patients received conventional GvHD prophylaxis based on antithymocyte globulin (ATG), cyclosporine (CsA), and methotrexate (Mtx) in the MMUD group only. Our study revealed that patients receiving post-transplant cyclophosphamide (PTCy) show decreased acute GvHD rates and CMV reactivation as well as a statistically lower number of CMV copies before and after antiviral treatment compared to the CsA + Mtx + ATG group. Taking into account chronic GvHD, the main predictors are donor age, ≥40 years, and haplo-HSCT administration. Furthermore, the survival rate of patients following MMUD-HSCT and receiving PTCy with tacrolimus and mycophenolate mofetil was more than eight times greater in comparison to patients receiving CsA + Mtx + ATG (OR = 8.31, p = 0.003). These data taken together suggest that the use of PTCy displays more benefits in terms of survival rate compared to ATG regardless of the type of transplantation performed. Nevertheless, more studies with a larger sample size are required to confirm the conflicting results in the literature studies.

Daily received support and relational functioning in HCT survivors and their caregivers.

OBJECTIVES: Numerous authors have expressed their interest in adjustment and social support in the context of cancer. However, none of the previous studies has directly examined the models describing the links between daily social support and adjustment fluctuation, particularly at the relational level. This study aimed to verify the additive and buffering models of daily received support regarding the relational level of patient-caregiver relationship, that is, the relationship-related stress and relationship satisfaction following hematopoietic cell transplantation (HCT). METHODS: Two hundred patient-caregiver dyads participated in a 28-day diary study that was started on the first day after post-HCT discharge. The participants rated the extent of daily relationship-related stress, relationship satisfaction, and received support every evening during the study. The analyses were based on the actor-partner interdependence moderation model. RESULTS: Daily deviations in received support were directly associated with concurrent and lagged daily deviations in relationship satisfaction, regardless of relationship-related stress level in both patients and caregivers. In addition, in caregivers, the effect of daily deviations in received support on relationship satisfaction depended on deviations in relationship-related stress and was significant on the days with higher relationship-related stress. CONCLUSIONS: The findings supported both the additive (in patients and caregivers) and the buffering hypotheses (in caregivers) of daily received support in patient-caregiver dyads during the first month following HCT. The theoretical and practical implications of the findings are further highlighted.

Increased Efficacy of Stem Cell Chemomobilization with Intermediate-Dose Cytarabine Plus Granulocyte Colony-Stimulating Factor (G-CSF) Compared with G-CSF Alone in Patients with Multiple Myeloma: Results of a Randomized Trial.

Mobilization of hematopoietic stem cells for patients with multiple myeloma (MM) may be done using either steady-state granulocyte colony-stimulating factor (G-CSF) or a combination of chemotherapy with G-CSF. The goal of this randomized, open-label, phase 3 trial was to compare the efficacy of chemomobilization using intermediate-dose cytarabine (ID-AraC) plus G-CSF with G-CSF alone in patients with MM referred for tandem autologous stem cell transplantation (autoSCT). The percentage of patients with stem cell yield of at least 5 × 106 CD34+ cells/kg was the primary endpoint. Ninety patients were enrolled, including 44 assigned to the ID-AraC arm and 46 in the G-CSF arm. The threshold number of CD34+ cells was reached in 43 patients (98%) in the ID-AraC arm and in 32 patients (70%) in the G-CSF arm (P = .0003). The median number of collected CD34+ cells was 20.2 × 106 cells/kg in the ID-AraC arm versus 5.9 × 106 cells/kg in the G-CSF arm (P < .000001). A single apheresis was sufficient to achieve the required number of harvested CD34+ cells in 37 patients (86%) in the ID-AraC arm and in 13 patients (41%) in the G-CSF arm (P = .00008). The times to both neutrophil and platelet recovery after autoSCT were significantly shorter in the patients mobilized with ID-AraC. This study provides the first evidence of the advantage of chemomobilization over G-CSF monotherapy in terms of efficacy. ID-AraC with G-CSF should be the preferred chemomobilization protocol for patients with MM scheduled to undergo tandem autoSCT.

Fluctuation in physical symptoms, coping, and mood in patients following hematopoietic stem cell transplantation: assessing mediation effects using a daily diary approach.

This study examines the indirect effect between parallel fluctuation in daily physical symptoms, symptom-related coping, and mood in patients following hematopoietic stem cell transplantation. Two models were analyzed with a within-person mediating role of coping and mood, respectively. Physical symptoms, coping (brooding, reflection, co-rumination, positive reframing, venting, acceptance, and active coping), and positive (PA) and negative affect (NA) were reported by 229 patients for 28 consecutive evenings after post-transplant hospital discharge. The mediating role of coping fluctuation was partially supported since a competitive model assuming coping reactivity was more reliable. Fluctuation in daily PA and NA mediated relationship of physical symptoms with brooding, co-rumination and venting. Daily changes in positive reframing, acceptance and reflection, partially mediated the association between changes in physical symptoms and mood. The study results indicate the usefulness of intervention addressed to the management of daily mood and stimulation of positive reframing and acceptance in post-HSCT patients.

Psychophysical well-being profiles in patients before hematopoietic stem cell transplantation.

OBJECTIVES: The literature offers very few in-depth reports on the time directly before hematopoietic stem cell transplantation (HSCT). Also, researchers have focused on selected aspects of psychophysical well-being and treated the sample as homogeneous. Thus, we chose to investigate distinct multidimensional well-being profiles (including anxiety, depressive symptoms, and health-related quality of life [HRQOL] domains) among patients just before HSCT, as well as profile predictors (generalized self-efficacy) and outcomes (transplant appraisal) on the basis of the transactional stress model. METHODS: Depression (CES-D), anxiety (HADS-A), HRQOL (EORTC QOL-C30), generalized self-efficacy (GSES), and transplant appraisal (single-item scale referred to threat and challenge) were measured in 290 patients (56.9% male; mean age = 47.28, SD = 13.79) after admission for HSCT (67.2% autologous). Unconditional and conditional latent profile analyses were applied. RESULTS: Four latent well-being profiles were identified: well-functioning (51%, highest well-being in all aspects), dysfunctional (10%, weakest functioning in all aspects), and 2 profiles with moderate HRQOL and high (5.6%) or low (33.4%) anxiety and depressive symptoms. Generalized self-efficacy predicted profile membership, controlling for demographic and clinical variables. The highest levels were observed in the well-functioning group (P < .01). Appraisal was predicted by latent profile analyses classes: low threat in the well-functioning group (P < .001) and the highest threat and challenge in the dysfunctional group (P < .01). CONCLUSIONS: The findings highlight the diverse nature of well-being in pre-HSCT patients and the manner in which transplant appraisal and generalized self-efficacy are related to different profiles of pre-HSCT multidimensional well-being, thus indicating the practical implications of the study.

Everyday life following hematopoietic stem cell transplantation: decline in physical symptoms within the first month and change-related predictors.

PURPOSE: Lower quality of life, especially in the physical domain (Physical-QOL), is common in patients after hematopoietic stem cell transplantation (HSCT). However, few studies explore changes in the Physical-QOL, i.e., physical symptoms, in everyday life of patients following HSCT. The present study addresses this gap by examining patient daily physical symptoms and their predictors in terms of demographic and clinical characteristics. METHODS: Physical symptoms were reported by 188 patients (56.9% men; aged 47.6 ± 13.4 years) for 28 consecutive days after post-HSCT hospital discharge. Multilevel modeling was used to investigate fixed and random effects for physical symptom changes over time. RESULTS: The results indicated that the initial level of physical symptoms (immediately after hospital discharge) systematically decreased over 28 days. Treatment toxicity (WHO scale; ß = 0.09, p < .01) and baseline depressive symptoms (CES-D scale; ß = 0.06, p < .01) were associated with the initial level of physical symptoms. Patients with more depressive symptoms before HSCT and with more adverse treatment effects presented with more physical symptoms immediately after hospital discharge. The type of transplant, diagnosis, and conditioning regimen differentiated the course of physical symptoms. Patients with leukemias and other myeloid neoplasms (ß = 0.05, p < .01), after allogeneic HSCT (ß = -0.06, p < .01), and with non-myeloablative conditioning (ß = -0.09, p < .01) showed a significant lower decrease in symptoms over time. Patients with multiple myeloma presented with the most rapid improvement (ß = -.03, p < .05). CONCLUSIONS: The findings suggest a heterogeneous and rather positive response to HSCT. Treatment-related conditions occurred to be a significant predictor of the intensity of change in physical functioning after HSCT.

