Coping and Modifiable Psychosocial Factors are Associated with Mood and Quality of Life in Patients with Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (GVHD) is one of most common complications following allogeneic hematopoietic cell transplantation (HCT) and the most significant contributor to morbidity and nonrelapse mortality. The physical burdens and psychosocial difficulties of these patients have not been described systematically. An exploration into the rates and correlates of mood and quality of life (QOL) in patients with chronic GVHD is necessary to develop a clinically relevant, evidence-based intervention to promote well-being. From July 2015 to July 2017, adult allogeneic HCT survivors with established moderate to severe chronic GVHD (N = 52) enrolled in a prospective, longitudinal study at a tertiary academic center. We examined the rates and correlates of depression and anxiety symptoms (Hospital Anxiety and Depression Scale) and explored whether constructs including coping strategies (Coping Inventory for Stressful Situations), symptom burden (Lee Symptom Assessment Scale), physical functioning (Human Activity Profile), and perceived social support (Medical Outcomes Study Social Support Survey) predicted QOL trajectory over time (Functional Assessment of Cancer Therapy-Bone Marrow Transplant) at the baseline, 3-month, and 6-month follow-up. Analyses adjusted for age, sex, chronic GVHD severity, and time since chronic GVHD diagnosis. At the baseline, 3-month, and 6-month follow-up, 32.7%, 31.1%, and 37.8% of patients reported clinically significant depression symptoms, and 30.8%, 20.0%, and 36.4% reported clinically elevated anxiety symptoms, respectively. Adjusting for covariates, greater use of negative emotion-oriented coping (ß = 0.20, P = .002), less use of task-oriented coping (ß = -0.10, P = .021), worse physical functioning (ß = -0.07, P = .004), and higher symptom burden (ß = 0.07, P = .002) were independently associated with depression symptoms at baseline. Greater use of negative emotion-oriented coping (ß = 0.28, P < .001) and worse physical functioning (ß = -0.05, P = .034) were independently associated with anxiety at baseline. Patients who used more negative emotion-oriented coping (ß = -0.58, P = .035), had less task-oriented (ß = 0.40, P = .028) and social diversion-oriented coping (ß = 0.35, P = .039), and had higher symptom burden (ß = -0.30, P = .001), worse physical functioning (ß = 0.32, P < .001), and lower perceived social support (ß = 6.47, P = .003) at baseline reported poorer QOL over time. The unmet physical and psychosocial needs of patients with chronic GVHD are substantial and warrant investigation into evidence-based interventions that may improve QOL and mood by targeting modifiable psychosocial constructs identified in this study.

Phase I Trial of Brentuximab Vedotin for Steroid-Refractory Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.

We conducted a phase I study of brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, for the treatment of steroid-refractory chronic graft-versus-host disease (cGVHD). A modified 3 + 3 study design was used with the primary endpoint to determine the maximum tolerated dose of BV in this population. Escalating doses of BV were planned, starting with .6 mg/kg every 3 weeks (dose level 0) and increasing by .3 mg/kg per dose level. BV was administered in 21-day cycles for up to 16 cycles of therapy. Nineteen patients were enrolled on the study, with 2 withdrawing consent before dosing. The median number of cycles of therapy was 4 (range, 1 to 16). Reasons for stopping therapy prematurely included toxicities (n = 9), patient decision (n = 3), lack of response (n = 2), and death (n = 1). There were 2 dose-limiting toxicities observed: posterior reversible encephalopathy syndrome (cohort 4, grade 3) and sepsis (cohort 4, grade 4). The maximum tolerated dose was not reached because the trial was prematurely closed due to toxicity. Seven patients (41%) developed grade 3 or 4 adverse events that were attributed to therapy, including 4 patients who developed moderate or severe peripheral neuropathy that led to cessation of treatment in each case. According to National Institutes of Health cGVHD response criteria, 8 patients (47%) experienced a partial response, whereas 9 patients (53%) had a lack of response. There were no complete responses observed. Eleven patients (65%) were able to decrease their systemic corticosteroid dose by ≥50% by 6 months after initiation of BV, including 3 patients who were able to stop corticosteroids completely. The median soluble CD30 level before therapy was 61.5 ng/mL (range, 7.8 to 474.9); however, we did not observe any association between soluble CD30 level and cGVHD severity at enrollment or clinical responses to BV. In conclusion, BV may have activity in treatment of steroid-refractory cGVHD, yet its use is limited by treatment-emergent toxicities, including peripheral neuropathy. Continued efforts to investigate targeted approaches to cGVHD that do not cause broad immunosuppression are needed.

Pilot study of a multimodal intervention to enhance sexual function in survivors of hematopoietic stem cell transplantation.

BACKGROUND: Although sexual dysfunction is common after hematopoietic stem cell transplantation (HCT), interventions to address sexual function are lacking. METHODS: We conducted a pilot study to assess the feasibility and preliminary efficacy of a multimodal intervention to address sexual dysfunction in allogeneic HCT survivors. Transplant clinicians screened HCT survivors ≥3 months post-HCT for sexual dysfunction causing distress. Those who screened positive attended monthly visits with a trained transplant clinician who: 1) performed an assessment of the causes of sexual dysfunction; 2) educated and empowered the patient to address his or her sexual concerns; and 3) implemented therapeutic interventions targeting the patient's needs. Feasibility was defined as having approximately 75% of patients who screened positive agreeing to participate and 80% attending at least 2 intervention visits. We administered the Patient-Reported Outcomes Measurement Information System (PROMIS) sexual function and satisfaction measure, the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS) to evaluate sexual function, quality of life (QOL), and mood, respectively, at baseline and 6 months postintervention. RESULTS: Approximately 33.1% of patients (50 of 151 patients) screened positive for sexual dysfunction causing distress and 94.0% (47 of 50 patients) agreed to participate, with 100% attending 2 intervention visits. Participants reported improvements in satisfaction (P<.0001) and interest in sex (P<.0001), as well as orgasm (P<.0001), erectile function (P<.0001), vaginal lubrication (P = .0001), and vaginal discomfort (P = .0005). At baseline, approximately 32.6% of participants were not sexually active, compared with 6.5% after the intervention (P = .0005). Participants reported improvement in their QOL (P<.0001), depression (P = .0002), and anxiety (P = .0019). CONCLUSIONS: A multimodal intervention to address sexual dysfunction integrated within the transplant clinic is feasible with encouraging preliminary efficacy for improving sexual function, QOL, and mood in HCT survivors. Cancer 2018;124:2438-46. © 2018 American Cancer Society.

Phase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia.

Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML], n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [CI], 1.0 to 17.4) and 24% (95% CI, 11 to 39), respectively. The 2-year relapse rate was 26% (95% CI, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD.