IMPORTANCEDuring 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 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 followup, and 149 patients (93.1%) completed 3-month follow-up. Intervention patients reported a smaller decrease in QOL from baseline to week 2 vs controls. Intervention patients had less increase in depression,loweranxiety,nodifferenceinfatigue,andlessincreaseinsymptomburden.At3months, intervention patients had higher QOL and less depression but no significant differences in anxiety, fatigue, or symptom burden. From baseline to week 2 after HCT, caregivers of intervention patients vs controls 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). Patient Outcomes Mean Score at Week 2 Mean Difference Between Groups (95% CI) P Value Standard Care Palliative Care Quality of life (change from baseline) −21.54 −14.72 −6.82 (−13.48 to −0.16) .045 Fatigue −13.65 −10.30 −3.34 (−7.25 to 0.56) .09 Symptom burden 23.14 17.35 5.80 (0.49 to 11.10) .03 Depression 3.92 2.43 1.49 (0.20 to 2.78) .02 Anxiety 1.12 −0.80 1.92 (0.83 to 3.01) <.001CONCLUSIONS 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.

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This is the first report of the deliberate induction of mixed lymphohematopoietic chimerism after a nonmyeloablative preparative regimen to treat a hematological malignancy and to provide allotolerance for a solid organ transplant.

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Six patients with renal failure due to multiple myeloma (MM) received simultaneous kidney and bone marrow transplantation (BMT) from HLA-identical sibling donors following nonmyeloablative conditioning, including cyclophosphamide (CP), peritransplant antithymocyte globulin and thymic irradiation. Cyclosporine (CyA) was given for approximately 2 months posttransplant, followed by donor leukocyte infusions. All six patients accepted their kidney grafts long-term. Three patients lost detectable chimerism but accepted their kidney grafts off immunosuppression for 1.3 to >7 years. One such patient had strong antidonor cytotoxic T lymphocyte (CTL) responses in association with marrow rejection. Two patients achieved full donor chimerism, but resumed immunosuppression to treat graft-versus-host disease. Only one patient experienced rejection following CyA withdrawal. He responded to immunosuppression, which was later successfully withdrawn. The rejection episode was associated with antidonor Th reactivity. Patients showed CTL unresponsiveness to cultured donor renal tubular epithelial cells. Initially recovering T cells were memory cells and were enriched for CD4 + CD25 + cells. Three patients are in sustained complete remissions of MM, despite loss of chimerism in two. Combined kidney/BMT with nonmyeloablative conditioning can achieve renal allograft tolerance and excellent myeloma responses, even in the presence of donor marrow rejection and antidonor alloresponses in vitro.

Background To investigate the impact of hospitalization for hematopoietic stem cell transplantation (HCT) on patients’ and family caregivers’ (FC) quality of life (QOL) and mood. Methods We conducted a longitudinal study of patients hospitalized for HCT and their FC. At baseline (6 days pre-HCT), day+1, and day+8 of HCT, we assessed QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation FACT-BMT), and mood (Hospital Anxiety and Depression Scale HADS). We administered the SF-36 to examine FC QOL [physical component scale (PCS), and mental component scale (MCS)]. To identify predictors of QOL changes, we used multivariable linear mixed models. Results We enrolled 97% of eligible patients undergoing autologous (n=30), myeloablative (n=30) or reduced intensity (n=30) allogeneic HCT. Patients’ QOL markedly declined (mean FACT-BMT 109.6 to 96.0, P < 0.0001) throughout hospitalization. The proportion of patients with depression (HADS-Depression> 7) more than doubled from baseline to day+8 (15.6% to 37.8%, P < 0.0001), whereas the proportion of patients with anxiety remained stable (22.2%, P = 0.8). These results remained consistent when data were stratified by HCT type. Baseline depression (β= −2.24, F=42.2, p < 0.0001) and anxiety (β= −0.63, F=4.4, p = 0.03) independently predicted worse QOL throughout hospitalization. FC QOL declined during patient’s hospitalization (PCS: 83.1 to 79.6, P= 0.03, MCS: 71.6 to 67.4, P = 0.04). 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.

Mixed lymphohematopoietic chimerism can be induced in mice with bone marrow transplantation (BMT) after a nonmyeloablative preparative regimen that includes cyclophosphamide, anti-T-cell antibody therapy, and thymic irradiation. These mixed chimeras are resistant to the induction of graft-versus-host disease (GVHD) after delayed donor leukocyte infusions (DLIs), despite a potent lymphohematopoietic graft-versus-host reaction that converts the mixed chimeric state to a full donor one. Based on this animal model, we initiated a trial of nonmyeloablative therapy with HLA-matched or -mismatched donor BMT and DLI for refractory hematologic malignancies. Twenty-one of 36 patients enrolled in this trial received a genotypically (n = 20) or phenotypically (n = 1) HLA-matched donor transplant; results reported here are for those patients only. Preparative therapy consisted of cyclophosphamide in doses of 150 to 200 mg/kg; peritransplant antithymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal radiation therapy); and cyclosporine. Eighteen of 20 evaluable patients developed persistent mixed lymphohematopoietic chimerism as defined by >1% donor peripheral white blood cells until at least day 35 posttransplantation. Ten patients received prophylactic DLI beginning 5 to 6 weeks after BMT for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-leukemia effect. Fourteen of 20 evaluable patients (70%) achieved an antitumor response; 8 of these responses were complete, and 6 were partial. Of the 8 evaluable patients who received prophylactic DLI, 6 showed conversion to full donor chimerism. Five of the 9 evaluable patients (56%) who received prophylactic DLI achieved a complete response, compared with 3 of 11 patients (27%) who did not receive prophylactic DLI. Currently 11 patients are alive, and 7 of these are free of disease progression at a median follow-up time of 445 days (range, 105-548 days) posttransplantation. Transplantation-related complications included cyclophosphamide-induced cardiac toxicity in 3 of 21 patients (14%) and grade II or greater GVHD in 6 patients (29%). One patient (5%) died from a complication of BMT, and 1 patient (5%) died from GVHD after 2 prophylactic DLIs were given for conversion of chimerism. In summary, mixed lymphohematopoietic chimerism was reproducibly induced after a novel nonmyeloablative preparative regimen incorporating chemotherapy, peritransplant antithymocyte globulin, and thymic irradiation, allowing for early administration of DLI in 10 of 21 patients. After treatment, striking antitumor responses were observed in the majority of patients with chemotherapy-refractory hematologic malignancies.

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.