Comparable safety profile of BeEAM (bendamustine, etoposide, cytarabine, melphalan) and BEAM (carmustine, etoposide, cytarabine, melphalan) as conditioning before autologous haematopoietic cell transplantation.

INTRODUCTION: BEAM (carmustine, etoposide, cytarabine, melphalan) is the most frequently used high-dose chemotherapy regimen for patients with lymphoma referred for autologous haematopoietic cell transplantation (autoHCT). Recently, a novel conditioning protocol containing bendamustine instead of carmustine (BeEAM) has been proposed to potentially increase the efficacy. AIM OF THE STUDY: The aim of this study was to retrospectively compare the safety profile of BEAM and BeEAM based on single-centre experience. MATERIAL AND METHODS: A total of 237 consecutive patients with lymphoma treated with either BEAM (n = 174) or BeEAM (n = 63), between the years 2011 and 2016, were included in the analysis. Clinical characteristics of both groups were comparable. Patients with Hodgkin's lymphoma (HL) constituted 49% of the BEAM group and 40% of the BeEAM group. RESULTS: Median time to neutrophil > 0.5 × 109/l recovery was 10 days in both groups (p = 0.29), while median time to platelet > 50 × 109/l recovery was 13 and 14 days after BEAM and BeEAM, respectively (p = 0.12). The toxicity profile was comparable except for arterial hypertension and severe hypokalaemia, which occurred more frequently after BeEAM compared to BEAM (p = 0.02 and p = 0.004, respectively). The rate of early mortality was 1.7% and 1.6%, respectively. The probabilities of the overall and progression-free survival were comparable for both groups (p = 0.73 and p = 0.55, respectively). CONCLUSIONS: Administration of bendamustine instead of carmustine as part of conditioning does not affect the engraftment or the toxicity profile of the regimen. Therefore, BeEAM may be safely used in patients with lymphoma undergoing autoHCT. Its efficacy requires evaluation in prospective studies.

Increased efficacy of intermediate-dose cytarabine + G-CSF compared to DHAP + G-CSF for stem cell mobilization in patients with lymphoma: an analysis by the polish lymphoma research group.

Salvage regimens, like DHAP (dexamethasone, cytarabine, and cisplatin) are frequently used for stem cell mobilization in lymphoma. The aim of this study was to compare the efficacy of DHAP + G-CSF with intermediate-dose cytarabine (ID-AraC) + G-CSF, recently proposed as an alternative schedule. Consecutive patients with Hodgkin's or non-Hodgkin lymphoma who had received at least 2 lines of chemotherapy, mobilized with either DHAP (n = 51) or ID-AraC (n = 50) + G-CSF were included in the analysis. AraC was administered at the dose of 400 mg/m [1] bid intravenously for 2 days followed by filgrastim starting from day 5. In the AraC group, 96 % of patients collected at least 2 × 10 [2] CD34(+) cells/kg compared to 71 % in the DHAP group (p = 0.0006). The CD34(+) cell yield was 9.3 (0-30.3) × 10 [2]/kg vs. 5.6 (0-24.8) × 10 [2]/kg, respectively (p = 0.006). A single apheresis was sufficient to achieve the threshold number of CD34(+) cells in 82 % of the cases after AraC compared to 45 % after DHAP (p = 0.001). We conclude that stem cell mobilization using ID-AraC is associated with a significantly higher efficacy than DHAP, allowing for collection of the transplant material in almost all patients with lymphoma. Our observation suggests that ID-AraC + G-CSF may be a preferable mobilization regimen in this setting.

