Sharing and caring: The impact of social support on quality of life and health outcomes in hematopoietic stem cell transplantation.

BACKGROUND: Social support is crucial for successful recovery after hematopoietic stem cell transplantation (HSCT) and has the potential to affect patient quality of life (QOL) and health outcomes. However, there are limited data on the relationship between a patient's perception of his or her social support and these outcomes. METHODS: The authors conducted a secondary analysis of 250 autologous and allogeneic HSCT recipients enrolled in 2 supportive care trials at Massachusetts General Hospital from April 2011 through February 2016. They assessed social support as a patient's perception of his or her social well-being via the social well-being subscale of the Functional Assessment of Cancer Therapy. The authors used multivariate regression analyses to examine the relationship between pretransplant social well-being and QOL (Functional Assessment of Cancer Therapy-Treatment Outcome Index), psychological distress (Hospital Anxiety and Depression Scale), posttraumatic stress disorder [PTSD] symptoms (PTSD Checklist), fatigue (Functional Assessment of Cancer Therapy-Fatigue), and health care utilization (hospitalizations and days alive and out of the hospital) 6 months after HSCT. RESULTS: Participants were on average 56.4 years old (SD, 13.3 years); 44% (n = 110) and 56% (n = 140) received autologous and allogeneic HSCT, respectively. Greater pre-HSCT social well-being was associated with higher QOL (B = 0.10; 95% CI, 0.06-0.13; P < .001), lower psychological distress (B = -0.21; 95% CI, -0.29 to -0.12; P < .001), and lower PTSD symptoms (B = -0.12; 95% CI, -0.19 to -0.06; P < .001). Pre-HSCT social well-being was not significantly associated with fatigue or health care utilization 6 months after HSCT. CONCLUSIONS: Patients with higher pre-HSCT perceptions of their social support reported better QOL and lower psychological distress 6 months after HSCT. These findings underscore the potential for social support as a modifiable target for future supportive care interventions to improve the QOL and care of HSCT recipients.

Multimodal psychosocial intervention for family caregivers of patients undergoing hematopoietic stem cell transplantation: A randomized clinical trial.

BACKGROUND: Caregivers of patients undergoing hematopoietic stem cell transplantation (HCT) experience an immense caregiving burden before, during, and after HCT. METHODS: We conducted an unblinded, randomized trial of a psychosocial intervention (BMT-CARE) for caregivers of patients undergoing autologous and allogeneic HCT at Massachusetts General Hospital. Caregivers were randomly assigned to BMT-CARE or usual care. BMT-CARE was tailored to the HCT trajectory and integrated treatment-related education and self-care with cognitive-behavioral skills to promote coping. Caregivers assigned to BMT-CARE met with a trained interventionist (a psychologist or a social worker) in person, via telephone, or via videoconferencing for 6 sessions starting before HCT and continuing up to day +60 after HCT. The primary endpoint was feasibility, which was defined as at least 60% of eligible caregivers enrolling and completing 50% or more of the intervention sessions. We assesed caregiver quality of life (QOL; Caregiver Oncology Quality of Life Questionnaire), caregiving burden (Caregiver Reaction Assessment), psychological distress (Hospital Anxiety and Depression Scale), self-efficacy (Cancer Self-Efficacy Scale-Transplant), and coping (Measures of Current Status) at baseline and 30 and 60 days after HCT. We used mixed linear effect models to assess the effect of BMT-CARE on outcomes longitudinally. RESULTS: We enrolled 72.5% of eligible caregivers (100 of 138), and 80% attended 50% or more of the intervention sessions. Caregivers randomized to BMT-CARE reported improved QOL (B = 6.11; 95% CI, 3.50-8.71; P < .001), reduced caregiving burden (B = -6.02; 95% CI, -8.49 to -3.55; P < .001), lower anxiety (B = -2.18; 95% CI, -3.07 to -1.28; P < .001) and depression symptoms (B = -1.23; 95% CI, -1.92 to -0.54; P < .001), and improved self-efficacy (B = 7.22; 95% CI, 2.40-12.03; P = .003) and coping skills (B = 4.83; 95% CI, 3.04-6.94; P < .001) in comparison with the usual-care group. CONCLUSIONS: A brief multimodal psychosocial intervention tailored for caregivers of HCT recipients is feasible and may improve QOL, mood, coping, and self-efficacy while reducing the caregiving burden during the acute HCT period.

High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML.

Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 World Health Organization classification and is associated with a favorable prognosis. Although previous studies have evaluated NPM1 in a binary fashion, little is known about the significance of its mutant allele burden at diagnosis, nor has the effect of comutations (other than FLT3) been extensively evaluated. We retrospectively used targeted sequencing data from 109 patients with de novo AML with mutated NPM1 to evaluate the potential significance of NPM1 variant allele frequency (VAF), comutations, and clinical parameters with regard to patient outcomes. We observed that high NPM1 VAF (uppermost quartile) correlated with shortened overall survival (median, 12.1 months vs not reached; P < .0001) as well as event-free survival (median, 7.5 vs 65.44 months; P < .0001) compared with the other NPM1-mutated cases. In both univariate and multivariable analyses, high NPM1 VAF had a particularly adverse prognostic effect in the subset of patients treated with stem-cell transplantation in first remission (P = .0004) and in patients with mutated DNMT3A (P < .0001). Our findings indicate that the prognostic effect of NPM1 mutation in de novo AML may be influenced by the relative abundance of the mutated allele.

Quality of life and mood predict posttraumatic stress disorder after hematopoietic stem cell transplantation.

BACKGROUND: During hospitalization for hematopoietic stem cell transplantation (HCT), patients experience a steep deterioration in quality of life (QOL) and mood. To our knowledge, the impact of this deterioration on patients' QOL and posttraumatic stress disorder (PTSD) symptoms after HCT is unknown. METHODS: We conducted a prospective longitudinal study of patients hospitalized for HCT. They assessed QOL using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) and depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) at the time of admission for HCT, during hospitalization, and 6 months after HCT. We also used the Hospital Anxiety and Depression Scale (HADS) to measure patients' anxiety and depression symptoms at baseline and during HCT hospitalization. The PTSD Checklist was used to assess for PTSD symptoms. Multivariable linear regression models were used to identify predictors of QOL and PTSD symptoms at 6 months. RESULTS: We enrolled 90 of 93 consecutively eligible patients (97%) undergoing autologous and allogeneic HCT. Data at 6 months were available for 67 participants. At 6 months, 28.4% of participants met the criteria for PTSD and 43.3% had clinically significant depression. On multivariable regression analyses adjusting for significant covariates, changes in QOL and depression scores from week 2 of HCT hospitalization to baseline predicted worse QOL (changes in scores between week 2 and baseline [Δ] QOL: ß, 0.94 [P<.0001] and Δ PHQ-9: ß, -2.59 [P = 0.001]) and PTSD symptoms (Δ QOL: ß, -0.40 [P<.0001] and Δ PHQ-9: ß, 1.26 [P<.0001]) at 6 months after HCT. CONCLUSIONS: Six months after HCT, a significant percentage of patients met the criteria for PTSD and depression. A decline in QOL and an increase in depressive symptoms during hospitalization for HCT were found to be the most important predictors of 6-month QOL impairment and PTSD symptoms. Therefore, managing symptoms of depression and QOL deterioration during HCT hospitalization may be critical to improving QOL at 6 months and reducing the risk of PTSD. Cancer 2016;122:806-812. © 2015 American Cancer Society.

Effect of Inpatient Palliative Care on Quality of Life 2 Weeks After Hematopoietic Stem Cell Transplantation: A Randomized Clinical Trial.

Importance: During hospitalization for hematopoietic stem cell transplantation (HCT), patients receive high-dose chemotherapy before transplantation and experience significant physical and psychological symptoms and poor quality of life (QOL). Objective: To assess the effect of inpatient palliative care on patient- and caregiver-reported outcomes during hospitalization for HCT and 3 months after transplantation. Design, Setting, and Participants: Nonblinded randomized clinical trial among 160 adults with hematologic malignancies undergoing autologous/allogeneic HCT and their caregivers (n = 94). The study was conducted from August 2014 to January 2016 in a Boston hospital; follow-up was completed in May 2016. Interventions: Patients assigned to the intervention (n=81) were seen by palliative care clinicians at least twice a week during HCT hospitalization; the palliative intervention was focused on management of physical and psychological symptoms. Patients assigned to standard transplant care (n=79) could be seen by palliative care clinicians on request. Main Outcomes and Measures: Primary: change in patient QOL from baseline to week 2; secondary: patient-assessed mood, fatigue, and symptom burden scores at baseline, 2 weeks, and 3 months after HCT and caregiver-assessed QOL and mood at baseline and 2 weeks after HCT. Results: Among 160 enrolled patients (mean age, 60 [SD, 13.3] years; 91 women [56.9%]; median hospital stay, 21 days) and 94 caregivers, 157 (98.1%) and 89 (94.7%), respectively, completed 2-week follow-up, and 149 patients (93.1%) completed 3-month follow-up. Patients in the intervention group reported a smaller decrease in QOL from baseline to week 2 (mean baseline score, 110.26; week 2 score, 95.46; mean change, -14.72) compared with patients in the control group (mean baseline score, 106.83; week 2 score, 85.42; mean change, -21.54; difference between groups, -6.82; 95% CI, -13.48 to -0.16; P = .045). Among the secondary outcomes, from baseline to week 2, patients in the intervention group vs those in the control group had less increase in depression (mean, 2.43 vs 3.94; mean difference, 1.52; 95% CI, 0.23-2.81; P = .02), lower anxiety (mean, -0.80 vs 1.12; mean difference, 1.92; 95% CI, 0.83-3.01; P < .001), no difference in fatigue (mean, -10.30 vs -13.65; mean difference, -3.34; 95% CI, -7.25 to 0.56; P = .09), and less increase in symptom burden (mean, 17.35 vs 23.14; mean difference, 5.80; 95% CI, 0.49-11.10; P = .03). At 3 months after HCT, intervention patients vs control patients had higher QOL scores (mean, 112.00 vs 106.66; mean difference, 5.34; 95% CI, 0.04-10.65; P = .048) and less depression symptoms (mean, 3.49 vs 5.19; mean difference, -1.70; 95% CI, -2.75 to -0.65; P = .002) but no significant differences in anxiety, fatigue, or symptom burden. From baseline to week 2 after HCT, caregivers of patients in the intervention group vs caregivers of patients in the control group reported no significant differences in QOL or anxiety but had a smaller increase in depression (mean, 0.25 vs 1.80; mean difference, 1.55; 95% CI, 0.14-2.96; P = .03). Conclusions and Relevance: Among adults at a single institution undergoing HCT for hematologic malignancy, the use of inpatient palliative care compared with standard transplant care resulted in a smaller decrease in QOL 2 weeks after transplantation. Further research is needed for replication and to assess longer-term outcomes and cost implications. Trial Registration: clinicaltrials.gov Identifier: NCT02207322.

Quality of life and mood of patients and family caregivers during hospitalization for hematopoietic stem cell transplantation.