The effect of an online acceptance and commitment intervention on the meaning-making process in cancer patients following hematopoietic cell transplantation: study protocol for a randomized controlled trial enhanced with single-case experimental design.

BACKGROUND: Hematopoietic cell transplantation (HCT) is a highly invasive and life-threatening treatment for hematological neoplasms and some types of cancer that can challenge the patient's meaning structures. Restoring meaning (i.e., building more flexible and significant explanations of the disease and treatment burden) can be aided by strengthening psychological flexibility by means of an Acceptance and Commitment Therapy (ACT) intervention. Thus, this trial aims to examine the effect of the ACT intervention on the meaning-making process and the underlying mechanisms of change in patients following HCT compared to a minimally enhanced usual care (mEUC) control group. The trial will be enhanced with a single-case experimental design (SCED), where ACT interventions will be compared between individuals with various pre-intervention intervals. METHODS: In total, 192 patients who qualify for the first autologous or allogeneic HCT will be recruited for a two-armed parallel randomized controlled trial comparing an online self-help 14-day ACT training to education sessions (recommendations following HCT). In both conditions, participants will receive once a day a short survey and intervention proposal (about 5-10 min a day) in the outpatient period. Double-blinded assessment will be conducted at baseline, during the intervention, immediately, 1 month, and 3 months after the intervention. In addition, 6-9 participants will be invited to SCED and randomly assigned to pre-intervention measurement length (1-3 weeks) before completing ACT intervention, followed by 7-day observations at the 2nd and 3rd post-intervention measure. The primary outcome is meaning-related distress. Secondary outcomes include psychological flexibility, meaning-making coping, meanings made, and well-being as well as global and situational meaning. DISCUSSION: This trial represents the first study that integrates the ACT and meaning-making frameworks to reduce meaning-related distress, stimulate the meaning-making process, and enhance the well-being of HCT recipients. Testing of an intervention to address existential concerns unique to patients undergoing HCT will be reinforced by a statistically rigorous idiographic approach to see what works for whom and when. Since access to interventions in the HCT population is limited, the web-based ACT self-help program could potentially fill this gap. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06266182. Registered on February 20, 2024.

Comparing the Outcomes of Matched and Mismatched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation with Different Anti-Thymocyte Globulin Formulations: A Retrospective, Double-Centre Experience on Behalf of the Polish Adult Leukemia Group.

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations-specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06-32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04-0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively).

Optimizing Outcomes in Mismatched Unrelated Donor Allogeneic Transplantation: Post-Transplant Cyclophosphamide's Dual Impact on Graft versus Host Disease Incidence and Overall Survival: Retrospective Analysis on Behalf of Polish Adult Leukemia Group.

Allogeneic hematopoietic cell transplantation (allo-HSCT) stands as an effective treatment method for various hematologic malignancies. However, graft-versus-host disease (GvHD), an intricate immunological phenomenon where donor immune cells target recipient tissues, remains a significant challenge, particularly in mismatched unrelated donors (MMUD). Post-transplant cyclophosphamide (PTCy) has emerged as a promising immunosuppressive strategy, revolutionizing haploidentical transplantation and demonstrating promise in MMUD settings. Background/Objectives: This study aimed to evaluate the impact of PTCy on MMUD allo-HSCT outcomes, specifically its effects on GvHD incidence and overall survival, compared to anthitymocyte globulin (ATG). Methods: One hundred seventy-four patients were classified into three groups based on the type of transplantation: PTCy-haplo (114/174; 65.5%), PTCy-MMUD (23/174; 13.2%), and ATG-MMUD (37/174; 21.2%). Results: Our findings showed that PTCy-MMUD significantly reduced acute GvHD occurrence compared to PTCy-haplo and ATG-MMUD approaches (p = 0.006). The delayed onset of acute GvHD in the PTCy-MMUD group suggests a more controlled immune reconstitution, contributing to the lower incidence. Importantly, PTCy-MMUD exhibited enhanced five-year overall survival rates, aligning with the notion that reduced GvHD correlates with improved patient outcomes (p = 0.032). Conclusions: We believe that this study contributes valuable insights into PTCy-MMUD's management, underscoring its potential to significantly reduce GvHD incidence and enhance survival outcomes. Although further investigations and clinical trials are warranted, this research underscores the promising role of PTCy-based GvHD prophylaxis in improving MMUD allo-HCT success.

Soluble MICA concentrations and genetic variability of MICA and its NKG2D receptor as factors affecting Graft-versus-Host Disease development after allogeneic haematopoietic stem cell transplantation.

Despite new treatment strategies, graft-versus-host disease (GvHD) remains a formidable complication after allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the impact of polymorphisms and expression of MICA and NKG2D receptor on the development of GvHD in allogeneic HSCT recipients. Soluble MICA (sMICA) concentration was measured in serum collected 30 days after transplantation and the genetic variability of MICA and NKG2D genes was evaluated. The frequency of NKG2D+NK cells was determined by flow cytometry before and (21, 30, 60 and 90 days) after transplantation. Recipients with acute GvHD grades II-IV carried the NKG2D rs1049174 C allele more frequently than controls or patients with no or mild disease. Patients with chronic GvHD had higher frequency of NKG2D expressing NK cells posttransplant, reflecting increased activity of their NK cells. Although no direct relationship between MICA SNPs and GvHD were observed, the presence of MICA rs1051792 GG genotype correlated with elevated sMICA levels and increased serum level of sMICA was associated with higher risk of chronic GvHD. Our findings suggest that sMICA concentration may serve as a potential biomarker for chronic GvHD and emphasize the impact of genetic variability of NKG2D and its surface expression on the HSCT outcome.

Unravelling the potential of TIM-3 gene polymorphism in allogeneic hematopoietic stem cell transplantation - a preliminary study.

BACKGROUND: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) molecule is a key regulator of the immune response by exerting an inhibitory effect on various types of immune cells. Understanding the role of TIM-3 in hematopoietic stem cell transplantation (HSCT) may improve transplant outcomes. Our study evaluated the potential association between TIM-3 polymorphisms, namely rs1036199 (A > C) or rs10515746 (C > A), changes which are located in exon 3 and the promoter region of the TIM-3 gene, and post-HSCT outcomes. METHODS: One-hundred and twenty allogeneic HSCT patients and their respective donors were enrolled and genotyped for TIM-3 single nucleotide polymorphisms (SNPs) using real-time PCR with TaqMan assays. RESULTS: We found that the presence of the rare alleles and heterozygous genotypes of studied SNP in recipients tended to protect against or increase the risk for acute graft-versus-host disease (aGvHD). For the rs1036199 polymorphism, recipients with the AC heterozygous genotype (p = 0.0287) or carrying the rarer C allele (p = 0.0334) showed a lower frequency of aGvHD development along all I-IV grades. A similar association was detected for the rs10515746 polymorphism as recipients with the CA genotype (p = 0.0095) or the recessive A allele (p = 0.0117) less frequently developed aGvHD. Furthermore, the rarer A allele of rs10515746 SNP was also associated with a prolonged aGvHD-free survival (p = 0.0424). Cytomegalovirus (CMV) infection was more common in patients transplanted with TIM-3 rs10515746 mismatched donors (p = 0.0229) and this association was also found to be independent of HLA incompatibility and pre-transplant CMV-IgG status. Multivariate analyses confirmed the role of these recessive alleles and donor-recipient TIM-3 incompatibility as an independent factor in aGvHD and CMV development. CONCLUSIONS: Polymorphism of TIM-3 molecule may affect the immune response in HSCT patients. The recessive alleles of rs1036199 and rs10515746 SNPs decreased the risk of developing aGvHD. TIM-3 donor-recipient genetic matching may also affect the risk of post-transplant CMV infection, indicating the potential value of genetic profiling in optimizing transplant strategies.

Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group.

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.