BACKGROUND: We conducted a study to investigate the impact of hospitalization for hematopoietic stem cell transplantation (HCT) on the quality of life (QOL) and mood of patients and family caregivers (FC). METHODS: We conducted a longitudinal study of patients who were hospitalized for HCT and their FC. We assessed QOL (using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation) and mood (using the Hospital Anxiety and Depression Scale) at baseline (6 days before HCT), day +1, and day +8 of HCT. We administered the Medical Outcomes Study Health Survey Short Form-36 to examine FC QOL (Physical Component Scale and Mental Component Scale). To identify predictors of changes in QOL, we used multivariable linear mixed models. RESULTS: We enrolled 97% of eligible patients undergoing autologous (30 patients), myeloablative (30 patients), or reduced intensity (30 patients) allogeneic HCT. Patients' QOL markedly declined (mean Functional Assessment of Cancer Therapy-Bone Marrow Transplantation score, 109.6 to 96.0; P<.0001) throughout hospitalization. The percentage of patients with depression (Hospital Anxiety and Depression Scale-Depression score of >7) more than doubled from baseline to day +8 (15.6% to 37.8%; P<.0001), whereas the percentage of patients with anxiety remained stable (22.2%; P = .8). These results remained consistent when data were stratified by HCT type. Baseline depression (ß, -2.24; F, 42.2 [P<.0001]) and anxiety (ß, -0.63; F, 4.4 [P =.03]) were found to independently predict worse QOL throughout hospitalization. FC QOL declined during the patient's hospitalization (physical component scale: 83.1 to 79.6 [P =.03] and mental component scale: 71.6 to 67.4 [P =.04]). CONCLUSIONS: Patients undergoing HCT reported a steep deterioration in QOL and substantially worsening depression during hospitalization. Baseline anxiety and depression predicted worse QOL during hospitalization, underscoring the importance of assessing pre-HCT psychiatric morbidity.

Difficulties in hematopoietic progenitor cell collection from a patient with TEMPI syndrome and severe iatrogenic iron deficiency.

BACKGROUND: Collection of hematopoietic progenitor cells by apheresis (HPC-A) requires separation of cells by density. Previous studies highlighted the challenges of HPC-A collection from patients with abnormal red blood cells (RBCs). TEMPI syndrome is a recently described condition defined by teleangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. Patients with TEMPI syndrome have responded to therapies used to treat plasma cell dyscrasias and may benefit from autologous HPC transplantation. We report HPC-A collection from a patient with TEMPI syndrome that was complicated by severe iron deficiency. STUDY DESIGN AND METHODS: The patient received granulocyte-colony-stimulating factor (G-CSF) and plerixafor for HPC mobilization and underwent 3 days of HPC-A collection. RESULTS: The patient presented for collection with a microcytic erythrocytosis. Over 3 days, approximately 50 L of whole blood was processed, and 2 × 10(8) CD34+ cells were collected (2.8 × 10(6) CD34+ cells/kg). The mean collection efficiency (CE), percentage of mononuclear cells, hematocrit (Hct), and RBC count were 18%, 90%, 14%, and 9 × 10(11) , respectively. Altering collection variables to avoid RBC contamination reduced CE. Ficoll preparations of the products after freeze-thaw showed RBC contamination and hemolysis. Postthaw viability exceeded 95%. The products were not RBC reduced or washed. There were no adverse reactions during or after infusion. CONCLUSIONS: HPC-A collection from a patient with TEMPI syndrome was complicated by microcytic erythrocytosis, leading to RBC contamination and hemolysis in the product. Adequate HPCs were collected and the patient tolerated infusion without RBC depletion or washing. Our report highlights difficulties of HPC-A collection from iron-deficient patients.

The fetal allograft revisited: does the study of an ancient invertebrate species shed light on the role of natural killer cells at the maternal-fetal interface?