MICB Genetic Variants and Its Protein Soluble Level Are Associated with the Risk of Chronic GvHD and CMV Infection after Allogeneic HSCT.

The aim of the present study was to determine the associations between the MICB genetic variability and the expression and the risk of development of post-transplant complications after allogeneic hematopoietic stem cell transplantation (HSCT). HSCT recipients and their donors were genotyped for two MICB polymorphisms (rs1065075, rs3828903). Moreover, the expression of a soluble form of MICB was determined in the recipients' serum samples after transplantation using the Luminex assay. Our results revealed a favorable role of the MICB rs1065075 G allele. Recipients with donors carrying this genetic variant were less prone to developing chronic graft-versus-host disease (cGvHD) when compared to recipients without any symptoms of this disease (41.41% vs. 65.38%, p = 0.046). Moreover, the MICB rs1065075 G allele was associated with a lower incidence of cytomegalovirus (CMV) reactivation, both as a donor (p = 0.015) and as a recipient allele (p = 0.039). The MICB rs1065075 G variant was also found to be associated with decreased serum soluble MICB (sMICB) levels, whereas serum sMICB levels were significantly higher in recipients diagnosed with CMV infection (p = 0.0386) and cGvHD (p = 0.0008) compared to recipients without those complications. A protective role of the G allele was also observed for the rs3828903 polymorphism, as it was more frequently detected among donors of recipients without cGvHD (89.90% vs. 69.23%; p = 0.013). MICB genetic variants, as well as serum levels of sMICB, may serve as prognostic factors for the risk of developing cGvHD and CMV infection after allogeneic HSCT.

Meaning-reconstruction factors and well-being in cancer survivor-caregiver dyads: Daily associations and mechanisms.

OBJECTIVE: The study aimed to expand the existing research on the meaning-making processes in cancer by examining (a) the relationship between daily meaning making and meanings made versus the emotional and social well-being in survivor-caregiver dyads, (b) whether meanings made moderated or mediated the meaning-making-well-being associations at the within- and between-dyad level, and (c) whether meaning factors varied across or within persons. METHODS: Two hundred dyads completed measures of meaning making, meanings made, positive and negative affect, and loneliness for 28 consecutive posthospitalization days following hematopoietic cell transplantation. Computations were based on the actor-partner interdependence model and its extensions, using multilevel structural equation modeling. RESULTS: Positive emotional effects of meanings made and mixed effects of meaning making were found. Meanings made mediated, but not moderated, the association between meaning making and affect. Meaning factors varied substantially between- but less so within-person. CONCLUSIONS: Further research on the meaning-making process and practical actions will require a greater focus on the level of the analysis, the role in the dyad, and interpersonal aspects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells.

Transplantation of hematopoietic stem cells (HSCT) is a procedure commonly used in treatment of various haematological disorders which is associated with significantly improved survival rates. However, one of its drawbacks is the possibility of development of post-transplant complications, including acute and chronic graft-versus-host disease (GvHD) or CMV infection. Various studies suggested that NK cells and their receptors may affect the transplant outcome. In the present study, patients and donors were found to significantly differ in the distribution of the NKG2A rs7301582 genetic variants - recipients carried the C allele more often than their donors (0.975 vs 0.865, p<0.0001). Increased soluble HLA-E (sHLA-E) levels detected in recipients' serum 30 days after transplantation seemed to play a prognostic and protective role. It was observed that recipients with higher sHLA-E levels were less prone to chronic GvHD (11.65 vs 6.33 pg/mL, p=0.033) or more severe acute GvHD grades II-IV (11.07 vs 8.04 pg/mL, p=0.081). Our results also showed an unfavourable role of HLA-E donor-recipient genetic incompatibility in CMV infection development after transplantation (OR=5.92, p=0.014). Frequencies of NK cells (both CD56dim and CD56bright) expressing NKG2C were elevated in recipients who developed CMV, especially 30 and 90 days post-transplantation (p<0.03). Percentages of NKG2C+ NK cells lacking NKG2A expression were also increased in these patients. Moreover, recipients carrying a NKG2C deletion characterized with decreased frequency of NKG2C+ NK cells (p<0.05). Our study confirms the importance of NK cells in the development of post-transplant complications and highlights the effect of HLA-E and NKG2C genetic variants, sHLA-E serum concentration, as well as NKG2C surface expression on transplant outcome.

Daily stress and received social support in hematopoietic cell transplant patient-caregiver dyads.

BACKGROUND AND OBJECTIVE: Reception of social support may foster adjustment in dyads facing cancer treatment. Still, understanding of the effects of received support in everyday life of patient-caregiver dyads remains limited. This study investigated whether the positive effect of daily received social support depends on daily stress levels and whether the effect differs by perspective (recipient vs. provider) in dyads undergoing hematopoietic cell transplantation (HCT). DESIGN AND METHODS: The sample comprised 200 patient-caregiver dyads after HCT. The participants completed measures of daily stress levels, received and provided social support as well as affect for 28 consecutive days. RESULTS: Regardless of daily stress levels, the caregivers reported better affect on days when they noticed more received support (recipient perspective), whereas the patients reported worse affect on days when they noticed more received support (recipient perspective) and/or when their caregivers reported higher provided support (provider perspective). CONCLUSION: The effects of daily received support were not related to the levels of daily stress in patient-caregiver dyads after HCT. Also, the effects varied by role (benefits in the caregivers vs. harm in the patients) and perspective (similarities in the patients vs. differences in the caregivers).

Daily analysis of autonomy support and well-being in patient-caregiver dyads facing haematopoietic cell transplantation.

OBJECTIVES: Caregivers may restore patient self-determination in disease by supporting their autonomy, and thus enhance their well-being. In this study, we investigated the between- and within-person effects of recipient-reported and provider-reported autonomy support on patient daily biopsychosocial well-being in patient-caregiver dyads following haematopoietic cell transplantation (HCT). DESIGN: A dyadic daily-diary study conducted for 28 days after patients' hospital discharge following HCT. METHODS: Patients and their caregivers (N = 200) participated in a 28-day daily-diary study. They completed measures of daily autonomy support reception (patients) and provision (caregivers), subjective physical health, affect (positive/negative), and relationship satisfaction. RESULTS: The patient's feeling of being supported in their autonomy was associated with their better positive affect and relationship satisfaction, both overall (between-person effect) and daily (within-person effect). Caregiver-reported overall and daily support of patient autonomy did not predict patient daily biopsychosocial well-being. CONCLUSIONS: These findings extended the evidence that autonomy support reported by patients facing HCT may have both accumulative and acute beneficial effects on their psychological and social well-being.

The role of psychological flexibility in the meaning-reconstruction process in cancer: The intensive longitudinal study protocol.

OBJECTIVES: Meaning-making is an important element of adapting to disease. However, this process is still poorly understood and the theoretical model has not been comprehensively verified yet, particularly in terms of complexity, dynamics, and intraindividual variability. The aim of this study is a deeper understanding of the meaning-reconstruction process in cancer and empirical verification of the integrative meaning-making model of coping extended by the psychological flexibility model. We postulate that psychological flexibility can foster the meaning-making in cancer by building more flexible and workable meaning-making explanations of disease. DESIGN: A daily-diary study conducted for 14 days in patients following the first autologous or allogeneic hematopoietic cell transplantation (HCT). METHODS: Participants (at least 150) will be requested to complete the daily-diary related to daily situational meaning, meaning-related distress, meaning-making, psychological flexibility, meanings made, and wellbeing for 14 days after hospital discharge following HCT. Also, baseline and follow-up assessment of global meaning, wellbeing, and meanings made will be performed. Statistical analysis of the data will be conducted using the multilevel and dynamic structural equation modeling. CONCLUSIONS: The study will fill in the gaps in health psychology in the understanding of the meaning-reconstruction process in cancer by within- and between-person verification of the integrative meaning-making model and its extension by the psychological flexibility model. The data obtained will be used in further research on the development of meaning-making by means of interventions based on psychological flexibility.