Human pregnancy poses a fundamental immunological problem because the placenta and fetus are genetically different from the host mother. Classical transplantation theory has not provided a plausible solution to this problem. Study of naturally occurring allogeneic chimeras in the colonial marine invertebrate, Botryllus schlosseri, has yielded fresh insight into the primitive development of allorecognition, especially regarding the role of natural killer (NK) cells. Uterine NK cells have a unique phenotype that appears to parallel aspects of the NK-like cells in the allorecognition system of B. schlosseri. Most notably, both cell types recognize and reject "missing self" and both are involved in the generation of a common vascular system between two individuals. Chimeric combination in B. schlosseri results in vascular fusion between two individual colonies; uterine NK cells appear essential to the establishment of adequate maternal-fetal circulation. Since human uterine NK cells appear to de-emphasize primary immunological function, it is proposed that they may share the same evolutionary roots as the B. schlosseri allorecognition system rather than a primary origin in immunity.

Combined Targeted Therapy for BRAF-Mutant, Treatment-Related Acute Myeloid Leukemia.

A 44-year-old woman with a prior history of myxoid liposarcoma who was previously treated with radiation, chemotherapy, and resection, was admitted with syncope and pancytopenia. She was diagnosed with a high-grade therapy-related myelodysplastic syndrome and treated with decitabine. Her disease soon progressed to overt acute myeloid leukemia (AML). She was treated with cytotoxic chemotherapy including cytarabine and topotecan, but she was not a candidate for further anthracycline exposure given her prior treatment for sarcoma and concern for cardiotoxicity. Her AML was refractory to two sequential induction regimens. Given that targeted genomic sequencing had revealed a BRAF V600E mutation with a high allelic fraction, she was then placed on combined targeted BRAF/MEK therapy with dabrafenib and trametinib for her refractory disease. This resulted in a dramatic response with clearance of circulating myeloblasts, restoration of normal hematopoiesis, a significant decrease in marrow leukemic burden, and a concordant decrease in the BRAF V600E allelic burden. The response was transient, however, with a rapid increase in circulating blasts a few weeks later. At the time of subsequent progression, four separate KRAS mutations were identified. She died approximately 4 months after her diagnosis from rapidly progressive AML.

Effect of Inpatient Palliative Care During Hematopoietic Stem-Cell Transplant on Psychological Distress 6 Months After Transplant: Results of a Randomized Clinical Trial.

Purpose Inpatient palliative care integrated with transplant care improves patients' quality of life (QOL) and symptom burden during hematopoietic stem-cell transplant (HCT). We assessed patients' mood, post-traumatic stress disorder (PTSD) symptoms, and QOL 6 months post-transplant. Methods We randomly assigned 160 patients with hematologic malignancies who underwent autologous or allogeneic HCT to inpatient palliative care integrated with transplant care (n = 81) or transplant care alone (n = 79). At baseline and 6 months post-transplant, we assessed mood, PTSD symptoms, and QOL with the Hospital Anxiety and Depression Scale and Patient Health Questionnaire, PTSD checklist, and Functional Assessment of Cancer Therapy-Bone Marrow Transplant. To assess symptom burden during HCT, we used the Edmonton Symptom Assessment Scale. We used analysis of covariance while controlling for baseline values to examine intervention effects and conducted causal mediation analyses to examine whether symptom burden or mood during HCT mediated the effect of the intervention on 6-month outcomes. Results We enrolled 160 (86%) of 186 potentially eligible patients between August 2014 and January 2016. At 6 months post-transplant, intervention participants reported lower depression symptoms on the Hospital Anxiety and Depression Scale and Patient Health Questionnaire (adjusted mean difference, -1.21 [95% CI, -2.26 to -0.16; P = .024] and -1.63 [95% CI, -3.08 to -0.19; P = .027], respectively) and lower PTSD symptoms (adjusted mean difference, -4.02; 95% CI, -7.18 to -0.86; P = .013), but no difference in QOL or anxiety. Symptom burden and anxiety during HCT hospitalization partially mediated the effect of the intervention on depression and PTSD at 6 months post-transplant. Conclusion Inpatient palliative care integrated with transplant care leads to improvements in depression and PTSD symptoms at 6 months post-transplant. Reduction in symptom burden and anxiety during HCT partially accounts for the effect of the intervention on these outcomes.